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Obite CP, Chukwudi EO, Uchechukwu M, Nwosu UI. Factor enhanced DeepSurv: A deep learning approach for predicting survival probabilities in cirrhosis data. Comput Biol Med 2025; 189:109963. [PMID: 40037171 DOI: 10.1016/j.compbiomed.2025.109963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 02/27/2025] [Accepted: 02/28/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND Over the years, various models, including both traditional and machine learning models, have been employed to predict survival probabilities for diverse survival datasets. The objective is to obtain models that provide more accurate estimates of survival probabilities. Certain datasets exhibit complex nonlinear effects and interactions between variables that may necessitate the application of deep learning algorithms to comprehend the underlying data generation process. METHOD In this paper, we introduced Factor Enhanced DeepSurv (FE-DeepSurv), a novel deep neural network designed to study complex structures and excels at filtering noise within predictors, thereby enhancing precision of survival probability estimates. FE-DeepSurv incorporates factor analysis to reduce predictor dimensionality, applies a transformation technique to account for data censoring, and employs a deep neural network to predict conditional failure probabilities for each time interval. These predictions are subsequently utilized to estimate survival probabilities for each subject. We applied our proposed model to study cirrhosis survival data, a secondary data from Mayo Clinic trial focused on primary biliary cirrhosis (PBC) of the liver and compared its performance with the Cox proportional hazard model (Cox model), random survival forest (RSF), DeepHit, and DeepSurv, using the concordance index (C-index), brier score (BS), and integrated brier score (IBS). RESULTS The results show that FE-DeepSurv outperforms many existing survival models. FE-DeepSurv's accurate predictions of survival probabilities and hazard rates can drive improvements in clinical practice, healthcare management, insurance risk assessment, and various other domains. CONCLUSIONS By adopting FE-DeepSurv, institutions can harness the power of advanced analytics to make more informed decisions, ultimately leading to better outcomes across multiple sectors.
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Affiliation(s)
- Chukwudi Paul Obite
- School of Mathematical and Statistical Sciences, Arizona State University, USA.
| | | | - Merit Uchechukwu
- Department of Statistics, Federal University of Technology, Owerri, Nigeria
| | - Ugochinyere Ihuoma Nwosu
- Department of Statistics, Federal University of Technology, Owerri, Nigeria; Department of Computing and Mathematics, Manchester Metropolitan University, UK
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Ismael NY, Usmael SA, Belay NB, Mekonen HD, Johannessen A, Orlien SM. Chronic hepatitis B virus infection in Eastern Ethiopia: Clinical characteristics and determinants of cirrhosis. World J Hepatol 2024; 16:995-1008. [PMID: 39086536 PMCID: PMC11287608 DOI: 10.4254/wjh.v16.i7.995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 06/14/2024] [Accepted: 07/05/2024] [Indexed: 07/26/2024] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) virus infection is a major cause of liver-associated morbidity and mortality, particularly in low-income countries. A better understanding of the epidemiological, clinical, and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia. AIM To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment. METHODS This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019. Baseline assessments included chemistry, serologic, and viral markers. χ 2 tests, Mann-Whitney U tests, and logistic regression analyses were used to identify the determinants of cirrhosis. Tenofovir disoproxil fumarate (TDF) was initiated using treatment criteria from the Ethiopian CHB pilot program. RESULTS A total of 132 patients (68.4%) were men, with a median age of 30 years [interquartile range (IQR): 24-38]. At enrollment, 60 (31.1%) patients had cirrhosis, of whom 35 (58.3%) had decompensated cirrhosis. Khat use, hepatitis B envelope antigen positivity, and a high viral load were independently associated with cirrhosis. Additionally, 66 patients (33.4%) fulfilled the treatment criteria and 59 (30.6%) started TDF. Among 29 patients who completed 24 months of treatment, the median aspartate aminotransferase to platelet ratio index declined from 1.54 (IQR: 0.66-2.91) to 1.10 (IQR: 0.75-2.53) (P = 0.002), and viral suppression was achieved in 80.9% and 100% of patients after 12 months and 24 months of treatment, respectively. Among the treated patients, 12 (20.3%) died within the first 6 months of treatment, of whom 8 had decompensated cirrhosis. CONCLUSION This study highlights the high prevalence of cirrhosis, initial mortality, and the efficacy of TDF treatment. Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.
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Affiliation(s)
- Nejib Y Ismael
- Department of Internal Medicine, Haramaya University, College of Health and Medical Sciences, Harar 252, Ethiopia
| | - Semir A Usmael
- Department of Internal Medicine, Haramaya University, College of Health and Medical Sciences, Harar 252, Ethiopia.
| | - Nega B Belay
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa 1000, Ethiopia
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Oslo 0450, Ullevål, Norway
| | - Hailemichael Desalegn Mekonen
- Internal Medicine, Gastroenterology and Hepatology Unit, Saint Paul's Hospital Millennium Medical College, Addis Ababa 1000, Ethiopia
- Department of Infectious Disease, Vestfold Hospital Trust, Tønsberg 3103, Norway
| | - Asgeir Johannessen
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Oslo 0450, Ullevål, Norway
- Department of Infectious Disease, Vestfold Hospital Trust, Tønsberg 3103, Norway
- Institute of Clinical Medicine, Oslo University, Oslo 0318, Norway
| | - Stian Ms Orlien
- Regional Centre for Imported and Tropical Diseases, Oslo University Hospital, Oslo 0450, Ullevål, Norway
- Department of Infectious Disease, Vestfold Hospital Trust, Tønsberg 3103, Norway
- Department of Pediatrics, Oslo University, Oslo 0450, Ullevål, Norway
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Yu L, Wang L, Xue Y, Ren Y, Liu T, Hu H. Causal associations between platelet count, alcohol consumption, and the risk of liver hepatocellular carcinoma based on a Mendelian randomization study. Front Endocrinol (Lausanne) 2024; 15:1400573. [PMID: 38841303 PMCID: PMC11151168 DOI: 10.3389/fendo.2024.1400573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 04/22/2024] [Indexed: 06/07/2024] Open
Abstract
Background and aims Liver hepatocellular carcinoma (LIHC) exhibits a multifactorial etiology, insidious onset, and a significantly low 5-year survival rate. We aimed to evaluate the causal impact of exposure factors (Alzheimer's disease, platelet count, ambidextrousness, cigarettes smoked per day, alcohol consumption, and endocarditis) on the risk of LIHC using a two-sample Mendelian randomization (MR) study. Methods Independent single nucleotide polymorphisms (SNPs) strongly associated with Alzheimer's disease, platelet count, ambidextrousness, daily cigarette consumption, alcohol intake, and endocarditis were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). Genetic summary statistics for LIHC came from a GWAS that included 168 cases and 372,016 controls of European individuals. Multivariable MR analyses were performed to find the causal association between 6 exposure factors and LIHC risk. The inverse-variance weighted (IVW)-MR was employed as the primary analysis, and the MR-Egger regression, LASSO regression, and weighted Median approaches were performed as complementary analyses. Results Multivariable MR analysis showed causal association between Alzheimer's disease [Odds ratio (OR) = 0.9999, 95% confidence intervals (CI) = 0.9998-0.9999, p = 0.0010], platelet count (OR = 0.9997, 95% CI = 0.9995-0.9999, p = 0.0066), alcohol consumption (OR = 0.9994, 95% CI = 0.9990-0.9999, p = 0.0098) and the LIHC outcome. After IVW-MR, MR-Egger and LASSO tests, the results are still significant. Next, we used different MR Methods to analyze platelet count, alcohol consumption, and Alzheimer's disease separately. Moreover, both funnel plots and MR-Egger intercepts provided compelling evidence to refute the presence of directional pleiotropy in the association between platelet count, alcohol consumption, Alzheimer's disease and the risk of LIHC. The IVW-MR analysis revealed a significant causal association between an elevated platelet count and a reduced risk of LIHC (OR = 0.9996, 95% CI= 0.9995-0.9998, p = 0.0005). Similarly, the analysis of weighted median revealed a negative correlation between platelet count and the risk of LIHC (OR = 0.9995, 95% CI = 0.9993-0.9999; p = 0.0160). Conversely, we observed a positive causal effect of alcohol consumption on the incidence of LIHC (OR = 1.0004, 95% CI = 0.9999-1.0009). However, no significant causal relationship was found between alcohol assumption, Alzheimer's disease, and LIHC susceptibility. Conclusions A significant causal relationship exists between platelet count, alcohol consumption, Alzheimer's disease, and an increased risk of LIHC. The study presents compelling evidence for a genetically predicted decreased susceptibility to LIHC based on platelet count. The research implies that elevated platelet count may serve as a protective mechanism against LIHC. These findings may inform clinical strategies for LIHC prevention.
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Affiliation(s)
- Lihua Yu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
- School of Medicine, Jiangnan University, Wuxi, China
| | - Leisheng Wang
- Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
- School of Medicine, Jiangnan University, Wuxi, China
| | - Yuzheng Xue
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Yilin Ren
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Tianhao Liu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Hao Hu
- Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
- School of Medicine, Jiangnan University, Wuxi, China
- Wuxi Institute of Hepatobiliary Surgery, Wuxi, China
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Sohail R, Hassan IH, Rukh M, Saqib M, Iftikhar M, Mumtaz H. Assessing Thrombocytopenia and Chronic Liver Disease in Southeast Asia: A Multicentric Cross-Sectional Study. Cureus 2023; 15:e43356. [PMID: 37700968 PMCID: PMC10493634 DOI: 10.7759/cureus.43356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2023] [Indexed: 09/14/2023] Open
Abstract
Background This multicentric cross-sectional study aimed to examine the prevalence of thrombocytopenia (TCP) and investigate the various causes of chronic liver disease (CLD) across 15 Southeast Asian (India, Pakistan, and Bangladesh) tertiary care centers over a three-month period. The study focused on assessing the fibrosis index (FI) and Model for End-Stage Liver Disease (MELD)-sodium (Na) score's capacity to grade and predict the progression and outcomes of patients with already diagnosed CLD. Methods The cross-sectional study enrolled 377 CLD patients. The study utilized admission registries from 15 tertiary care hospitals in Southeast Asia, spanning from April 2023 to June 2023. Various descriptive variables were collected, including gender, tobacco use (specifically, chewed tobacco), underlying etiology, presence of anemia, leukopenia, pancytopenia, infectious state, and liver cirrhosis diagnosed via traditional ultrasonography. This study examined liver failure indicators, including alanine transaminase levels, compensation status, TCP, and liver transplant (LT) listing. The MELD-Na score was the focus of frequency and percentage analysis. MELD-Na and FI medians and standard deviations were provided. Results The study of 377 patients with CLD found that TCP was present in 4% of patients and leukopenia was present in 12% of patients. The risk of TCP was significantly higher in leukopenic patients (89.5%) than in non-leukopenic patients (52.5%) (p = 0.003). The most common CLD cause was undiagnosable (31%), followed by autoimmune (26%), hepatitis C virus (21%), hepatitis B virus (14%), and schistosomiasis (8%). The majority of patients (98%) had decompensated liver disease. Of the patients, 64% had TCP, while 36% did not. The illness severity indicators MELD score and FI had mean ± SD values of 16.89 ± 6.42 and 4.1 ± 1.06, respectively. Similarly, the prevalence of LT needs among traditional ultrasonography-diagnosed cirrhotic patients was 83.1%, compared to 59.6% among non-cirrhotic patients (p = 0.001). Conclusion Leukopenia and TCP may be linked, which may affect CLD treatment and prognosis in this population. Non-invasive indicators like the FI and MELD-Na score can detect liver fibrosis and severity without invasive procedures, enhancing patient management. These findings highlight the need to improve early diagnosis methods for CLD in Southeast Asia and raise awareness among clinicians about effective diagnostic strategies for non-infectious causes of CLD.
