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Villanueva C, Tripathi D, Bosch J. Preventing the progression of cirrhosis to decompensation and death. Nat Rev Gastroenterol Hepatol 2025; 22:265-280. [PMID: 39870944 DOI: 10.1038/s41575-024-01031-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/06/2024] [Indexed: 01/29/2025]
Abstract
Two main stages are differentiated in patients with advanced chronic liver disease (ACLD), one compensated (cACLD) with an excellent prognosis, and the other decompensated (dACLD), defined by the appearance of complications (ascites, variceal bleeding and hepatic encephalopathy) and associated with high mortality. Preventing the progression to dACLD might dramatically improve prognosis and reduce the burden of care associated with ACLD. Portal hypertension is a major driver of the transition from cACLD to dACLD, and a portal pressure of ≥10 mmHg defines clinically significant portal hypertension (CSPH) as the threshold from which decompensating events may occur. In recent years, innovative studies have provided evidence supporting new strategies to prevent decompensation in cACLD. These studies have yielded major advances, including the development of noninvasive tests (NITs) to identify patients with CSPH with reasonable confidence, the demonstration that aetiological therapies can prevent disease progression and even achieve regression of cirrhosis, and the finding that non-selective β-blockers can effectively prevent decompensation in patients with cACLD and CSPH, mainly by reducing the risk of ascites, the most frequent decompensating event. Here, we review the evidence supporting new strategies to manage cACLD to prevent decompensation and the caveats for their implementation, from patient selection using NITs to ancillary therapies.
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Affiliation(s)
- Càndid Villanueva
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
- Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Ministerio de Sanidad, Madrid, Spain.
| | - Dhiraj Tripathi
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham Health Partners, Birmingham, UK
- Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Jaume Bosch
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Ministerio de Sanidad, Madrid, Spain
- Department of Visceral Surgery and Medicine (Hepatology), Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Harrison SA, Mayo P, Hobbs T, Zhao C, Canizares C, Foster R, McRae MP, Helmke SM, Everson GT. Rencofilstat Treatment Improves Liver Function in MASH With Advanced Fibrosis as Quantified by HepQuant DuO. Liver Int 2025; 45:e70036. [PMID: 39982177 DOI: 10.1111/liv.70036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 12/31/2024] [Accepted: 02/08/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND AND AIMS Rencofilstat inhibits cyclophilin to reduce hepatic inflammation and fibrosis, which, in turn, could improve liver function and reduce portal-systemic shunting. Since HepQuant quantifies liver function and portal-systemic shunting, it was used to measure the hepatic effects of rencofilstat treatment of MASH with advanced fibrosis. METHODS Seventy subjects with suspected ≥ F3 MASH, defined from liver biopsy or AGILE 3+ ≥ 0.53, were randomised to rencofilstat 75 mg/d (n = 24), 150 mg/d (n = 23) or 225 mg/d (n = 23), and tested by HepQuant at baseline, 60 and 120 days. The DuO version included oral dosing of d4-cholate and two blood samples (20 and 60 min). DuO's disease severity index (DSI) and portal-systemic shunting fraction (SHUNT%) were evaluated for changes from baseline at 60 and 120 days of rencofilstat treatment. RESULTS Across all subjects, there was a significant decrease in SHUNT% both at Day 60 (-1.67%, p = 0.0156) and Day 120 (-1.55%, p = 0.0441). In the 225 mg rencofilstat arm, 56% of subjects (10/18) were responders by Day 120 (p = 0.0549), and their DSIs improved with a mean change of -1.61 (p = 0.0190). Across all treatment arms, subjects with DSI > 18.3 at baseline had the greatest improvement with treatment (ΔDSI = -2.59, p = 0.0053). CONCLUSION Although further studies are warranted, the decreases in DSI and SHUNT% suggest that rencofilstat 225 mg/d improves hepatic function and portal-systemic shunting. HepQuant DuO is simple to administer, well-tolerated and a useful tool for detecting the hepatic effects of treatment. TRIAL REGISTRATION The study was registered at ClinicalTrials.gov, NCT05461105.
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Affiliation(s)
| | - Patrick Mayo
- Hepion Pharmaceuticals, Inc., Edison, New Jersey, United States
| | - Todd Hobbs
- Hepion Pharmaceuticals, Inc., Edison, New Jersey, United States
| | - Caroline Zhao
- Hepion Pharmaceuticals, Inc., Edison, New Jersey, United States
| | | | - Robert Foster
- Hepion Pharmaceuticals, Inc., Edison, New Jersey, United States
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Ko MY, Hsu YC, Yen HH, Huang SP, Su PY. The Effects of Pangenotypic Direct-Acting Antiviral Therapy on Lipid Profiles and Insulin Resistance in Chronic Hepatitis C Patients. Viruses 2025; 17:263. [PMID: 40007018 PMCID: PMC11861053 DOI: 10.3390/v17020263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/10/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Hepatitis C virus (HCV) eradication is usually associated with dyslipidemia. Most studies in this field have focused on genotype-specific direct-acting antivirals (DAAs), with research on pangenotypic DAAs being limited. This study examined how two pangenotypic DAA regimens, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), affect lipid profiles and insulin resistance after viral eradication in chronic HCV patients. A total of 100 patients (57 with GLE/PIB and 43 with SOF/VEL) treated between September 2020 and January 2022 were included in the retrospective analysis. This study found a significant increase in LDL and TC levels after treatment (p < 0.001), but no significant changes in triglycerides, high-density lipoprotein, HbA1C, or the Homeostatic Model Assessment of Insulin Resistance. According to a logistic regression analysis, higher baseline LDL or TC and lower baseline glucose are predictors of the degree of increase in LDL or TC following a sustained virological response. Both pangenotypic DAA regimens significantly impact lipid profiles, particularly LDL and TC, but not insulin resistance. This study emphasizes the need for more research into the long-term metabolic effects of DAAs.
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Affiliation(s)
- Meng-Yu Ko
- Division of Gastroenterology and Hepatology, Yuanlin Christian Hospital, Changhua 510012, Taiwan;
| | - Yu-Chung Hsu
- Division of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua 500209, Taiwan; (Y.-C.H.); (H.-H.Y.); (S.-P.H.)
| | - Hsu-Heng Yen
- Division of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua 500209, Taiwan; (Y.-C.H.); (H.-H.Y.); (S.-P.H.)
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan
| | - Siou-Ping Huang
- Division of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua 500209, Taiwan; (Y.-C.H.); (H.-H.Y.); (S.-P.H.)
| | - Pei-Yuan Su
- Division of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua 500209, Taiwan; (Y.-C.H.); (H.-H.Y.); (S.-P.H.)
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan
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Song L, Huang S, Yan H, Ma Q, Luo Q, Qiu J, Chen M, Li Z, Jiang H, Chen Y, Chen F, Du Y, Fu H, Zhao L, Zhao K, Qiu P. ADRB2 serves as a novel biomarker and attenuates alcoholic hepatitis via the SIRT1/PGC-1α/PPARα pathway: integration of WGCNA, machine learning and experimental validation. Front Pharmacol 2024; 15:1423031. [PMID: 39640486 PMCID: PMC11617210 DOI: 10.3389/fphar.2024.1423031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 11/08/2024] [Indexed: 12/07/2024] Open
Abstract
Background Alcoholic hepatitis is a severe inflammatory liver disease. In recent years, the incidence of AH has been on the rise, leading to an increasingly severe disease burden. Currently, there is a lack of specific biomarkers for the diagnosis and prognosis of AH in clinical practice. Therefore, the main objective of this study is to identify biomarkers closely associated with the progression of AH, to address the shortcomings in pathological diagnosis, and to identify potential therapeutic targets. Methods Bioinformatics and machine learning methods were used to comparatively study the differentially expressed genes (DEGs) between AH patients and healthy individuals by analyzing four mRNA microarray data sets obtained from the GEO database. Subsequently, the role of potential biomarkers in AH and their mechanism of action were further confirmed by AH patients and in vitro and in vivo experiments. Results Using differential analysis and WGCNA of the data set, a total of 167 key genes that may be related to AH were obtained. Among 167 genes, the LASSO logistic regression algorithm identified four potential biomarkers (KCNJ10, RPL21P23, ADRB2, and AC025279.1). Notably, ADRB2 showed biomarker potential in GSE28619, GSE94397, and E-MTAB-2664 datasets, and clinical liver samples. Furthermore, AH patients and in vivo experiments demonstrated ADRB2 inhibition and suppression of SIRT1/PPARα/PGC-1α signaling pathways, accompanied by elevated inflammatory factors and lipid deposition. In vitro experiments showed that ADRB2 overexpression mitigated the inhibition of the SIRT1/PPARα/PGC-1α signaling pathway, reversing the decrease in mitochondrial membrane potential, cell apoptosis, oxidative stress, and lipid deposition induced by alcohol exposure. Besides, the results also showed that ADRB2 expression in AH was negatively correlated with the levels of inflammatory factors (e.g., CCL2, CXCL8, and CXCL10). Conclusion This study points to ADRB2 as a promising biomarker with potential diagnostic and prognostic value in clinical cohort data. In addition, in AH patients, in vivo and in vitro experiments confirmed the key role of ADRB2 in the progression of AH. These findings suggest that ADRB2 may alleviate AH by activating the SIRT1/PPARα/PGC-1α pathway. This finding provides a new perspective for the diagnosis and treatment of AH.
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Affiliation(s)
- Li Song
- Tongde Hospital of Zhejiang Province affiliated to Zhejiang Chinese Medical University, Analysis and Testing Center, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shuo Huang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Honghao Yan
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qing Ma
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qihan Luo
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiang Qiu
- Department of Medicine, Hangzhou Normal University, Hangzhou, China
| | - Minxia Chen
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zongyuan Li
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - He Jiang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yufan Chen
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Fangming Chen
- Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yu Du
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Haozhe Fu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Lisha Zhao
- Tongde Hospital of Zhejiang Province affiliated to Zhejiang Chinese Medical University, Analysis and Testing Center, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Kanglu Zhao
- Zhejiang Rehabilitation Medical Center, Rehabilitation Hospital Area of the Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- School of Medicine, The Fourth Affiliated Hospital Zhejiang University, Yiwu, Zhejiang, China
| | - Ping Qiu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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Maezawa Y, Kodama Y, Ariga H, Kashimura J, Irie T. Hepatocellular Carcinoma Developing in a Patient 29 Years After Achieving Sustained Virologic Response for Hepatitis C With Interferon Therapy: A Case Report. Cureus 2024; 16:e74330. [PMID: 39720368 PMCID: PMC11667130 DOI: 10.7759/cureus.74330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2024] [Indexed: 12/26/2024] Open
Abstract
We report a case of an 87-year-old female with a ruptured hepatocellular carcinoma (HCC). She presented with sudden epigastric and right upper abdominal pain. The physical examination revealed mild tenderness in the right upper abdomen, a positive Murphy's sign, and no jaundice. Laboratory tests showed mild anemia and elevated PIVKA-II (prothrombin induced by vitamin K absence II) levels. Abdominal ultrasound and CT revealed a large hypervascular mass in the liver, along with ascites and portal vein thrombosis. The patient had received interferon therapy for hepatitis C virus (HCV) 29 years before her presentation and blood tests and imaging examinations had confirmed sustained undetectability for HCV ribonucleic acid (RNA) and the absence of HCC for five years following treatment. HCV RNA remained undetectable at the time of her admission, and it was presumed that it had been negative for 29 years post-treatment, with no evidence of re-exposure. The patient had not attended any follow-up appointments. While there have been no reported cases of a patient developing HCC 29 years after achieving sustained virologic response (SVR), our case suggests that the absence of HCC risk is not guaranteed, even after a prolonged period post-SVR. Therefore, periodic imaging tests such as abdominal ultrasound or CT may be beneficial in detecting potential HCC, even long after achieving SVR.
