The Role of Hepatic Steatosis in Chronic Hepatitis B Infection

Chronic hepatitis B (CHB) infection is a global public health burden, and is associated with substantial morbidity and mortality. Although viral factors such as hepatitis B virus (HBV) DNA, hepatitis B e antigen, and genotype are known determinants of risk for histologic progression and hepatocellular carcinoma (HCC), other host factors can also play key roles. Hepatic steatosis (fatty liver) is increasingly common in the general population as a reflection of a rising prevalence of obesity in both Western and Eastern countries. Whereas the impact of superimposed hepatic steatosis on chronic hepatitis C infection is well-described, its role in the natural history, management, and clinical outcomes of CHB remains less defined. This article summarizes existing evidence on the prevalence and risk factors for hepatic steatosis in CHB, proposed pathogenetic links between HBV and hepatic steatosis, impact on the risk for liver fibrosis and HCC, and implications for antiviral therapy.     

Insulin Resistance, Steatosis, and Fibrosis in Egyptian Patients with Chronic Hepatitis C Virus Infection

Background/Aim:

Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are common in Egypt, and their coexistence is expected. There is controversy regarding the influence of NAFLD on chronic HCV disease progression. This study evaluates the effect of NAFLD on the severity of chronic hepatitis C (CHC) (necroinflammation and fibrosis) and assesses the relative contribution of insulin resistance syndrome to the occurrence of NAFLD in patients with chronic HCV infection.

Patients and Methods:

Untreated consecutive adults with chronic HCV infection admitted for liver biopsy were included in this study. Before liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis.

Results:

Our study included 92 male patients. Their mean ± SD age and aspartate aminotransferase (AST) level were 42 ± 7.7 years (range 20-56) and 68 ± 41.7 U/L (range 16-214), respectively. The mean insulin level and insulin resistance index were 15.6 ± 18.3 mIU/mL (range 5.1-137.4) and 5.9 ± 15.2 (range 0.9-136.2), respectively. Fifty four percent of patients had steatosis and 65% had fibrosis. In multivariate analyses, steatosis was associated with insulin resistance and fibrosis was associated with high AST level, age ≥40 years, and steatosis.

Conclusions:

Steatosis is a histopathologic feature in >50% of patients with chronic HCV infection. Insulin resistance has an important role in the pathogenesis of steatosis, which represents a significant determinant of fibrosis together with high serum AST level and older age.     

Genetic Variants in Interleukin-28B Are Associated with Diabetes and Diabetes-Related Complications in Patients with Chronic Hepatitis C Virus Infection

Digestive Diseases and Sciences - Few studies have shown that host interleukin-28B (IL28B) genetic polymorphisms are associated with insulin resistance in patients with chronic hepatitis C virus...     

Direct-acting Antiviral Regimens for Patients with Chronic Infection of Hepatitis C Virus Genotype 3 in China

Hepatitis C virus (HCV) genotype (GT)3 infection is associated with a more rapid hepatic disease progression than the other genotypes. Hence, early HCV clearance slows down the disease progression and is important for improving prognosis in GT3-infected patients. Nevertheless, compared with other genotypes, GT3 is difficult-to-treat with direct-acting antivirals, especially in the presence of cirrhosis. Current guidelines recommend several regimens which have been proven to be effective in GT3-infected patients from the Western world (North America, Europe, and Oceania). In China, GT3 infection comprises 8.7–11.7% of the 10 million patients infected with HCV and has strikingly different characteristics from that in Western countries. Unlike the Western countries, where GT3a is the predominant subtype, GT3a and 3b each affect roughly half of Chinese GT3-infected patients, with 94–96% of the GT3b-infected patients carrying A30K+L31M double NS5A resistance-associated substitutions. Phase 3 clinical trials including GT3b-infected patients have suggested that GT3b infection is difficult to cure, making the regimen choice for GT3b-infected patients an urgent clinical gap to be filled. This review includes discussions on the epidemiology of HCV GT3 in China, recommendations from guidelines, and clinical data from both Western countries and China. The aim is to provide knowledge that will elucidate the challenges in treating Chinese GT3-infected patients and propose potential solutions and future research directions.     