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Affiliation(s)
- Ramsha Sohail
- Department of Medicine, Jackson Park Hospital, Chicago, USA
| | - Imran H Hassan
- Department of Medicine, Grantham and District Hospital, Grantham, GBR
| | - Mah Rukh
- Department of Medicine, Khyber Teaching Hospital, Peshawar, PAK
| | - Muhammad Saqib
- Department of Medicine, Khyber Teaching Hospital, Peshawar, PAK
| | | | - Hassan Mumtaz
- Department of Urology, Guy's and St. Thomas' Hospital, London, GBR
- General Practice, Surrey Docks Health Centre, London, GBR
- Department of Public Health, Health Services Academy, Islamabad, PAK
- Department of Clinical Research, Maroof International Hospital, Islamabad, PAK
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Koschade SE, Moser LM, Sokolovskiy A, Michael FA, Serve H, Brandts CH, Finkelmeier F, Zeuzem S, Trebicka J, Ferstl P, Ballo O. Bone Marrow Assessment in Liver Cirrhosis Patients with Otherwise Unexplained Peripheral Blood Cytopenia. J Clin Med 2023; 12:4373. [PMID: 37445409 DOI: 10.3390/jcm12134373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 06/25/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
We performed a retrospective single-center analysis to investigate the diagnostic yield of bone marrow puncture in patients with liver cirrhosis and cytopenia. Liver cirrhosis patients receiving bone marrow aspiration or biopsy for the diagnostic work-up of otherwise unexplained peripheral blood cytopenia at our institution between 2004 and 2020 were enrolled in this study. We evaluated findings from cytologic, histologic and immunologic assessment and final diagnostic outcomes. A total of 118 patients with a median age of 55 years and a median Child-Pugh score of B (8 points) were enrolled. The main etiologies of liver cirrhosis were viral hepatitis (B and C) or chronic alcohol consumption. The majority of patients (60%) exhibited concurrent anemia, leukocytopenia and thrombocytopenia. Bone marrow assessment revealed normal, unspecific or reactive alterations in 117 out of 118 patients (99%). One patient was diagnosed with myelodysplastic syndrome. Our findings suggest that peripheral blood cytopenia in patients with liver cirrhosis is rarely associated with a primary bone marrow pathology.
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Affiliation(s)
- Sebastian E Koschade
- Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Laura M Moser
- Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Artur Sokolovskiy
- Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Florian A Michael
- Department of Medicine, Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Hubert Serve
- Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Christian H Brandts
- Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
- University Cancer Center Frankfurt (UCT), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Fabian Finkelmeier
- Department of Medicine, Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department of Medicine, Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Jonel Trebicka
- Department of Medicine, Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
- Department of Internal Medicine B, University of Münster, 48149 Münster, Germany
| | - Philip Ferstl
- Department of Medicine, Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
| | - Olivier Ballo
- Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
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Schult D, Rasch S, Schmid RM, Lahmer T, Mayr U. EASIX Is an Accurate and Easily Available Prognostic Score in Critically Ill Patients with Advanced Liver Disease. J Clin Med 2023; 12:jcm12072553. [PMID: 37048641 PMCID: PMC10094870 DOI: 10.3390/jcm12072553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 03/18/2023] [Accepted: 03/22/2023] [Indexed: 03/31/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is associated with high mortality. Objective prognostic scores are important for treatment decisions. EASIX (Endothelial Activation and Stress Index) is a simple biomarker consisting of LDH, platelets, and creatinine, reflecting endothelial dysfunction after allogeneic stem cell transplantation. Considering endothelial dysfunction in the pathogenesis of ACLF, this study aimed to test the discriminative ability of EASIX in advanced liver disease. We retrospectively analysed the prognostic potential of EASIX to predict 28-day and 3-month mortality in a total of 188 liver cirrhotic patients requiring treatment at the intensive care unit. We evaluated the ability of EASIX to rule out early infections and predict the need for hemodialysis. EASIX performed moderately better than established scores in predicting 28-day mortality (AUC = 0.771) and was nearly equivalent (AUC = 0.791) to SOFA and APACHE-II in the prediction of 3-month mortality. Importantly, EASIX showed better diagnostic potential in ruling out clinically apparent infections than common proinflammatory markers (AUC = 0.861, p < 0.001) and showed suitable accuracy in predicting the need for hemodialysis (AUC = 0.833). EASIX is an accurate, objective and easily assessable biomarker for predicting mortality and complications in patients with advanced liver disease.
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Biolato M, Vitale F, Galasso T, Gasbarrini A, Grieco A. Minimum platelet count threshold before invasive procedures in cirrhosis: Evolution of the guidelines. World J Gastrointest Surg 2023; 15:127-141. [PMID: 36896308 PMCID: PMC9988645 DOI: 10.4240/wjgs.v15.i2.127] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 12/09/2022] [Accepted: 02/07/2023] [Indexed: 02/27/2023] Open
Abstract
Cirrhotic patients with severe thrombocytopenia are at increased risk of bleeding during invasive procedures. The need for preprocedural prophylaxis aimed at reducing the risk of bleeding in cirrhotic patients with thrombocytopenia who undergo scheduled procedures is assessed via the platelet count; however, establishing a minimum threshold considered safe is challenging. A platelet count ≥ 50000/μL is a frequent target, but levels vary by provider, procedure, and specific patient. Over the years, this value has changed several times according to the different guidelines proposed in the literature. According to the latest guidelines, many procedures can be performed at any level of platelet count, which should not necessarily be checked before the procedure. In this review, we aim to investigate and describe how the guidelines have evolved in recent years in the evaluation of the minimum platelet count threshold required to perform different invasive procedures, according to their bleeding risk.
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Affiliation(s)
- Marco Biolato
- Department of Medical and Surgical Sciences, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Department of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Federica Vitale
- Department of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Tiziano Galasso
- Department of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Department of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
| | - Antonio Grieco
- Department of Medical and Surgical Sciences, CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
- Department of Internal Medicine, Catholic University of Sacred Heart, Rome 00168, Italy
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Al-Dholae MHH, Salah MK, Al-Ashmali OY, Al Mokdad ASM, Al-Madwami MA. Thrombocytopenia (TCP), MELD Score, and Fibrosis Index (FI) Among Hospitalized Patients with Chronic Liver Disease (CLD) in Ma'abar City, Dhamar Governorate, Yemen: A Cross-Sectional Study. Hepat Med 2023; 15:43-50. [PMID: 37143507 PMCID: PMC10153436 DOI: 10.2147/hmer.s392011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 04/24/2023] [Indexed: 05/06/2023] Open
Abstract
Purpose This study sought to assess the prevalence of thrombocytopenia (TCP), underlying aetiologies of chronic liver disease, and the grading and prognostic systems for chronic liver disease (CLD) using non-invasive biomarkers: the Fibrosis index and the Model for End-Stage Liver Disease-Na (MELD-Na) Score, respectively. Patients and Methods This was a 15-month multi-centric cross-sectional study of 105 patients with chronic liver disease (CLD). The study was conducted using Sept 2019 to Nov 2020 admission records of CLD patients from Ma'abar City in Dhamar Governorate, Yemen. Results A total of 63 (60%) and 42 (40%) patients were identified as thrombocytopenic and non-thrombocytopenic, respectively. The means ± SD of the MELD score and FI were 19 ± 7.302 and 4.1 ± 1.06. TCP prevalence among leukopenic and non-leukopenic patients was 89.5% and 53.5%, respectively (P = 0.004). Likewise, the prevalence of traditional-ultrasonography-diagnosed cirrhotic patients needing liver transplantation (LT) was 82.3% versus 61.3% among corresponding non-cirrhotic patients (P = 0.000). Conclusion The prevalence of TCP among the participants of this study was similar to the global rate. However, the prevalence of decompensation was much higher among CLD patients than that found elsewhere, highlighting a need to improve methods for the early diagnosis of CLD in Yemen. This study also identified problems with the diagnostic work-up for non-infectious aetiologies of CLD. The findings suggest the need to improve clinician awareness about effective diagnostic strategies for these aetiologies.
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Affiliation(s)
| | - Mohammed Kassim Salah
- Department of Internal Medicine, Faculty of Medicine & Health Sciences, Thamar University, Dhamar, Yemen
| | - Omar Yahya Al-Ashmali
- Department of Pediatrics, Al-Wahda Teaching Hospital, Thamar University, Ma’abar City, Dhamar Governorate, Yemen
- Correspondence: Omar Yahya Al-Ashmali, Department of Paediatrics, Al-Wahda Teaching Hospital, Thamar University, Ma’abar City, Dhamar Governorate, Yemen, Tel +967777638063, Email
| | | | - Mohammed Ali Al-Madwami
- Department of Internal Medicine, Faculty of Medicine & Health Sciences, Thamar University, Dhamar, Yemen
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Abstract
Antiviral therapy has greatly improved the survival and reduced the incidence of adverse liver events such as hepatic decompensation and hepatocellular carcinoma in chronic hepatitis B patients with cirrhosis (hepatitis B virus [HBV]-cirrhosis). However, hepatitis B surface antigen loss, regarded as the ultimate goal of therapy or functional cure, was rarely achieved during long-term indefinite nucleos(t)ide analogues (Nuc) treatment. Emerging issues such as medication adherence and loss-to-follow-up may lead to increased risk of hepatic decompensation, even catastrophic life-threatening events. Studies have shown that finite therapy is feasible and reasonably safe, even in patients with HBV-cirrhosis. This review critically assesses the scientific evidence of the pros and cons for finite Nuc therapy in HBV-cirrhosis and proposes how to stop Nuc therapy and monitor the off-therapy patients. It also proposes the perspective and unsolved issues to be investigated in the future.
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Affiliation(s)
- Wen-Juei Jeng
- Liver Research Unit, Linkou Medical Center, Chang Gung University, Chang Gung Memorial Hospital, College of Medicine, Taoyuan, Taiwan.,Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yun-Fan Liaw
- Liver Research Unit, Linkou Medical Center, Chang Gung University, Chang Gung Memorial Hospital, College of Medicine, Taoyuan, Taiwan
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Zhang Y, Xie Y, Chen Q, Chen X, Dong Z, Tan X. Prevalence and co-infection of schistosomiasis/hepatitis B among rural populations in endemic areas in Hubei, China. Trans R Soc Trop Med Hyg 2021; 114:155-161. [PMID: 31722017 PMCID: PMC7064163 DOI: 10.1093/trstmh/trz086] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 07/16/2019] [Accepted: 07/24/2019] [Indexed: 12/19/2022] Open
Abstract
Background Both hepatitis B virus (HBV) infection and schistosomiasis are important public health problems in China. Concurrent infection between HBV and schistosomiasis is often observed in areas where schistosomiasis is endemic. The aim of this study was to determine the prevalence of schistosomiasis and HBV in schistosomiasis-affected areas, to explore whether schistosomiasis patients are more susceptible to HBV and to determine if the prevalence of HBV in high-endemic areas of schistosomiasis is higher than in low-endemic areas. Methods A total of 6526 participants from 13 villages in Hubei province were included in a cross-sectional study and blood samples were collected and examined. Qualitative variables were compared between groups using Pearson’s chi-squared test or Fisher’s exact test as appropriate. Results Of the 6526 participants, the overall prevalence was 8.27% for schistosomiasis and 2.67% for HBV. The prevalence of hepatitis B among participants who were Schistosoma antibody positive (25.37%) was higher than the prevalence in participants who were Schistosoma antibody negative (0.62%; χ2=1169.358, p<0.001, odds ratio 54.659). We also observed that there was no difference in the prevalence of hepatitis B between males and females in areas where schistosomiasis was endemic (χ2=1.827, p=0.177), but the prevalence of hepatitis B in middle-aged people was higher than in other age groups (χ2=47.877, p<0.001). Conclusions There was an association between schistosomiasis and HBV infection. However, more work is needed to find the causal relationship between schistosomiasis and HBV infection.