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Affiliation(s)
- Yosuke Maezawa
- Department of Internal Medicine, Mito Kyodo General Hospital, Mito, JPN
| | - Yukiko Kodama
- Department of Internal Medicine, Mito Kyodo General Hospital, Mito, JPN
| | - Hiroyuki Ariga
- Department of Gastroenterology, Mito Kyodo General Hospital, Mito, JPN
| | - Junya Kashimura
- Department of Gastroenterology, Mito Kyodo General Hospital, Mito, JPN
| | - Toshiyuki Irie
- Department of Radiology, Mito Kyodo General Hospital, Mito, JPN
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Al-Rawaf HA, Gabr SA, Iqbal A, Alghadir AH. Circulating microRNAs as potential biomarkers of physical activity in geriatric patients with HCV. BMC Mol Cell Biol 2024; 25:18. [PMID: 39030480 PMCID: PMC11264506 DOI: 10.1186/s12860-024-00514-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 07/09/2024] [Indexed: 07/21/2024] Open
Abstract
BACKGROUND Circulating microRNAs have been implicated in a diverse array of biological and pathological phenomena. Their potential utility as noninvasive biomarkers for screening and diagnosing various diseases has been proposed. OBJECTIVE This study aimed to explore the potential role of the miRNAs miR-122 and miR-486 as molecular biomarkers in the pathogenesis of hepatitis C virus (HCV) infection. Thus, miR-122 and miR-486 were detected in the serum of HCV patients and healthy controls. Moreover, the potential correlations of miR-122 and miR-486 with viral complications, such as physical activity, pain, muscle fatigue, and HCV infection, were identified. METHODS A total of 150 subjects aged 30 to 66 years were included in this study. The patients were classified as patients with chronic hepatitis C virus (CHC) (n = 110) or healthy controls (n = 40). Real-time polymerase chain reaction (PCR) analyses were performed to determine miR-122 and miR-486 expression. Physical activity (PA), pain score, HCV genotyping, viral overload, aspartate transaminase (AST), alanine transaminase (ALT), lactic acid dehydrogenase (LDH), creatine kinase (CK), and antioxidant status were also estimated by using prevalidated questionnaires, PCR, and spectrophotometric analyses. RESULTS Compared with those in normal controls, significant increases in the serum levels of miR-122 and miR-486 were reported in patients with CHC. In physically active CHC patients, there was a significant correlation between the expression of miRNAs and increased alanine transaminase (ALT), aspartate transaminase (AST), fibrosis scores, and inflammation activity, but no association was reported for hepatitis C virus (HCV) RNA or viral load. Additionally, significant decreases in LDH, CK, GSSG, and pain scores and increases in TAC, GSH, and the GSH/GSSG ratio were reported. Moreover, the expression of miR-122 and miR-486 was positively correlated with changes in body mass index (BMI) and liver fibrosis stage, as well as negatively correlated with sex, PA, TAC, GSH, GSSG, and the GSH/GSSG ratio. CONCLUSION MiR-122 and miR-486 expression levels were strongly correlated with physical activity, pain perception, and muscle fatigue biomarkers in HCV-infected patients. These miRNA levels were associated with elevated AST, ALT, fibrosis scores, LDH, CK, and antioxidant status, thus suggesting their potential as biomarkers for disease severity and oxidative stress. However, no correlation was observed with viral load or HCV-RNA expression, thus implying that these miRNAs may impact disease progression and symptoms through host factors, rather than directly affecting viral replication. In summary, the results demonstrated that molecular studies of miR-22 and miR-468 and their associations with PA, pain, adiposity, sex differences, and muscle fatigue, as well as routine biomarkers, could be useful as prognostic nanoninvasive biomarkers, thus providing novel therapeutic targets for CHC infection.
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Affiliation(s)
- Hadeel A Al-Rawaf
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, 11433, Saudi Arabia
| | - Sami A Gabr
- Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia
| | - Amir Iqbal
- Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia.
| | - Ahmad H Alghadir
- Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia
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Zheng S, Xue C, Li S, Zao X, Li X, Liu Q, Cao X, Wang W, Qi W, Du H, Zhang P, Ye Y. Liver cirrhosis: current status and treatment options using western or traditional Chinese medicine. Front Pharmacol 2024; 15:1381476. [PMID: 39081955 PMCID: PMC11286405 DOI: 10.3389/fphar.2024.1381476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 06/28/2024] [Indexed: 08/02/2024] Open
Abstract
Liver cirrhosis arises from liver fibrosis and necroinflammation caused by various mechanisms of hepatic injury. It is a prevalent condition in clinical practice characterized by hepatocellular dysfunction, portal hypertension, and associated complications. Despite its common occurrence, the etiology and pathogenesis of liver cirrhosis remain incompletely understood, posing a significant health threat. Effective prevention of its onset and progression is paramount in medical research. Symptoms often include discomfort in the liver area, while complications such as sarcopenia, hepatic encephalopathy, ascites, upper gastrointestinal bleeding, and infection can arise. While the efficacy of Western medicine in treating liver cirrhosis is uncertain, Chinese medicine offers distinct advantages. This review explores advancements in liver cirrhosis treatment encompassing non-pharmacological and pharmacological modalities. Chinese medicine interventions, including Chinese medicine decoctions, Chinese patent medicines, and acupuncture, exhibit notable efficacy in cirrhosis reversal and offer improved prognoses. Nowadays, the combination of Chinese and Western medicine in the treatment of liver cirrhosis also has considerable advantages, which is worthy of further research and clinical promotion. Standardized treatment protocols based on these findings hold significant clinical implications.
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Affiliation(s)
- Shihao Zheng
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Chengyuan Xue
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Size Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Xiaobin Zao
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaoke Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Liver Diseases Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Qiyao Liu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Xu Cao
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Liver Diseases Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Wei Wang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Wenying Qi
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Hongbo Du
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Liver Diseases Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Peng Zhang
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yongan Ye
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Liver Diseases Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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Hofmeister MG, Zhong Y, Moorman AC, Samuel CR, Teshale EH, Spradling PR. Temporal Trends in Hepatitis C-Related Hospitalizations, United States, 2000-2019. Clin Infect Dis 2023; 77:1668-1675. [PMID: 37463305 PMCID: PMC11017377 DOI: 10.1093/cid/ciad425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/06/2023] [Accepted: 07/13/2023] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND Hospitalization burden related to hepatitis C virus (HCV) infection is substantial. We sought to describe temporal trends in hospitalization rates before and after release of direct-acting antiviral (DAA) agents. METHODS We analyzed 2000-2019 data from adults aged ≥18 years in the National Inpatient Sample. Hospitalizations were HCV-related if (1) hepatitis C was the primary diagnosis, or (2) hepatitis C was any secondary diagnosis with a liver-related primary diagnosis. We analyzed characteristics of HCV-related hospitalizations nationally and examined trends in age-adjusted hospitalization rates. RESULTS During 2000-2019, there were an estimated 1 286 397 HCV-related hospitalizations in the United States. The annual age-adjusted hospitalization rate was lowest in 2019 (18.7/100 000 population) and highest in 2012 (29.6/100 000 population). Most hospitalizations occurred among persons aged 45-64 years (71.8%), males (67.1%), White non-Hispanic persons (60.5%), and Medicaid/Medicare recipients (64.0%). The national age-adjusted hospitalization rate increased during 2000-2003 (annual percentage change [APC], 9.4%; P < .001) and 2003-2013 (APC, 1.8%; P < .001) before decreasing during 2013-2019 (APC, -7.6%; P < .001). Comparing 2000 to 2019, the largest increases in hospitalization rates occurred among persons aged 55-64 years (132.9%), Medicaid recipients (41.6%), and Black non-Hispanic persons (22.3%). CONCLUSIONS Although multiple factors likely contributed, overall HCV-related hospitalization rates declined steadily after 2013, coinciding with the release of DAAs. However, the declines were not observed equally among age, race/ethnicity, or insurance categories. Expanded access to DAA treatment is needed, particularly among Medicaid and Medicare recipients, to reduce disparities and morbidity and eliminate hepatitis C as a public health threat.
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Affiliation(s)
- Megan G Hofmeister
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Yuna Zhong
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Anne C Moorman
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Christina R Samuel
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Eyasu H Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Philip R Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
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9
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Elbahrawy A, Atalla H, Mahmoud AA, Eliwa A, Alsawak A, Alboraie M, Madian A, Alashker A, Mostafa S, Alwassief A, Aly HH. Prediction and surveillance of de novo HCC in patients with compensated advanced chronic liver disease after hepatitis C virus eradication with direct antiviral agents. FRONTIERS IN VIROLOGY 2023; 3. [DOI: 10.3389/fviro.2023.1227317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The risk of hepatocellular carcinoma (HCC) diminishes in patients with hepatitis C virus (HCV)-related advanced chronic liver disease after virological cure. However, despite viral clearance, HCV-induced epigenetic alterations, immune dysregulations, and hepatic parenchymal injuries remain, contributing to de novo HCC occurrence. While HCC incidence is low (0.45 – 0.5%) in patients with advanced fibrosis (F3), the presence of liver cirrhosis and clinically significant portal hypertension increases the HCC risk. The cost-effectiveness of lifelong HCC surveillance in patients with compensated advanced chronic liver disease (cACLD) has sparked debate, raising questions about the most reliable noninvasive tests and stratification models for predicting HCC in patients with sustained virological response (SVR). Furthermore, identifying cACLD patients who may not require long-term HCC surveillance after SVR remains crucial. Several HCC risk stratification scores have been suggested for patients with cACLD, and emerging evidence supports individualized care based on personalized risk assessments. This review focuses on revising the pretreatment and posttreatment predictors of HCC, as well as the indications for HCC surveillance in cACLD patients treated with direct-acting antivirals.
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10
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Przybyszewski EM, Chung RT. Unmet Needs in the Post-Direct-Acting Antiviral Era: Hepatocarcinogenesis After Hepatitis C Virus Eradication. J Infect Dis 2023; 228:S226-S231. [PMID: 37703341 PMCID: PMC10499186 DOI: 10.1093/infdis/jiac447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023] Open
Abstract
Infection with chronic hepatitis C virus (HCV) is an important risk factor for hepatocellular carcinoma (HCC). Direct-acting antiviral therapy has transformed care for patients with HCV and reduces the risk of HCC. Despite HCV cure, a residual HCC risk remains in patients with advanced fibrosis and cirrhosis, with multiple mechanisms underlying subsequent hepatocarcinogenesis. Transcriptomic and proteomic signatures demonstrate the capacity for HCC risk stratification, and chemoprevention strategies are emerging. For now, pending more precise stratification, HCC surveillance of patients with cured HCV and advanced fibrosis or cirrhosis should continue.
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Affiliation(s)
- Eric M Przybyszewski
- Liver Center and Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Liver Center and Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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Rocha C, Doyle EH, Bowman CA, Fiel M, Stueck AE, Goossens N, Bichoupan K, Patel N, Crismale JF, Makkar J, Lewis S, Perumalswami PV, Schiano TD, Hoshida Y, Schwartz M, Branch AD. Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis. Cancer Med 2023; 12:10175-10186. [PMID: 37078924 PMCID: PMC10225173 DOI: 10.1002/cam4.5711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 01/06/2023] [Accepted: 02/07/2023] [Indexed: 04/21/2023] Open
Abstract
BACKGROUND Successful treatment of hepatitis C reduces liver inflammation and fibrosis; however, patients remain at risk of developing hepatocellular carcinoma (HCC). AIMS To identify risk factors for new-onset HCC in patients cured of hepatitis C. METHODS Imaging, histological, and clinical data on patients whose first HCC was diagnosed >12 months of post-SVR were analyzed. Histology of 20 nontumor tissues was analyzed in a blinded manner using the Knodel/Ishak/HAI system for necroinflammation and fibrosis/cirrhosis stage and the Brunt system for steatosis/steatohepatitis. Factors associated with post-SVR HCC were identified by comparison with HALT-C participants who did not develop post-SVR HCC. RESULTS Hepatocellular carcinoma was diagnosed in 54 patients (45 M/9F), a median of 6 years of post-SVR [interquartile range (IQR) =1.4-10y] at a median age of 61 years (IQR, 59-67). Approximately one-third lacked cirrhosis, and only 11% had steatosis on imaging. The majority (60%) had no steatosis/steatohepatitis in histopathology. The median HAI score was 3 (1.25-4), indicating mild necroinflammation. In a multivariable logistic regression model, post-SVR HCC was positively associated with non-Caucasian race (p = 0.03), smoking (p = 0.03), age > 60 years at HCC diagnosis (p = 0.03), albumin<3.5 g/dL (p = 0.02), AST/ALT>1 (p = 0.05), and platelets <100 × 103 cells/μL (p < 0.001). Alpha fetoprotein ≥4.75 ng/mL had 90% specificity and 71% sensitivity for HCC occurrence. Noncirrhotic patients had larger tumors (p = 0.002) and a higher prevalence of vascular invasion (p = 0.016) than cirrhotic patients. CONCLUSIONS One-third of patients with post-SVR HCC did not have liver cirrhosis; most had no steatosis/steatohepatitis. Hepatocellular carcinomas were more advanced in noncirrhotic patients. Results support AFP as a promising marker of post-SVR HCC risk.
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Affiliation(s)
- Chiara Rocha
- Department of Surgery—Transplant DivisionIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Erin H. Doyle
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount Sinai SchoolNew YorkNew YorkUSA
| | - Chip A. Bowman
- Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - M‐Isabel Fiel
- Department of PathologyIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Ashley E. Stueck
- Department of PathologyDalhousie UniversityHalifaxNova ScotiaCanada
| | - Nicolas Goossens
- Division of Liver Diseases, Department of MedicineTisch Cancer Institute, Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Kian Bichoupan
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Neal Patel
- Division of GastroenterologyDepartment of Medicine, Nuvance Health Danbury HospitalDanburyCTUSA
| | - James F. Crismale
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Jasnit Makkar
- Department of RadiologyColumbia UniversityNew YorkNew YorkUSA
| | - Sara Lewis
- Department of RadiologyIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | | | - Thomas D. Schiano
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Yujin Hoshida
- Department of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasTexasUSA
| | - Myron Schwartz
- Department of SurgeryIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Andrea D. Branch
- Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
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Baseline ALBI Grade Predicts Benefits After Splenectomy for Cirrhotic Patients with Hypersplenism. J Gastrointest Surg 2023:10.1007/s11605-023-05610-2. [PMID: 36759386 DOI: 10.1007/s11605-023-05610-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 01/14/2023] [Indexed: 02/11/2023]
Abstract
PURPOSE Splenectomy is an effective treatment for correcting cytopenia caused by hypersplenism secondary to cirrhosis. However, other potential benefits have not been well characterized. In this study, we investigated the value of splenectomy as it relates to improvement in hepatic function, liver regeneration, and health-related quality of life, and their association with baseline characteristics to clarify which patients may benefit the most from splenectomy. METHODS Patients with hypersplenism secondary to cirrhosis treated by splenectomy were retrospectively reviewed. Hepatic function was reflected by hematologic indices and albumin-bilirubin score. Liver volume was measured by imaging software, and quality-of-life was assessed by a 36-question short-form questionnaire. The changes in these three aspects after splenectomy were evaluated in the whole cohort and compared between subgroups. RESULTS The hepatic function of the patients significantly improved after splenectomy, and this was reflected by elevated serum albumin, shortened prothrombin time, and decreased albumin-bilirubin score. Patients with baseline albumin-bilirubin grade 2 or 3 and age < 56 years showed significantly decreased albumin-bilirubin score after splenectomy, whereas other subgroups did not. Moreover, liver volume increased remarkably after splenectomy in patients with baseline albumin-bilirubin grade 1, but not in those with grade 2 or 3. Significant improvement in quality-of-life occurred in the entire cohort after splenectomy, but more profound improvement was found in patients with albumin-bilirubin grade 2 or 3. CONCLUSIONS Splenectomy improves hepatic function, increases liver volume, and also improves quality-of-life in different subsets of patients with cirrhosis and hypersplenism. Baseline characteristics, such as albumin-bilirubin grade and age, are helpful in estimating the potential benefits of splenectomy for patients before surgery.
