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Zhang XF, Niu XF, Li LX, He X, Li ZJ, Liu ZW, Zhang DL, Ren H. Total bile acid is a useful tool for evaluating the risk of portal hypertension in patients with hepatocellular carcinoma who have undergone hepatectomy. Curr Med Res Opin 2025; 41:253-259. [PMID: 39943859 DOI: 10.1080/03007995.2025.2466720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 01/27/2025] [Accepted: 02/10/2025] [Indexed: 02/23/2025]
Abstract
OBJECTIVE Evaluating portal hypertension is crucial for patients with hepatocellular carcinoma (HCC) who are candidates for liver resection. Total bile acid (TBA) is an easily accessible marker, but its potential as a non-invasive indicator of portal hypertension in patients with HCC is yet to be fully established. METHODS This study included patients with HCC classified as Child-Pugh stage A who underwent liver resection at a referral hospital. Elevated TBA levels were defined as serum TBA >10 μmol/L, while normal levels were ≤10 μmol/L. RESULTS A total of 167 patients with HCC with Child-Pugh Class A who underwent liver resection were analyzed. The cohort was divided into normal (n = 125) and elevated TBA groups (n = 42). Compared to patients with normal TBA levels, those with elevated TBA had significantly higher 15-min indocyanine green retention rates (ICG R15) (p <0.001), higher Child-Pugh scores (p <0.001), more advanced Laennec fibrosis stages (p = 0.039), and a higher incidence of esophageal gastric varices (p = 0.001) and post-hepatectomy liver failure (p = 0.001). Multivariate analysis showed that elevated TBA was independently associated with ICG R15 (odds ratio [OR] = 1.150, 95% confidence interval [CI] = 1.055-1.254, p = 0.002), fibrosis stages (OR = 1.973, 95% CI = 1.026-3.796, p = 0.042), and Child-Pugh score (OR = 4.121, 95% CI = 1.367-12.424, p = 0.012). CONCLUSION Elevated TBA levels in patients with HCC with Child-Pugh class A are significantly associated with portal hypertension and a higher incidence of post-hepatectomy liver failure.
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Affiliation(s)
- Xiao-Feng Zhang
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xiao-Feng Niu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Li-Xin Li
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xi He
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Zhi-Jie Li
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Zhen-Wen Liu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Da-Li Zhang
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hui Ren
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
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Pedersen K, Poojari A, Colberg SF, Mechernsee SM, Iversen JF, Barrès R, Lykkesfeldt J, Tveden-Nyborg P. A Guinea Pig Model of Pediatric Metabolic Dysfunction-Associated Steatohepatitis: Poor Vitamin C Status May Advance Disease. Nutrients 2025; 17:291. [PMID: 39861421 PMCID: PMC11767659 DOI: 10.3390/nu17020291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 01/10/2025] [Accepted: 01/12/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Children and teenagers display a distinct metabolic dysfunction-associated steatohepatitis (MASH) phenotype, yet studies of childhood MASH are scarce and validated animal models lacking, limiting the development of treatments. Poor vitamin C (VitC) status may affect MASH progression and often co-occurs with high-fat diets and related metabolic imbalances. As a regulator of DNA methylation, poor VitC status may further contribute to MASH by regulating gene expression This study investigated guinea pigs-a species that, like humans, depends on vitC in the diet-as a model of pediatric MASH, examining the effects of poor VitC status on MASH hallmarks and global DNA methylation levels. Methods: Sixty-two juvenile guinea pigs were exposed to a high-fat diet for 16 weeks. Results: Juvenile guinea pigs exhibited hepatic histopathology representative of pediatric MASH, confirmed by portal inflammation and fibrosis. Consistent with pediatric MASH, juvenile guinea pigs displayed increased lobular and portal inflammation (p < 0.05 and p < 0.0001, respectively) but less steatosis (p < 0.001) compared to adults. Compared to the controls, the guinea pigs deprived in VitC showed lower body weight (p < 0.01), higher expression of hepatic inflammatory genes (p < 0.05), and a lower global hydroxymethylcytosine to methylcytosine ratio in the high-fat groups (p < 0.05). Conclusions: Our study validates guinea pigs as a model of pediatric MASH and suggests that VitC contributes to an altered gene expression signature through the regulation of DNA hydroxymethylation. We postulate that nutritional co-deficiencies in MASH, such as low VitC, may accelerate disease progression and deserve further attention.
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Affiliation(s)
- Kamilla Pedersen
- Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark; (K.P.); (S.F.C.); (S.M.M.); (J.L.)
| | - Ankita Poojari
- Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA;
| | - Simone Frederikke Colberg
- Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark; (K.P.); (S.F.C.); (S.M.M.); (J.L.)
| | - Stine Marguerite Mechernsee
- Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark; (K.P.); (S.F.C.); (S.M.M.); (J.L.)
| | - Jo Frøkjær Iversen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark; (J.F.I.); (R.B.)
| | - Romain Barrès
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark; (J.F.I.); (R.B.)
- Institut de Pharmacologie Moléculaire et Cellulaire, CNRS and Université de Nice Côte d’Azur, 06560 Valbonne, France
| | - Jens Lykkesfeldt
- Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark; (K.P.); (S.F.C.); (S.M.M.); (J.L.)
| | - Pernille Tveden-Nyborg
- Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark; (K.P.); (S.F.C.); (S.M.M.); (J.L.)
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Favere K, Van Hecke M, Eens S, Bosman M, Delputte PL, De Sutter J, Fransen E, Roskams T, Guns PJ, Heidbuchel H. The influence of endurance exercise training on myocardial fibrosis and arrhythmogenesis in a coxsackievirus B3 myocarditis mouse model. Sci Rep 2024; 14:12653. [PMID: 38825590 PMCID: PMC11144711 DOI: 10.1038/s41598-024-61874-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 05/10/2024] [Indexed: 06/04/2024] Open
Abstract
Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its finding as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging is often attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often have nonischaemic LGE. Previous studies have demonstrated an adverse effect of exercise on the course of acute viral myocarditis. In this study, we have investigated, for the first time, the impact of endurance training on longer-term outcomes such as myocardial fibrosis and arrhythmogenicity in a murine coxsackievirus B3 (CVB)-induced myocarditis model. Male C57BL/6J mice (n = 72) were randomly assigned to 8 weeks of forced treadmill running (EEX) or no exercise (SED). Myocarditis was induced 2 weeks later by a single intraperitoneal injection with CVB, versus vehicle in the controls (PBS). In a separate study, mice (n = 30) were subjected to pretraining for 13 weeks (preEEX), without continuation of exercise during myocarditis. Overall, continuation of exercise resulted in a milder clinical course of viral disease, with less weight loss and better preserved running capacity. CVB-EEX and preEEX-CVB mice tended to have a lower mortality rate. At sacrifice (i.e. 6 weeks after inoculation), the majority of virus was cleared from the heart. Histological assessment demonstrated prominent myocardial inflammatory infiltration and cardiomyocyte loss in both CVB groups. Inflammatory lesions in the CVB-EEX group contained higher numbers of pro-inflammatory cells (iNOS-reactive macrophages and CD8+ T lymphocytes) compared to these in CVB-SED. Treadmill running during myocarditis increased interstitial fibrosis [82.4% (CVB-EEX) vs. 56.3% (CVB-SED); P = 0.049]. Additionally, perivascular and/or interstitial fibrosis with extensive distribution was more likely to occur with exercise [64.7% and 64.7% (CVB-EEX) vs. 50% and 31.3% (CVB-SED); P = 0.048]. There was a numerical, but not significant, increase in the number of scars per cross-section (1.9 vs. 1.2; P = 0.195), with similar scar distribution and histological appearance in CVB-EEX and CVB-SED. In vivo electrophysiology studies did not induce sustained monomorphic ventricular tachycardia, only nonsustained (usually polymorphic) runs. Their cumulative beat count and duration paralleled the increased fibrosis between CVB-EEX and CVB-SED, but the difference was not significant (P = 0.084 for each). Interestingly, in mice that were subjected to pretraining only without continuation of exercise during myocarditis, no differences between pretrained and sedentary mice were observed at sacrifice (i.e. 6 weeks after inoculation and training cessation) with regard to myocardial inflammation, fibrosis, and ventricular arrhythmogenicity. In conclusion, endurance exercise during viral myocarditis modulates the inflammatory process with more pro-inflammatory cells and enhances perivascular and interstitial fibrosis development. The impact on ventricular arrhythmogenesis requires further exploration.
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Affiliation(s)
- Kasper Favere
- Laboratory of Physiopharmacology, GENCOR, University of Antwerp, 2610, Antwerp, Belgium.
- Research Group Cardiovascular Diseases, GENCOR, University of Antwerp, 2610, Antwerp, Belgium.
- Department of Cardiology, Antwerp University Hospital, 2650, Antwerp, Belgium.
- Department of Internal Medicine, Ghent University, 9000, Ghent, Belgium.
| | - Manon Van Hecke
- Translational Cell and Tissue Research, Department of Imaging and Pathology, University of Leuven, 3000, Leuven, Belgium
| | - Sander Eens
- Laboratory of Physiopharmacology, GENCOR, University of Antwerp, 2610, Antwerp, Belgium
- Research Group Cardiovascular Diseases, GENCOR, University of Antwerp, 2610, Antwerp, Belgium
| | - Matthias Bosman
- Laboratory of Physiopharmacology, GENCOR, University of Antwerp, 2610, Antwerp, Belgium
| | - Peter L Delputte
- Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, 2610, Antwerp, Belgium
| | - Johan De Sutter
- Department of Internal Medicine, Ghent University, 9000, Ghent, Belgium
| | - Erik Fransen
- Centre for Medical Genetics, University of Antwerp, 2610, Antwerp, Belgium
| | - Tania Roskams
- Translational Cell and Tissue Research, Department of Imaging and Pathology, University of Leuven, 3000, Leuven, Belgium
| | - Pieter-Jan Guns
- Laboratory of Physiopharmacology, GENCOR, University of Antwerp, 2610, Antwerp, Belgium
| | - Hein Heidbuchel
- Research Group Cardiovascular Diseases, GENCOR, University of Antwerp, 2610, Antwerp, Belgium
- Department of Cardiology, Antwerp University Hospital, 2650, Antwerp, Belgium
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Gunardi H, Alatas FS, Antarianto RD, Rahayatri TH. The Effect of Intrahepatic and Intrasplenic Administration of Mesenchymal Stem Cell to Liver Function and Degree of Liver Fibrosis in Common Bile Duct Ligation Model in Rabbit. J Pediatr Surg 2024; 59:634-639. [PMID: 38160190 DOI: 10.1016/j.jpedsurg.2023.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 12/03/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND Mesenchymal stem cells (MSC) is a promising alternative method in liver cirrhosis management. Several administration routes of MSC have been studied, but few studies compared one to another. The purpose of this study is to compare the intrahepatic and intrasplenic route of MSC administration in terms of liver function and degree of liver fibrosis in the bile duct ligation model in rabbits. METHOD Experimental study was conducted using rabbits (Oryctolagus cuniculus) model undergoing bile duct ligation (BDL). The subjects were randomized into 4 groups: sham surgery; bile duct ligation; bile duct ligation followed by intrahepatic route of MSC (BDL + IH MSC), and bile duct ligation followed by intrasplenic route of MSC (BDL + IS MSC). Umbilical cord mesenchymal stem cell (UC MSC) was administered on the fifth day after bile duct ligation, and the subjects were observed until the fourteenth day after bile duct ligation. The liver function was evaluated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total and direct bilirubin. The degree of fibrosis was evaluated with Laennec score, fibrosis area fraction, the number of viable and necrosis hepatocytes, and the number of hepatic progenitor cells. RESULT The subjects were randomized into 4 groups: 2 in sham surgery group, and 7 in each of the following groups: BDL, BDL + IH MSC and BDL + IS MSC groups. The mortality rate in BDL group was 57.1 %, while mortality in BDL + IH MSC and BDL + IS MSC groups were 14.3 % and 28.6 % respectively. No significant difference was found regarding liver function in each group, such as AST, ALT, total, and direct bilirubin. Histopathology examination in almost every subject undergone bile duct ligation (regardless of MSC administration) showed degree of fibrosis of Laennec 4B. Fibrosis area fraction, the number of viable and necrotic hepatocytes, and progenitor cells were analyzed; no significant difference was found between BDL + IH MSC and BDL + IS MSC groups, but the groups administered with MSC showed a larger number of viable hepatocytes compared to BDL group. No difference was found between BDL + IH MSC and BDL + IS MSC groups in terms of liver function and histologic parameters. CONCLUSION Administration of MSC increases the number of viable hepatocytes, but no difference was found in terms of liver function and degree of liver fibrosis between the intrahepatic route and intrasplenic route of administration. TYPE OF STUDY Animal Research, Randomized Controlled Study. LEVEL OF EVIDENCE Level I? (animal research is not indicated in the levels of evidence table in the journal website).