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Affiliation(s)
- Yupeng Zhang
- Wuhan University School of Medicine, No. 115, Donghu Road, Wuchang District, Wuhan city, Hubei Province, China
| | - Yaofei Xie
- Wuhan University School of Medicine, No. 115, Donghu Road, Wuchang District, Wuhan city, Hubei Province, China
| | - Qi Chen
- Wuhan University School of Medicine, No. 115, Donghu Road, Wuchang District, Wuhan city, Hubei Province, China
| | - Xuyu Chen
- Wuhan University School of Medicine, No. 115, Donghu Road, Wuchang District, Wuhan city, Hubei Province, China
| | - Zhuangzhuang Dong
- Wuhan University School of Medicine, No. 115, Donghu Road, Wuchang District, Wuhan city, Hubei Province, China
| | - Xiaodong Tan
- Wuhan University School of Medicine, No. 115, Donghu Road, Wuchang District, Wuhan city, Hubei Province, China
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Craxi A. EASL Recognition Awardee 2020: Prof. Giovanna Fattovich. J Hepatol 2020; 73:484-486. [PMID: 32807366 DOI: 10.1016/j.jhep.2020.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 02/06/2020] [Indexed: 12/04/2022]
Affiliation(s)
- Antonio Craxi
- Department of Internal Medicine, University of Palermo, Palermo, Italy.
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Chao D, Buddha H, Damodaran C, Tran L, Strong R, Jackson CS. Outcomes Comparison of the Veterans' Choice Program With the Veterans Affairs Health Care System for Hepatitis C Treatment. Fed Pract 2020; 37:S18-S24. [PMID: 32704227 PMCID: PMC7373074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
BACKGROUND The US Department of Veterans Affairs (VA) has been stressed by the large number of veterans requiring direct-acting antiviral (DAA) medications for hepatitis C virus (HCV) treatment. The Veterans Choice Program provides VA patients more options to receive treatment. This study compared the experience of veterans who received HCV treatment through the Veterans Choice Program and those that received treatment at the VA Loma Linda Healthcare System (VALLHCS) in fiscal year (FY) 2016. METHODS A chart review was performed on all veterans referred by VALLHCS to Choice for HCV treatment during FY 2016, and matched to veterans who received treatment at VALLHCS. Data collected included Fibrosis-4 score (Fib-4), platelet count, days elapsed between time of referral and time of appointment (wait time), rate of sustained virologic response at 12 weeks (SVR12), reason for treatment failure, and cost effectiveness. RESULTS One hundred veterans were referred to Choice; 71 were seen at least once by a Choice provider, and 61 completed a treatment course. Mean Fib-4 and platelet count was 1.9 and 228,000 for the Choice population and 3.4 and 158,000 for the VALLHCS population, respectively. There was no difference in SVR12 rate. Mean wait time was 42 days for Choice vs 29 days for VALLHCS (P < .001). Choice health care providers incurred a mean $8,561.40 in additional costs per veteran seen. CONCLUSIONS While treatment success rates were similar between Choice and VALLHCS, the degree of liver fibrosis was more advanced in the VALLHCS population. The wait time for care was longer with Choice compared with a direct referral within the VA. While Choice offers a potential solution to providing care for veterans, the current program has unique problems that must be considered.
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Affiliation(s)
- Daniel Chao
- , and are Physicians; and is a Pharmacist; all in the Gastroenterology Section at VA Loma Linda Healthcare System in California. is a Clinical Research Program Administrator at the University of California, Riverside. Daniel Chao, Chitra Damodaran, and Christian Jackson are Assistant Professors of Medicine and Richard Strong is an Associate Professor of Medicine, at Loma Linda University in California
| | - Hema Buddha
- , and are Physicians; and is a Pharmacist; all in the Gastroenterology Section at VA Loma Linda Healthcare System in California. is a Clinical Research Program Administrator at the University of California, Riverside. Daniel Chao, Chitra Damodaran, and Christian Jackson are Assistant Professors of Medicine and Richard Strong is an Associate Professor of Medicine, at Loma Linda University in California
| | - Chitra Damodaran
- , and are Physicians; and is a Pharmacist; all in the Gastroenterology Section at VA Loma Linda Healthcare System in California. is a Clinical Research Program Administrator at the University of California, Riverside. Daniel Chao, Chitra Damodaran, and Christian Jackson are Assistant Professors of Medicine and Richard Strong is an Associate Professor of Medicine, at Loma Linda University in California
| | - Linda Tran
- , and are Physicians; and is a Pharmacist; all in the Gastroenterology Section at VA Loma Linda Healthcare System in California. is a Clinical Research Program Administrator at the University of California, Riverside. Daniel Chao, Chitra Damodaran, and Christian Jackson are Assistant Professors of Medicine and Richard Strong is an Associate Professor of Medicine, at Loma Linda University in California
| | - Richard Strong
- , and are Physicians; and is a Pharmacist; all in the Gastroenterology Section at VA Loma Linda Healthcare System in California. is a Clinical Research Program Administrator at the University of California, Riverside. Daniel Chao, Chitra Damodaran, and Christian Jackson are Assistant Professors of Medicine and Richard Strong is an Associate Professor of Medicine, at Loma Linda University in California
| | - Christian S Jackson
- , and are Physicians; and is a Pharmacist; all in the Gastroenterology Section at VA Loma Linda Healthcare System in California. is a Clinical Research Program Administrator at the University of California, Riverside. Daniel Chao, Chitra Damodaran, and Christian Jackson are Assistant Professors of Medicine and Richard Strong is an Associate Professor of Medicine, at Loma Linda University in California
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13
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Ghany MG, Feld JJ, Chang KM, Chan HLY, Lok ASF, Visvanathan K, Janssen HLA. Serum alanine aminotransferase flares in chronic hepatitis B infection: the good and the bad. Lancet Gastroenterol Hepatol 2020; 5:406-417. [PMID: 32057301 DOI: 10.1016/s2468-1253(19)30344-9] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 08/08/2019] [Accepted: 08/12/2019] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis B virus (HBV) infection follows a dynamic and variable course. At different stages in the disease, hepatitis flares might occur, which can be challenging to predict and manage. Flares are believed to be primarily immune-mediated and might mark transitions to inactive disease or clearance of infection, but in certain scenarios they might also lead to hepatic decompensation or death. As such, understanding of the clinical significance of flares in different patient populations and different scenarios is important for optimal management. In this Review, we summarise what is known about flares in different stages of chronic HBV infection; describe flares in the context of the natural history of chronic infection; summarise the immunological mechanisms underlying flares, and describe flares in different clinical scenarios. Each section reviews existing knowledge and highlights key unanswered questions that need to be addressed to improve the understanding of flares, hopefully providing insights into their pathogenesis that can be used to improve current clinical management and ideally to further develop new curative therapeutic approaches for HBV infection. We also propose a working definition of an ALT flare to facilitate future research.
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Affiliation(s)
- Marc G Ghany
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Kyong-Mi Chang
- Medical Research, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, USA; Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Henry L Y Chan
- Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Kumar Visvanathan
- Department of Infectious Disease, St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.
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14
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Lun Yau AH, Galorport C, Coffin CS, Ko HH. Hepatocellular carcinoma screening practices among patients with chronic hepatitis B by Canadian gastroenterologists and hepatologists: An online survey. CANADIAN LIVER JOURNAL 2019; 2:199-209. [PMID: 35992766 PMCID: PMC9202808 DOI: 10.3138/canlivj.2019-0012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 06/27/2019] [Indexed: 08/31/2024]
Abstract
BACKGROUND xpert guidelines recommend hepatocellular carcinoma (HCC) surveillance among patients with high-risk chronic hepatitis B (CHB); however, physician screening practices are often variable. METHODS An online survey of HCC screening practice was distributed to members of the Canadian Association for the Study of the Liver. Data were analyzed using appropriate statistical tests with p < .05 significance. RESULTS Of 71 respondents, 86% (n = 61) were gastroenterologists or hepatologists, and 72% (n = 51) reported having been in clinical practice for more than 5 years. A significant number of survey respondents performed HCC screening without consideration of concomitant non-alcoholic fatty liver disease (50.7%); non-Asian, non-African ethnicity (46.4%); and family history of HCC (28.6%). Most (67.6%) performed screening with ultrasound (US) at the time of specialty clinic visits, 28.2% had an automatic recall system, and only 2.8% referred back to primary care physicians to organize screening. More than half (54.9%) included alpha-fetoprotein in screening. Obstacles to screening included lack of an automatic recall system (42.9%), patient non-compliance (30.0%), and limited US/MRI access (17.1%). CONCLUSIONS HCC screening practices with hepatitis B patients vary widely among Canadian specialists, especially in unique populations with limited data to inform screening recommendations. Implementation of an automatic recall system could potentially increase HCC surveillance.
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Affiliation(s)
- Alan Hoi Lun Yau
- Author Affiliation
Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, Canada
| | - Cherry Galorport
- Department of Medicine, Division of Gastroenterology, St. Paul’s Hospital, University of British Columbia, Vancouver, Canada
- on behalf of the Canadian Hepatitis B Network
| | - Carla S Coffin
- Department of Medicine, Division of Gastroenterology and Hepatology, Alberta Health Services, University of Calgary, Calgary, Alberta, Canada
- on behalf of the Canadian Hepatitis B Network
| | - Hin Hin Ko
- Department of Medicine, Division of Gastroenterology, St. Paul’s Hospital, University of British Columbia, Vancouver, Canada
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15
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Abdela J. Current Advance in Thrombopoietin Receptor Agonists in the Management of Thrombocytopenia Associated With Chronic Liver Disease: Focus on Avatrombopag. PLASMATOLOGY 2019; 12:1179545X19875105. [PMID: 31673229 PMCID: PMC6804364 DOI: 10.1177/1179545x19875105] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 08/20/2019] [Indexed: 12/22/2022]
Abstract
Chronic liver disease (CLD) is a condition that progresses over time toward advanced disease state which is known as liver cirrhosis. Liver cirrhosis leads to dangerous health problems among people living across the world. One such problem that observed in about 75% of cirrhotic patients is thrombocytopenia; which in turn associated with poor prognosis and recovery from CLD. Beyond these, thrombocytopenia in cirrhotic patients led to impairment of coagulation cascade and significantly influenced the utilization of effective mechanism in the management of CLD. By nature, treatment of CLD involves invasive diagnostic and treatment procedures; therefore, in the presence of thrombocytopenia implementing these methods put the lives of patients in a critical health problem due to increased risk of bleeding and mortality. Because of these reasons, prophylactic transfusion of platelets is considered to be one of the most effective options that reduce the risk of bleeding in patients with CLD that required to undergo an invasive procedure. Although platelet transfusion presented with significant advantages in facilitating the invasive procedure in patients with CLD, refractoriness with repeated use and various problems associated with its transfusion limit the continuous utilization of this important option. With these challenges and current advance in the knowledge of thrombopoiesis, the development of relatively safe and alternative drugs that enhance the production of platelets by interacting with thrombopoietin receptor agonists provides a promising option to platelet transfusion. The discovery and approval of romiplostim and eltrombopag in August 2008 and November 2008, respectively, for the treatment of chronic immune thrombocytopenia paved a way and followed by the Food and Drug Administration (FDA) approval of 2 potentially advantageous drugs, lusutrombopag, and avatrombopag, in 2018 for the treatment of thrombocytopenia in patients with CLD that required to undergo elective surgery. Therefore, this review aims to assess pathogenesis of thrombocytopenia and its challenges in the management of liver-related issues and, more importantly, gives emphasis to address the potential use of avatrombopag in the treatment of thrombocytopenia underlying CLD, its pharmacokinetics and pharmacodynamics, as well as its toxicological profiles by presenting the most commonly reported adverse events in various trials.