Association Between Helicobacter pylori Infection and Cirrhosis in Patients with Chronic Hepatitis C Virus

We evaluated, employing a logistic regression model, the association between Helicobacter pylori infection and cirrhosis in a cohort of 106 patients (57 males; mean age, 52.9 years; range, 20–78 years) with chronic hepatitis C virus (HCV) from Rosario, Argentina. HCV was confirmed by ELISA and PCR. H. pylori status was determined by ELISA. Of the 106 patients evaluated, 47 (44.3%) had cirrhosis. A total of 70.2% (33/47) of cirrhotic patients and 47.5% (28/59) of noncirrhotic patients were H. pylori-positive. In univariate analyses, cirrhosis was associated with age (P = 0.016) and H. pylori-positive status (P = 0.019) but not with gender (P = 0.28) or length of infection (P = 0.35). In multivariate analysis, H. pylori infection (P = 0.037; OR = 2.42; 95% CI = 1.06–5.53) and age (P = 0.033; OR = 1.04; 95% CI = 1.00–1.07) of patients remained significant and independently associated with cirrhosis. In conclusion, our results demonstrate an association between H. pylori infection and cirrhosis in patients with hepatitis C virus.     

Resistance-Associated Variants in Chronic Hepatitis C Patients Treated with Protease Inhibitors

Direct-acting antiviral agents in combination with pegylated interferon (PEG-IFN) and ribavirin (RBV) significantly improve sustained virologic response rate and reduce duration of therapy among both treatment-naïve and treatment-experienced patients with genotype 1 chronic hepatitis C. One of the most important considerations with both boceprevir and telaprevir is the potential development of resistant variants with therapy. Patients with poor intrinsic responsiveness to interferon, and those with incomplete virological suppression on protease inhibitor therapy, appear to be at higher risk for resistance. In this article we will define antiviral resistance and review the data on both in vitro and in vivo resistance to protease inhibitors, concentrating on data on boceprevir and telaprevir. We will also explore the significance of resistant variants present at the baseline, as well as the fate of the resistant variants and the ways to minimize the development of resistance to protease inhibitors.     

Bioelectrical Impedance Analysis for the Evaluation of Hepatic Fibrosis in Patients with Chronic Hepatitis C Infection

Bioelectrical impedance analysis (BIA) is a non-invasive technique that measures electrical resistance (R) and reactance (Xc), which are then used to calculate phase angle (PA). The aim of this pilot study was to assess whether BIA can differentiate between minimal and advanced hepatic fibrosis in patients with chronic hepatitis C (HCV) infection. Twenty patients with HCV participated in this study, and were divided into minimal (Metavir 1) and advanced (Metavir 3 or 4) fibrosis groups. We obtained BIA measurements (R and Xc) in several axes and calculated PA from each pair of measurements. We found no statistically significant differences between the two groups with respect to PA, R, or Xc for the whole body, the trunk or the right upper quadrant measurements in any axis. Mean whole body PA was 7.0 and 7.1 (P = 0.9) in the minimal and advanced fibrosis groups, respectively. Bioelectrical impedance analysis did not demonstrate the ability to distinguish between minimal and advanced degrees of hepatic fibrosis in patients with chronic HCV infection.     

Prevalence and Impact of Hepatic Steatosis on the Response to Antiviral Therapy in Saudi Patients with Genotypes 1 and 4 Chronic Hepatitis C

Background

Hepatic steatosis in hepatitis C virus (HCV)-infected patients has been shown to enhance the progression of liver fibrosis and decrease the response to antiviral therapy.

Aims

We aimed to determine the role of HCV genotype 4 (HCV-G4) in the prevalence of hepatic steatosis, its impact on antiviral therapy, and its associations and predictive factors in comparison to HCV-G1-infected patients.