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Ogawa E, Chien N, Kam L, Yeo YH, Ji F, Huang DQ, Cheung R, Nguyen MH. Association of Direct-Acting Antiviral Therapy With Liver and Nonliver Complications and Long-term Mortality in Patients With Chronic Hepatitis C. JAMA Intern Med 2023; 183:97-105. [PMID: 36508196 PMCID: PMC9856614 DOI: 10.1001/jamainternmed.2022.5699] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 10/19/2022] [Indexed: 12/14/2022]
Abstract
IMPORTANCE Chronic hepatitis C (CHC) and its complications are associated with high rates of morbidity and mortality. However, large-scale data analysis of the long-term liver and nonliver effects of direct-acting antiviral (DAA) treatment has been limited. OBJECTIVE To assess the association of hepatitis C virus elimination through DAA treatment with the risk of liver and nonliver morbidity and mortality during long-term follow-up among a large nationwide cohort of insured patients with CHC in the US. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective cohort study of 245 596 adult patients with CHC using data from the Optum Clinformatics Data Mart database, 2010 to 2021. Of the total cohort, 40 654 patients had received 1 or more prescriptions for DAA medication (without interferon), and 204 942 patients were untreated. EXPOSURE Treatment with a DAA. MAIN OUTCOMES AND MEASURES Incidence of hepatocellular carcinoma (HCC), liver decompensation, relevant nonliver events (nonliver cancer, diabetes, chronic kidney disease, cardiovascular disease), and overall mortality. RESULTS The DAA-treated cohort (vs untreated) were older (mean [SD] age, 59.9 [10.8] vs 58.5 [13.0] years; P < .001); more likely to be male (25 060 [62%] vs 119 727 [58%] men; P < .001) and White (23 937 [59%] vs 115 973 [57%]; P < .001) individuals; and more likely to have diabetes (10 680 [26%] vs 52 091 [25%]; P < .001) or cirrhosis (17 971 [44%] vs 60 094 [29%]; P < .001). Comparing DAA-treated with untreated patients, the incidence (per 1000 person-years) of liver outcomes (eg, decompensation, 28.2 [95% CI, 27.0-29.4] vs 40.8 [95% CI, 40.1-41.5]; P < .001, and HCC in compensated cirrhosis, 20.1 [95% CI, 18.4-21.9] vs 41.8 [95% CI, 40.3-43.3]; P < .001) and nonliver outcomes (eg, diabetes, 30.2 [95% CI, 35.4-37.7] vs 37.2 [95% CI, 36.6-37.9]; P < .001; and chronic kidney disease, 31.1 [95% CI, 29.9-32.2] vs 34.1 [95% CI, 33.5-34.7]; P < .001) were significantly lower in treated patients. The all-cause mortality rates per 1000 person-years were also significantly lower in DAA-treated compared with untreated patients (mortality, 36.5 [95% CI, 35.4-37.7] vs 64.7 [95% CI, 63.9-65.4]; P < .001). In multivariable regression analysis, DAA treatment was independently associated with a significant decrease in the risk of liver (adjusted hazard ratio [aHR] for HCC, 0.73; decompensation, 0.36), nonliver (aHR for diabetes, 0.74; chronic kidney disease, 0.81; cardiovascular disease, 0.90; nonliver cancer, 0.89), and mortality outcomes (aHR, 0.43). CONCLUSIONS AND RELEVANCE The findings of this retrospective cohort study indicate that DAA treatment for insured patients with CHC was associated with improved liver- and nonliver outcomes, and ultimately, with long-term overall survival.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Nicholas Chien
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Leslie Kam
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yee Hui Yeo
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Fanpu Ji
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Daniel Q. Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California
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14
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Inoue T, Tanaka Y. Noninvasive assessments of liver disease severity based on biomarkers. COMPREHENSIVE GUIDE TO HEPATITIS ADVANCES 2023:31-60. [DOI: 10.1016/b978-0-323-98368-6.00009-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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15
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Kaplan DE, Serper M, Kaushik A, Durkin C, Raad A, El-Moustaid F, Smith N, Yehoshua A. Cost-effectiveness of direct-acting antivirals for chronic hepatitis C virus in the United States from a payer perspective. J Manag Care Spec Pharm 2022; 28:1138-1148. [PMID: 36125059 PMCID: PMC10373042 DOI: 10.18553/jmcp.2022.28.10.1138] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND: Direct-acting antivirals (DAAs) have been a breakthrough therapeutic innovation in the treatment of chronic hepatitis C virus (HCV) with significantly improved efficacy, safety, and tolerability. OBJECTIVE: To evaluate the cost-effectiveness of treating patients with HCV with DAAs compared with pre-DAAs or no treatment over a lifetime horizon from the perspective of the US Veterans Affairs (VA) health care system. METHODS: A hybrid decision-tree and Markov model simulated the health outcomes of a cohort of 142,147 patients with HCV with an average age of 63 years. Demographic data, treatment rates and distribution, treatment efficacy by subpopulation, and health state costs were sourced from VA data. Treatment costs and utility values were sourced from publicly available databases and prior publications for older regimens. RESULTS: Over a lifetime horizon, the use of DAAs results in a significant reduction in advanced liver disease events compared with pre-DAA and no treatment. Total cost savings of $7 and $9 billion over a lifetime horizon (50 years) were predicted for patients who received DAA treatments compared with patients treated with pre-DAA treatments and those who were untreated, respectively. Cost savings were achieved quickly after treatment, with DAAs being inexpensive when compared with both the pre-DAA and untreated scenarios within 5 years. The DAA intervention dominated (ie, more effective and less costly) for both the pre-DAA and untreated strategies on both a per-patient and cohort basis. CONCLUSIONS: The use of DAA-based treatments in patients with HCV in the VA system significantly reduced long-term HCV-related morbidity and mortality, while providing cost savings within only 5 years of treatment. DISCLOSURES: This work was supported by Gilead Inc. Health Economic Outcomes Research group, grant number GS-US-18-HCV003. Drs Yehoshua and Kaushik are employees of Gilead in the Health Economic Outcome Research group. These individuals reviewed the manuscript but did not contribute to input or output of the Markov model. Maple Health Group (Dr El-Moustaid, Ms Raad, and Dr Smith) are consultants hired by Gilead for Markov modeling expertise. The model used in this study was previously published and peer reviewed. Data inputted into the model related to patient demographic, treatment outcomes, clinical outcomes, and costs were completely independent in derivation by Drs Kaplan, Serper, and Durkin and were not influenced by the funding sponsor. Dr Kaplan reports grants from Gilead Inc. during the conduct of the study and grants from Gilead Inc., other from Glycotest Inc., other from AstraZeneca, other from Exact Sciences, and other from Bayer outside the submitted work.
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Affiliation(s)
- David E Kaplan
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
- Gastroenterology Section, Philadelphia VA Medical Center, PA
| | - Marina Serper
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
- Gastroenterology Section, Philadelphia VA Medical Center, PA
- Center for Health Equity Research and Promotion, Philadelphia VA Medical Center, PA
| | | | - Claire Durkin
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
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Hsu WF, Lai HC, Chuang PH, Su WP, Chen SH, Chen HY, Wang HW, Huang GT, Peng CY. Posttreatment nonalcoholic fatty liver disease fibrosis scores for predicting liver-related complications in patients with chronic hepatitis C receiving direct-acting antiviral agents. J Viral Hepat 2022; 29:785-794. [PMID: 35657121 DOI: 10.1111/jvh.13715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 05/10/2022] [Accepted: 05/25/2022] [Indexed: 12/09/2022]
Abstract
Patients with chronic hepatitis C (CHC) have a higher prevalence of hepatic steatosis and dyslipidaemia than healthy individuals. We analysed noninvasive fibrosis assessments, especially nonalcoholic fatty liver disease (NAFLD)-related noninvasive fibrosis tests, for predicting liver-related complications and hepatocellular carcinoma (HCC) occurrence in patients with CHC. This retrospective study enrolled 590 consecutive patients with CHC having a sustained virologic response (SVR) to direct-acting antiviral agent (DAA) therapy. The NAFLD fibrosis score (NFS) exhibiting the highest value of area under the receiver operating characteristic curve (AUROC) was selected for comparison with the fibrosis-4 index (FIB-4). Of the 590 patients, 188 had metabolic syndrome. A multivariate Cox regression analysis identified total bilirubin at 3 or 6 months after DAA therapy (PW12), NFS at PW12 (hazard ratio [HR]: 2.125, 95% confidence interval [CI]: 1.058-4.267, p = .034) and alpha-fetoprotein (AFP) at PW12 (HR: 1.071, 95% CI: 1.005-1.142, p = .034) as the independent predictors of liver-related complications in all patients. In patients with metabolic syndrome, NFS and AFP values at PW12 were independent predictors of liver-related complications and HCC occurrence. Time-dependent NFS AUROC values at PW12 for 1-, 2- and 3-year liver-related complications were higher than NFS values at baseline in patients with metabolic syndrome. NFS at baseline or PW12 is a more effective predictor of liver-related complications than FIB-4 values in all patients. NFS at PW12 may be a useful predictor of liver-related complications and HCC development in patients with CHC with an SVR to DAA therapy, especially in those with metabolic syndrome.
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Affiliation(s)
- Wei-Fan Hsu
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Hsueh-Chou Lai
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Po-Heng Chuang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Pang Su
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Sheng-Hung Chen
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Hung-Yao Chen
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Wei Wang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Guan-Tarn Huang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
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Lockart I, Yeo MGH, Hajarizadeh B, Dore G, Danta M. HCC incidence after hepatitis C cure among patients with advanced fibrosis or cirrhosis: A meta-analysis. Hepatology 2022; 76:139-154. [PMID: 35030279 PMCID: PMC9303770 DOI: 10.1002/hep.32341] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/28/2021] [Accepted: 01/04/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS HCV cure reduces but does not eliminate the risk of HCC. HCC surveillance is recommended in populations where the incidence exceeds 1.5% per year. In cirrhosis, HCC surveillance should continue after HCV cure, although it is uncertain if this should be indefinite. For patients with advanced fibrosis (F3), guidelines are inconsistent in their recommendations. We evaluated the incidence of HCC after HCV cure among patients with F3 fibrosis or cirrhosis. APPROACH AND RESULTS This systematic review and meta-analysis identified 44 studies (107,548 person-years of follow-up) assessing the incidence of HCC after HCV cure among patients with F3 fibrosis or cirrhosis. The incidence of HCC was 2.1 per 100 person-years (95% CI, 1.9-2.4) among patients with cirrhosis and 0.5 per 100 person-years (95% CI, 0.3-0.7) among patients with F3 fibrosis. In a meta-regression analysis among patients with cirrhosis, older age (adjusted rate ratio [aRR] per 10-year increase in mean/median age, 1.32; 95% CI, 1.00-1.73) and prior decompensation (aRR per 10% increase in the proportion of patients with prior decompensation, 1.06; 95% CI, 1.01-1.12) were associated with an increased incidence of HCC. Longer follow-up after HCV cure was associated with a decreased incidence of HCC (aRR per year increase in mean/median follow-up, 0.87; 95% CI, 0.79-0.96). CONCLUSIONS Among patients with cirrhosis, the incidence of HCC decreases over time after HCV cure and is lowest in patients with younger age and compensated cirrhosis. The substantially lower incidence in F3 fibrosis is below the recommended threshold for cost-effective screening. The results should encourage the development of validated predictive models that better identify at-risk individuals, especially among patients with F3 fibrosis.