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Affiliation(s)
- Hardian Gunardi
- Pediatric Surgery Division, Department of Surgery, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia.
| | - Fatima Safira Alatas
- Department of Pediatric and Adolescent Health, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | | | - Tri Hening Rahayatri
- Pediatric Surgery Division, Department of Surgery, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
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Liu HZ, Song XQ, Zhang H. Sugar-coated bullets: Unveiling the enigmatic mystery 'sweet arsenal' in osteoarthritis. Heliyon 2024; 10:e27624. [PMID: 38496870 PMCID: PMC10944269 DOI: 10.1016/j.heliyon.2024.e27624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 03/01/2024] [Accepted: 03/04/2024] [Indexed: 03/19/2024] Open
Abstract
Glycosylation is a crucial post-translational modification process where sugar molecules (glycans) are covalently linked to proteins, lipids, or other biomolecules. In this highly regulated and complex process, a series of enzymes are involved in adding, modifying, or removing sugar residues. This process plays a pivotal role in various biological functions, influencing the structure, stability, and functionality of the modified molecules. Glycosylation is essential in numerous biological processes, including cell adhesion, signal transduction, immune response, and biomolecular recognition. Dysregulation of glycosylation is associated with various diseases. Glycation, a post-translational modification characterized by the non-enzymatic attachment of sugar molecules to proteins, has also emerged as a crucial factor in various diseases. This review comprehensively explores the multifaceted role of glycation in disease pathogenesis, with a specific focus on its implications in osteoarthritis (OA). Glycosylation and glycation alterations wield a profound influence on OA pathogenesis, intertwining with disease onset and progression. Diverse studies underscore the multifaceted role of aberrant glycosylation in OA, particularly emphasizing its intricate relationship with joint tissue degradation and inflammatory cascades. Distinct glycosylation patterns, including N-glycans and O-glycans, showcase correlations with inflammatory cytokines, matrix metalloproteinases, and cellular senescence pathways, amplifying the degenerative processes within cartilage. Furthermore, the impact of advanced glycation end-products (AGEs) formation in OA pathophysiology unveils critical insights into glycosylation-driven chondrocyte behavior and extracellular matrix remodeling. These findings illuminate potential therapeutic targets and diagnostic markers, signaling a promising avenue for targeted interventions in OA management. In this comprehensive review, we aim to thoroughly examine the significant impact of glycosylation or AGEs in OA and explore its varied effects on other related conditions, such as liver-related diseases, immune system disorders, and cancers, among others. By emphasizing glycosylation's role beyond OA and its implications in other diseases, we uncover insights that extend beyond the immediate focus on OA, potentially revealing novel perspectives for diagnosing and treating OA.
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Affiliation(s)
- Hong-zhi Liu
- Department of Orthopaedics, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xin-qiu Song
- The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Hongmei Zhang
- Department of Orthopaedics, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Chang X, Lv C, Wang B, Wang J, Song Z, An L, Chen S, Chen Y, Shang Q, Yu Z, Tan L, Li Q, Liu H, Jiang L, Xiao G, Chen L, Lu W, Hu X, Dong Z, Chen Y, Sun Y, Wang X, Li Z, Chen D, You H, Jia J, Yang Y. The utility of P-I-R classification in predicting the on-treatment histological and clinical outcomes of patients with hepatitis B and advanced liver fibrosis. Hepatology 2024; 79:425-437. [PMID: 37611260 PMCID: PMC10789381 DOI: 10.1097/hep.0000000000000563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 07/01/2023] [Indexed: 08/25/2023]
Abstract
BACKGROUND AND AIMS The predominantly progressive, indeterminate, and predominantly regressive (P-I-R) classification extends beyond staging and provides information on dynamic changes of liver fibrosis. However, the prognostic implication of P-I-R classification is not elucidated. Therefore, in the present research, we investigated the utility of P-I-R classification in predicting the on-treatment clinical outcomes. APPROACH AND RESULTS In an extension study on a randomized controlled trial, we originally enrolled 1000 patients with chronic hepatitis B and biopsy-proven histological significant fibrosis, and treated them for more than 7 years with entecavir-based therapy. Among the 727 patients with a second biopsy at treatment week 72, we compared P-I-R classification and Ishak score changes in 646 patients with adequate liver sections for the histological evaluation. Progressive, indeterminate, and regressive cases were observed in 70%, 17%, and 13% of patients before treatments and 20%, 14%, and 64% after 72-week treatment, respectively, which could further differentiate the histological outcomes of patients with stable Ishak scores. The 7-year cumulative incidence of HCC was 1.5% for the regressive cases, 4.3% for the indeterminate cases, and 22.8% for the progressive cases ( p <0.001). After adjusting for age, treatment regimen, platelet counts, cirrhosis, Ishak fibrosis score changes, and Laennec staging, the posttreatment progressive had a HR of 17.77 (vs. posttreatment regressive; 95% CI: 5.55-56.88) for the incidence of liver-related events (decompensation, HCC, and death/liver transplantation). CONCLUSIONS The P-I-R classification can be a meaningful complement to the Ishak fibrosis score not only in evaluating the histological changes but also in predicting the clinical outcomes.
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Affiliation(s)
- Xiujuan Chang
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Caihong Lv
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
| | - Bingqiong Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jing Wang
- Department of Hepatobiliary Disease, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan Province, China
| | - Zheng Song
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
| | - Linjing An
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shuyan Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Yongping Chen
- Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Qinghua Shang
- Department of Liver Diseases, the 960th Hospital of Chinese PLA Joint Logistics Support Force, Jinan, Shandong Province, China
| | - Zujiang Yu
- Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou, University, Zhengzhou, Henan Province, China
| | - Lin Tan
- Department of Liver Disease, Fuyang 2nd People’s Hospital, Fuyang, Anhui Province, China
| | - Qin Li
- Fuzhou Infectious Diseases Hospital, Fuzhou, Fujian Province, China
| | - Huabao Liu
- Traditional Chinese Medicine Hospital of Chongqing, Chongqing, China
| | - Li Jiang
- Department of Infectious Diseases, Southwest Hospital, Army Military Medical University, Chongqing, China
| | - Guangming Xiao
- Guangzhou 8th People's Hospital, Guangzhou, Guangdong Province, China
| | - Liang Chen
- Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai, China
| | - Wei Lu
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin, China
| | - Xiaoyu Hu
- National Integrative Medicine Clinical Base for Infectious Diseases and Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Zheng Dong
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yan Chen
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yameng Sun
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Xiaodong Wang
- Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Zhiqin Li
- Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou, University, Zhengzhou, Henan Province, China
| | - Da Chen
- Fuzhou Infectious Diseases Hospital, Fuzhou, Fujian Province, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Yongping Yang
- Department of Liver Disease, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Peking University 302 Clinical Medical School, Beijing, China
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Yoo HW, Park JW, Jung MJ, Yoo JJ, Kim SG, Kim YS. The prediction of liver decompensation using hepatic collagen deposition assessed by computer-assisted image analysis with Masson's trichrome stain. Scand J Gastroenterol 2024; 59:85-91. [PMID: 37724372 DOI: 10.1080/00365521.2023.2257823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 09/05/2023] [Accepted: 09/06/2023] [Indexed: 09/20/2023]
Abstract
BACKGROUND & AIM The current pathologic system classifies structural deformation caused by hepatic fibrosis semi-quantitatively, which may lead to a disagreement among pathologists. We measured hepatic fibrosis quantitatively using collagen proportionate area (CPA) in compensated cirrhotic patients and assessed its impact on predicting the development of liver decompensation. METHOD From January 2010 to June 2018, we assessed 101 patients who went through liver biopsy and received diagnosis as compensated cirrhosis with digital image analysis of CPA. Clinical and laboratory data were collected at the baseline and at the time of the last follow-up or progression to liver decompensation (LD). RESULT The mean age was 50.8 ± 10.5 years, and the most common etiology of liver disease was chronic hepatitis B (48.5%), followed by alcoholic hepatitis (18.8%). The mean CPA was 16.91 ± 9.60%. The mean CPA values were different in patients with and without LD development (21.8 ± 11.1 vs. 15.2 ± 8.5). During the median follow-up of 60.0 months, 26 out of 101 patients experienced LD. Older age (hazard ratio [HR],1.069; p = 0.015), prolonged international normalized ratio (HR, 6.449; p = 0.019) and higher CPA (HR, 1.049; p = 0.040) were independent predictors of liver decompensation on multivariate cox-regression analysis. When patients were divided according to the optimal CPA threshold (26.8%), higher CPA predicted LD better than lower CPA. (Log-rank test: p < 0.001). CONCLUSION CPA could be a useful quantitative prognostic value for patients with compensated cirrhosis.
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Affiliation(s)
- Hae Won Yoo
- Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Jae Woo Park
- Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Min Jung Jung
- Department of Pathology, SoonChunHyang University College of Medicine, Bucheon, Korea
| | - Jeong-Ju Yoo
- Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Sang Gyune Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
| | - Young Seok Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon, Korea
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Crawford JM, Bioulac-Sage P, Hytiroglou P. Structure, Function and Responses to Injury. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:1-95. [DOI: 10.1016/b978-0-7020-8228-3.00001-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Poorani R, Ganesan N, Neranchanaa R, Chaitra V, Kartikayan RK. Histologic scoring of liver biopsies for the prognosis of chronic liver disease at a tertiary care hospital in South India. Pathol Res Pract 2024; 253:155051. [PMID: 38160483 DOI: 10.1016/j.prp.2023.155051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 12/18/2023] [Accepted: 12/19/2023] [Indexed: 01/03/2024]
Abstract
OBJECTIVES The study aimed to evaluate the role of histologic scoring of liver biopsies using Ishak-modified histological activity index (HAI) and Laennec's scoring system in predicting chronic liver disease (CLD) prognosis in South India. METHODS A retrospective analysis of liver biopsy samples was conducted at a tertiary care hospital. The samples were scored using the Ishak-modified HAI and Laennec's scoring system for staging and grading CLD. Patient clinical data were retrieved and assessed using the Child-Pugh scoring system. Chi-squared test was used to test the association between categorical variables and the association with multiple categories was reported using Cramer's V correlation coefficient. A p-value < 0.05 was considered significant. RESULTS Out of 43 samples included in the study, 65.12% were male patients, with a mean age of 43.3 ± 13.9 years. Cirrhotic cases accounted for the highest proportion (65.12%, n = 28), followed by hepatitis cases (30%, n = 13). The predominant etiology was alcohol-related (44.19%, n = 19). Percutaneous liver biopsies constituted most of the samples (48.84%, n = 21), followed by transjugular (37.21%, n = 16) and ultrasonography-guided (11.63%, n = 6) biopsies. The correlation between Ishak-modified HAI stages and Child-Pugh scores was weak and insignificant (p = 0.71), while Laennec's scores showed a moderate but insignificant correlation with Child-Pugh scores (p = 0.066). CONCLUSION Histologic scoring of liver biopsies using the Ishak-modified HAI and Laennec's scoring system can provide valuable prognostic information for CLD. However, further research is needed to establish stronger correlations with clinical outcomes.
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Affiliation(s)
- R Poorani
- Department of Pathology, PSG Institute of Research and Medical Sciences, Coimbatore 641004, India
| | - Nidhya Ganesan
- Department of Pathology, PSG Institute of Research and Medical Sciences, Coimbatore 641004, India.
| | - R Neranchanaa
- Department of Pathology, PSG Institute of Research and Medical Sciences, Coimbatore 641004, India
| | - V Chaitra
- Department of Pathology, PSG Institute of Research and Medical Sciences, Coimbatore 641004, India
| | - R K Kartikayan
- Department of Gastroenterology, PSG Institute of Research and Medical Sciences, Coimbatore 641004, India
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10
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Guindi M. Liver fibrosis: the good, the bad, and the patchy-an update. Hum Pathol 2023; 141:201-211. [PMID: 36702358 DOI: 10.1016/j.humpath.2023.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 01/09/2023] [Indexed: 01/24/2023]
Abstract
The purpose of this article is to review fibrosis staging systems, reversibility of fibrosis, histologic pattern of fibrosis regression, and recently proposed fibrosis staging systems that address the more nuanced fibrosis information needed clinically for management purposes. In most chronic liver diseases, the extent of liver fibrosis often drives patient outcomes. The evolving knowledge of the reversibility of fibrosis and the observed patterns of fibrosis seen in the setting of remodeling/regression can create staging difficulties, and problems in applying the existing "conventional" staging systems. The heterogeneity of liver fibrosis in congestive liver disease is an emerging problem in biopsies from patients with congestive heart failure. The fibrosis staging in these biopsies is of significant import as it is used to determine suitability of some congestive heart disease patients for heart transplantation alone, dual heart and liver transplantation, or be denied transplantation. Pathologist should be aware of these newly recognized concepts, the recently proposed staging systems that attempt to incorporate these new fibrosis patterns and be able to apply the knowledge in daily practice.
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Affiliation(s)
- Maha Guindi
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA, 90048, USA.
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11
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Gu J, Liang BY, Zhang EL, Zhang ZY, Chen XP, Huang ZY. Scientific Hepatectomy for Hepatocellular Carcinoma. Curr Med Sci 2023; 43:897-907. [PMID: 37347369 DOI: 10.1007/s11596-023-2761-2] [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: 02/23/2023] [Accepted: 03/31/2023] [Indexed: 06/23/2023]
Abstract
With advances in imaging technology and surgical instruments, hepatectomy can be perfectly performed with technical precision for hepatocellular carcinoma (HCC). However, the 5-year tumor recurrence rates remain greater than 70%. Thus, the strategy for hepatectomy needs to be reappraised based on insights of scientific advances. Scientific evidence has suggested that the main causes of recurrence after hepatectomy for HCC are mainly related to underlying cirrhosis and the vascular spread of tumor cells that basically cannot be eradicated by hepatectomy. Liver transplantation and systemic therapy could be the solution to prevent postoperative recurrence in this regard. Therefore, determining the severity of liver cirrhosis for choosing the appropriate surgical modality, such as liver transplantation or hepatectomy, for HCC and integrating newly emerging immune-related adjuvant and/or neoadjuvant therapy into the strategy of hepatectomy for HCC have become new aspects of exploration to optimize the strategy of hepatectomy. In this new area, hepatectomy for HCC has evolved from a pure technical concept emphasizing anatomic resection into a scientific concept embracing technical considerations and scientific advances in underlying liver cirrhosis, vascular invasion, and systemic therapy. By introducing the concept of scientific hepatectomy, the indications, timing, and surgical techniques of hepatectomy will be further scientifically optimized for individual patients, and recurrence rates will be decreased and long-term survival will be further prolonged.