Methods

Treatment-naïve HCV patients who were started on pegylated interferon a-2b plus ribavirin therapy in two centers in Saudi Arabia were included. The severity of steatosis was assessed using the METAVIR and NAS (non-alcoholic fatty liver disease [NAFLD] activity score) scoring systems. Sustained virological response (SVR) was studied in relation to the degree of steatosis. Associations between steatosis and multiple demographic, laboratory, and virological factors were examined. HCV-G1 and HCV-G4 patients were compared.

Results

A total of 116 patients (HCV-G4 85 [73.3%]; HCV-G1 31 [26.7%]) were included. The mean age was 50.4 ± 10.7 years and 56.9% were males. In terms of steatosis grading using the NAS scoring system, 50% had steatosis grade 0, 26.7% grade 1, 14.7% grade 2, and 8.6% grade 3, while the overall staging of steatosis revealed that 43.1% had mild steatosis, 42.2% moderate, and 14.7% severe. Gamma-glutamyl transpeptidase (GGT), platelet count, body mass index (BMI), cholesterol level, presence of hyperlipidemia, liver histology stage, and grade were significantly correlated with hepatic steatosis in one or more of the statistical analyses. Twenty-two out of 55 patients (40.0%) had an SVR in the mild steatosis group, compared to 52.7% in the moderate group and 7.3% in the severe group (P = 0.03). The HCV genotype did not correlate with steatosis or SVR.

Conclusion

Our study confirms the high prevalence of steatosis in HCV-G4 and HCV-G1 patients, but with no difference in the grade or score of steatosis between the two genotypes. The grade of steatosis correlates with GGT, platelet count, and BMI, while the NAS score of steatosis correlates with response to antiviral therapy.     

Anti-ENA Antibodies in Patients with Chronic Hepatitis C Virus Infection

The aim of the study was to assess the prevalence of anti-extractable nuclear antigen (ENA) antibodies in patients with chronic HCV infection. We studied 69 consecutive patients with chronic hepatitis C, 59 control subjects with non-HCV liver diseases, and 22 control subjects with extrahepatic, non-immune-mediated, chronic diseases. Thirty-two (46.3%) of 69 patients with HCV infection had anti-ENA antibodies: 16 (23.1%) showed anti-SSA antibodies and 14 (20.2%) had anti-SSB antibodies. Four of the patients with HCV infection suffered from sicca syndrome and three of them had also anti ENA antibodies. The prevalence of anti-ENA antibodies was significantly higher in the anti-HCV subjects compared with both control groups. Twenty-six of 44 HCV-antibodies-positive females had anti-ENA antibodies, compared with 6 of 25 males, showing a sex related difference. In conclusion, our results outline a specific role of HCV infection in the induction of anti-ENA antibodies. Female sex seems a predisposing condition.     

Clinical Implications of Hepatic Steatosis in Patients with Chronic Hepatitis C: A Multicenter Study of U.S. Veterans

Studies have indicated a high prevalence of hepatic steatosis in patients with chronic hepatitis C (CHC). To address the impact of steatosis on the clinical course of CHC and treatment response requires large multicenter studies. The present study analyzed hepatitis C virus (HCV)-infected veterans enrolled in a U.S. Veteran Administration multicenter study of the epidemiology and response to interferon α-2b and ribavirin treatment. Of the 357 patients, 97.1% were males, with a mean age of 48.7±6.4 years, and 184 (51.5%) had hepatic steatosis. The mean body mass index (BMI) was 29.3±5.2 kg/m², including 37.1% who were obese (BMI, ≥30 kg/m²). Stage III–IV fibrosis was present in 111 of 334 (33.3%) of the patients. After adjusting for age, race, and history of alcohol use in the past 12 months, only stage III–IV fibrosis was independently and significantly associated with hepatic steatosis (P=0.03). There was a trend of association between obesity and steatosis independent of the other factors. Only HCV genotype was independently associated with a sustained virological response (SVR) to interferon α-2b and ribavirin treatment after adjusting for age, alcohol use, steatosis, BMI, stage III–IV fibrosis, serum AFP, and HCV load. In conclusion, analyses of our multicenter trial data demonstrated that the prevalence of hepatic steatosis is 51.5% in HCV-infected U.S. veterans. We found that steatosis is independently associated with stage III–IV fibrosis. However, only HCV genotype, and not steatosis, obesity, or stage III–IV fibrosis, was associated with SVR to interferon α-2b and ribavirin treatment. Other members of the VA HCV-001 Study Group are listed in the Appendix     