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Affiliation(s)
- Jemal Abdela
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
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16
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Peck‐Radosavljevic M, Simon K, Iacobellis A, Hassanein T, Kayali Z, Tran A, Makara M, Ben Ari Z, Braun M, Mitrut P, Yang S, Akdogan M, Pirisi M, Duggal A, Ochiai T, Motomiya T, Kano T, Nagata T, Afdhal N. Lusutrombopag for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Invasive Procedures (L-PLUS 2). Hepatology 2019; 70:1336-1348. [PMID: 30762895 PMCID: PMC6849531 DOI: 10.1002/hep.30561] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 02/10/2019] [Indexed: 12/21/2022]
Abstract
Thrombocytopenia may be associated with increased bleeding risk impacting timing and outcome of invasive procedures in patients with chronic liver disease (CLD). Lusutrombopag, a small-molecule, thrombopoietin (TPO) receptor agonist, was evaluated as a treatment to raise platelet counts (PCs) in patients with thrombocytopenia and CLD undergoing invasive procedures. L-PLUS 2 was a global, phase 3, randomized, double-blind, placebo-controlled study. Adults with CLD and baseline PCs < 50 × 109 /L were randomized to receive once-daily lusutrombopag 3 mg or placebo ≤ 7 days before an invasive procedure scheduled 2-7 days after the last dose. The primary endpoint was avoidance of preprocedure platelet transfusion and avoidance of rescue therapy for bleeding. A key secondary endpoint was number of days PCs were ≥ 50 × 109 /L throughout the study. Safety analysis was performed on patients who received at least one dose of study drug. This study occurred between June 15, 2015, and April 19, 2017, with a total of 215 randomized patients (lusutrombopag, 108; placebo, 107); 64.8% (70/108) of patients in the lusutrombopag group versus 29.0% (31/107) in the placebo group met the primary endpoint (P < 0.0001; difference of proportion 95% confidence interval [CI], 36.7 [24.9, 48.5]). The median duration of PCs ≥ 50 × 109 /L was 19.2 days with lusutrombopag (without platelet transfusion) compared with 0.0 in the placebo group (with platelet transfusion) (P = 0.0001). Most adverse events were mild or moderate in severity, and rates were similar in the lusutrombopag and placebo groups (47.7% and 48.6%, respectively). Conclusion: Lusutrombopag was superior to placebo for reducing the need for platelet transfusions and achieved durable PC response in patients with thrombocytopenia and CLD undergoing invasive procedures, with a safety profile similar to placebo.
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Affiliation(s)
- Markus Peck‐Radosavljevic
- Abteilung Innere Medizin & Gastroenterologiemit Zentraler Aufnahme & Erstversorgung, Klinikum Klagenfurt am WörtherseeKlagenfurtAustria
| | - Krzysztof Simon
- Department of Infectious Diseases and HepatologyWroclaw Medical UniversityWroclawPoland
| | - Angelo Iacobellis
- Division of GastroenterologyIstituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Casa Sollievo della SofferenzaSan Giovanni RotondoItaly
| | | | - Zeid Kayali
- Inland Empire Liver Foundation, University of CaliforniaRiverside, RialtoCA
| | - Albert Tran
- Institut national de la santé et la recherche médicale (INSERM), Unit 1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 8: “Chronic liver diseases associated with obesity and alcohol”NiceFrance,Centre Hospitalier Universitaire de NiceDigestive CenterNiceFrance
| | - Mihaly Makara
- Dél‐pesti Centrumkórház–Országos Hematológiai és Infektológiai IntézetBudapestHungary
| | - Ziv Ben Ari
- Liver Disease Center, Chaim Sheba Medical CenterRamat GanIsrael
| | - Marius Braun
- Department of GastroenterologyRabin Medical Center Belinson CampusPetah‐TikvaIsrael
| | - Paul Mitrut
- Spitalul Clinic Judetean de Urgenta CraiovaCraiovaRomania
| | - Sheng‐Shun Yang
- Division of Gastroenterology & Hepatology, Department of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan
| | - Meral Akdogan
- Department of GastroenterologyTürkiye Yüksek Ihtisas HospitalAnkaraTurkey
| | - Mario Pirisi
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | | | | | | | | | | | - Nezam Afdhal
- Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA
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17
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Kim NH, Kim HJ, Cho YK, Hong HP, Kim BI. Long-Term Efficacy and Safety of Partial Splenic Embolization in Hepatocellular Carcinoma Patients with Thrombocytopenia Who Underwent Transarterial Chemoembolization. J Korean Med Sci 2019; 34:e208. [PMID: 31373186 PMCID: PMC6676001 DOI: 10.3346/jkms.2019.34.e208] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 07/07/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Performing transarterial chemoembolization (TACE) is difficult with the occurrence of thrombocytopenia in cirrhotic patients with hepatocellular carcinoma (HCC). We aimed to evaluate the long-term efficacy and safety of partial splenic embolization (PSE) combined with TACE in patients with HCC with severe thrombocytopenia related to splenomegaly. METHODS We conducted a case-control study consisting of 18 HCC patients with severe thrombocytopenia (< 50 × 10⁹/L) who underwent PSE concurrently with TACE (PSE group) and 72 controls who underwent TACE alone (non-PSE group). RESULTS Mean platelet counts at 1 month and 1, 3, and 5 years after concurrent PSE and TACE significantly increased compared with baseline (all P < 0.05), whereas the platelet count did not significantly increase after TACE alone. In addition, the platelet count at several time points after treatment in the PSE group was significantly higher than that in the non-PSE group, although the baseline platelet count in the PSE group was significantly lower than that in the non-PSE group. The platelet increase after PSE significantly reduced the need for platelet transfusions (P = 0.040) and enabled the subsequent TACE procedures in time (P = 0.046). The leukocyte counts and hemoglobin concentrations after concurrent PSE and TACE were also significantly increased, without deterioration of Child-Turcotte-Pugh score and unexpected side effects. CONCLUSION PSE combined with TACE is effective in inducing and maintaining long-term thrombocytopenia improvement which reduces the need for the platelet transfusion and helps to perform initial and serial TACE, and is well-tolerated in patients with HCC and thrombocytopenia. PSE may be a promising treatment option for HCC patients with severe thrombocytopenia associated with splenomegaly who will undergo TACE.
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Affiliation(s)
- Nam Hee Kim
- Preventive Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hong Joo Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong Kyun Cho
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyun Pyo Hong
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung Ik Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
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18
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Xu H, Cai R. Avatrombopag for the treatment of thrombocytopenia in patients with chronic liver disease. Expert Rev Clin Pharmacol 2019; 12:859-865. [PMID: 31352834 DOI: 10.1080/17512433.2019.1649137] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Introduction: Thrombocytopenia is a common hematological abnormality in patients with chronic liver disease (CLD), occurring in 64%~84% of patients with cirrhosis or fibrosis. Due to the increased risk of bleeding, thrombocytopenia potentially affects management of CLD, such as surgery or liver biopsy. Avatrombopag is a new oral thrombopoietin (TPO) receptor agonist, activating TPO receptor and increasing megakaryocytic proliferation/differentiation and platelet production. Areas covered: This review summarizes the collected data concerning pharmacokinetics, clinical efficacy, safety and tolerability profiles of avatrombopag for the management of thrombocytopenia in patients with CLD. Expert opinion: Avatrombopag is recently approved by Food and Drug Administration (FDA) for the treatment of thrombocytopenia in patients with CLD who are scheduled to undergo a procedure. Based on the available clinical trials, avatrombopag is superior to placebo in reducing the need for platelet transfusions or rescue procedures for bleeding. Avatrombopag is also recommended as alternative to platelet transfusions.
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Affiliation(s)
- Hongming Xu
- Department of emergency, Yuyao People's Hospital , Yuyao , China
| | - Rong Cai
- Department of emergency, Yuyao People's Hospital , Yuyao , China
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19
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Scheiner B, Kirstein M, Popp S, Hucke F, Bota S, Rohr-Udilova N, Reiberger T, Müller C, Trauner M, Peck-Radosavljevic M, Vogel A, Sieghart W, Pinter M. Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma. Liver Cancer 2019; 8:203-217. [PMID: 31192156 PMCID: PMC6547277 DOI: 10.1159/000489833] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Accepted: 05/06/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Platelets have been reported to influence tumor biology and may promote metastasis. Traditionally, thrombocytopenia, a hallmark of cirrhosis, was associated with hepatocellular carcinoma (HCC) development. However, the impact of platelet count on outcome in patients with established HCC is not well studied. METHODS Outcomes of patients with cirrhosis diagnosed with HCC between 1995 and 2013 (derivation cohort) and 2000-2016 (validation cohort) who were not eligible for surgical treatment and did not receive antiplatelet therapy were retrospectively studied. Thrombocytopenia was defined as platelet count < 150 g/L. High mean platelet volume (MPV) was defined as ≥median value of the respective cohort (derivation cohort: ≥11 fL; validation cohort: ≥10.6 fL). RESULTS Among 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favorable baseline tumor characteristics: lower diameter of the largest nodule (5.6 ± 3.2 vs. 7.6 ± 4.2 cm), less extrahepatic spread (9.5 vs. 20.2%, both p < 0.001), less macrovascular invasion (21.2 vs. 31.0%, p = 0.005), and lower BCLC stages (63.0 vs. 73.4% BCLC C/D; p = 0.007) as compared to patients with normal platelet count. On univariate analysis, thrombocytopenia and larger MPV were associated with longer overall survival (OS) (thrombocytopenia: median OS [95% CI], 11.5 [9.3-13.8] vs. 5.5 [3.8-7.1] months; p = 0.001; MPV ≥11 fL: 11.7 [9.1-14.2] vs. 6.0 [4.4-7.6] months; p < 0.001). In multivariate analysis, the combined variable of thrombocytopenia and larger MPV was independently associated with longer OS (HR [95% CI], 0.80 [0.65-0.98]; p = 0.029). These results were confirmed in an independent external validation cohort of 525 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (15.3 [11.7-18.9] vs. 9.3 [7.4-11.2] months; p < 0.001). CONCLUSIONS Thrombocytopenia and higher MPV are associated with better outcome in patients with advanced HCC. These findings may prompt further clinical research on additive antiplatelet therapy in the prevention and management of HCC.
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Affiliation(s)
- Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Martha Kirstein
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Sabine Popp
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Florian Hucke
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria,Department of Gastroenterology and Hepatology, Endocrinology, Rheumatology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | - Simona Bota
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria,Department of Gastroenterology and Hepatology, Endocrinology, Rheumatology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | - Nataliya Rohr-Udilova
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Christian Müller
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria,Department of Gastroenterology and Hepatology, Endocrinology, Rheumatology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria,Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Wolfgang Sieghart
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria,*Matthias Pinter, MD, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18–20, AT–1090 Vienna (Austria), E-Mail
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20
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Coffin CS, Fung SK, Alvarez F, Cooper CL, Doucette KE, Fournier C, Kelly E, Ko HH, Ma MM, Martin SR, Osiowy C, Ramji A, Tam E, Villeneuve JP. Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada. CANADIAN LIVER JOURNAL 2018; 1:156-217. [PMID: 35992619 PMCID: PMC9202759 DOI: 10.3138/canlivj.2018-0008] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 08/01/2023]
Abstract
Hepatitis B virus (HBV) infection is an important public health problem in Canada. In keeping with evolving evidence and understanding of HBV pathogenesis, the Canadian Association for the Study of Liver Disease periodically publishes HBV management guidelines. The goals of the 2018 guidelines are to (1) highlight the public health impact of HBV infection in Canada and the need to improve diagnosis and linkage to care, (2) recommend current best-practice guidelines for treatment of HBV, (3) summarize the key HBV laboratory diagnostic tests, and (4) review evidence on HBV management in special patient populations and include more detail on management of HBV in pediatric populations. An overview of novel HBV tests and therapies for HBV in development is provided to highlight the recent advances in HBV clinical research. The aim and scope of these guidelines are to serve as an up-to-date, comprehensive resource for Canadian health care providers in the management of HBV infection.