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Affiliation(s)
- Jin Gu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Bin-Yong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Er-Lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zun-Yi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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12
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Pantelidou P, Sinakos E, Germanidis G, Pagkalidou E, Haidich AB, Akriviadis E, Hytiroglou P. Assessment of histologic risk factors for hepatocellular carcinoma in patients with chronic hepatitis B of advanced stage. Pathol Res Pract 2023; 249:154741. [PMID: 37586217 DOI: 10.1016/j.prp.2023.154741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 08/03/2023] [Accepted: 08/03/2023] [Indexed: 08/18/2023]
Abstract
Histologic markers of increased risk for hepatocellular carcinoma can provide useful information for the management of patients with chronic hepatitis B. The expression of epithelial cell adhesion molecule (EpCAM, a marker of hepatic progenitor cells), p21 (a marker of hepatocyte senescence), glutamine synthetase (a marker of perivenular hepatocytes) and CD34 (a marker of sinusoidal capillarization) were assessed by immunohistochemistry in 52 liver biopsy specimens from patients with advanced stage chronic hepatitis B. Nineteen patients developed hepatocellular carcinoma during a follow-up period of 133 months. The findings were compared with those of 18 liver biopsy specimens from patients with early-stage chronic hepatitis B and 6 liver biopsy specimens without significant pathologic findings. EpCAM expression in hepatocytes was significantly increased in specimens with advanced stage, as compared with all other specimens. EpCAM positivity in over 30 % of hepatocytes was only seen in 3 specimens from patients who subsequently developed hepatocellular carcinoma. The expression of p21, glutamine synthetase and CD34 was not associated with hepatocellular carcinoma development. Nevertheless, glutamine synthetase immunostains highlighted zonality abnormalities that were useful in chronic hepatitis B staging. In conclusion, extensive immunopositivity of hepatocytes for EpCAM in chronic hepatitis B may represent a marker of increased hepatocellular carcinoma risk. Glutamine synthetase immunostaining represents a useful adjunct in determining the stage of chronic hepatitis B in diagnostic practice.
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Affiliation(s)
- Pavlina Pantelidou
- Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Emmanouil Sinakos
- Fourth Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Georgios Germanidis
- First Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Eirini Pagkalidou
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Anna Bettina Haidich
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Evangelos Akriviadis
- Fourth Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Prodromos Hytiroglou
- Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Greece.
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13
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Pedersen K, Ipsen DH, Skat-Rørdam J, Lykkesfeldt J, Tveden-Nyborg P. Dietary Long-Chain Fatty Acids Accelerate Metabolic Dysfunction in Guinea Pigs with Non-Alcoholic Steatohepatitis. Nutrients 2023; 15:nu15112445. [PMID: 37299406 DOI: 10.3390/nu15112445] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/17/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
The composition of dietary fatty acids may be important for the development and progression of metabolic syndrome and non-alcoholic steatohepatitis (NASH). This study investigated the effect of two high-fat diets based on coconut oil, containing predominantly medium-chain fatty acids (MCFA), or cocoa butter, containing mainly long-chain fatty acids (LCFA), on glucose homeostasis and NASH in guinea pigs following 16 and 32 weeks of diet. At week 16, glucose intolerance was increased in the LCFA animals compared to the MCFA animals (p < 0.001), with both groups differing from the controls by week 32 (p < 0.0001), supported by increased hemoglobin A1c (p < 0.05). NASH was present in both high-fat groups from week 16, with advancing fibrosis appearing more progressive in the LCFA animals at week 16. In agreement, gene expression showed overall increased expression of NASH target genes in the LCFA animals compared to the MCFA animals at weeks 16 and 32 (p < 0.05 and p < 0.0001, respectively). The LCFA animals also displayed increased plasma uric acid at both time points (p < 0.05), a phenomenon linked to NASH in humans. In conclusion, this study reports that a diet high in LCFA promotes metabolic imbalance and may accelerate NASH-associated hepatic fibrosis. This highlights the importance of a critical evaluation of fatty acid composition when investigating NASH-associated endpoints.
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Affiliation(s)
- Kamilla Pedersen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
| | - David Højland Ipsen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
- Integrated Physiology Research, Obesity and NASH Pharmacology, Novo Nordisk A/S, 2760 Måløv, Denmark
| | - Josephine Skat-Rørdam
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
| | - Jens Lykkesfeldt
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
| | - Pernille Tveden-Nyborg
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
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14
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Chen S, Wang B, Zhou J, Wu X, Meng T, Liu H, Wang T, Zhao X, Wu S, Kong Y, Ou X, Jia J, Wee A, You H, Sun Y. A new glutamine synthetase index to evaluate hepatic lobular restoration in advanced fibrosis during anti-HBV therapy. J Med Virol 2023; 95:e28555. [PMID: 36738235 DOI: 10.1002/jmv.28555] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/29/2023] [Accepted: 02/01/2023] [Indexed: 02/05/2023]
Abstract
Hepatic lobular architecture distortion is a deleterious turning point and a crucial histological feature of advanced liver fibrosis in chronic liver diseases. Regression of fibrosis has been documented in chronic hepatitis B (CHB) patients. However, whether lobular architecture could be restored following fibrosis regression after antiviral therapy is still unclear. Glutamine synthetase (GS) is generally expressed by perivenular hepatocytes around hepatic veins (HV). In this study, we defined abnormal lobular architecture (GSPT ) as GS expressing in the vicinity of portal tracts (PT), which denotes parenchymal extinction and lobular collapse. We defined normal lobular architecture (GSHV ) as GS positivity area not approximating PTs. Therefore, we propose a new GS-index, defined as the percentage of GSHV /(GSHV + GSPT ), to evaluate the extent of architectural disruption and restoration. We evaluated 43 CHB patients with advanced fibrosis (Ishak stage ≥4). Posttreatment liver biopsy was performed after 78 weeks of anti-HBV therapy. The median GS-index improved from 7% (interquartile range [IQR]: 0%-23%) at baseline to 36% (IQR: 20%-57%) at Week 78 (p < 0.001). Totals of 22 patients (51%) had significant GS-index improvement from 0% (IQR: 0%-13%) to 55% (IQR: 44%-81%), while the other half had almost no change between 17% (IQR: 0%-33%) to 20% (IQR: 12%-31%). When GS-index78w ≥ 50% was used to define hepatic lobular restoration, 37% of patients (16/43) achieved lobular restoration, with much improvement in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (median value of ∆/Baseline in ALT: restored vs. nonrestored was 79.1% vs. 48.8%, p = 0.018; median value of ∆/Baseline in AST: restored vs. nonrestored was 69.1% vs. 32.5%, p = 0.005). More importantly, lobular restoration correlated with fibrosis regression (median value of ∆/Baseline in Ishak stage: restored vs. nonrestored was 25.0% vs. 0%, p = 0.008). Therefore, in the era of antiviral therapy for CHB, restoration of hepatic lobular architecture is achievable in patients with advanced fibrosis. GS-index provides additional insight into fibrosis regression that goes beyond collagen degradation.
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Affiliation(s)
- Shuyan Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Bingqiong Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Jialing Zhou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Xiaoning Wu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Tongtong Meng
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Hui Liu
- Department of Pathology, Beijing You-an Hospital, Capital Medical University, Beijing, China
| | - Tailing Wang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Xinyan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Shanshan Wu
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing, China
| | - Xiaojuan Ou
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Aileen Wee
- Department of Pathology, National University Hospital, Singapore, Singapore
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
| | - Yameng Sun
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China
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15
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Niaz Q, Tavangar SM, Mehreen S, Ghazi-Khansari M, Jazaeri F. Evaluation of statins as a new therapy to alleviate chronotropic dysfunction in cirrhotic rats. Life Sci 2022; 308:120966. [PMID: 36150464 DOI: 10.1016/j.lfs.2022.120966] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 09/06/2022] [Accepted: 09/12/2022] [Indexed: 11/28/2022]
Abstract
AIMS Liver cirrhosis defines by regenerative nodules and fibrotic septa, causing a complication called cirrhotic cardiomyopathy (CCM) with chronotropic hypo-responsiveness. In addition to lowering cholesterol levels, statins yield antioxidant and anti-inflammatory effects. In liver diseases animal models, statins have been shown to decrease hepatic inflammation, fibrogenesis, and portal pressure (PP). Therefore, we evaluated the atorvastatin effect on the heart in cirrhotic rats. MATERIALS AND METHODS Bile duct ligation (BDL) or sham operation performed on male Wistar rats and grouped as cirrhotic; BDL/Saline, BDL/Ator-7d(days) (Atorvastatin 15 mg/kg/day), and BDL/Ator-14d groups, or control; Sham/Saline, Sham/Ator-7d, and Sham/Ator-14d groups. Corrected QT interval (QTc interval), chronotropic responses, serum brain natriuretic peptides (BNP), heart tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and malondialdehyde (MDA) levels were studied along with atrial Ras homolog family member A (RhoA) and endothelial nitric oxide synthase (eNOS) gene expression. KEY FINDINGS The chronotropic responses decreased in BDL/Saline and increased in BDL/Ator-7d group. The QTc interval, BNP, TNF-α, and MDA levels increased in BDL/Saline and decreased in BDL/Ator-14d group. The Nrf2 level did not change in BDL/Saline and increased in BDL/Ator-14d group. The liver inflammation and fibrosis increased in BDL/Saline and did not affect BDL/Ator-7d and BDL/Ator-14d groups. The RhoA expression was down-regulated in BDL/Saline, BDL/Ator-7d, and BDL/Ator-14d groups. The eNOS expression did not change in BDL/Saline and down-regulated in BDL/Ator-14d group. SIGNIFICANCE Atorvastatin alleviates the chronotropic hypo-responsiveness and down-regulates the atrial RhoA and eNOS gene expression along with anti-inflammatory, antioxidant, and anti-stress effects in CCM.
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Affiliation(s)
- Qamar Niaz
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology and Toxicology, Faculty of Bio-Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Seyed Mohammad Tavangar
- Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sania Mehreen
- Department of Zoology, Faculty of Fisheries and Wildlife, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Mahmoud Ghazi-Khansari
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Farahnaz Jazaeri
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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16
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Romero-Cristóbal M, Clemente-Sánchez A, Peligros MI, Ramón E, Matilla AM, Colón A, Alonso S, Catalina MV, Fernández-Yunquera A, Caballero A, García R, López-Baena JÁ, Salcedo MM, Bañares R, Rincón D. Liver and spleen volumes are associated with prognosis of compensated and decompensated cirrhosis and parallel its natural history. United European Gastroenterol J 2022; 10:805-816. [PMID: 36065767 PMCID: PMC9557954 DOI: 10.1002/ueg2.12301] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 08/14/2022] [Indexed: 12/30/2022] Open
Abstract
Objective Cirrhosis is characterized by the complex interplay among biological, histological and haemodynamic events. Liver and spleen remodelling occur throughout its natural history, but the prognostic role of these volumetric changes is unclear. We evaluated the relationship between volumetric changes assessed by multidetector computerised tomography (MDCT) and landmark features of cirrhosis. Methods We included consecutive cirrhotic patients who underwent liver transplantation (LT) or hepatocellular carcinoma (HCC) resection in whom dynamic MDCT was available. Different volumetric indices were calculated. Fibrosis was evaluated by the collagen proportional area and Laennec sub‐stages. Correlation and logistic regression analysis were performed to explore associations of volumetric indexes and fibrosis with key prognostic features across the clinical stages of cirrhosis. Results 185 patients were included (146 LT; 39 HCC); the predominant aetiology was viral hepatitis (51.35%); 65.9% had decompensated disease and 85.08% clinically significant portal hypertension (CSPH). The standardised liver volume and liver‐spleen volume ratio negatively correlated with Model for End‐stage Liver Disease (MELD), albumin and hepatic venous pressure gradient (HVPG) and were significantly lower in decompensated patients. The liver segmental volume ratio (segments I–III/segments IV–VIII) best captured the characteristic features of the compensated phase, showing a positive correlation with HVPG and a good discrimination between patients with and without CSPH and varices. Volumetric changes and fibrosis severity were independently associated with key prognostic events, with no association between these two parameters. Conclusions Liver and spleen volumetric indices evolve differently along the natural history of cirrhosis and are associated with key prognostic factors in each phase, regardless of fibrosis severity and portal hypertension.
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Affiliation(s)
| | - Ana Clemente-Sánchez
- Liver Unit and Digestive Department H.G.U, Gregorio Marañón, Madrid, Spain.,CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
| | | | - Enrique Ramón
- Department of Radiology, H.G.U, Gregorio Marañón, Madrid, Spain
| | - Ana-María Matilla
- Liver Unit and Digestive Department H.G.U, Gregorio Marañón, Madrid, Spain.,CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
| | - Arturo Colón
- Liver Transplant and Hepatobiliary Surgery Unit, H.G.U, Gregorio Marañón, Madrid, Spain
| | - Sonia Alonso
- Liver Unit and Digestive Department H.G.U, Gregorio Marañón, Madrid, Spain.,CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain
| | | | | | - Aranzazu Caballero
- Liver Unit and Digestive Department H.G.U, Gregorio Marañón, Madrid, Spain
| | - Rita García
- CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain.,Department of Internal Medicine, H.G.U, Gregorio Marañón, Madrid, Spain
| | | | - María-Magdalena Salcedo
- Liver Unit and Digestive Department H.G.U, Gregorio Marañón, Madrid, Spain.,CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University, Madrid, Spain
| | - Rafael Bañares
- Liver Unit and Digestive Department H.G.U, Gregorio Marañón, Madrid, Spain.,CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University, Madrid, Spain
| | - Diego Rincón
- Liver Unit and Digestive Department H.G.U, Gregorio Marañón, Madrid, Spain.,CIBEREHD, Instituto de Salud Carlos III, Madrid, Spain.,School of Medicine, Complutense University, Madrid, Spain
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17
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Liang BY, Gu J, Xiong M, Zhang EL, Zhang ZY, Lau WY, Wang SF, Guan Y, Chen XP, Huang ZY. Histological Severity of Cirrhosis Influences Surgical Outcomes of Hepatocellular Carcinoma After Curative Hepatectomy. J Hepatocell Carcinoma 2022; 9:633-647. [PMID: 35909916 PMCID: PMC9329680 DOI: 10.2147/jhc.s368302] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/07/2022] [Indexed: 11/23/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is frequently associated with cirrhosis. The present study investigated the impact of histological severity of cirrhosis on surgical outcomes for HCC and further developed novel nomograms to predict postoperative recurrence and survival. Methods A total of 1524 consecutive patients undergoing curative hepatectomy for HCC between 1999 and 2015 were retrospectively studied. Cirrhotic severity was histologically staged according to the Laennec staging system. Short- and long-term outcomes were investigated. Recurrence-free survival (RFS) and overall survival (OS) predictive nomograms were constructed based on the results of multivariate analysis. The predictive accuracy of the nomograms was measured by the concordance index (C-index) and calibration. Results Patients in the severe cirrhosis group had significantly higher morbidity and mortality rates than patients in the no, mild, and moderate cirrhosis groups. The 5-year RFS and OS rates were 36.8% and 64.5%, respectively, in the no cirrhosis group, compared to 34.8% and 60.4% in the mild cirrhosis group, 17.3% and 43.4% in the moderate cirrhosis group, and 6.1% and 20.1% in the severe cirrhosis group. Long-term survival outcomes were significantly worse as cirrhotic severity was increased. The C-index was 0.727 for the RFS nomogram and 0.746 for the OS nomogram. Calibration curves showed good agreement between actual observations and nomogram predictions. The 2 nomograms had a superior discriminatory ability to predict RFS and OS compared to other staging systems. Conclusion Histological severity of cirrhosis significantly affected surgical outcomes in HCC patients undergoing curative hepatectomy. The novel nomograms, including histological severity of cirrhosis, showed an accurate prediction of postoperative recurrence and survival.
