International Journal of Hepatology
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Acceptance rate13%
Submission to final decision36 days
Acceptance to publication20 days
CiteScore4.400
Journal Citation Indicator0.640
Impact Factor-

Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management

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International Journal of Hepatology publishes research related to medical, surgical, pathological, biochemical, and physiological aspects of hepatology and management of disorders affecting the liver, gallbladder, biliary tree and pancreas.

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International Journal of Hepatology maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.

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Research Article

Role of High-Density Lipoprotein Cholesterol (HDL-C) as a Clinical Predictor of Decompensation in Patients with Chronic Liver Disease (CLD)

Introduction. Systemic inflammation triggered by bacterial products like lipopolysaccharides (LPS) in the circulation is an important factor leading to decompensation in patients with chronic liver disease (CLD). High-density lipoprotein cholesterol (HDL-C) has a significant role in innate immune response to LPS in the circulation and could therefore increase the risk for decompensation in patients with CLD. In this study, we have explored the role of HDL-C as a prognostic marker for decompensation. Methods. This was a prospective, observational, cohort study where consecutive patients with CLD were included. Patients with cholestatic liver disease and hepatocellular carcinoma were excluded. Fasting lipids were measured in all patients at the time of recruitment. Each patient was carefully followed up for development of decompensation events such as new-onset/worsening ascites, hepatic encephalopathy, or variceal bleed during follow-up. Results. A total of 170 patients were included (mean age years, ). At the end of follow-up, 97/170 patients (57%) had decompensation events. Mean HDL-C levels were significantly lower among patients with decompensation ( mg/dL vs.  mg/dL; value 0.004). Using ROC analysis, cut-off for HDL-C of 36.4 mg/dL was identified. On multivariate analysis, HDL-C (; 95% CI 2.39-15.39) was found to have an independent association with risk of decompensation. Conclusions. HDL-C level (<36.4 mg/dL) is a reliable marker for risk of decompensation and can be a useful addition to existing prognostic scoring systems in CLD. It can be a valuable tool to streamline treatment protocols and prioritise liver transplantation.

Research Article

Diastolic Dysfunction Is a Predictor of Poor Survival in Patients with Decompensated Cirrhosis

Background. Left ventricular diastolic dysfunction (LVDD) appears to be the earliest cardiac disturbance in cirrhosis patients. There are many previous reports reporting the significance of severity of LVDD on the outcome of liver transplantation or TIPS insertion, a few Indian studies have addressed the role of LVDD on survival in decompensated cirrhosis. The objective of this study is to assess the effect of LVDD on the survival of decompensated cirrhotic patients. Methods. We prospectively evaluated 92 decompensated cirrhotic patients from April 2015 to March 2017 at IMS and SUM Hospital, Bhubaneswar, India. 2D echocardiography with tissue Doppler imaging was used to evaluate cardiac function, as per the American society of echocardiography guidelines. The primary endpoint was to evaluate the effect of LVDD on overall mortality. Results. Ninety-two decompensated cirrhotic patients were evaluated in this prospective cohort study. Twenty-eight out of 92 patients (30%) died due to liver-related complications after a follow-up of 24 months. The decompensated cirrhotic patients with had a significantly higher ratio ( vs. , ) suggesting severe LV dysfunction in advanced cirrhosis. Patients with had significantly higher MELD score and Child-Pugh score ( vs. ; vs. , , respectively) as compared to the group. In Cox proportional hazard multivariate analysis, (HR 2.72, 95% CI 1.07-6.9, ) and serum albumin (HR 0.32, 95% CI 0.14-0.7, ) were found to be independent predictors of mortality in decompensated cirrhotic patients. Conclusion: The presence of LVDD and low serum albumin were independent predictors of mortality in decompensated cirrhotic patients. Hence, LVDD is an indicator of advanced cirrhosis and mortality.

Research Article

Supplementation with Branched-Chain Amino Acids Induces Unexpected Deleterious Effects on Astrocyte Survival and Intracellular Metabolism with or without Hyperammonemia: A Preliminary In Vitro Study

Introduction. Ammonia is a key component in the pathogenesis of hepatic encephalopathy. Branched-chain amino acids (BCAA) have been reported to improve the symptoms of HE induced by hyperammonemia; however, we recently reported that ammonia increases intracellular levels of BCAA and exerts toxic effects on astrocytes. Objectives. This follow-up study was designed to confirm the direct effects of BCAA on human astrocytes and clarify their underlying mechanisms using metabolome analysis and evaluation of associated signaling. Methods. We performed cytotoxicity and cell proliferation tests on astrocytes following BCAA treatment with and without ammonium chloride (NH4Cl) and then compared the results with the effects of BCAA on hepatocytes and neurons. Subsequently, we used metabolomic analysis to investigate intracellular metabolite levels in astrocytes with and without BCAA treatment. Results. The astrocytes showed increased leakage of intracellular lactate dehydrogenase and reduced proliferation rate upon BCAA treatment. Interestingly, our analysis showed a BCAA-induced impairment of intracellular glycolysis/glyconeogenesis as well as amino acid and butyric acid metabolism. Furthermore, BCAA treatment was found to cause decreased levels of Glut-1 and phosphorylated GSK-3β and mTOR in astrocytes. Conclusions. Although further investigations of the effect of BCAA on human astrocytes with hyperammonemia are needed, our work demonstrates that BCAA supplementation has direct negative effects on astrocyte survival and intracellular metabolism.