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Affiliation(s)
- Ian Lockart
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia
- St. Vincent’s HospitalSydneyNew South WalesAustralia
| | - Malcolm G. H. Yeo
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia
| | - Behzad Hajarizadeh
- The Kirby InstituteUniversity of New South WalesSydneyNew South WalesAustralia
| | - Gregory J. Dore
- St. Vincent’s HospitalSydneyNew South WalesAustralia
- The Kirby InstituteUniversity of New South WalesSydneyNew South WalesAustralia
| | - Mark Danta
- Faculty of MedicineSt. Vincent's Clinical SchoolUniversity of New South WalesSydneyNew South WalesAustralia
- St. Vincent’s HospitalSydneyNew South WalesAustralia
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Mezina A, Krishnan A, Woreta TA, Rubenstein KB, Watson E, Chen PH, Rodriguez-Watson C. Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis C patients. World J Clin Cases 2022; 10:5566-5576. [PMID: 35979107 PMCID: PMC9258363 DOI: 10.12998/wjcc.v10.i17.5566] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 12/16/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases. Fibrosis progression varies markedly in patients with hepatitis C virus (HCV). Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV. AIM To investigate changes in liver stiffness measured by transient elastography (TE) in a large, racially diverse cohort of United States patients with chronic hepatitis C (CHC). METHODS We evaluated the differences in liver stiffness between patients treated with direct-acting antiviral (DAA) therapy and untreated patients. Patients had ≥ 2 TE measurements and no prior DAA exposure. We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment, controlling for age, sex, race, diabetes, smoking status, human immunodeficiency virus status, baseline alanine aminotransferase, and baseline liver stiffness. Separate regression models analyzed the change in liver stiffness as measured by kPa, stratified by cirrhosis status. RESULTS Of 813 patients, 419 (52%) initiated DAA treatment. Baseline liver stiffness was 12 kPa in 127 (16%). Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients, respectively. There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment (0.016 kPa/month; CI: -0.051, 0.084) or in the untreated group (0.001 kPa/mo; CI: -0.090, 0.092), controlling for covariates. A higher baseline kPa score was independently associated with decreased liver stiffness. CONCLUSION DAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated patients.
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Affiliation(s)
- Anya Mezina
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States
| | - Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Kevin B Rubenstein
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
| | - Eric Watson
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Carla Rodriguez-Watson
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
- Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, United States
- Innovation in Medical Evidence Development and Surveillance (IMEDS) Program, Reagan-Udall Foundation for the FDA, Washington, 20036, United States
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Stratton ML, Ansara ED, Ifeachor AP, Houck KK, Liangpunsakul S, Binger KJ. Assessment of hepatitis C monitoring adherence after viral eradication in veterans with substance use to improve care and surveil reinfection. Ment Health Clin 2022; 12:181-186. [PMID: 35801159 PMCID: PMC9190266 DOI: 10.9740/mhc.2022.06.181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 01/25/2022] [Indexed: 11/17/2022] Open
Abstract
Introduction Hepatitis C virus (HCV) incidence rates are rising for patients with substance use and/or SUDs. Guidelines provide monitoring recommendations to ensure remission after successful treatment. The study's objective was to identify gaps in follow-up for patients with documented substance use and/or SUD through assessment of adherence to guideline-recommended HCV RNA lab 12 months post-treatment. Methods Patients treated for HCV through the Veteran Health Indiana Hepatitis C Pharmacy Clinic were retrospectively evaluated. Subjects were categorized based on the provider assigned for follow-up care after 12-week sustained virologic response (SVR12) labs (primary care provider [PCP] or HCV provider). The primary outcome was HCV RNA obtained 11 to 13 months post-treatment. Secondary outcomes were HCV RNA detected post-treatment, substance use, engagement in substance use treatment, and engagement with social work. Results Two hundred forty-one patients were included in the HCV provider cohort and 139 in the PCP cohort. Forty-one patients did not have a specified clinic for follow-up treatment, and 20 patients did not achieve SVR12. Sixty-one patients (28%) in the HCV provider cohort completed a 12-month HCV RNA within 11 to 13 months post-treatment vs 15 patients (11%) in the PCP cohort (P ≤ .01). One patient had HCV RNA detected post-treatment. Discussion This study reveals inadequate HCV post-treatment follow-up for patients with substance use and/or SUD. SUD is a chronic disease that requires continued monitoring to prevent complications. Further studies are needed to identify reinfection rates and improvements of care in this population.
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Affiliation(s)
| | - Elayne D. Ansara
- 2 Clinical Pharmacy Practitioner – Mental Health, Veteran Health Indiana, Indianapolis, Indiana
| | - Amanda P. Ifeachor
- 3 Clinical Pharmacy Practitioner – Ambulatory Care (Gastrointestinal/Hepatitis C Virus Clinics), Veteran Health Indiana, Indianapolis, Indiana
| | - Kelly K. Houck
- 4 Facility Pain Management, Opioid Safety, and Prescription Drug Monitoring Program (PMOP) Coordinator, Veteran Health Indiana, Indianapolis, Indiana
| | - Suthat Liangpunsakul
- 5 Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana and Associate Chief of Staff for Research service and Hepatologist, Gastroenterology Section, Medicine Service, Veteran Health Indiana, Indianapolis, Indiana
| | - Katie J. Binger
- 6 Clinical Pharmacy Practitioner – Mental Health, Veteran Health Indiana, Indianapolis, Indiana
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Fukumoto T, Minami T, Moriyama M, Yamada T, Wake T, Kinoshita MN, Fujiwara N, Nakagomi R, Nakatsuka T, Sato M, Enooku K, Nakagawa H, Fujishiro M, Shiina S, Koike K, Tateishi R. Improved prognosis of hepatitis C-related hepatocellular carcinoma in the era of direct-acting antivirals. Hepatol Commun 2022; 6:2496-2512. [PMID: 35641233 PMCID: PMC9426397 DOI: 10.1002/hep4.2010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/08/2022] [Accepted: 04/24/2022] [Indexed: 11/30/2022] Open
Abstract
The prognostic impact of direct‐acting antivirals (DAAs) on patients with hepatitis C‐related hepatocellular carcinoma (C‐HCC) is still unclear. This study aimed to evaluate the prognosis of C‐HCC in the DAA era. We enrolled 1237 consecutive patients with treatment‐naive C‐HCC who underwent radical radiofrequency ablation between 1999 and 2019. We also enrolled 350 patients with nonviral HCC as controls. We divided these patients into three groups according to the year of initial treatment: 1999–2005 (cohort 1), 2006–2013 (cohort 2), and 2014–2019 (cohort 3). The use of antiviral agents and their effect in patients with C‐HCC was investigated. Overall survival was evaluated for each cohort using the Kaplan‐Meier method and a multivariable Cox proportional hazards regression model. Sustained virologic response (SVR) was achieved in 52 (10%), 157 (26%), and 102 (74%) patients with C‐HCC in cohorts 1–3, respectively. The 3‐ and 5‐year survival rates of patients with C‐HCC were 82% and 59% in cohort 1; 80% and 64% in cohort 2; and 86% and 78% in cohort 3, respectively (p = 0.003). Multivariable analysis adjusted for age, liver function, and tumor extension showed that the prognosis of C‐HCC improved in cohort 3 compared to cohort 1 (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], 0.32–0.73; p < 0.001), whereas the prognosis of nonviral HCC did not improve significantly (aHR, 0.96; 95% CI, 0.59–1.57; p = 0.88). The prognosis of C‐HCC drastically improved with the advent of DAAs.
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Affiliation(s)
- Tsuyoshi Fukumoto
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Makoto Moriyama
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomoharu Yamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Taijiro Wake
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | - Naoto Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryo Nakagomi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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21
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Politi J, Guerras JM, Donat M, Belza MJ, Ronda E, Barrio G, Regidor E. Favorable impact in hepatitis C-related mortality following free access to direct-acting antivirals in Spain. Hepatology 2022; 75:1247-1256. [PMID: 34773281 DOI: 10.1002/hep.32237] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 11/01/2021] [Accepted: 11/05/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Free treatments for HCV infection with direct-acting antivirals became widespread in Spain in April 2015. We aimed to test whether, after this intervention, there was a more favorable change in population mortality from HCV-related than from non-HCV-related causes. APPROACH AND RESULTS Postintervention changes in mortality were assessed using uncontrolled before-after and single-group interrupted time series designs. All residents in Spain during 2001-2018 were included. Various underlying death causes were analyzed: HCV infection; other HCV-related outcomes (HCC, liver cirrhosis, and HIV disease); and non-C hepatitis, other liver diseases, and nonhepatic causes as control outcomes. Changes in mortality after the intervention were first assessed by rate ratios (RRs) between the postintervention and preintervention age-standardized mortality rates. Subsequently, using quasi-Poisson segmented regression models, we estimated the annual percent change (APC) in mortality rate in the postintervention and preintervention periods. All mortality rates were lower during the postintervention period, although RRs were much lower for HCV (0.53; 95% CI, 0.51-0.56) and HIV disease than other causes. After the intervention, there was a great acceleration of the downward mortality trend from HCV, whose APC went from -3.2% (95% CI, -3.6% to -2.8%) to -18.4% (95% CI, -20.6% to -16.3%). There were also significant accelerations in the downward trends in mortality from HCC and HIV disease, while they remained unchanged for cirrhosis and slowed or reversed for other causes. CONCLUSIONS These results suggest that the favorable changes in HCV-related mortality observed for Spain after April 2015 are attributable to scaling up free treatment with direct-acting antivirals and reinforce that HCV eradication is on the horizon.
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Affiliation(s)
- Julieta Politi
- National Epidemiology CenterInstituto de Salud Carlos IIIMadridSpain
- Preventive Medicine and Public Health Training Unit PSMar-UPF-ASPB (Parc de Salut Mar-Pompeu Fabra University, Agència de Salut Pública de Barcelona)BarcelonaSpain
- National School of Public HealthInstituto de Salud Carlos IIIMadridSpain
| | - Juan-Miguel Guerras
- National Epidemiology CenterInstituto de Salud Carlos IIIMadridSpain
- CIBER Epidemiología y Salud PúblicaMadridSpain
| | - Marta Donat
- National School of Public HealthInstituto de Salud Carlos IIIMadridSpain
- CIBER Epidemiología y Salud PúblicaMadridSpain
| | - María J Belza
- National School of Public HealthInstituto de Salud Carlos IIIMadridSpain
- CIBER Epidemiología y Salud PúblicaMadridSpain
| | - Elena Ronda
- CIBER Epidemiología y Salud PúblicaMadridSpain
- Preventive Medicine and Public Health AreaUniversidad de AlicanteAlicanteSpain
| | - Gregorio Barrio
- National School of Public HealthInstituto de Salud Carlos IIIMadridSpain
- CIBER Epidemiología y Salud PúblicaMadridSpain
| | - Enrique Regidor
- CIBER Epidemiología y Salud PúblicaMadridSpain
- Department of Public Health & Maternal and Child HealthFaculty of MedicineUniversidad ComplutenseMadridSpain
- Instituto de Investigación Sanitaria del Hospital Clínico San CarlosMadridSpain
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22
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Inukai Y, Imai N, Yamamoto K, Ito T, Ishizu Y, Honda T, Okamoto S, Kanematsu T, Suzuki N, Matsushita T, Ishigami M, Fujishiro M. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia. Ann Hepatol 2022; 27:100545. [PMID: 34571264 DOI: 10.1016/j.aohep.2021.100545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. PATIENTS AND METHODS The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. RESULTS Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years. Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. CONCLUSION Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.
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Affiliation(s)
- Yosuke Inukai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine.
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Shuichi Okamoto
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine
| | | | - Nobuaki Suzuki
- Department of Transfusion Medicine, Nagoya University Hospital
| | - Tadashi Matsushita
- Department of Clinical Laboratory, Nagoya University Hospital; Department of Transfusion Medicine, Nagoya University Hospital
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
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23
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Matsumoto K, Miyaaki H, Fukushima M, Sasaki R, Haraguchi M, Miuma S, Nakao K. The impact of single-nucleotide polymorphisms on liver stiffness and controlled attenuation parameter in patients treated with direct-acting antiviral drugs for hepatitis C infection. Biomed Rep 2022; 16:9. [PMID: 34987793 PMCID: PMC8719319 DOI: 10.3892/br.2021.1492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 11/18/2021] [Indexed: 11/18/2022] Open
Abstract
Single-nucleotide polymorphisms (SNPs) of patatin-like phospholipase domain-containing 3 (PNPLA3), tolloid-like protein 1 (TLL1) and interleukin-28 (IL28) have been identified as susceptibility factors for liver steatosis, inflammation and fibrosis in patients with hepatitis C virus (HCV) infection. Here, whether these polymorphisms affected predispositions to changes in liver stiffness (LS) and controlled attenuation parameter (CAP) following direct-acting antiviral (DAA) therapy was assessed. The changes in LS and steatosis in 77 HCV-infected patients receiving DAA therapy were compared with PNPLA3, TLL1 and IL28 genotypes, using CAP, FibroScan and Virtual Touch tissue quantification (VTTQ) before treatment and 12 weeks after the end of the treatment. VTTQ results showed that LS significantly decreased in PNPLA3 CC (P=0.035), TLL1 AA (P=0.011) and IL28B TT (P=0.005) genotypes; no significant differences were observed in PNPLA3 CG/GG, TLL1 AT/TT and IL28B TG/GG. FibroScan results showed that LS significantly decreased in TLL1 AA (P=0.028) and IL28B TT (P=0.032), with no significant difference in PNPLA3 CC. No significant differences were observed in PNPLA3 CG/GG, TLL1 AT/TT and IL28B TG/GG groups. CAP was significantly increased in PNPLA3 CG/GG (P=0.039 and P<0.05) and IL28B TT (P=0.014); no significant difference was observed in PNPLA3 CC and all genotypes of TLL1 and IL28B TG/GG. Therefore, these results indicated that SNPs could predict changes in LS and steatosis after DAA therapy.