Insulin Resistance Is Common in Patients with Predominantly Genotype 3 Chronic Hepatitis C

Hepatitis C virus (HCV) infection has been associated with insulin resistance or diabetes mellitus, but data are controversial on the role of different HCV genotypes in causing insulin resistance. We have designed a study aimed at determining insulin resistance in patients with chronic hepatitis C with predominant genotype 3. Insulin resistance was measured using a homeostasis model of assessment for insulin resistance in 85 non-diabetic, non-cirrhotic patients with chronic hepatitis C (genotype 3 = 54). The results were compared with 38 biopsy-proven patients with non-alcoholic fatty liver disease and 25 age- and body mass index-matched healthy volunteers. Patients with chronic hepatitis C had a higher fasting insulin and homeostasis model of assessment for insulin resistance values than healthy volunteers (P = 0.0001). A large number of patients with chronic hepatitis C showed evidence of insulin resistance than healthy controls [53 (62.3%) vs. 4 (16%), respectively] (P < 0.0001). Of the various risk factors studied for insulin resistance in patients with chronic hepatitis C, higher waist (P = 0.010) and higher serum triglycerides (P = 0.002) were found to correlate with HOMA-insulin resistance. There was no difference in insulin resistance amongst patients with genotype 1 or 3, respectively. Based on these results, we conclude that insulin resistance is common among non-diabetic, non-cirrhotic patients with chronic hepatitis C. A majority of these patients had genotype 3, but there was no difference in insulin resistance between genotype 1 and genotype 3 patients.     

Hepatic Steatosis Index in the Detection of Fatty Liver in Patients with Chronic Hepatitis B Receiving Antiviral Therapy

Background/AimsThe hepatic steatosis index (HSI) is a noninvasive method to assess the severity of hepatic steatosis. Antiviral therapy (AVT) can impact aspartate aminotransferase and alanine aminotransferase levels, which are the main components of the HSI. Thus, we investigated the accuracy of the HSI in detecting hepatic steatosis in patients with chronic hepatitis B (CHB) receiving AVT, compared with those not receiving AVT and in those with nonalcoholic fatty liver disease (NAFLD).MethodsPatients with CHB or NAFLD who underwent a magnetic resonance imaging proton density fat fraction (MRI-PDFF) evaluation between March 2010 and March 2019 were recruited. Hepatic steatosis was diagnosed when the PDFF exceeded 5%. Area under the receiver operating characteristic curve (AUROC) analysis was used to assess the diagnostic accuracy of the HSI in the detection of hepatic steatosis.ResultsThe mean age of the study population (189 men and 116 women; 244 with CHB [184 with and 60 without AVT] and 61 with NAFLD) was 55.6 years. The AUROC values for detecting hepatic steatosis were similar between patients with CHB (0.727; p<0.001) and those with NAFLD (0.739; p=0.002). However, when patients with CHB were subdivided into those receiving and not receiving AVT, the AUROC value decreased slightly in patients with CHB receiving AVT compared to those without not receiving AVT (0.707; p=0.001 vs 0.779; p=0.001).ConclusionsDespite a slight attenuation, the diagnostic accuracy of the HSI in patients with CHB receiving AVT in detecting hepatic steatosis was still acceptable. Further large-scale studies are required for validation.