Research Article

Infrahepatic Inferior Vena Cava Clamping Reduces Blood Loss during Liver Transection for Cholangiocarcinoma

Background. Major hepatectomy is the mainstay of the treatment for cholangiocarcinoma. Infrahepatic inferior vena cava (IVC) clamping is an effective maneuver for reducing blood loss during liver transection. The impact of this procedure on major hepatectomy for cholangiocarcinoma is unknown. This study evaluated the effect of infrahepatic IVC clamping on blood loss during liver transection. Methods. Clinical and pathological data were collected retrospectively for 116 cholangiocarcinoma patients who underwent major hepatectomy between January 2015 and December 2016, to investigate the benefit of infrahepatic IVC clamping. Two of five surgeons adapted the policy performing infrahepatic IVC clamping during liver transection in all cases. Patients, therefore, were divided into those (; 33.6%) who received infrahepatic IVC clamping during liver transection (C1) and those (; 66.4%) who did not (C0). Results. The patients’ backgrounds, operative parameters, and extent of hepatectomy did not differ significantly between the 2 groups, except for gender. A significantly lower blood loss (), blood transfusion (), and rate of vascular inflow occlusion requirement () were observed in the C1 group. The respective blood losses in the C1 group and the C0 group were 498.9 (95% CI: 375.8-622.1) and 685.6 (95% CI: 571-800.2) millilitres. Conclusions. The current study found infrahepatic IVC clamping during liver transection for cholangiocarcinoma reduces blood loss, blood transfusion, and rate of vascular inflow occlusion requirement.

Research Article

Prevalence of Hepatic Encephalopathy from a Commercial Medical Claims Database in the United States

Introduction. Hepatic encephalopathy (HE), a complication of cirrhosis, is associated with increased healthcare resource utilization and mortality, and impaired quality of life. Information on the prevalence of HE in the US general population is limited. Methods. Prevalence of HE was estimated by sequential stepwise data analysis of the Symphony Health anonymized patient-level data (APLD) claims database. First, years with International Classification of Diseases ninth/tenth edition, clinical modification (ICD-9/10-CM), and codes for cirrhosis from 2018 medical and hospital claims were used to estimate prevalence of cirrhosis within the data set and number of patients with cirrhosis in the US general population. Second, patients diagnosed with cirrhosis in the APLD data set from 2015–2016 with an HE ICD-9/10-CM code within 1 year of cirrhosis diagnosis were used to deduce the prevalence of HE within the data set and estimate the number of patients with HE in the US general population. Last, US DiagnosticSource data on serum ammonia level laboratory results measured within ±2 days of a confirmed HE event were merged with the APLD HE data set, then applied to the US general population. Results. Medical and hospital claims data were available for 272,256 patients with cirrhosis in 2018. An estimated 536,856 US adults had a diagnosis of cirrhosis (prevalence of 0.21%) in 2018. This proportion applied to the estimated number of patients with cirrhosis in the United States resulted in a prevalence estimate of 201,858 cirrhosis patients with HE in 2018. When factoring in serum ammonia data, prevalence was conservatively estimated as approximately 196,000 cirrhosis patients with HE and serum ammonia . Conclusions. In this longitudinal cohort–based study, it was estimated that ≈202,000 patients had HE in the United States in 2018, representing a considerable burden to society and payers.

Research Article

The Influence of Donor and Recipient Complement C3 Polymorphisms on Liver Transplant Outcome

Despite early reports of an impact of complement C3 polymorphism on liver transplant patient and graft survival, subsequent evidence has been conflicting. Our aim was to clarify the contributions of donor and recipient C3 genotype, separately and together, on patient and graft outcomes and acute rejection incidence in liver transplant recipients. Eight donor/recipient groups were analyzed according to their genotype and presence or absence of C3 F allele (FFFS, FFSS, FSFF, FSFS, FSSS, SSFF, SSFS, and SSSS) and correlated with clinical outcomes of patient survival, graft survival, and rejection. The further impact of brain death vs. circulatory death during liver donation was also considered. Over a median 5.3 y follow-up of 506 patients with clinical information and matching donor and recipient tissue, five-year patient and graft survival (95% confidence interval) were 90(81-91)% and 77(73-85)%, respectively, and 72(69-94)% were rejection-free. Early disadvantages to patient survival were associated with donor C3 F variant, especially in brain-death donors. Recipient C3 genotype was an independent determinant of graft survival by Cox proportional hazards analysis (hazard ratio 0.26, ), and the C3 F donor variant was again associated with worse liver graft survival, particularly in brain-death donors. C3 genotype did not independently determine rejection incidence, but a greater proportion of recipient C3 F carriers were rejection-free in the circulatory death, but not the brain-death cohort. Cox proportional hazards analysis revealed significant effects of acute rejection on patient survival (hazard ratio 0.24, ), of retransplantation on rejection risk (hazard ratio 6.3, ), and of donor type (circulatory-death vs. brain-death) on rejection incidence (hazard ratio 4.9, ). We conclude that both donor and recipient complement C3 genotype may influence patient and graft outcomes after liver transplantation but that the type of liver donor is additionally influential, possibly via the inflammatory environment of the transplant.

International Journal of Hepatology
 Journal metrics
Acceptance rate13%
Submission to final decision36 days
Acceptance to publication20 days
CiteScore4.400
Journal Citation Indicator0.640
Impact Factor-
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