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Affiliation(s)
- Kosuke Matsumoto
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Masanori Fukushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
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24
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Sánchez-Azofra M, Fernández I, García-Buey ML, Domínguez-Domínguez L, Fernández-Rodríguez CM, Mancebo A, Bonet L, Ryan P, Gea F, Díaz-Sánchez A, García-Mayor M, Martín-Carbonero L, Castillo P, Manzano ML, González-Moreno L, Pulido F, Gutiérrez ML, Moreno JM, García-Amengual IM, Cuevas G, Guerrero A, Rivero-Fernández M, Portales ME, Montes ML, Olveira A. Hepatocellular carcinoma risk in hepatitis C stage-3 fibrosis after sustained virological response with direct-acting antivirals. Liver Int 2021; 41:2885-2891. [PMID: 34392590 DOI: 10.1111/liv.15032] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 07/04/2021] [Accepted: 08/11/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Patients with chronic hepatitis C and stage 3 fibrosis are thought to remain at risk of hepatocellular carcinoma after sustained virological response. We investigated this risk in a large cohort of patients with well-defined stage 3 fibrosis. METHODS We performed a multicentre, ambispective, observational study of chronic hepatitis C patients with sustained virological response after treatment with direct-acting antivirals started between January and December 2015. Baseline stage 3 was defined in a two-step procedure: we selected patients with transient elastography values of 9.5-14.5 kPa and subsequently excluded those with nodular liver surface, splenomegaly, ascites or collaterals on imaging, thrombopenia or esophago-gastric varices. Patients were screened twice-yearly using ultrasound. RESULTS The final sample comprised 506 patients (median age, 57.4 years; males, 59.9%; diabetes, 17.2%; overweight, 44.1%; genotype 3, 8.9%; HIV coinfection, 18.4%; altered liver values, 15.2%). Median follow-up was 33.7 (22.1-39.1) months. Five hepatocellular carcinomas and 1 cholangiocarcinoma were detected after a median of 29.4 months (95% CI: 26.8-39.3), with an incidence of 0.47/100 patients/year (95% CI: 0.17-1.01). In the multivariate analysis, only males older than 55 years had a significant higher risk (hazard ratio 7.2 [95% CI: 1.2-41.7; P = .029]) with an incidence of 1.1/100 patients/year (95% CI: 0.3-2.8). CONCLUSIONS In a large, well-defined cohort of patients with baseline hepatitis C stage-3 fibrosis, the incidence of primary liver tumours was low after sustained virological response and far from the threshold for cost-effectiveness of screening, except in males older than 55 years.
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Affiliation(s)
| | | | | | - Lourdes Domínguez-Domínguez
- HIV Unit, Internal Medicine Department, 12 de Octubre University Hospital, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital, Madrid, Spain
| | | | - Antonio Mancebo
- Gastroenterology Department, Albacete University Hospital, Albacete, Spain
| | - Lucía Bonet
- Gastroenterology Department, Son Espases University Hospital, Palma de Mallorca, Spain
| | - Pablo Ryan
- HIV Unit, Internal Medicine Department, Infanta Leonor University Hospital, Madrid, Spain
| | - Francisco Gea
- Gastroenterology Department, Ramón y Cajal University Hospital, Madrid, Spain
| | - Antonio Díaz-Sánchez
- Gastroenterology Department, Sureste University Hospital, Arganda del Rey, Spain
| | - Marian García-Mayor
- Gastroenterology Department, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain
| | - Luz Martín-Carbonero
- HIV Unit, Internal Medicine Department, La Paz University Hospital, Madrid, Spain
| | - Pilar Castillo
- Gastroenterology Department, La Paz University Hospital, Madrid, Spain
| | - María L Manzano
- Gastroenterology Department, 12 de Octubre University Hospital, Madrid, Spain
| | | | - Federico Pulido
- HIV Unit, Internal Medicine Department, 12 de Octubre University Hospital, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital, Madrid, Spain
| | - María L Gutiérrez
- Gastroenterology Department, Hospital Universitario Fundación Alcorcón, University Rey Juan Carlos, Madrid, Spain
| | - José M Moreno
- Gastroenterology Department, Albacete University Hospital, Albacete, Spain
| | | | - Guillermo Cuevas
- HIV Unit, Internal Medicine Department, Infanta Leonor University Hospital, Madrid, Spain
| | - Antonio Guerrero
- Gastroenterology Department, Ramón y Cajal University Hospital, Madrid, Spain
| | | | - María E Portales
- Gastroenterology Department, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain
| | - María L Montes
- HIV Unit, Internal Medicine Department, La Paz University Hospital, Madrid, Spain
| | - Antonio Olveira
- Gastroenterology Department, La Paz University Hospital, Madrid, Spain
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25
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Broquetas T, Herruzo-Pino P, Mariño Z, Naranjo D, Vergara M, Morillas RM, Forns X, Carrión JA. Elastography is unable to exclude cirrhosis after sustained virological response in HCV-infected patients with advanced chronic liver disease. Liver Int 2021; 41:2733-2746. [PMID: 34525253 DOI: 10.1111/liv.15058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 08/23/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Liver fibrosis and transient elastography (TE) correlation in hepatitis C virus (HCV)-infected patients with compensated advanced chronic liver disease (cACLD) after the sustained virological response (SVR) is unknown. AIMS To evaluate TE accuracy at identifying cirrhosis 3 years after HCV-eradication. METHODS Prospective, multi-centric study including HCV-cACLD patients before direct-acting antivirals (DAA). Diagnostic accuracy of TE (area under ROC, AUROC) to identify cirrhosis 3 years after SVR was evaluated. RESULTS Among 746 HCV-infected patients (95.4% with TE ≥10 kPa), 76 (10.2%) underwent a liver biopsy 3 years after SVR. Before treatment, 46 (63%) showed a TE>15 kPa. The TE before DAA was the best variable for predicting cirrhosis (METAVIR, F4) after SVR (AUROC = 0.79). Liver function parameters, serological non-invasive tests (APRI and FIB-4), and TE values improved after SVR. However, liver biopsy 3 years after HCV elimination (median time = 38.4 months) showed cirrhosis in 41 (53.9%). Multivariate analysis (OR (95% CI), P) showed that HCV-genotype 3 (20.81 (2.12-201.47), .009), and TE before treatment (1.21 (1.09-1.34), <.001) were the only variables associated with cirrhosis after SVR. However, the accuracy of TE after SVR was poor (AUROC = 0.75) and 6 (27.3%) out of 22 patients with a TE <8 kPa had cirrhosis. Similar results were found with APRI and FIB-4 scores. CONCLUSIONS Cirrhosis is present, 3 years after SVR, in more than half of HCV-cACLD patients even with the normalisation of liver function parameters, serological non-invasive tests and TE values. The low diagnostic accuracy of non-invasive methods after SVR reinforces the need for long-term surveillance.
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Affiliation(s)
- Teresa Broquetas
- Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona, Spain.,Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
| | - Paula Herruzo-Pino
- Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Dolores Naranjo
- Gastrointestinal and Hepatobiliary Pathology Section, Department of Pathology, Hospital del Mar, Barcelona, Spain
| | - Mercedes Vergara
- Liver Unit, Digestive Disease Department, Parc Taulí Sabadell Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Rosa Mª Morillas
- Hepatology Department, Hospital Germans Trias i Pujol, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - José A Carrión
- Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona, Spain.,Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
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26
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Hsu WF, Tsai PC, Chen CY, Tseng KC, Lai HC, Kuo HT, Hung CH, Tung SY, Wang JH, Chen JJ, Lee PL, Chien RN, Lin CY, Yang CC, Lo GH, Tai CM, Lin CW, Kao JH, Liu CJ, Liu CH, Yan SL, Bair MJ, Su WW, Chu CH, Chen CJ, Lo CC, Cheng PN, Chiu YC, Wang CC, Cheng JS, Tsai WL, Lin HC, Huang YH, Huang JF, Dai CY, Chuang WL, Yu ML, Peng CY. Hepatitis C virus eradication decreases the risks of liver cirrhosis and cirrhosis-related complications (Taiwanese chronic hepatitis C cohort). J Gastroenterol Hepatol 2021; 36:2884-2892. [PMID: 33963615 DOI: 10.1111/jgh.15538] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 04/30/2021] [Accepted: 05/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new-onset liver cirrhosis (LC) in patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS Taiwanese chronic hepatitis C cohort (T-COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10 693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new-onset LC and liver-related complications (DLD or HCC). RESULTS Of the 10 693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow-up duration was 4.38 ± 2.79 years, with overall 46 798 person-years. The 10-year cumulative incidence rates of new-onset LC were 5.0% (95% confidence interval [CI]: 3.2-7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4-32.4) in those without SVR (hazard ratio [HR]: 0.22, P < 0.001). The 10-year cumulative incidence rates of liver-related complications were 21.4% (95% CI: 11.1-37.2) in patients with cirrhosis with SVR and 47.0% (95% CI: 11.1-86.0) in those without SVR after adjustment for age, sex, and competing mortality (HR: 0.52, P < 0.001). CONCLUSIONS Hepatitis C virus eradication with PR therapy decreased the incidence of new-onset LC in noncirrhotic patients and the incidence of liver-related complications in cirrhotic patients with CHC.
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Affiliation(s)
- Wei-Fan Hsu
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Pei-Chein Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Hsueh-Chou Lai
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Shui-Yi Tung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Ron-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chi-Chieh Yang
- Division of Gastroenterology, Department of Internal Medicine, Show-Chwan Memorial Hospital, Changhua, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, and School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, and School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, and School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, The National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, The National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, The National Taiwan University Hospital, Taipei, Taiwan
| | - Sheng-Lei Yan
- Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Cheng-Hsin Chu
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chih-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Ching-Chu Lo
- Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chia-Chi Wang
- Division of Gastroenterology, Department of Internal Medicine, Tzuchi Hospital, Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
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Kang Q, Xu J, Luo H, Tan N, Chen H, Cheng R, Pan J, Han Y, Yang Y, Liu D, Xi H, Yu M, Xu X. Direct antiviral agent treatment leads to rapid and significant fibrosis regression after HCV eradication. J Viral Hepat 2021; 28:1284-1292. [PMID: 34105867 DOI: 10.1111/jvh.13558] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 04/22/2021] [Accepted: 05/21/2021] [Indexed: 12/14/2022]
Abstract
Limited data are currently available regarding fibrosis progression after hepatitis C virus (HCV) eradication. The goal of the present study was to evaluate the effects of HCV eradication on liver stiffness measurements (LSMs), aspartate aminotransferase/platelet ratio index (APRI) scores, fibrosis-4(FIB-4) scores, chitinase-3-like protein 1 (CHI3L1) levels and Golgi protein 73 (GP73) levels in patients with chronic hepatitis C (CHC). One hundred and two patients who received direct antiviral agents (DAAs) therapy at Peking University First Hospital participated in the present study. Clinical information and serum samples were collected at baseline, at the end of treatment (EOT), and at the weeks 12, 24 and 48 after treatment (W12, W24 and W48, respectively). Of the 102 patients, 51 had mild-to-moderate fibrosis (F1/F2), and 51 had advanced fibrosis (F3/F4). The LSMs improved for all patients at the EOT, with observed changes of 2.85 kPa, and the decrease continued to W12. However, a more pronounced improvement was noted for the advanced fibrosis (F3/F4) patients, with a change of 3.6 kPa from baseline to the EOT. Significant decreases between the baseline and EOT measurements were observed in the APRI and FIB-4 scores [0.64 (0.39-1.21) vs. 0.35 (0.26-0.52), p<0.001; 2.53 (1.30-3.91) vs. 1.87 (0.89-2.5), p<0.001], after which the values decreased until W12, with no significant difference observed. Serum CHI3L1 and GP73 levels were profoundly decreased at the EOT compared with those at baseline [134.07 (154.49) vs. 103.75 (98.04), p=0.025; 98.24 (64.76) vs. 88.91 (50.89), p=0.002]. DAA treatments could significantly improve liver fibrosis of CHC patients as evidenced by decreased liver stiffness, APRI scores and FIB-4 scores. Improvements in liver fibrosis markers (especially serum CHI3L1 and GP73) were prominent in patients with advanced fibrosis, indicating that serum CHI3L1 and GP73 could be noninvasive markers for monitoring fibrosis in CHC patients. Significance Statement The prospective cohort evaluated the effect of direct antiviral agents (DAAs) on fibrosis regression after hepatitis C virus (HCV) eradication of Chinese people in the real-world study. This study highlighted that rapid and significant fibrosis regression rather than reduction in inflammation was achieved with DAA treatment, and this regression could be detected as early as the end of treatment. We found the serum CHI3L1 and GP73 levels can be used to monitor changes in fibrosis in CHC patients.