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Affiliation(s)
- Carla S. Coffin
- Cumming School of Medicine, University of Calgary, Calgary, Alberta
| | - Scott K. Fung
- Faculty of Medicine, University of Toronto, Toronto, Ontario
| | - Fernando Alvarez
- Centre hospitalier de l’université de Montréal (CHUM)—CHU Sainte-Justine, Montreal, Québec
| | - Curtis L. Cooper
- Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Karen E. Doucette
- Division of Infectious Diseases, University of Alberta, Edmonton, Alberta
| | - Claire Fournier
- Department of Medicine, Université de Montréal, Montreal, Québec
| | - Erin Kelly
- Division of Gastroenterology, Department of Medicine, University of Ottawa, Ottawa, Ontario
| | - Hin Hin Ko
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia
| | - Mang M Ma
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta
| | | | - Carla Osiowy
- Viral Hepatitis and Bloodborne Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba
| | - Alnoor Ramji
- St. Paul’s Hospital, Vancouver, British Columbia
| | - Edward Tam
- LAIR Centre, Vancouver, British Columbia
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Hypoalbuminemia is Associated With Significantly Higher Liver Transplant Waitlist Mortality and Lower Probability of Receiving Liver Transplant. J Clin Gastroenterol 2018; 52:913-917. [PMID: 29356783 DOI: 10.1097/mcg.0000000000000984] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
GOALS To evaluate the predictive value of hypoalbuminemia on liver transplant (LT) waitlist survival and probability of receiving LT among adults with end-stage liver disease (ESLD). BACKGROUND Growing evidence reports on the negative prognostic value of hypoalbuminemia among ESLD patients awaiting LT. METHODS Using 2003 to 2015 United Network for Organ Sharing data, we retrospectively evaluated the impact of mild-moderate (2.5 to 3.4 g/dL) and severe hypoalbuminemia (<2.5 g/dL) on waitlist survival and probability of receiving LT among US adults awaiting LT. Outcomes were stratified by liver disease etiology and presence of hepatocellular carcinoma (HCC), and evaluated using Kaplan-Meier and multivariate Cox proportional hazards models. RESULTS Among 128,450 adults listed for LT, 27.1% had normal albumin (≥3.5 g/dL), 53.7% mild-moderate hypoalbuminemia (2.5 to 3.4 g/dL), and 19.2% severe hypoalbuminemia (<2.5 g/dL) at time of listing. Patients with severe hypoalbuminemia had significantly lower 1-year waitlist survival compared with those with normal albumin (80.4% vs. 95.2%; P<0.001). On multivariate regression, severity of hypoalbuminemia was associated with increasing waitlist mortality, even after correcting for model for end stage liver disease-sodium and HCC [albumin, 2.5 to 3.4 g/dL: hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.62-2.01; P<0.001; <2.5 g/dL: HR, 2.46; 95% CI, 2.20-2.76; P<0.001]. Patients with hypoalbuminemia had significantly lower probability of receiving LT compared with those with normal albumin (albumin <2.5 g/dL: HR, 0.80; 95% CI, 0.78-0.83; P<0.001). CONCLUSIONS ESLD patients with hypoalbuminemia have lower probability of LT despite significantly higher waitlist mortality compared with patients with normal albumin. If validated by further studies, incorporation of albumin into prognostication systems may improve the performance of US donor organ allocation systems.
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Xu X, Zhang C, Shi C, Hu N, Sun B, Kong D, Xu J. Antiviral therapy effectively improves liver hemodynamics as evidenced by serum biomarker and contrast-enhanced ultrasound examinations in patients with hepatitis B cirrhosis. PeerJ 2018; 6:e5484. [PMID: 30225162 PMCID: PMC6139013 DOI: 10.7717/peerj.5484] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 07/29/2018] [Indexed: 12/29/2022] Open
Abstract
Background and Aims To prospectively evaluate the effects of antiviral therapy on liver hemodynamics in patients with hepatitis B cirrhosis. Methods Seventy consecutive eligible HBV-related cirrhotic inpatients were enrolled in the prospective study. Fifty-two received different nucleoside analogs monotherapy and 18 denied antiviral therapy. Their liver biochemistry profiles and HBV-DNA were measured at the baseline and every 3 months. Peripheral blood vWF and sCD163, as well as liver ultrasound Doppler parameters including portal vein diameter (PVD), portal vein velocity (PVV), portal vein congestion index (PV-CI), hepatic vein damping index (HV-DI), hepatic arterial arrival time (HAAT), hepatic vein arrival time (HVAT) and intrahepatic cycle time (HV-HA), were measured at the baseline and the follow-up periods. Results In the antiviral group, all patients achieved complete virologic and liver biochemical responses after 3-month antiviral treatment. Furthermore, the response states were maintained till the follow-up endpoint. However, in the non-antiviral group, HBV DNA replication resulted in higher levels of ALT and AST compared to the baseline values (P < 0.05). In the antiviral group, PVD, PV-CI, HV-DI, vWF-Ag and sCD163 were all significantly reduced than the baseline values (P < 0.05), and PVV was significantly increased than the baseline value (P < 0.05). Conclusions Antiviral therapy could effectively suppress hepatocyte inflammation and alleviate the dysfunction of intrahepatic vascular endothelial and hepatic macrophages, which might improve hepatic hemodynamic function in HBV-related cirrhosis.
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Affiliation(s)
- Xiaoyong Xu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chaoxue Zhang
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chen Shi
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Naizhong Hu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Bin Sun
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Derun Kong
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jianming Xu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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23
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Terrault N, Chen YC, Izumi N, Kayali Z, Mitrut P, Tak WY, Allen LF, Hassanein T. Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology 2018; 155:705-718. [PMID: 29778606 DOI: 10.1053/j.gastro.2018.05.025] [Citation(s) in RCA: 168] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 04/30/2018] [Accepted: 05/11/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with thrombocytopenia and chronic liver disease (CLD) may require platelet transfusions before scheduled procedures to decrease risk of bleeding. We performed 2 randomized, placebo-controlled, phase 3 trials in patients with thrombocytopenia and CLD undergoing scheduled procedures to evaluate the safety and efficacy of avatrombopag in increasing platelet counts in this patient population. METHODS In the ADAPT-1 and ADAPT-2 studies, adults with thrombocytopenia and CLD (n = 231 and n = 204, respectively) were in 1 of 2 cohorts according to their baseline platelet count (below 40 × 109/L or 40 to below 50 × 109/L) and within each cohort were randomized (2:1) to receive 5 daily doses of avatrombopag (60 mg if baseline platelet count below 40 × 109/L or 40 mg if 40 to below 50 × 109/L) or placebo. ADAPT-1 was conducted at 75 study sites in 20 countries, from February 2014 through January 2017, and ADAPT-2 was conducted at 74 sites in 16 countries, from December 2013 through January 2017. The primary endpoint was the proportion of patients not requiring platelet transfusions or rescue procedures for bleeding up to 7 days after a scheduled procedure. RESULTS In the ADAPT-1 study, 65.6% of patients who received 60 mg avatrombopag and 88.1% of patients who received 40 mg avatrombopag met the primary endpoint compared with 22.9% and 38.2% of patients receiving placebo, respectively (P < .0001 for both). In the ADAPT-2 study, 68.6% of patients who received 60 mg avatrombopag and 87.9% of patients who received 40 mg avatrombopag met the primary endpoint compared with 34.9% and 33.3% of patients who received placebo, respectively (P < .001 for both). Avatrombopag led to a measured increase in platelet counts and increased the proportion of patients who achieved the target platelet count ≥ 50 × 109/L on procedure day vs placebo. The incidence and severity of adverse events were similar for the avatrombopag and placebo groups and were consistent with those expected in the CLD population. CONCLUSIONS In 2 phase 3 randomized trials, avatrombopag was superior to placebo in reducing the need for platelet transfusions or rescue procedures for bleeding in patients with thrombocytopenia and CLD undergoing a scheduled procedure. ClinicalTrials.gov nos.: NCT01972529 and NCT01976104.
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Affiliation(s)
- Norah Terrault
- University of California San Francisco, San Francisco, California.
| | - Yi-Cheng Chen
- Chang Gung Memorial Hospital and University, Taoyuan, Taiwan
| | | | - Zeid Kayali
- Inland Empire Liver Foundation, Rialto, California
| | - Paul Mitrut
- University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | | | - Lee F Allen
- Dova Pharmaceuticals, Durham, North Carolina
| | - Tarek Hassanein
- Southern California GI and Liver Centers, Coronado, California
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Nagaoki Y, Aikata H, Daijyo K, Teraoka Y, Honda F, Nakamura Y, Hatooka M, Morio K, Fujino H, Nakahara T, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Ochi H, Chayama K. Risk factors for exacerbation of gastroesophageal varices and portosystemic encephalopathy during treatment with nucleos(t)ide analogs for hepatitis B virus-related cirrhosis. Hepatol Res 2018; 48:264-274. [PMID: 29114970 DOI: 10.1111/hepr.12996] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 10/11/2017] [Accepted: 11/03/2017] [Indexed: 12/18/2022]
Abstract
AIM The aim of this study was to determine the risk factors for worsening of gastroesophageal varices (GEVs) and development of portosystemic encephalopathy in patients with hepatitis B virus (HBV)-related cirrhosis during nucleos(t)ide analog (NA) treatment. METHODS One hundred and thirty-seven patients with HBV-related cirrhosis were enrolled in this retrospective cohort study. Findings of portal hemodynamics with computed tomography, liver function, and endoscopic examinations during NA treatment were assessed. RESULTS Among 137 patients, feeding vessels for GEVs (left gastric vein, posterior gastric vein, and short gastric vein) were present in 56 (41%) patients, and extrahepatic portosystemic shunt (paraesophageal vein, paraumbilicul vein, and splenorenal shunt) were present in 36 (26%) patients at the start of NA treatment. Although NA treatment was successful, significant improvements were not observed in portosystemic collateral vessels 3 years after NA treatment and GEVs were exacerbated in 48 (35%) patients. The cumulative 5- and 10-year exacerbation rate of GEVs was 27% and 50%, respectively. By multivariate analysis, the existence of feeding vessels for GEVs at the start of NA treatment was the independent predictive factor for the exacerbation of GEVs (P < 0.001). Eight patients who had extrahepatic portosystemic shunt at the start of NA treatment developed portosystemic encephalopathy during follow-up. The 3- and 5-year incidence of that was 5% and 8%, respectively. CONCLUSIONS The presence of portosystemic collateral vessels at the start of NA treatment increases the risk of GEVs worsening and development of portosystemic encephalopathy in patients with HBV-related cirrhosis, despite improvement of liver function and success in reducing viral loads with NA treatment.