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Affiliation(s)
- Bin-Yong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Jin Gu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Min Xiong
- Department of Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Er-Lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Zun-Yi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Wan-Yee Lau
- Faculty of Medicine, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, People's Republic of China
| | - Shao-Fa Wang
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Yan Guan
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
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18
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Elsharkawy A, Samir R, El-Kassas M. Fibrosis regression following hepatitis C antiviral therapy. World J Hepatol 2022; 14:1120-1130. [PMID: 35978676 PMCID: PMC9258254 DOI: 10.4254/wjh.v14.i6.1120] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 04/16/2022] [Accepted: 05/12/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is one of the most common causes of liver pathology. It is a major etiological factor of continuous liver injury by triggering an uncontrolled inflammatory response, causing liver fibrosis and cirrhosis. Liver fibrosis is a dynamic process that can be reversible upon timely cessation of the injurious agent, which in cases of HCV is represented by the sustained virological response (SVR) following antiviral therapies. Direct-acting antiviral therapy has recently revolutionized HCV therapy and minimized complications. Liver fibrosis can be assessed with variable invasive and non-invasive methods, with certain limitations. Despite the broad validation of the diagnostic and prognostic value of non-invasive modalities of assessment of liver fibrosis in patients with HCV, the proper interpretation of liver stiffness measurement in patients after SVR remains unclear. It is also still a debate whether this regression is caused by the resolution of liver injury following treatment of HCV, rather than true fibrosis regression. Regression of liver fibrosis can possess a positive impact on patient's quality of life reducing the incidence of complications. However, fibrosis regression does not abolish the risk of developing hepatocellular carcinoma, which mandates regular screening of patients with advanced fibrosis.
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Affiliation(s)
- Aisha Elsharkawy
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| | - Reham Samir
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt.
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Prognostic Nomograms Based on the Cirrhotic Severity Scoring for Preoperative Prediction of Long-Term Outcomes in Patients with HBV-Related Hepatocellular Carcinoma and Child-Pugh Grade A Liver Function. JOURNAL OF ONCOLOGY 2022; 2022:7031674. [PMID: 35637856 PMCID: PMC9148252 DOI: 10.1155/2022/7031674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 05/03/2022] [Indexed: 02/08/2023]
Abstract
Background Cirrhotic severity scoring (CSS) is a noninvasive method that can predict histological severity of cirrhosis. This study is aimed at assessing the predictive value of CSS on long-term outcomes after curative hepatectomy for patients with hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) and Child-Pugh grade A liver function and further developing novel nomograms to preoperatively predict posthepatectomy recurrence and survival. Methods Consecutive patients who underwent curative hepatectomy for HCC between 2008 and 2014 were retrospectively studied. According to the CSS, patients were subclassified into 3 groups: no/mild, moderate, and severe cirrhosis. The impact of CSS on recurrence-free survival (RFS) and overall survival (OS) was assessed. Furthermore, RFS and OS nomograms were developed. Results The 5-year RFS and OS rates were 36.1% and 62.8% in the no/mild cirrhosis group, compared with 28.4% and 56.2% in the moderate cirrhosis group, and 16.2% and 33.0% in the severe cirrhosis group. Long-term survival outcomes were significantly worse with the increment of cirrhotic severity. CSS, alpha-fetoprotein level, tumor size, tumor number, and macrovascular invasion were identified as independent predictors of both RFS and OS. Besides, albumin-bilirubin grade was an independent risk factor of OS not RFS. RFS- and OS-predictive nomograms based on these preoperative variables were built. For these 2 nomograms, the C-indexes were 0.696 and 0.732, respectively. Calibration curves exhibited good agreement between actual observation and nomogram prediction. Conclusions CSS was a predictor for long-term outcomes in HCC patients after curative hepatectomy. The novel nomograms exhibited accurate preoperative prediction of posthepatectomy recurrence and OS.
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Dezső K, Paku S, Kóbori L, Thorgeirsson SS, Nagy P. What Makes Cirrhosis Irreversible?-Consideration on Structural Changes. Front Med (Lausanne) 2022; 9:876293. [PMID: 35572980 PMCID: PMC9091510 DOI: 10.3389/fmed.2022.876293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/04/2022] [Indexed: 11/17/2022] Open
Abstract
Several studies have shown that liver fibrosis, and even cirrhosis can be reversed, disproving the old “dogma” that cirrhosis is irreversible. In addition to scaring, vascular alterations appear to be critically important in the progression of chronic liver diseases. To overcome the “tipping-point” of cirrhosis, we need to understand in depth what might make it irreversible in some cases. Morphologically, the initial, as well as the advanced stages of cirrhosis are characterized by specific structural changes. The hallmark of the initial stage is the division of the original liver parenchyma by centro-central or porto-portal septa. No significant vascular changes are observed in this stage. The advanced stage is characterized by several morphological alterations: (i) The main feature is the parenchymal extinction, with intact portal vein branches, hepatic artery branches, and biliary ductules; (ii) In the extinct areas we observed numerous loops in the ductular network, indicating the disruption of the hepato-biliary junctions; (iii) Although the ductular progenitor cells are able to generate hepatocytes via the budding process, the newly formed hepatocyte nodules cannot re-establish the original lobular architecture due to their disorganized growth. In conclusion, this regenerative process characteristic for the advanced stage, contributes to circulatory disorders, perpetuates parenchymal injury and may lead to the irreversibility of cirrhosis.
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Affiliation(s)
- Katalin Dezső
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - Sándor Paku
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - László Kóbori
- Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary
| | - Snorri S Thorgeirsson
- Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute, National Institute of Health (NIH), Bethesda, MD, United States
| | - Péter Nagy
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
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21
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Diagnostic Value of Serum Chitinase-3-Like Protein 1 for Liver Fibrosis: A Meta-analysis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:3227957. [PMID: 35360517 PMCID: PMC8961437 DOI: 10.1155/2022/3227957] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 12/08/2021] [Accepted: 01/03/2022] [Indexed: 02/07/2023]
Abstract
Background Serum chitinase-3-like protein 1 (CHI3L1) is a promising marker for diagnosing liver fibrosis. This meta-analysis was carried out to assess the diagnostic performance of serum CHI3L1 for the estimation of liver fibrosis. Methods Systematic searches were performed on PubMed, Embase, Web of Science, Scopus, the Cochrane Library, Google Scholar, Sinomed, the China National Knowledge Infrastructure (CNKI), the Chinese Medical Journal Database, and the Wanfang databases for available studies. The primary studies were screened strictly according to inclusion and exclusion criteria, and sensitivity, specificity, and other measures of accuracy of serum CHI3L1 for evaluating liver fibrosis were pooled with 95% confidence intervals. I2 was calculated to assess heterogeneity, and sources of heterogeneity were explored by subgroup analysis. Deeks' test was used to assess for publication bias, and likelihood ratio was used to determine posttest probability. Results Our research integrated 11 articles, accounting for 1897 patients older than 18 years old. The pooled sensitivity and specificity for significant fibrosis, advanced fibrosis, and cirrhosis were 0.79 and 0.82 with an area under the receiver operating characteristic curve (AUC) of 0.85, 0.81 and 0.83 with an AUC of 0.91, and 0.72 and 0.74 with an AUC of 0.85, respectively. Random-effects models were used to assess for significant heterogeneity, and subgroup analysis showed that age and aetiology of included patients were likely sources of heterogeneity. No potential publication bias was found for serum CHI3L1 in the diagnosis of significant fibrosis, advanced fibrosis, or cirrhosis, and posttest probability was moderate. Conclusion Measurement of serum CHI3L1 is a feasible diagnostic tool for liver fibrosis.
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22
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Chen T, Huang Z, Chen W, Ding R, Li N, Cui H, Wu F, Liang C, Cong X. Potential cardioprotective influence of bupropion against CCl4-triggered cirrhotic cardiomyopathy. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2021.103599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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23
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Venkatesh SK, Torbenson MS. Liver fibrosis quantification. Abdom Radiol (NY) 2022; 47:1032-1052. [PMID: 35022806 PMCID: PMC9538706 DOI: 10.1007/s00261-021-03396-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 12/19/2021] [Accepted: 12/20/2021] [Indexed: 12/14/2022]
Abstract
Liver fibrosis (LF) is the wound healing response to chronic liver injury. LF is the endpoint of chronic liver disease (CLD) regardless of etiology and the single most important determinant of long-term liver-related clinical outcomes. Quantification of LF is important for staging, to evaluate response to treatment and to predict outcomes. LF is traditionally staged by liver biopsy. However, liver biopsy is invasive and suffers from sampling errors when biopsy size is inadequate; therefore, non-invasive tests (NITs) have found important roles in clinical care. NITs include simple laboratory-based serum tests, panels of serum tests, and imaging biomarkers. NITs are validated against the liver biopsy and will be used in the future for evaluation of nearly all CLDs with invasive liver biopsy reserved for some cases. Both serum tests and some imaging biomarkers such as elastography are currently used clinically as surrogate markers for LF. Several other imaging biomarkers are still considered research and awaiting clinical application in the future. As the evaluation of imaging biomarkers will likely become the norm in the future, understanding pathogenesis of LF is important. Knowledge of properties measured by imaging biomarkers and its correlation with LF is important to understand the application of NITs by abdominal radiologists. In this review, we present a brief overview of pathogenesis of LF, spatiotemporal evolution of LF in different CLD, and severity assessment with liver biopsy. This will be followed by a brief discussion on properties measured by imaging biomarkers and their relationship to the LF.
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Affiliation(s)
- Sudhakar K Venkatesh
- Abdominal Imaging Division, Department of Radiology, Mayo Clinic, 200, First Street SW, Rochester, MN, 55905, USA.
| | - Michael S Torbenson
- Anatomic Pathology Division, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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24
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Han SK, Kim MY, Kang SH, Baik SK. Application of ultrasound for the diagnosis of cirrhosis/portal hypertension. J Med Ultrason (2001) 2022; 49:321-331. [PMID: 35179669 DOI: 10.1007/s10396-022-01191-w] [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: 10/29/2021] [Accepted: 12/03/2021] [Indexed: 11/28/2022]
Abstract
With advances in technologic approaches in patients with cirrhosis, including the improvement of management, a simple, one-step approach for advanced fibrotic state of the liver is clinically useful. Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential, current diagnostic tests have not kept pace with the progression of this new paradigm. There are unmet needs in primary care centers with respect to patients with cirrhosis. Liver biopsy and measurement of hepatic venous pressure gradient in patients with cirrhosis are the gold standards for the estimation of hepatic fibrosis, and they have diagnostic and prognostic value. However, both approaches are invasive and cannot be used repeatedly in clinical practice. Ultrasonography (US) is safe, easy to perform, inexpensive, and yields numerical and accurate results. Conventionally, the size of the liver and spleen, bluntness of the liver edge, nodularity of the liver surface, and coarseness of the liver parenchyma have been known as useful parameters for hepatic fibrosis or portal hypertension (PHT) in chronic liver disease. Additionally, some functional US indices including Doppler and CEUS-based examination have been suggested as promising markers for diagnosing cirrhosis and PHT. Identification of the reproducibility and long-term prognostic value through further investigations can demonstrate the clinical usefulness of functional US indices, which are characterized as quantitative parameters for hepatic fibrosis and PHT.
