International Journal of Hepatology最新文献

Objective: Viral hepatitis is an endemic disease in Chad. However, few studies have documented coinfection cases and their impact on cardiovascular risk. This study is aimed at analyzing hepatitis B, E and dengue coinfection in a Chadian cohort and gauge its effect on lipidemia. Patients and Methods. From February to May 2021, 179 subjects were recruited from the Department of Gastroenterology and Internal Medicine of the National Reference University Hospital of N'Djamena and tested for viral hepatitis markers, including HBsAg and IgM/IgG anti-HEV and dengue infection, using the NS1/IgM/IgG kit. Serum transaminases and biomarkers of lipid profiles were assayed by colorimetry, and atherogenic indexes (AI) and coronary risk (CRI) were calculated.

Results: Of the 179 subjects surveyed, 21.22% (38/179) tested positive for hepatitis B, 20% (27/135) for hepatitis E, and 1.66% (2/120) for dengue. However, most of the patients were found to be asymptomatic. Hepatitis B/E coinfection was more frequent in the study population (5.02%; 9/179) than dengue/hepatitis E coinfection (0.83%; 1/120; IgM). The prevalence of anti-HEV IgG antibodies was higher (18.52%) than that of IgM (1.48%). Furthermore, IgG antibodies levels in HEV-monoinfected subjects (11.05 ± 1.93 IU/mL, N = 15) were significantly higher (p < 0.05) than in coinfected patients (5.40 ± 1.31 IU/mL, N = 9). Subjects coinfected with HEV/HBV were associated with a significantly higher risk of lipodystrophy (coronary risk: 88.89% vs. 35.3%, relative risk (RR) = 2.55; p = 0.014), than HEV-monoinfected subjects, as evidenced by higher mean levels of triglycerides levels (219.88 ± 14.67 mg/dL vs. 191.82 ± 4.66  mg/dL, p < 0.05), more reduced HDL-C levels (9.05 ± 1.62 mg/dL vs. 18.93 ± 2.35 mg/dL, p < 0.05), increased mean CRI (13.81 ± 2.39 vs. 6.89 ± 1.93, p < 0.01), and AI (1.46 ± 0.10 vs. 1.05 ± 0.05, p < 0.01) values. However, they had normal transaminase values and a lower risk of developing a liver injury, although not significant (alanine aminotransferase: 0% vs. 29.4%, RR = 1, p = 0.128; aspartate aminotransferase: 0% vs. 5.88%, p = 1) than this group.

Conclusion: HBV/HEV coinfection is frequent in the Chadian cohort and associated with an important risk of dyslipidemia. Further research is required to elucidate the mechanism of action.

Background: Assessment of hepatic venous pressure gradient (HVPG) is the most reliable, though invasive method for evaluation of portal hypertension. Non-invasive, elastography-based techniques are well established in diagnosis, but not in monitoring of portal hypertension. The aim of our prospective study was to determine the value of acoustic radiation force impulse (ARFI) elastography technique of the liver and spleen in diagnosis and monitoring of portal hypertension.

Methods: We prospectively assessed portal hypertension by HVPG and corresponding elastography of the liver and spleen in 31 patients with liver cirrhosis and an indication for primary prophylaxis by non-cardio selective beta-blockers. Investigations were performed at baseline and a follow-up visit after 6-8 weeks. To address the known large variability of values for spleen elastography, well-defined corresponding areas in the spleen were used for baseline and follow-up elastography. Sensitivity, specificity, and AUC-ROC values for both spleen and liver elastography monitoring of portal hypertension were calculated.

Results: Liver but not spleen elastography significantly correlated with HVPG results and was suitable for initial evaluation of portal hypertension. However, changes in HVPG results did not show any correlation with alterations of ARFI values from baseline to follow-up visits both for liver and spleen elastography. Spleen stiffness results were not homogeneous across the whole organ differing significantly between the upper, hilar, and bottom placed investigation areas.

Conclusions: In this prospective study ARFI-based assessment of liver elastography showed itself suitable for initial assessment but not for monitoring of portal hypertension. Spleen elastography was not appropriate for both, evaluation and monitoring of portal hypertension. A possible explanation for this new data that are in some contrast to previously published results is the degree of portal hypertension in our study, a comparatively short follow-up period, and well-defined investigation areas for spleen elastography in repetitive ARFI investigations. This trial is registered with NCT03315767.

Background and aims: The cellular mechanism of liver injury related to arsenic toxicity is ill defined. It is thought that oxidative stress and mitochondrial dysfunction may play some role in arsenic-induced liver damage. In this study, we evaluated subcellular events within the primary cultured mouse hepatocytes when exposed to inorganic arsenic.

Methods: Primary cultured mouse hepatocytes were treated with 10 μM arsenic for different time periods. Reactive oxygen species (ROS) formation, functional changes of the lysosome and mitochondria, and mode of hepatocytes death were studied by laser confocal microscopy, fluorescence spectroscopy, and flow cytometry. Expression of proapoptotic member of the BCL-2 family of genes BAX and antiapoptotic BCL-2 mRNA expression were studied by real-time PCR. Cytochrome c expression was studied by Western blotting.