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Affiliation(s)
- Qian Kang
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Jinghang Xu
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Hao Luo
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Ning Tan
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Hongyu Chen
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Ran Cheng
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Jiali Pan
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Yifan Han
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Yuqing Yang
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Dan Liu
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Hongli Xi
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Min Yu
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Xiaoyuan Xu
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
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28
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Kaibori M, Yoshii K, Kashiwabara K, Kokudo T, Hasegawa K, Izumi N, Murakami T, Kudo M, Shiina S, Sakamoto M, Nakashima O, Matsuyama Y, Eguchi S, Yamashita T, Takayama T, Kokudo N, Kubo S. Impact of hepatitis C virus on survival in patients undergoing resection of intrahepatic cholangiocarcinoma: Report of a Japanese nationwide survey. Hepatol Res 2021; 51:890-901. [PMID: 34041804 DOI: 10.1111/hepr.13676] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 05/13/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022]
Abstract
AIM We reviewed the data of a nationwide follow-up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass-forming (MF) type, and combined mass-forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC). METHODS In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV-related ICC (n = 138, 14.4%), hepatitis B virus (HBV)-related ICC (n = 43, 4.5%) and non-virus-related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score-matching to compare outcomes after surgery between HCV-related (n = 102) and non-virus-related ICC cases (n = 102). RESULTS We successfully matched HCV-related and non-virus-related ICC cases with similar liver function and tumor characteristics. Patients with HCV-related ICC had significantly shorter recurrence-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37-0.88, p = 0.011) than patients with non-virus-related ICC. Cox proportional hazard analysis showed that HCV-related ICC offered a worse prognosis than non-virus-related ICC. CONCLUSIONS HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC.
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Affiliation(s)
- Masaki Kaibori
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Kengo Yoshii
- Department of Mathematics and Statistics in Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kosuke Kashiwabara
- Biostatistics Division, Clinical Research Support Center, Central Coordinating Unit, The University of Tokyo, Tokyo, Japan
| | - Takashi Kokudo
- Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takamichi Murakami
- Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Yutaka Matsuyama
- Department of Biostatics, School of Public Health University of Tokyo, Tokyo, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tatsuya Yamashita
- Advanced Preventive Medical Research Center, Kanazawa University, Kanazawa, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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29
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Kim E, Park SH. [Diagnosis and Severity Assessment of Alcohol-Related Liver Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 76:60-64. [PMID: 32839367 DOI: 10.4166/kjg.2020.76.2.60] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 07/31/2020] [Accepted: 08/03/2020] [Indexed: 11/03/2022]
Abstract
A diagnosis of alcohol-related liver disease (ALD) requires information on the history of excessive alcohol consumption (average intake of 40 g or more in men and 20 g or more in women a day). Furthermore, blood tests, such as GGT, AST, ALT, and mean corpuscular volume, and imaging studies, including abdominal ultrasound or transient elastography, are also useful. A liver biopsy can be useful for confirming the diagnosis and has prognostic value. ALD includes alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis, and in most cases, clinical manifestations can overlap. The prognostic scoring systems of ALD are limited mainly to alcoholic hepatitis, and the early mortality and treatment response can be predicted using various scoring systems. This review summarizes how to diagnose and evaluate the severity of ALD in clinical practice.
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Affiliation(s)
- Eunju Kim
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Seung Ha Park
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
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30
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Granito A, Muratori L, Lalanne C, Quarneti C, Ferri S, Guidi M, Lenzi M, Muratori P. Hepatocellular carcinoma in viral and autoimmune liver diseases: Role of CD4+ CD25+ Foxp3+ regulatory T cells in the immune microenvironment. World J Gastroenterol 2021; 27:2994-3009. [PMID: 34168403 PMCID: PMC8192285 DOI: 10.3748/wjg.v27.i22.2994] [Citation(s) in RCA: 120] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/09/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
More than 90% of cases of hepatocellular carcinoma (HCC) occurs in patients with cirrhosis, of which hepatitis B virus and hepatitis C virus are the leading causes, while the tumor less frequently arises in autoimmune liver diseases. Advances in understanding tumor immunity have led to a major shift in the treatment of HCC, with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells. Regulatory T cells (Tregs) are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression, invasiveness, as well as metastasis. Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function. Notably, Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor (ICI) immunotherapy. Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity, it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events (irAEs). Since the use of ICI becomes common in oncology, with an increasing number of new ICI currently under clinical trials for cancer treatment, the occurrence of irAEs is expected to dramatically rise. Herein, we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease, and we discuss their involvement in irAEs due to the new immunotherapies.
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Affiliation(s)
- Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna 40138, Italy
- Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
| | - Luigi Muratori
- Division of Internal Medicine and Immunorheumatology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, University of Bologna, Bologna 40138, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
| | - Claudine Lalanne
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna 40138, Italy
| | - Chiara Quarneti
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna 40138, Italy
| | - Silvia Ferri
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna 40138, Italy
| | - Marcello Guidi
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, Bologna 40138, Italy
| | - Marco Lenzi
- Division of Internal Medicine and Immunorheumatology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, University of Bologna, Bologna 40138, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
| | - Paolo Muratori
- Division of Internal Medicine, Morgagni-Pierantoni Hospital, Forlì 47100, Italy
- Department of Science for the Quality of Life, University of Bologna, Bologna 40138, Italy
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31
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Granito A, Forgione A, Marinelli S, Renzulli M, Ielasi L, Sansone V, Benevento F, Piscaglia F, Tovoli F. Experience with regorafenib in the treatment of hepatocellular carcinoma. Therap Adv Gastroenterol 2021; 14:17562848211016959. [PMID: 34104211 PMCID: PMC8165525 DOI: 10.1177/17562848211016959] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
Abstract
Regorafenib is a diphenylurea oral multikinase inhibitor, structurally comparable to sorafenib, which targets a variety of kinases implicated in angiogenic and tumor growth-promoting pathways. Regorafenib was the first agent to positively show significant survival advantage as a second-line therapy in patients with unresectable hepatocellular carcinoma (HCC) who had previously failed first-line treatment with sorafenib. Recent evidence has shown that its antitumor efficacy is due to a comprehensive spectrum of tumor neo-angiogenesis and proliferation inhibition and immunomodulatory effects on the tumor microenvironment, which plays a crucial role in tumor development. This review addresses the rationale and supporting evidence for regorafenib's efficacy in HCC that led to regorafenib's approval as a second-line therapy. In addition, we review proof from clinical practice studies that validate the RESORCE trial results. We discuss regorafenib's potential role in the newly emerging therapeutic strategy based on combination with immune checkpoint blockade and its possible extensibility to patient categories not enrolled in the registrative study.
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Affiliation(s)
- Alessandro Granito
- Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Via Albertoni 15, Bologna, 40138, Italy
- Division of Internal Medicine IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Antonella Forgione
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Sara Marinelli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luca Ielasi
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Vito Sansone
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Francesca Benevento
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
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Granito A, Marinelli S, Forgione A, Renzulli M, Benevento F, Piscaglia F, Tovoli F. Regorafenib Combined with Other Systemic Therapies: Exploring Promising Therapeutic Combinations in HCC. J Hepatocell Carcinoma 2021; 8:477-492. [PMID: 34079777 PMCID: PMC8165211 DOI: 10.2147/jhc.s251729] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 03/25/2021] [Indexed: 02/05/2023] Open
Abstract
Regorafenib was the first drug to demonstrate a survival benefit as a second-line agent after sorafenib failure in patients with unresectable hepatocellular carcinoma (HCC). Recent studies have shown that its mechanism of action is not only limited to its very broad spectrum of inhibition of angiogenesis, tumor proliferation, spread, and metastasis, but also to its immunomodulatory properties that have favorable effects on the very intricate role that the tumor microenvironment plays in carcinogenesis and tumor growth. In this review, we discuss rationale and evidence supporting regorafenib efficacy in HCC and that led to its approval as a second-line treatment, after sorafenib failure. We also discuss the evidence from clinical practice studies that confirm the results previously achieved in clinical trials. Finally, we analyze the potential role of regorafenib in emerging combined treatment approach with immunotherapy strategies using immune checkpoint blockade and its potential extension to patient categories not included in the registrative study.
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Affiliation(s)
- Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Sara Marinelli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Antonella Forgione
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Matteo Renzulli
- Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesca Benevento
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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33
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Mandorfer M, Simbrunner B. Prevention of First Decompensation in Advanced Chronic Liver Disease. Clin Liver Dis 2021; 25:291-310. [PMID: 33838851 DOI: 10.1016/j.cld.2021.01.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 10/20/2020] [Indexed: 01/31/2023]
Abstract
The first occurrence of decompensation constitutes a watershed moment in the natural history of chronic liver disease; it denotes a point of no return in a relevant proportion of patients. Preventive strategies may profoundly decrease cirrhosis-related morbidity and mortality. Removing the primary etiologic factor and cofactors, is key; however, a considerable proportion of patients require additional etiology-independent treatment strategies that target important pathomechanisms promoting decompensation (ie, portal hypertension and systemic inflammation). This article explains the importance of preventing first decompensation and summarizes the evidence for etiologic and etiology-independent (most important, nonselective beta-blockers and statins) therapies.
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Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
| | - Benedikt Simbrunner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
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34
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Lok ASF. Is Sustained Virologic Response to Direct-acting Antivirals a Valid Surrogate Endpoint for Clinical Outcomes of Hepatitis C? Clin Infect Dis 2021; 72:787-788. [PMID: 32052046 DOI: 10.1093/cid/ciaa147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Accepted: 02/10/2020] [Indexed: 11/14/2022] Open
Affiliation(s)
- Anna Suk-Fong Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
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35
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Krassenburg LAP, Zanjir WR, Georgie F, Stotland E, Janssen HLA, Hansen BE, Feld JJ. Evaluation of Sustained Virologic Response as a Relevant Surrogate Endpoint for Long-term Outcomes of Hepatitis C Virus Infection. Clin Infect Dis 2021; 72:780-786. [PMID: 32052014 PMCID: PMC7935378 DOI: 10.1093/cid/ciaa144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 02/11/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The causal link of sustained virologic response (SVR) with outcome has been challenged. With improved SVR rates with direct-acting antivirals (DAAs), the benefit of SVR would be expected to diminish if the association with outcome is not causal. METHODS Data were collected for patients starting treatment with interferon (IFN) or DAAs between June 2006 and December 2016. To control for disease severity, criteria for the IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial determined IFN-eligibility. Clinical events were decompensation, hepatocellular carcinoma, liver transplantation, and all-cause mortality. RESULTS In 1078 IDEAL-eligible patients, 1306 treatments occurred (52% IFN, 49% DAAs). Cirrhosis was present in 30% DAAs vs 21% IFN (P < .001). SVR was 97% with DAAs vs 52% with IFN (P < .0001). The 24-month cumulative event-free survival was 99% for IFN and 97% for DAAs with SVR (P = .08) and 96% and 75%, respectively, for non-SVR (P = .01). SVR was associated with improved event-free survival with an adjusted hazard ratio of 0.21 (95% confidence interval, .06-.71; P = .01). Using inverse probability of treatment weighting to match IFN nonresponders with DAA-treated patients, the 24-month event-rate was 1.1% with DAAs compared to 3.4% in IFN nonresponders (P = .005), highlighting the clinical benefit of maximizing SVR. CONCLUSIONS In IFN-eligible patients, SVR is more commonly achieved with DAAs and confers a similar clinical benefit as in those treated with IFN. The reduced event-rate with DAAs compared to IFN, despite similar disease severity, confirm that SVR alters prognosis leading to improved clinical outcomes.
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Affiliation(s)
- Lisette A P Krassenburg
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.,Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Wayel R Zanjir
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Firas Georgie
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Emily Stotland
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Bettina E Hansen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.,Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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Nakanishi R, Shimizu T, Kumagai K, Takai A, Marusawa H. Genetic Pathogenesis of Inflammation-Associated Cancers in Digestive Organs. Pathogens 2021; 10:453. [PMID: 33918902 PMCID: PMC8069378 DOI: 10.3390/pathogens10040453] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/12/2021] [Accepted: 04/08/2021] [Indexed: 12/20/2022] Open
Abstract
Epidemiological, clinical, and biological studies convincingly demonstrate that chronic inflammation predisposes to the development of human cancers. In digestive organs, inflammation-associated cancers include colitis-associated colorectal cancers, Helicobacter pylori-associated gastric cancer, as well as Barrett's esophagus and esophageal adenocarcinoma associated with chronic duodenogastric-esophageal reflux. Cancer is a genomic disease, and stepwise accumulation of genetic and epigenetic alterations of tumor-related genes leads to the development of tumor cells. Recent genome analyses show that genetic alterations, which are evoked by inflammation, are latently accumulated in inflamed epithelial cells of digestive organs. Production of reactive oxygen and aberrant expression of activation-induced cytidine deaminase, a nucleotide-editing enzyme, could be induced in inflamed gastrointestinal epithelial cells and play a role as a genomic modulator of inflammation-associated carcinogenesis. Understanding the molecular linkage between inflammation and genetic alterations will open up a new field of tumor biology and provide a novel strategy for the prevention of inflammation-associated tumorigenesis.