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Affiliation(s)
- Yuko Nagaoki
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Kana Daijyo
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Fumi Honda
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Yuki Nakamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Masahiro Hatooka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Liver Research Project Center, Hiroshima University, Hiroshima, Japan.,Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan.,Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan
| | - Hidenori Ochi
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan.,Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.,Liver Research Project Center, Hiroshima University, Hiroshima, Japan.,Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan
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Erdem MG, Çil EÖ, Tükek T, Helvacı ŞA. Evaluation of platelet and mean platelet volume levels in patients with liver cirrhosis. ARCHIVES OF CLINICAL AND EXPERIMENTAL MEDICINE 2018. [DOI: 10.25000/acem.390029] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Konerman MA, Lok AS. Epidemiology, Diagnosis, and Natural History of Hepatitis B. ZAKIM AND BOYER'S HEPATOLOGY 2018:474-484.e4. [DOI: 10.1016/b978-0-323-37591-7.00032-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Peck-Radosavljevic M. Thrombocytopenia in chronic liver disease. Liver Int 2017; 37:778-793. [PMID: 27860293 DOI: 10.1111/liv.13317] [Citation(s) in RCA: 183] [Impact Index Per Article: 22.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 11/04/2016] [Indexed: 12/12/2022]
Abstract
Thrombocytopenia is a common haematological disorder in patients with chronic liver disease. It is multifactorial and severity of liver disease is the most influential factor. As a result of the increased risk of bleeding, thrombocytopenia may impact upon medical procedures, such as surgery or liver biopsy. The pathophysiology of thrombocytopenia in chronic liver disease has long been associated with the hypothesis of hypersplenism, where portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen. Other mechanisms of importance include bone marrow suppression by toxic substances, such as alcohol or viral infection, and immunological removal of platelets from the circulation. However, insufficient platelet recovery after relief of portal hypertension by shunt procedures or minor and transient recovery after splenic artery embolization have caused many to question the importance and relative contribution of this mechanism to thrombocytopenia. The discovery of the cytokine thrombopoietin has led to the elucidation of a central mechanism. Thrombopoietin is predominantly produced by the liver and is reduced when liver cell mass is severely damaged. This leads to reduced thrombopoiesis in the bone marrow and consequently to thrombocytopenia in the peripheral blood of patients with advanced-stage liver disease. Restoration of adequate thrombopoietin production post-liver transplantation leads to prompt restoration of platelet production. A number of new treatments that substitute thrombopoietin activity are available or in development.
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Affiliation(s)
- Markus Peck-Radosavljevic
- Department of Gastroenterology, Hepatology, Endocrinology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
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Liang XE, Zhong C, Huang L, Yang S, Zhu Y, Chen Y, Hou J. Optimization of hepatitis B cirrhosis detection by stepwise application of transient elastography and routine biomarkers. J Gastroenterol Hepatol 2017; 32:459-465. [PMID: 27346683 DOI: 10.1111/jgh.13475] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/16/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Significant inflammation may overestimate liver stiffness and result in false positive diagnosis by transient elastography for chronic hepatitis B (CHB) cirrhosis detection. This study tries to further improve the performance by stepwise combination with routine biomarkers. METHODS A total of 236 compensated CHB patients with alanine transferase lower than five times upper limit of normal, liver biopsies, transient elastography, and routine blood tests were included. Performance of stepwise combination of transient elastography and routine biomarkers was analyzed. RESULTS The area under the receiver operating characteristics curve for detecting cirrhosis was 0.876 for transient elastography, 0.794 for fibrosis index based on the four factors (FIB-4), 0.765 for age-platelet index (API), 0.715 for aspartate aminotransferase-platelet ratio index (APRI), and 0.661 for alanine-aspartate aminotransferase ratio, respectively. The numbers for significant fibrosis were 0.844, 0.662, 0.595, 0.695, and 0.510 in the same order. The proportion of patients determined as cirrhosis or non-cirrhosis was 66.5% by transient elastography, 41.1% by FIB-4, 14.4% by API, and 24.2% by APRI, respectively; the numbers for significant fibrosis were 55.5% by transient elastography, 11.9% by APRI, and none by the other serum markers. Stepwise combination of transient elastography and FIB-4/APRI increased positive predictive value of confirming cirrhosis diagnosis from 0.677 to 0.808 and 0.724, respectively; and the proportion of patients being determined in the state of cirrhosis and obviating liver biopsy was up to 76%. CONCLUSION By transient elastography-based stepwise combination with readily available serum markers, performance of detecting compensated CHB cirrhosis could be significantly improved in terms of diagnosis accuracy and proportion of obviating liver biopsy.
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Affiliation(s)
- Xie Er Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chunxiu Zhong
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Liwen Huang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shuling Yang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Youfu Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yongpeng Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinlin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Abstract
The goal in patients with immune active hepatitis B virus (HBV) infection is to significantly suppress viral replication and prevent progression of fibrosis to cirrhosis and liver decompensation and decrease the incidence of hepatocellular carcinoma. This is achievable by the highly active antivirals, entecavir and tenofovir, which are considered first-line therapy in most patients with immune active hepatitis C virus and after liver transplantation to prevent HBV recurrence. Patients with decompensated cirrhosis should be referred for liver transplantation and treated with first-line antivirals as early as possible, with the goal of achieving complete viral suppression in the shortest time possible.
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Affiliation(s)
| | - Tarek I Hassanein
- Southern California Research Center, Coronado, CA 92118, USA; University of California, San Diego School of Medicine, San Diego, CA, USA.
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Zheng JN, Zou TT, Zou H, Zhu GQ, Ruan LY, Cheng Z, Van Poucke S, Zheng MH. Comparative efficacy of oral nucleotide analogues for the prophylaxis of hepatitis B virus recurrence after liver transplantation: a network meta-analysis. Expert Rev Anti Infect Ther 2016; 14:979-987. [PMID: 27491868 DOI: 10.1080/14787210.2016.1220831] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 08/02/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Prophylactic nucleos(t)ide anologues against hepatitis B virus (HBV) recurrence after liver transplantation (LT) include lamivudine, entecavir, tenofovir, adefovir. Since the most effective strategies for post-LT remain inconclusive, we aimed to compare 6 different treatment options (lamivudine, entecavir, tenofovir, adefovir, lamivudine plus adefovir, lamivudine plus tenofovir) in terms of HBV recurrence after LT using network meta-analysis. METHODS The search identified seventeen studies involving 6 different prophylactic regimens covering 7274 patients. RESULTS Compared with entecavir, lamivudine plus tenofovir (OR 2.00, 95%CI 0.02-183.29), lamivudine plus adefovir, (OR 2.83, 95%CI 0.18-33.57), tenofovir (OR 1.11, 95%CI 0.22-5.80), adefovir (OR 3.78, 95%CI 0.59-22.16), lamivudine (OR 4.62, 95%CI 1.75-11.39) were associated with an increased risk of HBV recurrence. CONCLUSION Entecavir resulted with the highest probability (31%) as the best prophylactic option on reducing the risk of HBV recurrence. Entecavir is the preferred oral NAs treatment compared to other five different prophylactic regimens in the prevention of HBV recurrence after LT.
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Affiliation(s)
- Ji-Na Zheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Tian-Tian Zou
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- c School of the Second Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Hai Zou
- d Department of Infection Diseases , Zhejiang Provincial People's Hospital , Hangzhou , China
| | - Gui-Qi Zhu
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Lu-Yi Ruan
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Zhang Cheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Sven Van Poucke
- e Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy , Ziekenhuis Oost-Limburg , Genk , Belgium
| | - Ming-Hua Zheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
- f Institute of Hepatology , Wenzhou Medical University , Wenzhou , China
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Liang XE, Dai L, Yang SL, Zhong CX, Peng J, Zhu YF, Chen YP, Hou JL. Combining routine markers improves the accuracy of transient elastography for hepatitis B cirrhosis detection. Dig Liver Dis 2016; 48:512-518. [PMID: 26965782 DOI: 10.1016/j.dld.2016.02.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 02/08/2016] [Accepted: 02/10/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Vibration Controlled Transient Elastography (VCTE) is a non-invasive test for liver fibrosis and cirrhosis but may be inaccurate in some patients, especially in those with chronic hepatitis B. This study aims at improving the accuracy of VCTE in cirrhosis detection by combining ultrasound and routine blood parameters. METHODS Hepatitis B patients with liver biopsies samples ≥20mm underwent VCTE, ultrasound and blood tests, and were divided into training set (n=170) and validation set (n=75). RESULTS An algorithm consisting of VCTE, international normalization ratio (INR), ultrasonic hepatic vessel and platelet count (CIR-4) and a VCTE-based cirrhosis six-index score (CIR-6) comprised VCTE, INR, platelet, albumin, ultrasonic hepatic vessel and liver parenchyma were derived. In training set, area under receiver operating characteristics curve of CIR-6 and CIR-4 to detect cirrhosis was 0.946 and 0.945, respectively, which was superior to that of VCTE 0.907. CIR-4 could save more liver biopsies. In validation set, CIR-6 detected cirrhosis with accuracy similar to that in training set. However, the sensitivity of CIR-4 and VCTE in validation set lowered to 0.538 and 0.846, respectively. CONCLUSIONS Combining routine markers improve the accuracy of VCTE for cirrhosis detection in hepatitis B patients. CIR-6 may be more valuable.
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Affiliation(s)
- Xie Er Liang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lin Dai
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shu Ling Yang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chun Xiu Zhong
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jie Peng
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - You Fu Zhu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yong Peng Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Jin Lin Hou
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Giles M, Visvanathan K, Lewin S, Bowden S, Locarnini S, Spelman T, Sasadeusz J. Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Gut 2015; 64:1810-5. [PMID: 25431458 DOI: 10.1136/gutjnl-2014-308211] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Accepted: 10/31/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Unique immunological changes occur during pregnancy; the impact of which, on virological and biochemical markers of hepatitis B infection is not well established. Rapid changes in the immunological profile post partum and consequent rebound of the inflammatory response may result in hepatic flares. METHODS Women with chronic hepatitis B were recruited during pregnancy into this observational study. Demographic and clinical data were collected together with virological and biochemical parameters at two time points during pregnancy (early and late) and two time points post partum (between 6 weeks and 12 weeks and at 12 months). Outcomes analysed included changes in HBV DNA, hepatitis B e antigen (HBeAg) status and flares of hepatitis. RESULTS One hundred and twenty-six women were recruited. Twenty-seven women out of 108 with postpartum bloods (25%) met our definition of a postpartum flare (ALT range 38-1654). Using univariate analysis HBeAg status, younger age, gravida and parity were associated with a flare. On multivariate analysis HBeAg positivity at baseline fell just outside of statistical significance in predicting a postpartum flare (p=0.051). CONCLUSIONS 25% of women with chronic hepatitis B will demonstrate increased liver inflammation in the postpartum period. This is usually asymptomatic and resolves spontaneously. This is more likely if the woman is HBeAg-positive at baseline (2.56 times the risk), although flares also commonly occur in HBeAg-negative women.
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Affiliation(s)
- Michelle Giles
- Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Victoria, Australia Department of Infectious Diseases, the Royal Women's Hospital, Melbourne, Victoria, Australia Monash Infectious Diseases, Monash Health, Melbourne, Victoria, Australia
| | - Kumar Visvanathan
- Monash Infectious Diseases, Monash Health, Melbourne, Victoria, Australia Department of Medicine, St. Vincents Hospital, University of Melbourne, Melbourne, Victoria, Australia
| | - Sharon Lewin
- Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Victoria, Australia Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia
| | - Scott Bowden
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Tim Spelman
- Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Victoria, Australia
| | - Joe Sasadeusz
- Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Victoria, Australia Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
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Honda K, Seike M, Murakami K. Benefits of nucleos(t)ide analog treatments for hepatitis B virus-related cirrhosis. World J Hepatol 2015; 7:2404-2410. [PMID: 26464756 PMCID: PMC4598611 DOI: 10.4254/wjh.v7.i22.2404] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/02/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs (NUCs) became established as a safe and effective treatment for hepatitis B, it was difficult to suppress the activity of the hepatitis B virus (HBV). Currently, many patients with hepatitis or cirrhosis associated with HBV are treated with NUCs for an extended period of time, and the effects, benefits, and limitations of these treatments have been apparent. This article reviews HBV-related cirrhosis, its natural course and survival, histological improvement after NUC treatments, treatment effects for decompensated cirrhosis, the incidence of hepatocellular carcinoma (HCC) after NUC treatments, and the efficacy of NUC treatments before and after the treatment of patients for HBV-related HCC. Of particular interest are the histological improvements, including regression of fibrosis, that have been achieved with NUC treatments. Liver function of patients with decompensated cirrhosis has significantly improved regardless of the type of NUC applied, and treatment with NUCs has reduced the incidence of HCC in cirrhotic patients. However, cirrhosis remains the strongest risk factor for HCC occurrence following NUC treatments, and the long-term cumulative incidence of HCC after NUC treatments remains high. When recurrence does occur, it is important to reconsider the treatment modality according to the degree of improved liver function that was achieved.