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Affiliation(s)
- Seul Ki Han
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, 220-701, Republic of Korea
| | - Moon Young Kim
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, 220-701, Republic of Korea.,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.,Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, 220-701, Republic of Korea.,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, 220-701, Republic of Korea. .,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. .,Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
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25
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Chen Z, Lin Z, Yu J, Zhong H, Zhuo X, Jia C, Wan Y. Mitofusin-2 Restrains Hepatic Stellate Cells' Proliferation via PI3K/Akt Signaling Pathway and Inhibits Liver Fibrosis in Rats. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:6731335. [PMID: 35083025 PMCID: PMC8786480 DOI: 10.1155/2022/6731335] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/20/2021] [Accepted: 12/24/2021] [Indexed: 12/20/2022]
Abstract
The mitochondrial GTPase mitofusin-2 (MFN2) gene can suppress the cell cycle and regulate cell proliferation in a number of cell types. However, its function in hepatic fibrosis remains largely unexplored. We attempted to understand the mechanism of MFN2 in hepatic stellate cell (HSC) proliferation and the development of hepatic fibrosis. Rat HSC-T6 HSC were cultured and transfected by adenovirus- (Ad-) Mfn2 or its negative control (NC) vector (Ad-green fluorescent protein (GFP)); a rat liver cirrhosis model was established via subcutaneous injection with carbon tetrachloride (CCl4). Seventy-two rats were randomly divided into four groups: CCl4, Mfn2, GFP, and NC. Ad-Mfn2 or Ad-GFP was transfected into the circulation via intravenous injection at day 1, 14, 28, 42, or 56 after the first injection of CCl4 in the Mfn2/GFP groups. Biomarkers related to HSC proliferation and the development of hepatic fibrosis were detected using western blotting, hematoxylin-eosin and Masson staining, and immunohistochemistry. In vitro, Mfn2 interfered specifically with platelet-derived growth factor- (PDGF-) induced signaling pathway (phosphatidylinositol 3-kinase- (PI3K-) AKT), inhibiting HSC-T6 cell activation and proliferation. During the process of hepatic fibrosis in vivo, extracellular collagen deposition and the expression of fibrosis-related proteins increased progressively, while Mfn2 expression decreased gradually. Upregulating Mfn2 expression at the early stage of fibrosis impeded the process, triggered the downregulation of type I collagen, and antagonized the formation of factors associated with liver fibrosis. Mfn2 suppresses HSC proliferation and activation and exhibits antifibrotic potential in early-stage hepatic fibrosis. Therefore, it may represent a significant therapeutic target for eradicating hepatic fibrosis.
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Affiliation(s)
- Zhiping Chen
- Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
| | - Zeyu Lin
- Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
| | - Jiandong Yu
- Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
| | - Haifeng Zhong
- Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou Hospital Affiliate to Sun Yat-Sen University, Meizhou 514021, Guangdong Province, China
| | - Xianhua Zhuo
- Department of Gastrointestinal Endoscopy, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
| | - Changku Jia
- Department of Hepatobiliary Surgery, The Affiliated Hangzhou First People's Hospital,School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Yunle Wan
- Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China
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26
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Ehsan N, Sweed D, Elsabaawy M. Evaluation of HCV-related liver fibrosis post-successful DAA therapy. EGYPTIAN LIVER JOURNAL 2021; 11:56. [DOI: 10.1186/s43066-021-00129-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 06/11/2021] [Indexed: 12/11/2022] Open
Abstract
Abstract
Background
The rapidly developing era of direct-acting antiviral regimens (DAAs) for more than one hepatitis C virus (HCV) genotype had certainly alleviated HCV burden all over the world. Liver fibrosis is the major dramatic complication of HCV infection, and its progression leads to cirrhosis, liver failure, and hepatocellular carcinoma. The impact of DAAs on liver fibrosis had been debatably evaluated with undetermined resolution.
Main body
The aim of this review is to accurately revise the effects of DAA regimens on liver fibrosis which can either be regression, progression, or non-significant association. Liver fibrosis regression is a genuine fact assured by many retrospective and prospective clinical studies. Evaluation could be concluded early post-therapy reflecting the dynamic nature of the process.
Conclusions
The ideal application of DAA regimens in treating HCV has to be accomplished with efficient non-invasive markers in differentiating proper fibrosis evaluation from necroinflammation consequences. Liver biopsy is the gold standard that visualizes the dynamic of fibrosis regression.
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27
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Bosch J, Chung C, Carrasco-Zevallos OM, Harrison SA, Abdelmalek MF, Shiffman ML, Rockey DC, Shanis Z, Juyal D, Pokkalla H, Le QH, Resnick M, Montalto M, Beck AH, Wapinski I, Han L, Jia C, Goodman Z, Afdhal N, Myers RP, Sanyal AJ. A Machine Learning Approach to Liver Histological Evaluation Predicts Clinically Significant Portal Hypertension in NASH Cirrhosis. Hepatology 2021; 74:3146-3160. [PMID: 34333790 DOI: 10.1002/hep.32087] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 06/23/2021] [Accepted: 06/28/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS The hepatic venous pressure gradient (HVPG) is the standard for estimating portal pressure but requires expertise for interpretation. We hypothesized that HVPG could be extrapolated from liver histology using a machine learning (ML) algorithm. APPROACH AND RESULTS Patients with NASH with compensated cirrhosis from a phase 2b trial were included. HVPG and biopsies from baseline and weeks 48 and 96 were reviewed centrally, and biopsies evaluated with a convolutional neural network (PathAI, Boston, MA). Using trichrome-stained biopsies in the training set (n = 130), an ML model was developed to recognize fibrosis patterns associated with HVPG, and the resultant ML HVPG score was validated in a held-out test set (n = 88). Associations between the ML HVPG score with measured HVPG and liver-related events, and performance of the ML HVPG score for clinically significant portal hypertension (CSPH) (HVPG ≥ 10 mm Hg), were determined. The ML-HVPG score was more strongly correlated with HVPG than hepatic collagen by morphometry (ρ = 0.47 vs. ρ = 0.28; P < 0.001). The ML HVPG score differentiated patients with normal (0-5 mm Hg) and elevated (5.5-9.5 mm Hg) HVPG and CSPH (median: 1.51 vs. 1.93 vs. 2.60; all P < 0.05). The areas under receiver operating characteristic curve (AUROCs) (95% CI) of the ML-HVPG score for CSPH were 0.85 (0.80, 0.90) and 0.76 (0.68, 0.85) in the training and test sets, respectively. Discrimination of the ML-HVPG score for CSPH improved with the addition of a ML parameter for nodularity, Enhanced Liver Fibrosis, platelets, aspartate aminotransferase (AST), and bilirubin (AUROC in test set: 0.85; 95% CI: 0.78, 0.92). Although baseline ML-HVPG score was not prognostic, changes were predictive of clinical events (HR: 2.13; 95% CI: 1.26, 3.59) and associated with hemodynamic response and fibrosis improvement. CONCLUSIONS An ML model based on trichrome-stained liver biopsy slides can predict CSPH in patients with NASH with cirrhosis.
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Affiliation(s)
- Jaime Bosch
- Department of Biomedical Research, University of Bern, Bern, Switzerland
- University of Barcelona-IDIBAPS and CIBERehd, Barcelona, Spain
| | | | | | | | | | | | - Don C Rockey
- Medical University of South Carolina, Charleston, SC
| | | | | | | | | | | | | | | | | | - Ling Han
- Gilead Sciences, Inc, Foster City, CA
| | | | | | - Nezam Afdhal
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
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Broquetas T, Herruzo-Pino P, Mariño Z, Naranjo D, Vergara M, Morillas RM, Forns X, Carrión JA. Elastography is unable to exclude cirrhosis after sustained virological response in HCV-infected patients with advanced chronic liver disease. Liver Int 2021; 41:2733-2746. [PMID: 34525253 DOI: 10.1111/liv.15058] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 08/23/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Liver fibrosis and transient elastography (TE) correlation in hepatitis C virus (HCV)-infected patients with compensated advanced chronic liver disease (cACLD) after the sustained virological response (SVR) is unknown. AIMS To evaluate TE accuracy at identifying cirrhosis 3 years after HCV-eradication. METHODS Prospective, multi-centric study including HCV-cACLD patients before direct-acting antivirals (DAA). Diagnostic accuracy of TE (area under ROC, AUROC) to identify cirrhosis 3 years after SVR was evaluated. RESULTS Among 746 HCV-infected patients (95.4% with TE ≥10 kPa), 76 (10.2%) underwent a liver biopsy 3 years after SVR. Before treatment, 46 (63%) showed a TE>15 kPa. The TE before DAA was the best variable for predicting cirrhosis (METAVIR, F4) after SVR (AUROC = 0.79). Liver function parameters, serological non-invasive tests (APRI and FIB-4), and TE values improved after SVR. However, liver biopsy 3 years after HCV elimination (median time = 38.4 months) showed cirrhosis in 41 (53.9%). Multivariate analysis (OR (95% CI), P) showed that HCV-genotype 3 (20.81 (2.12-201.47), .009), and TE before treatment (1.21 (1.09-1.34), <.001) were the only variables associated with cirrhosis after SVR. However, the accuracy of TE after SVR was poor (AUROC = 0.75) and 6 (27.3%) out of 22 patients with a TE <8 kPa had cirrhosis. Similar results were found with APRI and FIB-4 scores. CONCLUSIONS Cirrhosis is present, 3 years after SVR, in more than half of HCV-cACLD patients even with the normalisation of liver function parameters, serological non-invasive tests and TE values. The low diagnostic accuracy of non-invasive methods after SVR reinforces the need for long-term surveillance.
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Affiliation(s)
- Teresa Broquetas
- Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona, Spain.,Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
| | - Paula Herruzo-Pino
- Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Dolores Naranjo
- Gastrointestinal and Hepatobiliary Pathology Section, Department of Pathology, Hospital del Mar, Barcelona, Spain
| | - Mercedes Vergara
- Liver Unit, Digestive Disease Department, Parc Taulí Sabadell Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Rosa Mª Morillas
- Hepatology Department, Hospital Germans Trias i Pujol, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS, University of Barcelona, Barcelona, Spain
| | - José A Carrión
- Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona, Spain.,Universitat Autònoma de Barcelona (UAB), Departament de Medicina de la UAB, Barcelona, Spain
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29
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Wu PS, Hsieh YC, Lee KC, Huang YH, Hou MC, Lin HC. Mac-2 binding protein glycosylation isomer is a potential biomarker to predict portal hypertension and bacterial infection in cirrhotic patients. PLoS One 2021; 16:e0258589. [PMID: 34648567 PMCID: PMC8516253 DOI: 10.1371/journal.pone.0258589] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/30/2021] [Indexed: 11/25/2022] Open
Abstract
Objectives Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel plasma biomarker for liver fibrosis, but less is known about its role in portal hypertension. We aimed to evaluate the association between M2BPGi and hepatic venous pressure gradient (HVPG) and to investigate its predictive value on prognosis of cirrhotic patients. Methods Forty-eight cirrhotic patients who underwent HVPG measurement in Taipei Veterans General hospital were retrospectively enrolled. The Spearman’s correlation test was used to analyze the correlation between plasma M2BPGi levels and HVPG and other parameters. Cox proportional hazards regression models were used to identify predictors for clinical outcomes. Results Plasma M2BPGi levels were higher in cirrhotic patients than healthy subjects and significantly correlated with HVPG levels (rs = 0.45, p = 0.001). On multivariate Cox regression analysis, higher plasma M2BPGi levels [≥ 6 cut-off index (C.O.I)] did not predict mortality within five years for cirrhotic patients and the result was similar in patients without hepatocellular carcinoma. Interestingly, M2BPGi ≥ 6 C.O.I was a potential predictor of bacterial infection within five years [Hazar ratio (HR) = 4.51, p = 0.003]. However, M2BPGi failed to predict occurrence of other cirrhosis-related complications, including variceal bleeding, ascites formation, spontaneous bacterial peritonitis, hepatorenal syndrome and hepatic encephalopathy. Conclusion Plasma M2BPGi levels positively correlated with HVPG and higher serum M2BPGi levels might have a potential role in predicting development of bacterial infection for cirrhotic patients with portal hypertension.
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Affiliation(s)
- Pei-Shan Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yun-Cheng Hsieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Kuei-Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- * E-mail: (KCL); (HCL)
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- * E-mail: (KCL); (HCL)
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Jain D, Sreenivasan P, Inayat I, Deng Y, Ciarleglio MM, Garcia-Tsao G. Thick Fibrous Septa on Liver Biopsy Specimens Predict the Development of Decompensation in Patients With Compensated Cirrhosis. Am J Clin Pathol 2021; 156:802-809. [PMID: 33940622 DOI: 10.1093/ajcp/aqab024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES In compensated cirrhosis, thick fibrous septa and small nodules on liver biopsy specimens correlate with the presence of clinically significant portal hypertension (CSPH). In turn, CSPH is the strongest predictor of cirrhosis decompensation. The aim of the study was to correlate liver biopsy specimen characteristics with the development of decompensation in patients with compensated cirrhosis. METHODS Patients with compensated cirrhosis and a concurrent liver biopsy specimen were reviewed. Semiquantitative grading of septal thickness and nodule size was performed. Primary end point was development of clinical decompensation. In total, 168 patients (median age, 49 years; 76% men) were included in the study; the most common etiology was viral. RESULTS In a median follow-up of 50 months, 43 (26%) patients developed clinical decompensation (60% ascites, 16% encephalopathy, 12% variceal hemorrhage, 7% jaundice, and 5% mixed). On univariate analysis, septal width was significantly associated with decompensation, but nodule size was not. On multivariate analysis including model for end-stage liver disease score, serum albumin, and septal width, albumin and septal width were independent predictors of decompensation. CONCLUSIONS Histologic cirrhosis in compensated patients can be subclassified by severity based on septal thickness, with thick septa denoting worse prognosis.