Results: Fluorescence spectroscopy as well as flow cytometric analysis revealed that arsenic-induced formation of ROS was time dependent. Confocal microscopy showed initiation of ROS formation from periphery of the hepatocytes at 30 min of arsenic exposure that progressed to central part of the hepatocytes at 3 h of arsenic exposure. The ROS formation was found to be NADPH oxidase (NOX) dependent. This low level of intracellular ROS induced lysosomal membrane permeabilization (LMP) and subsequently released cathepsin B to the cytosol. The LMP further increased intracellular ROS which in turn triggered induction of mitochondrial permeability transition (MPT). Pretreatment of hepatocytes with LMP inhibitor bafilomycin A (BafA) significantly decreased, and LMP inducer chloroquine (ChQ) significantly increased the production of ROS suggesting that LMP preceded enhanced ROS generation in response to arsenic. MPT was accompanied with increase in BAX : BCL2 mRNA ratio resulting in upregulation of caspase 3 and increased hepatocyte apoptosis.

Conclusion: Although arsenic-related oxidative liver injury is well established, neither the site of origin of ROS nor the early sequence of events in arsenic toxicity due to ROS is known. We believe that our study provides evidences elucidating the early sequence of events that culminates in the death of the mouse hepatocytes during arsenic exposure.

Background: The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients.

Methods: A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI.

Results: No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects' age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067-4.578, P = 0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316-18.310, P < 0.001), and LR to ENH (OR: 5.252, 95% CI 2.010-14.858, P = 0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605-11.023, P = 0.004).

Conclusions: Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.

Background: Hepatitis B virus infection is a major global health burden accounting for 2.7% of all deaths globally. Being part of the health care system, the risk of exposure to hepatitis B viral infection among medical and health science students is found to be high. In Ethiopia, particularly in this study area, very little is known about the practice of students towards hepatitis B virus infection prevention and its associated factors.

Objective: The aim of this study was to assess the practice towards hepatitis B virus infection prevention and its associated factors among undergraduate students at Hawassa University College of Medicine and Health Sciences, Hawassa, Ethiopia, 2021.

Methods and materials: An institution-based cross-sectional study was conducted from May 15 to June 15, 2021, among undergraduate students who had clinical exposure. The 404 sampled participants were recruited using a systematic random sampling technique. Data was collected using a structured self-administered questionnaire. Data was entered into EpiData version 4.6.0 and was exported to SPSS version 25 for analysis. Association between the dependent and independent variables was computed using the bivariate and multivariate logistic regression model. Odds ratio was calculated. Results were interpreted as significant if P value is <0.05 at 95% CI.

Result: This study revealed that 277 (69.9%) of the students were in the age group of 20-24 years and 266 (67.2%) were males. Out of 396 participants, about half 199 (50.3%) 95% CI (0.452-553) had a good practice towards hepatitis B virus infection prevention. Only 43.4% of the study participants had been completely vaccinated against hepatitis B virus. Age (20-24 years) (AOR = 2.736), 95% CI (1.130-6.625), and good knowledge (AOR = 1.990), 95% CI (1.207-3.282) were factors significantly associated with the practice towards hepatitis B virus infection prevention. Conclusion and Recommendation. The current study showed that about half of the study participants had good practice towards hepatitis B virus infection prevention but more than half were not completely vaccinated against HBV. Age and knowledge were factors significantly associated. It is recommended to give training for students on hepatitis B virus infection prevention. It is also advisable to screen and vaccinate students before they start their clinical attachments.

Background and aims: Childbirth in women with cirrhosis is increasing and associated with a higher risk of perinatal outcomes compared to the general population. Whether pregnancy influences the risk of liver-related events compared to nonpregnant women with cirrhosis is unclear. This study evaluates the association between pregnancy and liver-related outcomes in women with compensated cirrhosis. Approach and Results. Population-based retrospective matched cohort study in Ontario, Canada, using routinely collected healthcare data. Pregnant women with compensated cirrhosis and without prior history of decompensation between 2000 and 2016 were identified and matched to nonpregnant women with compensated cirrhosis on age, etiology of cirrhosis, and socioeconomic status in a 1 : 2 ratio. The association between pregnancy and the composite outcome of nonmalignant decompensation, liver transplant (LT), and death up to two years after cohort entry was estimated using the multivariate Cox proportional hazard regression adjusting for potential confounders. Overall, 5,403 women with compensated cirrhosis were included (1,801 pregnant; 3,602 nonpregnant; median age 31 years (IQR 27-34); 60% nonalcoholic fatty liver disease, 34% viral hepatitis). After two years of follow-up, only 19 (1.1%) pregnant women had a liver-related event compared to 319 (8.9%) nonpregnant women. Pregnant women with compensated cirrhosis had a lower hazard of a liver-related event compared to nonpregnant women (aHR 0.14, 95% CI 0.09-0.22, P < .001).

Conclusions: Pregnancy in women with compensated cirrhosis is not associated with increased liver-related events compared to nonpregnant women. These results can facilitate counselling women with cirrhosis of child-bearing age and suggests that pregnancy may not accelerate liver disease progression.

Background: Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease.

Methods: A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson's chi-square, multinomial logistic regression, and Mann-Whitney U tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A p < 0.05 was considered statistically significant.

Results: Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (p < 0.05). Genotype D was significantly associated with elevated viral load and direct bilirubin (p < 0.05). The recombinant genotype D/E was significantly associated with elevated viral load (p < 0.05). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (p < 0.05).

Conclusion: There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.