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Diagnostic Value of Conventional and Doppler Ultrasound Findings in Liver Fibrosis in Patients with Chronic Viral Hepatitis. J Med Ultrasound 2015. [DOI: 10.1016/j.jmu.2014.10.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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Xu Y, Zhang YG, Wang X, Qi WQ, Qin SY, Liu ZH, Jiao J, Wang JB. Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis. World J Gastroenterol 2015; 21:7869-76. [PMID: 26167087 PMCID: PMC4491974 DOI: 10.3748/wjg.v21.i25.7869] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Revised: 03/04/2015] [Accepted: 05/11/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the clinical outcomes of 240-wk treatment with entecavir (0.5 mg) in Chinese nucleoside-naive patients with cirrhosis. METHODS A total of 204 nucleoside-naive patients with compensated (n = 96) or decompensated (n = 108) hepatitis B virus (HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital (Jilin University, Changchun, China) who were treated with entecavir (0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment (baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level < 500 copies/mL, the association of interleukin-28B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ(2) test. RESULTS At week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level < 500 copies/mL. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype (CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pugh class A disease was significantly increased at week 240 (68%) from the baseline (47%; P < 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240 (25%) from the baseline (39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points (7.11 ± 1.80 vs 3.53 ± 1.35, P < 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points (5.58 ± 0.50 vs 4.32 ± 0.81, P < 0.01). CONCLUSION Entecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.
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Hsiang JC, Gane EJ, Bai WW, Gerred SJ. Type 2 diabetes: a risk factor for liver mortality and complications in hepatitis B cirrhosis patients. J Gastroenterol Hepatol 2015; 30:591-9. [PMID: 25250942 DOI: 10.1111/jgh.12790] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/11/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM The effect of type 2 diabetes mellitus (DM) on morbidity and mortality among hepatitis B virus (HBV) cirrhosis patients is poorly defined. We assess the effect of DM on the HBV cirrhosis outcomes and survival. METHODS A retrospective study of HBV cirrhosis patients who sought care at a sole public hospital in a geographically defined region, from year 2000 to 2012. Cirrhosis complications, liver transplantations, and mortality were reviewed. Primary outcome is the composite of liver-related and overall mortality or orthotopic liver transplantation (OLT). RESULTS Two hundred twenty-three patients entered into the final analysis; 50 patients (22.4%) have DM at cirrhosis diagnosis. Seventy-two percent of DM patients have DM for more than 5 years at cirrhosis diagnosis. The incidence of hepatocellular carcinoma (HCC) was 25.4 and 60.5 per 1000 patient-years for non-DM and DM patients, respectively (P = 0.006). In multivariate analysis, DM was a predictor of HCC (hazard ratio [HR] 2.36, [1.14-4.85], P = 0.02), hepatic complications (HR 2.04, [1.16-3.59], P = 0.01), liver mortality or OLT (HR 2.26, [1.05-4.86], P = 0.04), and overall mortality or OLT (HR 2.25, [1.96-4.22], P = 0.01). Insulin and/or sulphonylurea use and poor diabetic control (glycosylated hemoglobin ≥ 7.0%) were predictors of HCC and cirrhosis complications (all P < 0.05). The 5-year liver-related mortality or OLT rate was 23.4% for DM patients and 9.4% for non-DM patients, respectively (P = 0.009). CONCLUSION The presence of DM and poor diabetic control at cirrhosis diagnosis significantly increase the rate of cirrhosis complications and reduced survival in patients with HBV cirrhosis. Improving diabetic control should be essential part of the cirrhosis care in these patients.
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Affiliation(s)
- John C Hsiang
- Middlemore Hospital, Counties Manukau District Health Board, South Auckland, New Zealand
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Thio CL, Hawkins C. Hepatitis B Virus and Hepatitis Delta Virus. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015:1815-1839.e7. [DOI: 10.1016/b978-1-4557-4801-3.00148-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abstract
It is now 50 years since the discovery of the hepatitis B virus (HBV), and, despite the availability of a prophylactic vaccine for more than 20 years, HBV infection remains a disease of significant global health burden. It is estimated that more than 240 million people are chronically infected with HBV and, therefore, are at risk for the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). The risk of clinical complications has traditionally been higher in older males with hepatitis B e antigen (HBeAg)-positive disease, high-grade liver necroinflammation, and progressive fibrosis. Recent advances in the understanding of the natural history of chronic HBV infection have identified an important role for plasma HBV DNA levels as a marker of risk for clinical outcomes. Among adults, persistent high-level HBV replication is associated with an increased risk of cirrhosis, as well as HCC development. This has led to the therapeutic focus on achieving sustained viral suppression. There is an emerging role for quantitative hepatitis B surface antigen (HBsAg) levels as a marker of natural history. Low levels of HBsAg have been associated with sustained immune control, HBsAg seroclearance, as well as lower risk of HCC. In this work, we review the natural history of HBV infection, with a focus on the determinants of clinical outcomes in patients with chronic hepatitis B (CHB) infection.
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Farrell C, Hayes SC, Wire M, Zhang J. Population pharmacokinetic/pharmacodynamic modelling of eltrombopag in healthy volunteers and subjects with chronic liver disease. Br J Clin Pharmacol 2014; 77:532-44. [PMID: 24117976 DOI: 10.1111/bcp.12244] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2012] [Accepted: 01/17/2013] [Indexed: 12/29/2022] Open
Abstract
AIMS To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of eltrombopag in chronic liver disease (CLD). METHODS The PK/PD model was developed using data from 79 CLD patients using nonlinear mixed-effects modelling. RESULTS The PK of eltrombopag were described by a two-compartment model with dual sequential first-order absorption. Gender, race and severity of CLD were predictors of the apparent clearance of eltrombopag. The PD of eltrombopag in CLD were adequately described by a four-compartment lifespan model, in which eltrombopag stimulated platelet precursor production rate. East Asian CLD patients were less sensitive to the stimulatory effect of eltrombopag. Following a daily dose regimen of 50 mg eltrombopag, the time to achieve peak platelet counts was longer for the CLD population compared with patients who had immune thrombocytopenic purpura, but was comparable to patients with hepatitis C. Likewise, it took a longer time for platelet counts to rebound back to baseline once eltrombopag treatment was discontinued. CONCLUSIONS The time course of the platelet response in CLD was different from that in immune thrombocytopenic purpura but comparable to that in hepatitis C.
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Affiliation(s)
- Colm Farrell
- ICON Development Solutions, Marlow, Buckinghamshire, UK
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41
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Myers RP, Tandon P, Ney M, Meeberg G, Faris P, Shaheen AAM, Aspinall AI, Burak KW. Validation of the five-variable Model for End-stage Liver Disease (5vMELD) for prediction of mortality on the liver transplant waiting list. Liver Int 2014; 34:1176-83. [PMID: 24256642 DOI: 10.1111/liv.12373] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Accepted: 10/31/2013] [Indexed: 12/23/2022]
Abstract
BACKGROUND Modifications to the Model for End-Stage Liver Disease (MELD) have been proposed to improve prioritization of liver transplant (LT) candidates. Using a U.S. database, we derived a revised MELD including sodium and albumin [5-variable MELD (5vMELD)] that improved prediction of waiting list mortality. Our objectives were to confirm the association between hypoalbuminaemia and mortality and to externally validate 5vMELD in Canadian LT candidates. METHODS Among adults registered on the LT waiting list at the University of Alberta (01/2000-10/2009), Cox regression determined the association between albumin and 1-year waiting list mortality. The discrimination of MELD, MELDNa and 5vMELD for predicting 1-year mortality were compared using c-statistics. RESULTS Among 677 patients, 17% died and 51% underwent LT within 1 year of listing. Median serum albumin was 3.1 g/dl (IQR 2.6-3.6) and 70% of patients were hypoalbuminaemic (albumin <3.5 g/dl). One-year mortality in patients with normal serum albumin and hypoalbuminaemia were 14% and 29% respectively (P = 0.004). For patients with serum albumin between 2.0 and 4.0 g/dl, an approximately linear, inverse relationship was observed between albumin and 1-year mortality [adjusted hazard ratio (HR) 1.45; 95% CI 1.03-2.03; P = 0.03]. For this outcome, the c-statistic of 5vMELD (0.778) was superior to those of MELD (0.754) and MELDNa (0.765) (both P ≤ 0.05). CONCLUSIONS Hypoalbuminaemia is an independent predictor of mortality on the LT waiting list. Compared with MELD and MELDNa, 5vMELD improves prediction of mortality suggesting that modification of these scores to include serum albumin should be considered as a means of prioritizing LT candidates.
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Affiliation(s)
- Robert P Myers
- Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
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Xie Q, Hu X, Zhang Y, Jiang X, Li X, Li J. Decreasing hepatitis B viral load is associated with a risk of significant liver fibrosis in hepatitis B e antigen positive chronic hepatitis B. J Med Virol 2014; 86:1828-37. [PMID: 25145769 DOI: 10.1002/jmv.24000] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2014] [Indexed: 12/19/2022]
Abstract
Alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA levels and age are used commonly to assess liver histology in chronic hepatitis B. Increasing levels of HBV DNA are associated with the increasing prevalence of significant fibrosis in HBeAg-negative patients. It is unclear whether these data can be applied to HBeAg-positive patients. In present study, liver biopsies were performed and clinical parameters were measured in 234 treatment-naive chronic HBeAg-positive patients. The proportion of significant fibrosis in patients with ALT 1-2 × ULN was similar to in patients with ALT more than 2 × ULN (48.4% vs. 51.8%). Patients over 30 years of age (>30 years) had a higher prevalence of significant fibrosis than patients 30 years of age and younger (61.0% vs. 33.6%). Negative correlation between HBV DNA levels and significant fibrosis was observed in patients >30 years. The optimal level of serum HBV DNA to evaluate low risk of significant fibrosis was ≥6.7 log10 IU/ml. Patients with serum HBV DNA levels ≥8.5 log10 IU/ml all had no significant fibrosis, however, patients with HBV DNA levels <4.7 log10 IU/ml all had significant fibrosis. Logistic regressions showed that age, aspartate aminotransferase, platelet count, and HBV DNA levels were independent predictors of significant fibrosis. In summary, older age, elevated ALT, and lower HBV DNA levels are associated with significant fibrosis. Decreasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis in patients >30 years. The threshold of HBV DNA levels for treatment of HBeAg-positive patients needs to be combined with age.