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Affiliation(s)
- Dhanpat Jain
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Prithvi Sreenivasan
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
- Section of Digestive Diseases, VA-CT Healthcare System, West Haven, CT, USA
| | - Irteza Inayat
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
- Section of Digestive Diseases, VA-CT Healthcare System, West Haven, CT, USA
| | - Yanhong Deng
- Yale Center for Analytical Sciences, Yale University School of Public Health, New Haven, CT, USA
| | - Maria M Ciarleglio
- Yale Center for Analytical Sciences, Yale University School of Public Health, New Haven, CT, USA
| | - Guadalupe Garcia-Tsao
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
- Section of Digestive Diseases, VA-CT Healthcare System, West Haven, CT, USA
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31
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Li J, Tao HS, Li J, Wang WQ, Sheng WW, Huang ZY, Zhang EL. Effect of Severity of Liver Cirrhosis on Surgical Outcomes of Hepatocellular Carcinoma After Liver Resection and Microwave Coagulation. Front Oncol 2021; 11:745615. [PMID: 34692526 PMCID: PMC8526975 DOI: 10.3389/fonc.2021.745615] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 09/16/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Liver resection (LR) and percutaneous microwave coagulation therapy (PMCT) are both considered as radical treatments for small hepatocellular carcinoma (HCC). However, it is still unclear whether to select LR or PMCT in HCC patients with different degrees of liver cirrhosis. The purpose of this study was to compare the efficacy of LR and PMCT in the treatment of solitary and small HCC accompanied with different degrees of liver cirrhosis. METHODS In this study, 230 patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function were retrospectively reviewed. Among these patients, 122 patients underwent LR, and 108 received PMCT. The short- and long-term outcomes were compared between these two procedures. Severity of liver cirrhosis was evaluated by using clinical scoring system (CSS) as previously published. Subgroup analysis based on CSS was performed to evaluate the effect of severity of liver cirrhosis on surgical outcomes after LR and PMCT. RESULTS There was no mortality within 90 days in both groups. Major complications were significantly more frequent in the LR group than in the PMCT group (18.8% vs. 4.6%, p<0.001). However, LR provided better surgical outcomes than PMCT. The 5-year overall survival (OS) rates for the LR and PMCT groups were 65.2% and 42%, respectively (p=0.006), and the corresponding disease-free survival (DFS) rates were 51.7% and 31.5%, respectively (p=0.004). Nevertheless, subgroup analysis showed that PMCT provided long-term outcomes that were similar to LR and lower surgical complications in HCC patients with CSS score≥4. CONCLUSIONS LR may provide better OS and DFS rates than PMCT for patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function irrespective of liver cirrhosis. PMCT should be viewed as the optimal treatment for solitary and small HCC with severe cirrhosis.
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Affiliation(s)
- Jiang Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hepatobiliary Surgery, The First Affiliated Hospital, College of Medicine, Shihezi University, Shihezi, China
| | - Hai-su Tao
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wen-qiang Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei-wei Sheng
- Department of General Surgery, People’s Hospital of Wuning County, Jiujiang, China
| | - Zhi-yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Er-lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Lackner C, Stauber RE, Davies S, Denk H, Dienes HP, Gnemmi V, Guido M, Miquel R, Paradis V, Schirmacher P, Terracciano L, Berghold A, Pregartner G, Binder L, Douschan P, Rainer F, Sygulla S, Jager M, Rautou PE, Bumbu A, Horhat A, Rusu I, Stefanescu H, Detlefsen S, Krag A, Thiele M, Cortez-Pinto H, Moreno C, Gouw ASH, Tiniakos DG. Development and prognostic relevance of a histologic grading and staging system for alcohol-related liver disease. J Hepatol 2021; 75:810-819. [PMID: 34126105 DOI: 10.1016/j.jhep.2021.05.029] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 04/18/2021] [Accepted: 05/11/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS The SALVE Histopathology Group (SHG) developed and validated a grading and staging system for the clinical and full histological spectrum of alcohol-related liver disease (ALD) and evaluated its prognostic utility in a multinational cohort of 445 patients. METHODS SALVE grade was described by semiquantitative scores for steatosis, activity (hepatocellular injury and lobular neutrophils) and cholestasis. The histological diagnosis of steatohepatitis due to ALD (histological ASH, hASH) was based on the presence of hepatocellular ballooning and lobular neutrophils. Fibrosis staging was adapted from the Clinical Research Network staging system for non-alcoholic fatty liver disease and the Laennec staging system and reflects the pattern and extent of ALD fibrosis. There are 7 SALVE fibrosis stages (SFS) ranging from no fibrosis to severe cirrhosis. RESULTS Interobserver κ-value for each grading and staging parameter was >0.6. In the whole study cohort, long-term outcome was associated with activity grade and cholestasis, as well as cirrhosis with very broad septa (severe cirrhosis) (p <0.001 for all parameters). In decompensated ALD, adverse short-term outcome was associated with activity grade, hASH and cholestasis (p = 0.038, 0.012 and 0.001, respectively), whereas in compensated ALD, hASH and severe fibrosis/cirrhosis were associated with decompensation-free survival (p = 0.011 and 0.001, respectively). On multivariable analysis, severe cirrhosis emerged as an independent histological predictor of long-term survival in the whole study cohort. Severe cirrhosis and hASH were identified as independent predictors of short-term survival in decompensated ALD, and also as independent predictors of decompensation-free survival in compensated ALD. CONCLUSION The SALVE grading and staging system is a reproducible and prognostically relevant method for the histological assessment of disease activity and fibrosis in ALD. LAY SUMMARY Patients with alcohol-related liver disease (ALD) may undergo liver biopsy to assess disease severity. We developed a system to classify ALD under the microscope by grading ALD activity and staging the extent of liver scarring. We validated the prognostic performance of this system in 445 patients from 4 European centers.
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Affiliation(s)
- Carolin Lackner
- Institute of Pathology, Medical University of Graz, Austria.
| | - Rudolf E Stauber
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Susan Davies
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Helmut Denk
- Institute of Pathology, Medical University of Graz, Austria
| | - Hans Peter Dienes
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Viviane Gnemmi
- Université Lille, Canther, Inserm, UMR-S 1277, CHU Lille, Service de Pathologie, Lille, France
| | - Maria Guido
- Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Rosa Miquel
- Liver Histopathology Laboratory, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Valerie Paradis
- Assistance Publique-Hôpitaux de Paris, Service d'Anatomie et de Cytologie Pathologiques, Hôpital Universitaire Beaujon, France; Université Paris Diderot, CNRS, Centre de Recherche sur l'Inflammation (CRI), Paris, France; Département Hospitalo-Universitaire (DHU) UNITY, Clichy, France
| | - Peter Schirmacher
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
| | - Luigi Terracciano
- Anatomic Pathology Institute, Humanitas University Research Hospital, Rozzano, Milano, Italy
| | - Andrea Berghold
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Gudrun Pregartner
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Lukas Binder
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Philipp Douschan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Florian Rainer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | | | - Marion Jager
- Université de Paris, AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Inserm, UMR 1149, Paris, France
| | - Pierre-Emmanuel Rautou
- Université de Paris, AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Inserm, UMR 1149, Paris, France
| | - Andreea Bumbu
- Liver Unit, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania; Liver Research Club, Cluj-Napoca, Romania
| | - Adelina Horhat
- Liver Unit, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania; Liver Research Club, Cluj-Napoca, Romania
| | - Ioana Rusu
- University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania
| | - Horia Stefanescu
- Liver Unit, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania; Liver Research Club, Cluj-Napoca, Romania
| | - Sönke Detlefsen
- Department of Pathology, Odense University Hospital, Odense C, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense C, Denmark
| | - Aleksander Krag
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense C, Denmark; Department of Gastroenterology and Hepatology and OPEN, Odense Patient data Explorative Network, Odense University Hospital, Odense C, Denmark
| | - Maja Thiele
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense C, Denmark; Department of Gastroenterology and Hepatology and OPEN, Odense Patient data Explorative Network, Odense University Hospital, Odense C, Denmark
| | - Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Portugal
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Annette S H Gouw
- Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, Netherlands
| | - Dina G Tiniakos
- Transitional and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Department of Pathology, Aretaieio Hospital, Medical School, National & Kapodistrian University of Athens, Athens 11528, Greece
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Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease. Sci Rep 2021; 11:19275. [PMID: 34588540 PMCID: PMC8481285 DOI: 10.1038/s41598-021-98776-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 09/01/2021] [Indexed: 12/03/2022] Open
Abstract
Reliable and available non-invasive methods for hepatic fibrosis assessment are important in chronic liver disease (CLD). Our aim was to compare stepwise algorithms combining standard ultrasound with serum markers and transient elastography (TE) for detecting advanced fibrosis (F3-4) and cirrhosis. Retrospective single center study between 2012 and 2018 of CLD patients with biopsy, TE, blood tests, and liver ultrasound parameters of surface nodularity (SN), lobar redistribution, and hepatic vein nodularity. Our cohort included 157 patients (51.6% males), mean age 47.6 years, predominantly non-alcoholic fatty liver disease and viral hepatitis (61%), with F3-4 prevalence of 60.5%. Area under the curve for F3-4 was 0.89 for TE ≥ 9.6 kPa and 0.80 for FIB-4 > 3.25. In multivariate modeling, TE ≥ 9.6 kPa (OR 21.78) and SN (OR 3.81) had independent association with F3-4; SN (OR 5.89) and TE ≥ 10.2 kPa (OR 15.73) were independently associated with cirrhosis. Two stepwise approaches included FIB-4 followed by SN or TE; sensitivity and specificity of stepwise SN were 0.65 and 1.00, and 0.89 and 0.33 for TE ≥ 9.6 kPa, respectively. Ultrasound SN and TE were independently predictive of F3-4 and cirrhosis in our cohort. FIB-4 followed by SN had high specificity for F3-4.
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Hepatocellular carcinoma in primary sclerosing cholangitis and primary biliary cholangitis: a clinical and pathological study in an uncommon but emerging setting. Virchows Arch 2021; 479:1131-1143. [PMID: 34414507 DOI: 10.1007/s00428-021-03183-6] [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: 04/18/2021] [Revised: 08/01/2021] [Accepted: 08/10/2021] [Indexed: 11/09/2022]
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are biliary tract pathologies with increased risk of HCC, although HCC is more commonly associated with viral hepatitis and steatohepatitis. HCC risk stratification in PBC/PSC populations may help select patients for surveillance. We hypothesized that metabolic syndrome associated diagnoses and co-morbid nonalcoholic fatty liver disease (NAFLD) may be risk factors for HCC in patients with PBC and PSC. We undertook a multi-institutional case control study of PSC (19 cases, 38 controls) and PBC (39 cases and controls) patients with advanced fibrosis, matched for known HCC risk factors of age and sex, who had native liver explant or resection specimens. In the PSC population, HCC risk was significantly associated with multiple metabolic syndrome associated diagnoses (OR 13, p = 0.02), hyperlipidemia (OR 29, p = 0.03), and obesity (OR 6.8, p = 0.01). In the PBC cohort, only type 2 diabetes was a risk factor for HCC (OR 4.7, p = 0.03). In the PSC cohort, thick fibrous septae were associated with HCC risk (OR 3.4, p = 0.04). No other pathologic features of the nonneoplastic liver were significantly associated with HCC, including features of NAFLD such as macrovesicular steatosis, pericellular fibrosis, and steatohepatitis. Metabolic syndrome associated diagnoses, specifically type 2 diabetes among PBC patients, is associated with HCC risk in patients with biliary type cirrhosis. However, we found no evidence that HCC risk is related to co-morbid NAFLD, indicating a likely distinct mechanism of metabolic syndrome-associated carcinogenesis in these populations.
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Liang BY, Gu J, Xiong M, Zhang EL, Zhang ZY, Chen XP, Huang ZY. Tumor size may influence the prognosis of solitary hepatocellular carcinoma patients with cirrhosis and without macrovascular invasion after hepatectomy. Sci Rep 2021; 11:16343. [PMID: 34381132 PMCID: PMC8357938 DOI: 10.1038/s41598-021-95835-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 07/27/2021] [Indexed: 12/15/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is usually associated with varying degrees of cirrhosis. Among cirrhotic patients with solitary HCC in the absence of macro-vascular invasion, whether tumor size drives prognosis or not after hepatectomy remains unknown. This study aimed to investigate the prognostic impact of tumor size on long-term outcomes after hepatectomy for solitary HCC patients with cirrhosis and without macrovascular invasion. A total of 813 cirrhotic patients who underwent curative hepatectomy for solitary HCC and without macrovascular invasion between 2001 and 2014 were retrospectively studied. We set 5 cm as the tumor cut-off value. Propensity score matching (PSM) was performed to minimize the influence of potential confounders including cirrhotic severity that was histologically assessed according to the Laennec staging system. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after PSM. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival. These results were further confirmed in the PSM cohort of 235 pairs of patients. In cirrhotic patients with solitary HCC and without macrovascular invasion, tumor size may significantly affect the prognosis after curative hepatectomy.
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Affiliation(s)
- Bin-Yong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Jin Gu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Min Xiong
- Department of Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Er-Lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Zun-Yi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China.
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Gu J, Zhang E, Liang B, Zhang Z, Chen X, Xiong M, Huang Z. Liver Collagen Contents Are Closely Associated with the Severity of Cirrhosis and Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma and Child-Pugh Grade A Liver Function. Ann Surg Oncol 2021; 28:4227-4235. [PMID: 33452603 DOI: 10.1245/s10434-020-09557-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/23/2020] [Indexed: 01/27/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is usually accompanied by different severities of cirrhosis, which is a risk factor for posthepatectomy liver failure (PHLF). Collagen proportional area (CPA) measurements can quantitatively determine the collagen contents of liver tissue. This study explored the impact of CPA on PHLF, and further investigated the correlation between CPA and a non-invasive method, namely cirrhotic severity scoring (CSS), previously proposed by our team. METHODS A total of 224 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between 2017 and 2019 were retrospectively studied. Quantitative digital image analysis of resected liver tissues was used for the CPA measurement. Risk factors for PHLF were subjected to univariate and multivariate analyses, and the correlation between CPA and CSS was analyzed. RESULTS Overall, 28 (12.5%) patients experienced PHLF. Patients with PHLF had higher CPA values than those without PHLF (p < 0.001). Multivariate analysis showed CPA and extent of hepatectomy to be independent risk factors for PHLF. CPA values were divided into four stages based on their quartiles (C1: < 6.6%; C2: 6.6-10.7%; C3: 10.7-18.0%; C4: ≥ 18.0%). The incidence of PHLF increased with increasing CPA stages (p < 0.001). Furthermore, CSS was significantly correlated with CPA (r = 0.720; p < 0.001). The incidence of PHLF also increased with increasing severity of cirrhosis evaluated by CSS (p < 0.001). CONCLUSIONS In HCC patients with Child-Pugh grade A liver function, cirrhosis could be staged by liver collagen contents, which significantly influenced PHLF. Furthermore, CSS was useful in the preoperative evaluation of cirrhotic severity.