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Affiliation(s)
- Risa Nakanishi
- Department of Gastroenterology, Red Cross Osaka Hospital, Osaka 543-8555, Japan;
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; (T.S.); (K.K.); (A.T.)
| | - Takahiro Shimizu
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; (T.S.); (K.K.); (A.T.)
| | - Ken Kumagai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; (T.S.); (K.K.); (A.T.)
| | - Atsushi Takai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; (T.S.); (K.K.); (A.T.)
| | - Hiroyuki Marusawa
- Department of Gastroenterology, Red Cross Osaka Hospital, Osaka 543-8555, Japan;
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Soliman Z, El Kassas M, Elsharkawy A, Elbadry M, Hamada Y, ElHusseiny R, M El-Nahaas S, Fouad R, Esmat G, Abdel Alem S. Improvement of platelet in thrombocytopenic HCV patients after treatment with direct-acting antiviral agents and its relation to outcome. Platelets 2021; 32:383-390. [PMID: 32250721 DOI: 10.1080/09537104.2020.1742313] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 02/21/2020] [Indexed: 12/11/2022]
Abstract
Little is known about evolution of platelet count after treatment with direct-acting antiviral agents (DAAs). The study aimed to evaluate the changes in platelet count after treatment with DAAs among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis. A total of 915 chronic HCV patients with advanced fibrosis and cirrhosis who were treated with different DAAs-based regimens were retrospectively enrolled in final analysis. Included patients were those with thrombocytopenia (TCP). Platelet count was recorded at baseline, end of treatment (EOT) and 24-weeks after EOT (SVR24). Changes in platelet count and its relation to SVR were analyzed. The overall SVR24 rate was 98.8%. The platelet count showed statistically significant improvement from baseline to EOT (107 (84-127) × 103/mm3 vs. 120 (87-153) × 103/mm3(P = <0.0001) but remained unchanged thereafter to SVR24. Among responders, the platelet count significantly increased at SVR24 compared to baseline (P = <0.0001) but in relapsers, there was improvement in platelet count that didn't reach statistical significance (P = 0.9). Logistic regression analysis showed that higher Child-Pugh score and more advanced fibrosis at baseline were significant predictors of decreasing of platelet count and development of severe TCP at SVR24. Among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis, the platelet count improved after treatment with DAAs regardless to treatment response.
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Affiliation(s)
- Zeinab Soliman
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Elbadry
- Tropical Medicine and Gastroenterology Department, Aswan University, Aswan, Egypt
| | - Yasser Hamada
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ramy ElHusseiny
- Internal Medicine Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Saeed M El-Nahaas
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of research development, Badr University, Cairo, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Huynh T, Hu KQ. Excellent Safety and Sustained Virologic Response to Direct-Acting Antivirals Treatment in HCV-Infected Geriatric Patients: A Real-World Data. Dig Dis Sci 2021; 66:1327-1334. [PMID: 32405981 DOI: 10.1007/s10620-020-06286-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 04/17/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) are current standard of HCV treatment (Rx). However, data remain lacking on real-world safety, patterns of biochemical, virologic responses, and sustained virologic response (SVR12) rate in geriatric patients. AIMS The present study assessed clinical presentation, safety, SVR12 rate, dynamic changes in HCV RNA, ALT, and AFP in geriatric patients (age ≥ 65 year old, G1) versus non-geriatric patients (G2) with chronic hepatitis C and received DAA treatment. METHODS This was a single-center, retrospective study on 183 patients with DAA Rx and 12-week post-Rx follow-up. RESULTS There were no significant differences in patterns of biochemical and virologic responses between the two groups. Undetectable HCV RNA rates were 67.2% versus 75.7% (p = 0.22) and 77.3% versus 84.3% (p = 0.24) at Rx week 2 and Rx week 4, respectively. The SVR12 rate was comparable in 2 groups, 94.1% (G1) versus 95.7% (G2, p = 0.64). ALT normalization rates were 91.2% versus 91.3% (p = 0.98), 92.6% versus 93.9% (p = 0.74), and 97.1% versus 97.4% (p = 0.89) at Rx week 2, post-Rx week12, and post-Rx week 24, respectively. AFP normalization was lower in G1 with 89.7% versus 95.7% (p = 0.12), 77.9% versus 87.8% (p = 0.08), and 79.4% versus 92.2% (p = 0.01), at Rx week 2, and post-Rx week 12, and post-Rx week 24, respectively. Both groups showed similar side effects profile including fatigue 11.8% versus 12.2% (p = 0.93) and headache 11.8% versus 13.9% (p = 0.68). CONCLUSION Based on our real-world data, geriatric patients had excellent and comparable treatment outcomes with non-geriatric patients in safety and SVR12 rates to different DAA regimens.
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Affiliation(s)
- Tung Huynh
- Department of Pharmacy, University of California Irvine Medical Center, Orange, CA, USA
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California Irvine, School of Medicine, 101 The City Drive, Building 56, Ste. 801, Orange, CA, 92868, USA.
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Garuti F, Neri A, Avanzato F, Gramenzi A, Rampoldi D, Rucci P, Farinati F, Giannini EG, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Sacco R, Cabibbo G, Marra F, Mega A, Morisco F, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Missale G, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Trevisani F. The changing scenario of hepatocellular carcinoma in Italy: an update. Liver Int 2021; 41:585-597. [PMID: 33219585 DOI: 10.1111/liv.14735] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 10/26/2020] [Accepted: 11/13/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS Epidemiology of hepatocellular carcinoma (HCC) is changing in most areas of the world. This study aimed at updating the changing scenario of aetiology, clinical presentation, management and prognosis of HCC in Italy during the last 15 years. METHODS Retrospective analysis of the Italian Liver Cancer (ITA.LI.CA) database included 6034 HCC patients managed in 23 centres from 2004 to 2018. Patients were divided into three groups according to the date of cancer diagnosis (2004-2008, 2009-2013 and 2014-2018). RESULTS The main results were: (i) a progressive patient ageing; (ii) a progressive increase of non-viral cases and, particularly, of 'metabolic' and 'metabolic + alcohol' HCCs; (iii) a slightly decline of cases diagnosed under surveillance, but with an incremental use of the semiannual schedule; (iv) a favourable cancer stage migration; (v) an increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) an improved overall survival (adjusted for the lead time in surveyed patients) in the last calendar period, particularly in viral patients; (viii) a large gap between the number of potential candidates (according to oncologic criteria and age) to liver transplant and that of transplanted patients. CONCLUSIONS During the last 15 years several aspects of HCC scenario have changed, as well as its management. The improvement in patient survival observed in the last period was likely because of a larger use of thermal ablation with respect to the less effective alcohol injection and to an improved management of intermediate stage patients.
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Affiliation(s)
- Francesca Garuti
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Andrea Neri
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesca Avanzato
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Annagiulia Gramenzi
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Davide Rampoldi
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Paola Rucci
- Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Edoardo G Giannini
- Department of Internal Medicine, Gastroenterology Unit, University of Genova, IRCCS Policlinico San Martino, Genova, Italy
| | - Fabio Piscaglia
- Internal Medicine-Piscaglia Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | | | | | - Marco Zoli
- Internal Medicine-Zoli Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Napoli "Federico II", Napoli, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Unit, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy
| | | | - Francesco G Foschi
- Department of Internal Medicine, Ospedale per gli Infermi of Faenza, Faenza, Italy
| | - Gabriele Missale
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria of Parma, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli "Federico II", Napoli, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria of Sassari, Sassari, Italy
| | - Maurizia R Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Franco Trevisani
- Semeiotics Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Mangoud NOM, Ali SA, El Kassas M, Soror SH. Chitinase 3-like-1, Tolloid-like protein 1, and intergenic gene polymorphisms are predictors for hepatocellular carcinoma development after hepatitis C virus eradication by direct-acting antivirals. IUBMB Life 2021; 73:474-482. [PMID: 33347699 DOI: 10.1002/iub.2444] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/19/2020] [Accepted: 12/20/2020] [Indexed: 02/02/2023]
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer death in Egypt. There is still a risk for HCC development even after eradicating hepatitis C virus (HCV) by direct-acting antivirals (DAAs). Chitinase-3-like-protein-1 (CHI3L1), a biomarker for predicting many diseases, plays an essential role in inflammation, angiogenesis, and antiapoptosis. Tolloid-like protein 1 (TLL1) may be involved in hepatic fibrogenesis and carcinogenesis. This study aimed to determine the role and combined effect of CHI3L1 (rs880633), TLL1 (rs1503298), and an intergenic (rs597533) polymorphisms on the risk of developing HCC in Egyptian patients after achieving sustained virological response (SVR) by DAAs. Blood samples were collected from 68 HCC patients, 77 non-HCC subjects, and 80 healthy controls. The DNA was extracted and analyzed for rs880633, rs1503298, and rs597533 using Genotyping TaqMan™ assay. The result of the present study showed a significant difference in genotypes and alleles frequencies in both (rs880633) and (rs597533) in HCC group as compared to healthy control and also as compared to the non-HCC group. However, regarding to (rs1503298) genotypes and alleles between the HCC and non-HCC groups, there were no significant differences. Combined polymorphism in more than one gene simultaneously showed a higher risk to HCC after SVR than an individual locus. Both allelic and genotypic variations of the CHI3L1 gene (rs880633) and an intergenic (rs597533) seemed to be significant predictors confirming a great risk for HCC susceptibility in Egyptian patients achieved SVR. Patients with a polymorphism in more than one gene showed an increased risk to HCC after SVR rather than individual locus.
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Affiliation(s)
- Nadia O M Mangoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
| | - Sahar A Ali
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Helwan, Egypt
| | - Sameh H Soror
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
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Abstract
Hepatocellular carcinoma is among the leading causes of morbidity and mortality. Owing to the current epidemic of metabolic syndrome, the population affected by nonalcoholic fatty liver disease/nonalcoholic steatohepatitis continues to increase and now comprises a significant portion with those with hepatocellular carcinoma. The World Health Organization goal of obtaining universal hepatitis B virus vaccination has led to a global effort to improve vaccination, prevent mother-to-child transmission, and implement linkage to care to avoid the development of hepatocellular carcinoma. In contrast with the decreased burden of chronic hepatitis C virus, there has been an increase in new-onset acute hepatitis C virus.
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Development of Hepatocellular Carcinoma in a Patient with Chronic Hepatitis C 21 Years after Achieving a Sustained Virological Response to Interferon Therapy. Case Reports Hepatol 2020; 2020:8824974. [PMID: 33123390 PMCID: PMC7582091 DOI: 10.1155/2020/8824974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 09/30/2020] [Accepted: 10/06/2020] [Indexed: 12/04/2022] Open
Abstract
A 77-year-old man with chronic hepatitis C (CH-C) infection, who achieved a sustained virological response (SVR) to interferon (IFN) therapy, was followed up regularly. Before IFN therapy, he did not have metabolic diseases, and the histological diagnosis of his chronic hepatitis was stage-3 fibrosis. After achieving SVR, the fibrosis-4 (FIB-4) index level dropped once but gradually increased. 21 years after SVR, hepatocellular carcinoma (HCC) was diagnosed by dynamic computed tomography. The HCC was 12 mm in diameter. The HCC was treated with radiofrequency ablation. CH-C patients with advanced fibrosis require long-term follow-up, even after achieving SVR.
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Rao H, Xie Q, Shang J, Gao Z, Chen H, Sun Y, Jiang J, Niu J, Zhang L, Wang L, Zhao L, Li J, Yang R, Zhu S, Li R, Wei L. Real-world clinical outcomes among individuals with chronic HCV infection in China: CCgenos study. Antivir Ther 2020; 24:473-483. [PMID: 31566575 DOI: 10.3851/imp3334] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2019] [Indexed: 10/25/2022]
Abstract
BACKGROUND This 5-year follow-up of the CCgenos cross-sectional study aimed to observe real-life outcomes in a cohort of 997 Han Chinese patients with chronic HCV infection and to explore the impacts of HCV genotype, patient characteristics and treatment status. METHODS Clinical information and centralized HCV RNA measures were collected every 6/3 months for untreated/treated patients. Overall disease progression was defined as ≥1 of: de novo development of cirrhosis, Child-Turcotte-Pugh score increased by ≥2 points (if cirrhosis at baseline), progression to decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant or death. Cox regression assessed risk factors for the time from estimated infection to cirrhosis or HCC. Logistic regression assessed risk factors for incidence rates of cirrhosis and overall disease progression. RESULTS 281 of 514 patients enrolled across China completed 5 years of follow-up. Overall disease progression occurred in 36/364 (9.9%) treated patients and 35/148 (23.6%) untreated patients (odds ratio = 0.35; 95% CI 0.21, 0.59; P<0.0001). Overall disease progression occurred in 6/231 (2.6%) patients achieving sustained virological response at 24 weeks (SVR24) versus 11/82 (13.4%) who did not (P=0.0002). Cirrhosis development was significantly associated with abnormal aspartate aminotransferase (AST), age ≥40 years, body mass index ≥28 kg/m2, HCV GT1, platelet count <100×109/l, and AST to platelet ratio index (APRI) ≥2 (multivariate Cox regression, P<0.05). HCC was significantly associated with HCV GT1 and platelet count <100×109/l (multivariate Cox regression, P<0.05). CONCLUSIONS Achieving SVR24 significantly reduced the probability of overall disease progression but no significant difference was seen for both cirrhosis and HCC during 5 years of follow-up.