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Affiliation(s)
- Qinxiu Xie
- Department of Infectious Disease, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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Xu X, Yue M, Jiang L, Deng X, Zhang Y, Zhang Y, Zhu D, Xiao W, Zhou Z, Yao W, Kong J, Yu X, Wei J. Genetic variants in human leukocyte antigen-DP influence both hepatitis C virus persistence and hepatitis C virus F protein generation in the Chinese Han population. Int J Mol Sci 2014; 15:9826-9843. [PMID: 24897020 PMCID: PMC4100124 DOI: 10.3390/ijms15069826] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 05/19/2014] [Accepted: 05/21/2014] [Indexed: 12/16/2022] Open
Abstract
Chronic hepatitis C is a serious liver disease that often results in cirrhosis or hepatocellular carcinoma. The aim of this study was to assess the association of human leukocyte antigen-DP (HLA-DP) variants with risk of chronic hepatitis C virus (HCV) or anti-F antibody generation. We selected two single nucleotide polymorphisms (SNPs) in a region including HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277534) and genotyped SNPs in 702 cases and 342 healthy controls from the Chinese population using TaqMan SNP genotyping assay. Moreover, the exon 2 of the HLA-DPA1 and HLA-DPB1 genes were amplified and determined by sequencing-based typing (SBT). The results showed that rs3077 significantly increased the risk of chronic HCV infection in additive models and dominant models (odds ratio (OR) = 1.32 and 1.53). The rs3077 also contributed to decrease the risk of anti-F antibody generation in additive models and dominant models (OR = 0.46 and 0.56). Subsequent analyses revealed the risk haplotypes (DPA1*0103-DPB1*0501 and DPA1*0103-DPB1*0201) and protective haplotypes (DPA1*0202-DPB1*0501 and DPA1*0202-DPB1*0202) to chronic HCV infection. Moreover, we also found that the haplotype of DPA1*0103-DPB1*0201 and DPA1*0202-DPB1*0202 were associated with the anti-F antibody generation. Our findings show that genetic variants in HLA-DP gene are associated with chronic HCV infection and anti-F antibody generation.
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Affiliation(s)
- Xiaodong Xu
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China.
| | - Ming Yue
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Longfeng Jiang
- Department of Infectious Diseases, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
| | - Xiaozhao Deng
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China.
| | - Yongxiang Zhang
- Department of Infectious Diseases, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
| | - Yun Zhang
- Institute of Disease Control and Prevention, Huadong Research Institute for Medicine and Biotechnics, Nanjing 210002, China.
| | - Danyan Zhu
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China.
| | - Wen Xiao
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
| | - Zhenxian Zhou
- Department of Clinical Laboratory, Nanjing Second Hospital, Nanjing 210003, China.
| | - Wenjuan Yao
- Department of Pharmacology, Nantong University Medical College, Nantong 226019, China.
| | - Jing Kong
- School of Life Science and Chemical Engineering, Huaiyin Institute of Technology, Huaian 223003, China.
| | - Xiaojie Yu
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China.
| | - Juan Wei
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing 210029, China.
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Park YH, Kim BK, Kim JK, Kim HC, Kim DY, Park JY, Han KH, Kim SU, Shin SH, Hahn KY, Ahn SH. Long-term outcomes of chronic hepatitis B virus infection in the era of antiviral therapy in Korea. J Gastroenterol Hepatol 2014; 29:1005-1011. [PMID: 24325579 DOI: 10.1111/jgh.12478] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/23/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC), and ultimately liver-related deaths. Recently, owing to potent antiviral therapy with minimal side-effects, sustained suppression of hepatitis B virus replication can be achieved, thereby preventing such complications. We aimed to reappraise clinical courses regarding disease progression in the era of antiviral therapy. METHODS Between 2001 and 2005, treatment-naïve Korean CHB patients without cirrhosis were enrolled and followed up for at least 5 years. During follow up, antiviral therapy was commenced according to Korean Association for the Study of the Liver guidelines, if eligible, and ultrasonography and laboratory and clinical assessment were performed regularly. Primary end-points were development of cirrhosis, hepatic decompensation, HCC, or liver-related deaths. RESULTS Of 360 patients, 323 (89.7%) received antiviral therapy such as lamivudine (70.6%), entecavir (8.7%), or telbivudine (6.5%). During follow up, cirrhosis developed in 29 (8.1%), hepatic decompensation in 4 (1.1%), and HCC in 15 (4.2%) patients. Annual incidences of cirrhosis, hepatic decompensation, and HCC were 1.05%, 0.14%, and 0.53% per person-year, respectively. Age was an independent predictor for developing cirrhosis (hazard ratio [HR] 1.075, 95% confidence interval [CI] 1.037-1.116; P < 0.001), whereas age (HR 1.060, 95% CI 1.012-1.111; P = 0.014) and cirrhosis (HR 17.470, 95% CI 5.081-60.063; P < 0.001) were those for developing HCC. CONCLUSIONS In the era of antiviral therapy, overall clinical courses have been much improved since introduction of lamivudine in 1999. However, patients with older age or cirrhosis are still subject to HCC development despite appropriate antiviral therapy, necessitating cautious surveillance.
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Affiliation(s)
- Yoon Hea Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Deng YR, Yoshida K, Jin QL, Murata M, Yamaguchi T, Tsuneyama K, Moritoki Y, Niu JQ, Matsuzaki K, Lian ZX. Reversible phospho-Smad3 signalling between tumour suppression and fibrocarcinogenesis in chronic hepatitis B infection. Clin Exp Immunol 2014; 176:102-11. [PMID: 24372395 DOI: 10.1111/cei.12259] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2013] [Indexed: 12/24/2022] Open
Abstract
Transforming growth factor (TGF)-β, type I receptor (TβRI) and c-Jun N-terminal kinases (JNK) phosphorylate Smad3 differentially to create 2 isoforms phosphorylated (p) at the COOH-terminus (C) or at the linker region (L) and regulate hepatocytic fibrocarcinogenesis. This study aimed to compare the differences between how hepatitis B virus (HBV) infection affected hepatocytic Smad3 phosphorylated isoforms before and after anti-viral therapy. To clarify the relationship between Smad3 phosphorylation and liver disease progression, we studied 10 random patients in each stage of HBV-related fibrotic liver disease (F1-4) and also 10 patients with HBV-associated HCC. To examine changes in phosphorylated Smad3 signalling before and after anti-HBV therapies, we chose 27 patients with chronic hepatitis B who underwent baseline and follow-up biopsies at 52 weeks from the start of nucleoside analogue treatments (Lamivudine 100 mg daily or Telbivudine 600 mg daily). Fibrosis stage, inflammatory activity and phosphorylated Smad3 positivity in the paired biopsy samples were compared. Hepatocytic pSmad3C signalling shifted to fibrocarcinogenic pSmad3L signalling as the livers progressed from chronic hepatitis B infection to HCC. After nucleoside analogue treatment, serum alanine aminotransferase (ALT) and HBV-DNA levels in 27 patients with HBV-related chronic liver diseases were decreased dramatically. Decrease in HBV-DNA restored pSmad3C signalling in hepatocytes, while eliminating prior fibrocarcinogenic pSmad3L signalling. Oral nucleoside analogue therapies can suppress fibrosis and reduce HCC incidence by successfully reversing phosphorylated Smad3 signalling; even liver disease progressed to cirrhosis in chronic hepatitis B patients.
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Affiliation(s)
- Y-R Deng
- Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei, China; Intensive Care Unit, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China
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Becker CE, Kretzmann NA, Mattos AAD, Veiga ABGD. Melting curve analysis for the screening of hepatitis B virus genotypes A, D and F in patients from a general hospital in southern Brazil. ARQUIVOS DE GASTROENTEROLOGIA 2014; 50:219-25. [PMID: 24322195 DOI: 10.1590/s0004-28032013000200039] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Accepted: 06/18/2013] [Indexed: 01/04/2023]
Abstract
CONTEXT Hepatitis B virus (HBV) can cause fulminant hepatitis, cirrhosis and hepatocellular carcinoma, and is one of the most common causes of acute and chronic liver failure. The genetic variants of HBV can be decisive for the evolution of these diseases as well as for the election of therapy. OBJECTIVES The aim of this study was to evaluate and standardize an in house methodology based on the analysis of the melting curve polymerase chain reaction (PCR) of real-time (qPCR) to screen for genotypes A, D and F of HBV in patients from a hospital in Rio Grande do Sul, Brazil. METHODS We evaluated 104 patients presumably with HBV chronic infection. Viral DNA was extracted from plasma and viral genotypes and different mutations were determined using PCR-based protocols. RESULTS A PCR-based methodology was standardized for the analysis of genotypes A, D and F of HBV. The technique was based in a nested PCR with the final step consisting of a multiplex real-time PCR, using the melting curve as a tool for the differentiation of fragments. A higher frequency of genotype D (44.4%), followed by genotype A (22.2%) and genotype F (3.7%) was observed. CONCLUSION The standardized assay, a nested PCR-multiplex qPCR using specific primers, provides a rapid and accurate method for the differentiation of HBV genotypes that are more frequent in Southern Brazil - A, D and F. This method can be applied in the clinical practice.
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Affiliation(s)
- Carlos Eduardo Becker
- Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Medicina: Hepatologia
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Reticulocyte Count and Hemoglobin Concentration Predict Survival in Candidates for Liver Transplantation. Transplantation 2014; 97:463-9. [DOI: 10.1097/01.tp.0000437429.12356.03] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Suh CH, Kim SY, Kim KW, Lim YS, Lee SJ, Lee MG, Lee J, Lee SG, Yu E. Determination of normal hepatic elasticity by using real-time shear-wave elastography. Radiology 2014; 271:895-900. [PMID: 24555633 DOI: 10.1148/radiol.14131251] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE To determine normal reference values of liver elasticity and measurement reliability by using real-time shear-wave elastography (SWE) in patients with a range of ages and body mass index (BMI) measurements, with presence or absence of hepatic steatosis. MATERIALS AND METHODS The institutional review board approved this study, and informed consent was waived because of the retrospective nature of the study. Two hundred thirty-eight patients who underwent SWE and ultrasonography-guided liver biopsies on the same day were identified retrospectively. The median kilopascal value of three consecutive measurements was used as a representative value for each subject. One hundred ninety-six patients who were potential donors for living-donor liver transplantation and had biopsy-proven normal (123 nonsteatotic and 73 steatotic) livers as the only histologic abnormality were included in the study. Reference ranges of normal hepatic elasticity were calculated by using lower and upper limits at the 2.5 and 97.5 percentiles. With the upper value of the reference range as a cutoff value, the sensitivity and specificity for the diagnosis of hepatic fibrosis were calculated. Measurement reliability was evaluated by using the intraclass correlation coefficient (ICC). To investigate the effects of potential confounding factors (age, hepatic steatosis, and BMI) on liver elasticity, the Pearson correlation test and the Student t test were performed. RESULTS The reference range of normal hepatic elasticity was 2.6-6.2 kPa. With 6.2 kPa as a cutoff value, the sensitivity and specificity for the diagnosis of hepatic fibrosis were 91% (20 of 22 subjects) and 95.9% (188 of 196 subjects), respectively. The overall ICC for the elasticity measurements was 0.924. The potential confounding factors that we considered had negligible effects on the elasticity values. CONCLUSION Hepatic elasticity values measured with SWE in histologically proven normal livers ranged from 2.6 to 6.2 kPa, with high measurement reliability. The effect of the potential confounding factors on liver elasticity was negligible.
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Affiliation(s)
- Chong Hyun Suh
- From the Department of Radiology and Research Institute of Radiology (C.H.S., S.Y.K., K.W.K., S.J.L., M.G.L.), Department of Gastroenterology (Y.S.L.), Department of Clinical Epidemiology & Biostatistics (J.B.L.), Department of Liver Transplantation Surgery (S.G.L.), and Department of Pathology (E.Y.), Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea
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Calvaruso V, Craxì A. Regression of fibrosis after HBV antiviral therapy. Is cirrhosis reversible? Liver Int 2014; 34 Suppl 1:85-90. [PMID: 24373083 DOI: 10.1111/liv.12395] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Long-lasting HBV-DNA suppression is considered to be the best surrogate end-point of antiviral therapy in patients with hepatitis B virus (HBV) related chronic hepatitis or cirrhosis, and it is a prerequisite to prevent liver-related complications and improve survival. Treatment with oral antiviral drugs in patients with HBV cirrhosis is effective in restoring liver function and improving survival even in those with decompensated cirrhosis. These agents are generally well-tolerated for long-term treatment, and several evidences have demonstrated that they are able to reverse liver fibrosis and prevent the occurrence of HCC.
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Affiliation(s)
- Vincenza Calvaruso
- Gastroenterology and Hepatology Unit, University of Palermo, Palermo, Italy
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