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Affiliation(s)
- Jin Gu
- Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Erlei Zhang
- Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Binyong Liang
- Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zunyi Zhang
- Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoping Chen
- Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Xiong
- Department of Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Zhiyong Huang
- Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Pfisterer N, Unger LW, Reiberger T. Clinical algorithms for the prevention of variceal bleeding and rebleeding in patients with liver cirrhosis. World J Hepatol 2021; 13:731-746. [PMID: 34367495 PMCID: PMC8326161 DOI: 10.4254/wjh.v13.i7.731] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 05/14/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Portal hypertension (PH), a common complication of liver cirrhosis, results in development of esophageal varices. When esophageal varices rupture, they cause significant upper gastrointestinal bleeding with mortality rates up to 20% despite state-of-the-art treatment. Thus, prophylactic measures are of utmost importance to improve outcomes of patients with PH. Several high-quality studies have demonstrated that non-selective beta blockers (NSBBs) or endoscopic band ligation (EBL) are effective for primary prophylaxis of variceal bleeding. In secondary prophylaxis, a combination of NSBB + EBL should be routinely used. Once esophageal varices develop and variceal bleeding occurs, standardized treatment algorithms should be followed to minimize bleeding-associated mortality. Special attention should be paid to avoidance of overtransfusion, early initiation of vasoconstrictive therapy, prophylactic antibiotics and early endoscopic therapy. Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding, and potentially in Child B patients with active bleeding at endoscopy. The use of carvedilol, safety of NSBBs in advanced cirrhosis (i.e. with refractory ascites) and assessment of hepatic venous pressure gradient response to NSBB is discussed. In the present review, we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.
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Affiliation(s)
- Nikolaus Pfisterer
- Medizinische Abteilung für Gastroenterologie und Hepatologie, Klinik Landstraße/Krankenanstalt Rudolfstiftung, Vienna 1030, Austria
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna 1090, Austria
| | - Lukas W Unger
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna 1090, Austria
- Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, United Kingdom.
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna 1090, Austria
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna 1090, Austria
- Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna 1090, Austria
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Zhang EL, Li J, Li J, Wang WQ, Gu J, Huang ZY. Sub-Classification of Cirrhosis Affects Surgical Outcomes for Early Hepatocellular Carcinoma Independent of Portal Hypertension. Front Oncol 2021; 11:671313. [PMID: 34094970 PMCID: PMC8173036 DOI: 10.3389/fonc.2021.671313] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 04/28/2021] [Indexed: 12/17/2022] Open
Abstract
Severity of liver cirrhosis is distinct from clinical portal hypertension because there exist different degrees of liver cirrhosis in hepatocellular carcinoma (HCC) patients without significant clinical portal hypertension. Whether severity of cirrhosis affects surgical outcomes for HCC patients in absence of portal hypertension or not remains unclear. This study aims to analyze the effect of cirrhotic severity on surgical outcomes for HCC patients with hepatitis B virus (HBV) infection in absence of portal hypertension. This retrospective study enrolled 166 patients who underwent curative resection for a single HCC ≤5 cm in absence of portal hypertension between February 2011 and December 2013. Liver cirrhosis was sub-classified into no/mild (no/F4A) and moderate/severe (F4B/F4C) according to the Laennec scoring system. The surgical outcomes and complications were analyzed. The surgical mortality was zero in this study. Major complications were apparently higher in the F4B/F4C group than in the no/F4A group (17.0% vs 7.4%, p <0.001). The 1-year, 3-year and 5-year overall survival (OS) rates were 98.5, 88.1 and 80%, respectively, in the no/F4A group, which were significantly higher than those in the F4B/F4C group (98.0, 69.2 and 54.7%, p = 0.001). Microscopic vascular invasion, absence of tumor capsule and severity of liver cirrhosis were independent risk factors of surgical outcomes for HCC patients without portal hypertension. In conclusion, severity of liver cirrhosis affected surgical outcomes for early-stage HCC patients independent of portal hypertension.
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Affiliation(s)
| | | | | | | | | | - Zhi-yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wu J, Chen Y, Zuo C, Kuang N, Li R, Li Q, Ruan J, Cui E, Xu R, Yu J. A novel index for staging hepatitis B related liver cirrhosis in patients with hepatocellular carcinoma. Sci Prog 2021; 104:368504211018052. [PMID: 34003700 PMCID: PMC10454776 DOI: 10.1177/00368504211018052] [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] [Indexed: 11/16/2022]
Abstract
Information on the stage of liver cirrhosis is essential for prognostication and decisions on surgical planning for hepatocellular carcinoma (HCC) patients. But a non-invasive liver cirrhosis staging model is still lacking. The aim of our study was to develop a non-invasive model based on routine clinical parameters to evaluate the severity of cirrhosis in hepatitis B related HCC patients. A total of 226 HCC patients with chronic hepatitis B virus (HBV) infection who had liver resection were analyzed in this retrospective study. We found that platelets, prothrombin activity, maximum oblique diameter of right hepatic lobe and spleen length were the independent predictors of liver cirrhosis in HCC patients. By cumulating the weight of risk scores of independent variables, we constructed the PPMS (PLT/PTA/maximum oblique diameter of right hepatic lob/spleen length) index. The areas under the receiver operating characteristic curves (AUROC) of PPMS index were 0.820, 0.667, and 0.650 in predicting ≥cirrhosis 1 (C1), ≥cirrhosis 2 (C2), and ≥cirrhosis 3 (C3), respectively. The optimal cut-off value of the PPMS index for predicting ≥C1, ≥C2, and ≥C3 was 4.392, 4.471, and 4.784, respectively. And the corresponding sensitivity was 63.1%, 63.2%, and 64.7%, the corresponding specificity was 89.4%, 64.3%, and 62.5%, respectively. Our study constructed a non-invasive liver cirrhosis index (PPMS) could distinguish patients from different stages of liver cirrhosis, which might add more preoperative information for HCC patients.
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Affiliation(s)
- Juanhua Wu
- Department of Hepatobiliary Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
| | - Yunyang Chen
- Department of Hepatobiliary Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
| | - Chaohai Zuo
- Department of Hepatobiliary Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
| | - Naile Kuang
- Department of Hepatobiliary Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
| | - Ronggang Li
- Department of Pathology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
| | - Qing Li
- Department of Pathology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
| | - Jianqiu Ruan
- Department of Ultrasound, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
| | - Enming Cui
- Department of Radiology, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
| | - Ruiyun Xu
- Department of Hepatobiliary Surgery, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jiexiong Yu
- Department of Hepatobiliary Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-Sen University, Jiangmen, Guangdong, China
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Kim BK. The cutoff of transient elastography for the evaluation of portal hypertension should be different according to the etiology? Clin Mol Hepatol 2021; 27:91-93. [PMID: 33317235 PMCID: PMC7820203 DOI: 10.3350/cmh.2020.0311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 11/10/2020] [Accepted: 11/10/2020] [Indexed: 12/13/2022] Open
Affiliation(s)
- Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Gu J, Zhang E, Liang B, Zhang Z, Long X, Xiang S, Wang W, Chen X, Huang Z. Author's Reply: Use of Direct Liver Stiffness Measurement in Evaluating the Severity of Liver Cirrhosis in Patients with Hepatocellular Carcinoma. World J Surg 2021; 45:344-345. [PMID: 33108490 DOI: 10.1007/s00268-020-05845-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Jin Gu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Erlei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Binyong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Zunyi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Xin Long
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Shuai Xiang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Wenqiang Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China.
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Kořínková L, Pražienková V, Černá L, Karnošová A, Železná B, Kuneš J, Maletínská L. Pathophysiology of NAFLD and NASH in Experimental Models: The Role of Food Intake Regulating Peptides. Front Endocrinol (Lausanne) 2020; 11:597583. [PMID: 33324348 PMCID: PMC7726422 DOI: 10.3389/fendo.2020.597583] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 10/28/2020] [Indexed: 12/12/2022] Open
Abstract
Obesity, diabetes, insulin resistance, sedentary lifestyle, and Western diet are the key factors underlying non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases in developed countries. In many cases, NAFLD further progresses to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and to hepatocellular carcinoma. The hepatic lipotoxicity and non-liver factors, such as adipose tissue inflammation and gastrointestinal imbalances were linked to evolution of NAFLD. Nowadays, the degree of adipose tissue inflammation was shown to directly correlate with the severity of NAFLD. Consumption of higher caloric intake is increasingly emerging as a fuel of metabolic inflammation not only in obesity-related disorders but also NAFLD. However, multiple causes of NAFLD are the reason why the mechanisms of NAFLD progression to NASH are still not well understood. In this review, we explore the role of food intake regulating peptides in NAFLD and NASH mouse models. Leptin, an anorexigenic peptide, is involved in hepatic metabolism, and has an effect on NAFLD experimental models. Glucagon-like peptide-1 (GLP-1), another anorexigenic peptide, and GLP-1 receptor agonists (GLP-1R), represent potential therapeutic agents to prevent NAFLD progression to NASH. On the other hand, the deletion of ghrelin, an orexigenic peptide, prevents age-associated hepatic steatosis in mice. Because of the increasing incidence of NAFLD and NASH worldwide, the selection of appropriate animal models is important to clarify aspects of pathogenesis and progression in this field.
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Affiliation(s)
- L. Kořínková
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia
| | - V. Pražienková
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia
| | - L. Černá
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia
| | - A. Karnošová
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia
| | - B. Železná
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia
| | - J. Kuneš
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia
- Institute of Physiology, Czech Academy of Sciences, Prague, Czechia
| | - Lenka Maletínská
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia
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Yang N, Chen H, Gao Y, Zhang S, Lin Q, Ji X, Li N, Xu W, Liu Y, Jin S. Tanshinone IIA exerts therapeutic effects by acting on endogenous stem cells in rats with liver cirrhosis. Biomed Pharmacother 2020; 132:110815. [PMID: 33113421 DOI: 10.1016/j.biopha.2020.110815] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 09/18/2020] [Accepted: 09/25/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Liver cirrhosis (LC), the major pathway for the progression and development of chronic liver disease, is an advanced stage of liver disease. It is the third most common chronic noncommunicable disease after cardiovascular diseases and malignant tumors. Tanshinone IIA (Tan), an extract of Salvia miltiorrhiza (S. miltiorrhiza), has been proven to promote the proliferation and differentiation of stem cells. Moreover, its protective effect in liver injury has received widespread attention. The present study investigated whether Tan plays a therapeutic role in LC by promoting endogenous stem cell proliferation and differentiation. MATERIALS AND METHODS LC models were established by intraperitoneal injection of an olive oil solution containing 50 % carbon tetrachloride (CCL4) combined with 10 % alcohol in the drinking water. After successful model establishment, the animals were randomly divided into four groups and injected with physiological saline or low-, medium-, or high-dose (10, 20, or 40 mg/kg) Tan for seven consecutive days. The protective effect of Tan on LC was observed by western blotting, serological examination and histopathological staining. Furthermore, immunofluorescence double-labeling of 5-bromo-2-deoxyuridine (BrdU) and the liver cell markers albumin and CK-18 or the liver stem cell markers EPCAM and OV-6 was used to evaluate the proliferation and differentiation of endogenous liver stem cells. RESULTS We confirmed successful establishment of the LC model by observing transaminase levels and hematoxylin-eosin (HE) and Masson staining of liver sections in CCL4-treated and healthy rats. After Tan treatment, HE and Masson staining of paraffin sections of liver tissue showed that Tan treatment significantly improved histological injury to the liver. Serological tests showed that albumin-bilirubin (ALBI) scores and models for end-stage liver disease (MELD) were lower. Immunofluorescence and immunohistochemical staining showed that the newly proliferated cells were colocalized with ALB, OV-6, EPCAM, and CK-18, indicating that new expression of these markers occurred after Tan injection. All results were most significant in the medium-dose treatment group. CONCLUSION Tan can alleviate liver injury induced by CCL4 combined with alcohol in rats and plays a therapeutic role in LC by promoting the proliferation and differentiation of endogenous liver stem cells.
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Affiliation(s)
- Ningning Yang
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Haoyuan Chen
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Yang Gao
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Sijia Zhang
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Qiuchi Lin
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Xuechun Ji
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Ning Li
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Wanying Xu
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Ying Liu
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
| | - Shizhu Jin
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Nan Gang District, Harbin, Heilongjiang Province, 150081, China.
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Moreau J, Bouzy P, Guillard J, Untereiner V, Garnotel R, Marchal A, Gobinet C, Terryn C, Sockalingum GD, Thiéfin G. Analysis of Hepatic Fibrosis Characteristics in Cirrhotic Patients with and without Hepatocellular Carcinoma by FTIR Spectral Imaging. Molecules 2020; 25:molecules25184092. [PMID: 32906799 PMCID: PMC7570752 DOI: 10.3390/molecules25184092] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/31/2020] [Accepted: 09/04/2020] [Indexed: 12/12/2022] Open
Abstract
The evolution of cirrhosis is marked by quantitative and qualitative modifications of the fibrosis tissue and an increasing risk of complications such as hepatocellular carcinoma (HCC). Our purpose was to identify by FTIR imaging the spectral characteristics of hepatic fibrosis in cirrhotic patients with and without HCC. FTIR images were collected at projected pixel sizes of 25 and 2.7 μm from paraffinized hepatic tissues of five patients with uncomplicated cirrhosis and five cirrhotic patients with HCC and analyzed by k-means clustering. When compared to the adjacent histological section, the spectral clusters corresponding to hepatic fibrosis and regeneration nodules were easily identified. The fibrosis area estimated by FTIR imaging was correlated to that evaluated by digital image analysis of histological sections and was higher in patients with HCC compared to those without complications. Qualitative differences were also observed when fibrosis areas were specifically targeted at higher resolution. The partition in two clusters of the fibrosis tissue highlighted subtle differences in the spectral characteristics of the two groups of patients. These data show that the quantitative and qualitative changes of fibrosis tissue occurring during the course of cirrhosis are detectable by FTIR imaging, suggesting the possibility of subclassifying cirrhosis into different steps of severity.