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Affiliation(s)
- Huiying Rao
- Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Peking University People's Hospital, Beijing, China
| | - Qing Xie
- Shanghai Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China
| | - Jia Shang
- Henan Provincial People's Hospital, Zhengzhou, China
| | - Zhiliang Gao
- The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hong Chen
- The First Affiliated Hospital of Lanzhou University, Lanzhou, China
| | | | - Jianning Jiang
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Junqi Niu
- The First Hospital of Jilin University, Changchun, China
| | - Lunli Zhang
- The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Lei Wang
- The Second Hospital of Shandong University, Jinan, China
| | - Longfeng Zhao
- The First Affiliated Hospital of Shanxi Medical University, Taiyuan, China
| | - Jun Li
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ruifeng Yang
- Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Peking University People's Hospital, Beijing, China
| | - Siyun Zhu
- Bristol-Myers Squibb, Shanghai, China
| | - Runqin Li
- Bristol-Myers Squibb, Shanghai, China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
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Li CF, Tsao SM, Liao HH, Chen SC, Lee YT. Treatment of chronic hepatitis C regiments containing with recombinant interferon in patients with sustained virological response predicts risk of hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore) 2020; 99:e22435. [PMID: 33019424 PMCID: PMC7535677 DOI: 10.1097/md.0000000000022435] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.
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Affiliation(s)
- Chien-Feng Li
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
| | - Shih-Ming Tsao
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
| | - Hsien-Hua Liao
- School of Medicine, Chung Shan Medical University
- Department of Plastic Surgery
| | - Shiuan-Chih Chen
- School of Medicine, Chung Shan Medical University
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yuan-Ti Lee
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
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Pérez-Pérez A, Sánchez-Jiménez F, Vilariño-García T, Sánchez-Margalet V. Role of Leptin in Inflammation and Vice Versa. Int J Mol Sci 2020; 21:E5887. [PMID: 32824322 PMCID: PMC7460646 DOI: 10.3390/ijms21165887] [Citation(s) in RCA: 173] [Impact Index Per Article: 34.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/07/2020] [Accepted: 08/14/2020] [Indexed: 12/15/2022] Open
Abstract
Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of adaptive response that are called into action when other homeostatic mechanisms are insufficient. Although considerable progress has been made in understanding the cellular and molecular events that are involved in the acute inflammatory response to infection and tissue injury, the causes and mechanisms of systemic chronic inflammation are much less known. The pathogenic capacity of this type of inflammation is puzzling and represents a common link of the multifactorial diseases, such as cardiovascular diseases and type 2 diabetes. In recent years, interest has been raised by the discovery of novel mediators of inflammation, such as microRNAs and adipokines, with different effects on target tissues. In the present review, we discuss the data emerged from research of leptin in obesity as an inflammatory mediator sustaining multifactorial diseases and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. On the other direction, chronic inflammation, either from autoimmune or infectious diseases, or impaired microbiota (dysbiosis) may impair the leptin response inducing resistance to the weight control, and therefore it may be a cause of obesity. Thus, we are reviewing the published data regarding the role of leptin in inflammation, and the other way around, the role of inflammation on the development of leptin resistance and obesity.
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Affiliation(s)
- Antonio Pérez-Pérez
- Department of Medical Biochemistry and Molecular Biology, and Immunology, Virgen Macarena University Hospital, University of Seville, 41009 Seville, Spain; (F.S.-J.); (T.V.-G.)
| | | | | | - Víctor Sánchez-Margalet
- Department of Medical Biochemistry and Molecular Biology, and Immunology, Virgen Macarena University Hospital, University of Seville, 41009 Seville, Spain; (F.S.-J.); (T.V.-G.)
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Vidal-Castiñeira JR, López-Vázquez A, Diaz-Bulnes P, Díaz-Coto S, Márquez-Kisinousky L, Martínez-Borra J, Navascues CA, Sanz-Cameno P, de la Vega J, Astudillo A, Rodríguez M, López-Larrea C. Genetic contribution of endoplasmic reticulum aminopeptidase 1 polymorphisms to liver fibrosis progression in patients with HCV infection. J Mol Med (Berl) 2020; 98:1245-1254. [PMID: 32647953 DOI: 10.1007/s00109-020-01948-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 06/24/2020] [Accepted: 06/30/2020] [Indexed: 12/21/2022]
Abstract
The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses, trimming peptides and loading onto HLA class I molecules. Coding single nucleotide polymorphisms within ERAP1 are associated with autoimmune diseases, viral infections, and cancer development. Our purpose was to analyze the influence of ERAP1 variants on fibrogenesis in hepatitis C virus (HCV)-infected patients. A range of ERAP1 polymorphisms were genotyped in 722 unrelated Caucasian patients diagnosed with chronic HCV from two Spanish cohorts. Patients were classified according to their fibrosis stage. Paraffin-embedded tissue microarrays were constructed to assess ERAP1 expression (HCV = 38; alcoholic = 20) by immunohistochemistry. A statistical algorithm was applied to derive a fibrogenesis prediction model. The ERAP1 variants rs30187/T (K528, pc < 0.001) and rs27044/G (Q730, pc < 0.001) were related with severe fibrosis. These results were validated in the two independent cohorts. Furthermore, patients with the rs30187/T allele had stronger ERAP1 protein expression than those with the rs30187/C (p < 0.05). The statistical model showed that patients with rs30187 C/T and T/T genotypes took 15.58 years (median) to develop advanced fibrosis, but this value was 32.08 years in patients carrying C/C genotype (p < 0.005). ERAP1 variants may influence the clinical course of fibrogenesis in HCV-infected patients. These polymorphisms could be exploited as constitutive new markers of fibrosis evolution. The results highlight the possibility of using modulators of ERAP1 to generate a protective immune response against chronic HCV infection. KEY MESSAGES: What is known Several ERAP1 polymorphisms are associated with autoimmune diseases and cancer. ERAP1 trims peptides to HLA class I presentation. What is new here ERAP1 polymorphisms are associated with fibrogenesis. The ERAP1 polymorphisms genotype could help us in clinical management of patients. Potential translational impact The use of modulators of ERAP1 could generate a protective response depending on SNPs.
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Affiliation(s)
- Jose Ramón Vidal-Castiñeira
- Translational Immunology Laboratory, Health Research Institute of the Principality of Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Antonio López-Vázquez
- Translational Immunology Laboratory, Health Research Institute of the Principality of Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain.,Immunology Service, Hospital Universitario Central de Asturias, Av. de Roma s/n, 33011, Oviedo, Spain
| | - Paula Diaz-Bulnes
- Translational Immunology Laboratory, Health Research Institute of the Principality of Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain
| | | | - Leonardo Márquez-Kisinousky
- Translational Immunology Laboratory, Health Research Institute of the Principality of Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Jesús Martínez-Borra
- Translational Immunology Laboratory, Health Research Institute of the Principality of Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain.,Immunology Service, Hospital Universitario Central de Asturias, Av. de Roma s/n, 33011, Oviedo, Spain
| | - Carmen A Navascues
- Gastroenterology Service, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Paloma Sanz-Cameno
- Liver Unit, Gastroenterology Service, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid and CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Juan de la Vega
- Gastroenterology Service, Hospital San Agustín, Avilés, Spain
| | - Aurora Astudillo
- Pathology Service, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Manuel Rodríguez
- Gastroenterology Service, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Carlos López-Larrea
- Translational Immunology Laboratory, Health Research Institute of the Principality of Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain. .,Immunology Service, Hospital Universitario Central de Asturias, Av. de Roma s/n, 33011, Oviedo, Spain.
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Musa NI, Mohamed IE, Abohalima AS. Impact of treating chronic hepatitis C infection with direct-acting antivirals on the risk of hepatocellular carcinoma recurrence. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-00035-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Abstract
Background
The impact of direct-acting antivirals (DAAs) remains a debate, whether they accelerate the recurrence rate of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after curative therapy. We evaluated the impact of direct-acting antiviral therapy on the rate of recurrence of HCV-related hepatocellular carcinoma following intervention in Egyptian patients.
Results
The results of the study represented an HCC recurrence rate of 38% in patients who received direct-acting antiviral therapy after HCC intervention versus 62% in those who did not receive antiviral therapy. In group I, according to the Barcelona Clinic of Liver Cancer (BCLC) staging, a higher recurrence rate was observed (57.9%) among patients who were classified as BCLC stage B.
Conclusions
HCC patients who did not receive direct-acting antiviral therapy after HCC intervention had a greater risk of HCC recurrence. DAAs did not increase the risk of HCC recurrence following HCC treatment; however, it did not abolish it. Close monitoring of patients after antiviral therapy is recommended.
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Shiha G, Mousa N, Soliman R, Nnh Mikhail N, Adel Elbasiony M, Khattab M. Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study. J Viral Hepat 2020; 27:671-679. [PMID: 32050037 DOI: 10.1111/jvh.13276] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 11/03/2019] [Accepted: 01/13/2020] [Indexed: 12/11/2022]
Abstract
Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%-8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long-term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis-related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow-up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow-up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow-up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942-2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407-3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333-1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.
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Affiliation(s)
- Gamal Shiha
- Egyptian Liver Research Institute and Hospital (ELRIAH), El-Mansoura, Egypt
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nasser Mousa
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Reham Soliman
- Egyptian Liver Research Institute and Hospital (ELRIAH), El-Mansoura, Egypt
- Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt
| | - Nabiel Nnh Mikhail
- Egyptian Liver Research Institute and Hospital (ELRIAH), El-Mansoura, Egypt
- Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Assuit, Egypt
| | - Mohamed Adel Elbasiony
- Egyptian Liver Research Institute and Hospital (ELRIAH), El-Mansoura, Egypt
- Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mahmoud Khattab
- Internal Medicine Department, Faculty of Medicine, Minya University, Minya, Egypt
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Balmaceda JB, Aepfelbacher J, Belliveau O, Chaudhury CS, Chairez C, McLaughlin M, Silk R, Gross C, Kattakuzhy S, Rosenthal E, Kottilil S, Kleiner DE, Hadigan C. Long-term changes in hepatic fibrosis following hepatitis C viral clearance in patients with and without HIV. Antivir Ther 2020; 24:451-457. [PMID: 31359874 DOI: 10.3851/imp3327] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND While acute changes in hepatic fibrosis are recognized shortly after achieving sustained virological response (SVR) using direct-acting antiviral therapies, long-term outcomes for the growing population of successfully treated patients with HCV remain uncertain. The aim of this study is to characterize long-term changes in fibrosis following SVR in patients with and without HIV and to identify potential factors associated with progression or regression of fibrosis. METHODS We completed a prospective longitudinal study of 162 subjects with HCV (34% HIV-coinfected) with pre-treatment fibrosis stage determined by liver biopsy and post-SVR transient elastography. Progression of fibrosis was defined as a two-stage or greater increase in fibrosis, while regression was defined as a two-stage or greater decrease at last follow-up. The median duration of follow-up was 4.1 years. RESULTS Fibrosis progression occurred in 4% of subjects while regression occurred in 7% and 89% were stable and did not differ by HIV coinfection. Fibrosis progression was associated with increased body mass index (BMI), hepatic steatosis and smoking pack-years. In a multivariable logistic regression, HIV coinfection (P=0.009), lower steatosis score (P<0.05) and lower smoking pack-years (P=0.0007) were associated with a lower fibrosis score at last follow-up. CONCLUSIONS We identify potentially important relationships between BMI, hepatic steatosis and smoking, and changes in hepatic fibrosis post-SVR in patients with and without HIV coinfection. Attention to modifiable risk factors such as body weight and smoking may reduce the risk of liver disease progression in the growing population of successfully treated chronic HCV patients.
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Affiliation(s)
- Julia B Balmaceda
- National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Julia Aepfelbacher
- National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Olivia Belliveau
- National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Chloe S Chaudhury
- National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Cheryl Chairez
- National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Mary McLaughlin
- National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Rachel Silk
- Division of Clinical Care and Research, Institute of Human Virology, Department of Medicine, University of Maryland, Baltimore, MD, USA
| | - Chloe Gross
- Division of Clinical Care and Research, Institute of Human Virology, Department of Medicine, University of Maryland, Baltimore, MD, USA
| | - Sarah Kattakuzhy
- Division of Clinical Care and Research, Institute of Human Virology, Department of Medicine, University of Maryland, Baltimore, MD, USA
| | - Elana Rosenthal
- Division of Clinical Care and Research, Institute of Human Virology, Department of Medicine, University of Maryland, Baltimore, MD, USA
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, Department of Medicine, University of Maryland, Baltimore, MD, USA
| | | | - Colleen Hadigan
- National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
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Screening for Hepatocellular Carcinoma in HIV-Infected Patients: Current Evidence and Controversies. Curr HIV/AIDS Rep 2020; 17:6-17. [PMID: 31933273 DOI: 10.1007/s11904-019-00475-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE OF REVIEW This review aims to summarize evidence regarding hepatocellular carcinoma (HCC) screening in the specific context of HIV infection and discuss areas of uncertainty. RECENT FINDINGS It has not been definitely established if HCC incidence in HIV/HCV-coinfected patients with cirrhosis is above the 1.5%/year threshold that makes screening cost-effective. Outside cirrhosis or HBV infection, available data do not support surveillance. The performance of currently recommended ultrasound (US) screening strategy is poor in HIV-infected patients, as rates of early-stage HCC detection are low. Magnetic resonance imaging-based surveillance strategies or liquid biopsy are innovative approaches that should be specifically tested in this setting. HIV-infected patients with cirrhosis are at risk of HCC. US surveillance identifies patients with early-stage HCC who will benefit of curative therapies, although the quality of the evidence supporting screening remains limited. The HIV population should be a priority group to assess and validate new surveillance strategies.
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