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Affiliation(s)
- Johanna Moreau
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51097 Reims, France; (J.M.); (P.B.); (J.G.); (R.G.); (A.M.); (C.G.); (G.D.S.)
- Service d’Hépato-Gastroentérologie et de Cancérologie Digestive, Centre Hospitalier Universitaire de Reims, 51092 Reims, France
| | - Pascaline Bouzy
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51097 Reims, France; (J.M.); (P.B.); (J.G.); (R.G.); (A.M.); (C.G.); (G.D.S.)
| | - Julien Guillard
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51097 Reims, France; (J.M.); (P.B.); (J.G.); (R.G.); (A.M.); (C.G.); (G.D.S.)
| | - Valérie Untereiner
- Université de Reims Champagne-Ardenne, Plateforme en Imagerie Cellulaire et Tissulaire (PICT), 51097 Reims Cedex, France; (V.U.); (C.T.)
| | - Roselyne Garnotel
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51097 Reims, France; (J.M.); (P.B.); (J.G.); (R.G.); (A.M.); (C.G.); (G.D.S.)
- Laboratoire de Biochimie-Pharmacologie-Toxicologie, Centre Hospitalier Universitaire de Reims, 51092 Reims, France
| | - Aude Marchal
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51097 Reims, France; (J.M.); (P.B.); (J.G.); (R.G.); (A.M.); (C.G.); (G.D.S.)
- Service d’Anatomie et Cytologie Pathologique, Centre Hospitalier Universitaire de Reims, 51100 Reims, France
| | - Cyril Gobinet
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51097 Reims, France; (J.M.); (P.B.); (J.G.); (R.G.); (A.M.); (C.G.); (G.D.S.)
| | - Christine Terryn
- Université de Reims Champagne-Ardenne, Plateforme en Imagerie Cellulaire et Tissulaire (PICT), 51097 Reims Cedex, France; (V.U.); (C.T.)
| | - Ganesh D. Sockalingum
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51097 Reims, France; (J.M.); (P.B.); (J.G.); (R.G.); (A.M.); (C.G.); (G.D.S.)
| | - Gérard Thiéfin
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51097 Reims, France; (J.M.); (P.B.); (J.G.); (R.G.); (A.M.); (C.G.); (G.D.S.)
- Service d’Hépato-Gastroentérologie et de Cancérologie Digestive, Centre Hospitalier Universitaire de Reims, 51092 Reims, France
- Correspondence: ; Tel.: +33-6-87517-344; Fax: +33-3-26788-836
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Dubois M, Sciarra A, Trépo E, Marot A, Saldarriaga J, Moreno C, Sempoux C, Deltenre P. Histologic parameter score does not predict short-term survival in severe alcoholic hepatitis. United European Gastroenterol J 2020; 8:1003-1012. [PMID: 32778003 DOI: 10.1177/2050640620949737] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIM The alcoholic hepatitis histologic score has been proposed as a new prognostic tool to assess the risk of death in alcoholic hepatitis. We aimed to evaluate its prognostic value in patients with severe alcoholic hepatitis. METHODS Liver biopsies were analysed independently by two pathologists according to the alcoholic hepatitis histologic score. The Laennec staging system was also used to evaluate fibrosis. RESULTS One hundred and seven patients were included, and 89% of the patients received corticosteroids. The alcoholic hepatitis histologic score was available in 105 patients. Histologic scoring showed mild, moderate and severe scores in 10, 29 and 66 patients, respectively. Laennec staging was available for 53 patients, among whom 49 had cirrhosis, including 7 with Laennec 4A, 15 with 4B and 27 with 4C. Survival rates in mild, moderate and severe alcoholic hepatitis histologic score groups were 90%, 72% and 69% at 28 days (p = 0.6), 80%, 52% and 63% at 3 months (p = 0.3), and 70%, 41% and 58% at 6 months (p = 0.3), respectively. Within the alcoholic hepatitis histologic score, fibrosis demonstrated the best interobserver reproducibility (agreement = 100%, Κ = 1.00). Compared to patients with Laennec 4B or 4C cirrhosis, survival rates for patients without cirrhosis or with Laennec 4A cirrhosis were 100% vs 83% at 28 days (p = 0.16), 91% vs 68% at 3 months (p = 0.13), and 82% vs 64% at 6 months (p = 0.2), respectively. In multivariate analysis adjusted for age and for model for end-stage liver disease score, the alcoholic hepatitis histologic score and Laennec stage were not associated with 6-month mortality. CONCLUSIONS The alcoholic hepatitis histologic score is not predictive of short-term survival in this cohort of patients with severe alcoholic hepatitis.
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Affiliation(s)
- Margaux Dubois
- Division of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland
| | - Amedeo Sciarra
- Department of Clinical Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Université Libre de Bruxelles, Brussels, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Astrid Marot
- Department of Gastroenterology and Hepatology, Université Catholique de Louvain, Yvoir, Belgium
| | - Joan Saldarriaga
- Department of Clinical Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Université Libre de Bruxelles, Brussels, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Christine Sempoux
- Department of Clinical Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Université Libre de Bruxelles, Brussels, Belgium.,Department of Gastroenterology and Hepatology, clinique Saint-Luc, Belgium
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Gu J, Zhang E, Liang B, Zhang Z, Long X, Xiang S, Wang W, Chen X, Huang Z. Use of Direct Liver Stiffness Measurement in Evaluating the Severity of Liver Cirrhosis in Patients with Hepatocellular Carcinoma. World J Surg 2020; 44:2777-2783. [PMID: 32322938 DOI: 10.1007/s00268-020-05528-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Severity of liver cirrhosis plays an important role in determining the safe extents of hepatectomy in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate whether direct liver stiffness measurement can help surgeons to evaluate the severity of liver cirrhosis in HCC patients. METHODS Overall, 119 HCC patients who underwent open hepatectomy were retrospectively studied. The severity of liver cirrhosis was histologically staged using the Laennec staging system. Direct liver stiffness measurement was performed during operation using a sclerometer device named LX-C Shaw hardmeter, and its efficacy in assessing the severity of liver cirrhosis was compared with that of transient elastography (TE) and cirrhotic severity scoring (CSS) previously proposed by our team. RESULTS Liver stiffness measured by LX-C Shaw hardmeter was significantly correlated with the severity of liver cirrhosis. Spearman correlation coefficients for the correlation between the severity of liver cirrhosis and direct liver stiffness measurement, TE, and CSS were 0.751, 0.454, and 0.705, respectively (all P < 0.001). The areas under the receiver operating characteristic curves (AUCs) of direct liver stiffness measurement were 0.891 for moderate cirrhosis and 0.944 for severe cirrhosis and superior to those of TE (0.735 and 0.776, respectively) and CSS (0.888 and 0.905, respectively). CONCLUSIONS Direct liver stiffness measurement is a useful method in evaluating the severity of liver cirrhosis in HCC patients.
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Affiliation(s)
- Jin Gu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Erlei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Binyong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Zunyi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Xin Long
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Shuai Xiang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Wenqiang Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, 430030, China.
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Dong W, Yu H, Zhu YY, Xian ZH, Chen J, Wang H, Shi CC, Jin GZ, Dong H, Cong WM. A Novel Pathological Scoring System for Hepatic Cirrhosis with Hepatocellular Carcinoma. Cancer Manag Res 2020; 12:5537-5547. [PMID: 32753967 PMCID: PMC7354953 DOI: 10.2147/cmar.s223417] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 05/17/2020] [Indexed: 12/12/2022] Open
Abstract
Purpose This study aimed to propose an effective quantitative pathological scoring system and to establish nomogram to assess the stage of cirrhosis and predict postoperative survival of hepatocellular carcinoma (HCC) with cirrhosis patients after hepatectomy. Methods The scoring system was based on a retrospective study on 163 patients who underwent partial hepatectomy for HCC with cirrhosis. The clinicopathological and follow-up data of 163 HCC with cirrhosis patients who underwent hepatectomy in our hospital from 2010 to 2014 were retrospectively reviewed. A scoring system was established based on the total value of independent predictive factors of cirrhosis. The results were validated using 97 patients operated on from 2011 to 2015 at the same institution. Nomogram was then formulated using a multivariate Cox proportional hazards model to analyze. Results The scoring system was ultimately composed of 4 independent predictive factors and was divided into 3 levels. The new cirrhosis system score strongly correlated with Child–Pugh score (r=0.8058, P<0.0001) 3 months after surgery; higher cirrhosis system scores predicted poorer liver function and stronger liver damage 3 months after surgery. Then, a four-factor nomogram for survival prediction was established. The concordance indices were 0.79 for the survival-prediction nomogram. The calibration curves showed good agreement between predictions by the nomogram and actual survival outcomes. Conclusion This new scoring system of cirrhosis can help us predict the liver function and liver injury 3 months after surgery, and the nomogram enabled accurate predictions of risk of overall survival in patients of HCC with cirrhosis after hepatectomy.
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Affiliation(s)
- Wei Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, The Ministry of Education, Shanghai 200438, People's Republic of China
| | - Hua Yu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, The Ministry of Education, Shanghai 200438, People's Republic of China
| | - Yu-Yao Zhu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, The Ministry of Education, Shanghai 200438, People's Republic of China
| | - Zhi-Hong Xian
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, The Ministry of Education, Shanghai 200438, People's Republic of China
| | - Jia Chen
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, The Ministry of Education, Shanghai 200438, People's Republic of China
| | - Hao Wang
- Department of Hepatobiliary Diseases, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China
| | - Chun-Chao Shi
- Second Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China
| | - Guang-Zhi Jin
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200050, People's Republic of China
| | - Hui Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, The Ministry of Education, Shanghai 200438, People's Republic of China
| | - Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China.,Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Second Military Medical University, The Ministry of Education, Shanghai 200438, People's Republic of China
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Xu LM, Liu P. Guidelines for diagnosis and treatment of hepatic fibrosis with integrated traditional Chinese and Western medicine (2019 edition). JOURNAL OF INTEGRATIVE MEDICINE 2020; 18:203-213. [PMID: 32331978 DOI: 10.1016/j.joim.2020.03.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 09/25/2019] [Indexed: 12/16/2022]
Abstract
In 2006, the Hepatology Committee of Chinese Association of Integrative Medicine issued the "Guidelines for the Prevention and Treatment of Liver Fibrosis with Integrated Traditional Chinese and Western Medicine." In recent years, the fields of Chinese medicine, Western medicine, and integrative medicine have made rapid advances in basic and clinical research into chronic liver disease, and accumulated new evidence for the prevention and treatment of hepatic fibrosis. Therefore, in order to meet clinical needs, liver disease experts of integrated traditional Chinese and Western medicine were united to revise the previous guidelines in order to help physicians make correct and reasonable decisions in the diagnosis and treatment of hepatic fibrosis.
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Affiliation(s)
- Lie-Ming Xu
- Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Ping Liu
- Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Gu J, Zhang E, Liang B, Zhang Z, Chen X, Huang Z. Effectiveness comparison of indocyanine green retention test with the cirrhotic severity scoring in evaluating the pathological severity of liver cirrhosis in patients with hepatocellular carcinoma and Child-Pugh grade A liver function. World J Surg Oncol 2020; 18:79. [PMID: 32326968 PMCID: PMC7181509 DOI: 10.1186/s12957-020-01854-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 04/13/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown. METHODS Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared. RESULTS Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality. CONCLUSIONS CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.
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Affiliation(s)
- Jin Gu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Erlei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Binyong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Zunyi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, China.
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Point shear wave elastography predicts fibrosis severity and steatohepatitis in alcohol-related liver disease. Hepatol Int 2019; 14:270-280. [PMID: 31858403 DOI: 10.1007/s12072-019-10009-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 12/03/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND Point shear wave elastography (pSWE) is a convenient noninvasive tool for assessing liver fibrosis in chronic liver disease. However, there is little information on the correlation between pSWE and the histological findings of alcohol-related liver disease (ALD). Thus, we investigated the diagnostic performance of pSWE in discriminating the fibrosis stage of patients with ALD. METHODS A total of 251 Korean patients with ALD were prospectively enrolled. The diagnostic performance of pSWE was evaluated on the basis of histological fibrosis severity according to Kleiner/Brunt et al.'s criteria and the Laennec classification. RESULTS Median liver stiffness on pSWE significantly increased as liver fibrosis stage increased (p < 0.001). Liver stiffness measurement proved to be an excellent diagnostic indicator in the evaluation of a ≥ F2 stage (area under the receiver operating characteristics curve [AUROC] 0.93; cutoff > 1.46 m/s), ≥ F3 stage (AUROC 0.90; cutoff > 1.47 m/s), and F4 stage (AUROC 0.91; cutoff > 1.66 m/s). Compared with noninvasive serum fibrosis tests, pSWE had the highest AUROC for predicting ≥ F2, ≥ F3, and = F4 stages and the highest Obuchowski index (0.931 ± 0.007; all p < 0.001). The AUROC for discriminating steatohepatitis from simple steatosis was 0.93 (> 1.49 m/s) and the AUROC for discriminating cirrhosis with steatohepatitis from cirrhosis without steatohepatitis was 0.92 (> 2.52 m/s). CONCLUSION pSWE not only gives an accurate indication of liver fibrosis stage in ALD, but also can allow patients with severe alcoholic steatohepatitis to begin corticosteroid treatment without exposing them to the risks of liver biopsy. CLINICAL TRIAL REGISTRATION Clincialtrials.gov Identifier NCT01943318.
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