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.     

The Association of Genetic Variants with Hepatic Steatosis in Patients with Genotype 1 Chronic Hepatitis C Infection

Background

Single-nucleotide polymorphisms (SNPs) in the IL28B and PNPLA3 gene regions have been associated with hepatic steatosis in genotype 1 (G1) chronic HCV infection but their clinical impacts remain to be determined.

Aim

We sought to validate these associations and to explore their impact on treatment response to peginterferon and ribavirin therapy.

Methods

A total of 972 G1 HCV-infected Caucasian patients were genotyped for the SNPs rs12979860 (IL28B) and rs2896019 (PNPLA3). Multivariable analysis tested IL28B and PNPLA3 for association with the presence of any steatosis (>0 %); clinically significant steatosis (>5 %); steatosis severity (grade 0–3/4); and the interacting associations of the SNPs and hepatic steatosis to sustained viral response (SVR).

Results

IL28B and PNPLA3 polymorphisms were associated with the presence of any steatosis (rs12979860, p = 1.87 × 10^?7; rs2896019, p = 7.56 × 10^?4); clinically significant steatosis (rs12979860, p = 1.82 × 10^?3; rs2896019, p = 1.27 × 10^?4); and steatosis severity (rs12979860, p = 2.05 × 10^?8; rs2896019, p = 2.62 × 10^?6). Obesity, hypertriglyceridemia, hyperglycemia, liver fibrosis, and liver inflammation were all independently associated with worse steatosis. Hepatic steatosis was associated with lower SVR, and this effect was attenuated by IL28B. PNPLA3 had no independent association with SVR.

Conclusions

IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis. IL28B attenuates the association between steatosis and SVR. Remediable metabolic risk factors remain important, independently of these polymorphisms, and remain key therapeutic goals to achieve better outcomes for patients with HCV-associated hepatic steatosis.     

Diabetes Mellitus Is Associated with Impaired Response to Antiviral Therapy in Chronic Hepatitis C Infection

Insulin resistance may promote hepatic fibrosis in chronic hepatitis C (HCV) and has emerged as a cofactor in failure to achieve sustained viral response (SVR). Aims (1) To assess the association of diabetes mellitus (DM) in HCV patients to the severity of hepatic fibrosis and to the response to antiviral treatment. (2) To assess the safety of pegylated interferon and ribavirin combination therapy (Peg IFN/RBV) in diabetic HCV patients. Methods HCV diabetics (n = 61) were identified. A 2:1 matching control group was used to identify independent factors of advanced fibrosis and treatment failure. Results Compared to HCV non-diabetics, HCV diabetics were more likely to have steatosis (P < 0.0001) and advanced fibrosis (P = 0.003). Patients’ age, Caucasian ethnicity, obesity, and histologic activity index were independently associated with advanced fibrosis (P < 0.05). Only 23% of HCV diabetics achieved SVR compared to 46% of HCV non-diabetics (P = 0.003). DM, genotype 1, high baseline viral load, and African-American ethnicity were independently associated with less SVR (P < 0.05). Significant adverse events were more common in HCV diabetics compared to HCV non-diabetics (P = 0.001). Side effects did not increase in patients receiving PEG IFN/RBV and insulin sensitizers. Conclusion DM was associated with impaired virologic response to PEG IFN/RBV in HCV patients. Adverse events during therapy were more frequent in diabetic compared to non-diabetic HCV patients.     

Direct-Acting Antiviral Therapy Outcomes in Canadian Chronic Hepatitis C Telemedicine Patients

IntroductionMany of the 300,000 HCV-infected Canadians live in under-served and remote areas without access to HCV healthcare specialists. Telemedicine (TM) and advances in HCV management can facilitate linkage of these marginalized patients to healthcare.Materials and MethodsA cohort database analysis was performed on patients followed at The Ottawa Hospital and Regional Viral Hepatitis Program between January 2012 and August 2016. We compared patient characteristics, fibrosis work-up and antiviral treatment outcomes in TM (n = 157) and non-TM (n = 1,130) patients (The Ottawa Hospital Viral Hepatitis Outpatient Clinic) residing in Eastern Ontario.ResultsTM patients were more often infected with genotype 3 (25.9% vs. 16.4%), were more commonly Indigenous (7.0% vs. 2.2%) had a history of injection drug use (70.1% vs. 54.9%) and incarceration (46.5% vs 35.5%). Groups were comparable in age (48.9 years), gender (63.7% male) and cirrhotic stage (24.0%). 59.2% of TM patients underwent transient elastography during regional outreach blitzes compared to 61.8% of non-TM patients (p = 0.54). Overall, half as many TM patients initiated antiviral therapy as non-TM patients (27.4% vs. 53.8%, p < 0.001). The introduction of DAA regimens is bridging this gap (22.2% of TM patients vs. 34.3% of non-TM patients). SVR rates with interferon-free, DAA regimens were 94.7% and 94.8% in TM and non-TM groups (p = 0.99).ConclusionOur TM program engages and retains a population that faces many barriers to effective HCV treatment. TM patients initiated HCV therapy and achieved high SVR rates comparable to those obtained using traditional models of care.     

Recreational Drug and Psychosocial Profile in Chronic Hepatitis C Patients Seeking Antiviral Therapy

Background and aims. Practitioners treating hepatitis C (HCV) provide healthcare to a special population with high rates of substance abuse and psychiatric disorders. We investigated the psychosocial profile in HCV patients and tested what variables affect commencement of antiviral therapy.Material and methods. Recreational drug use (RDU), marijuana (THC), alcohol use, and psychiatric history were initially investigated with a questionnaire prior to history and physical. Following an educational intervention, we reinterrogated patients for RDU and THC use, and revision of initial statement was documented. Variables affecting commencement of antiviral therapy were analysed with logistic regression.Results. Out of 153 patients, 140 (92%) answered the questionnaire. Intervention increased total yield by 6%, however, 39% (11/28) of those initially denying use revised their statement. Drug screening identified 9 more patients with RDU/THC use. Half of patients consuming alcohol were heavy drinkers, and psychiatric disease was identified in 54%. Only 73 (48%) of 139 patients eligible for antivirals received treatment. Multivariable analysis revealed that younger patients (OR = 1.04, 95% CI 1.01-1.08), and those testing positive on drug screen (OR = 0.41, 95% CI 0.19-0.92) were less likely to be treated. Denial by insurance and loss to follow-up were the most common reasons for not starting antiviral treatment.Conclusion. Substance abuse is highly prevalent among HCV patients, and it is difficult to tell prior from current users. Integral care of HCV patients should include a diligent screen for substance abuse and rehabilitation referral, aiming to increase the pool of patients eligible for antiviral therapy. This can only be achieved through a multidisciplinary approach.     

A Polymorphism in the Microsomal Triglyceride Transfer Protein Can Predict the Response to Antiviral Therapy in Egyptian Patients with Chronic Hepatitis C Virus Genotype 4 Infection

Background/Aims

A polymorphism in the microsomal triglyceride transfer protein (MTP) is associated with hepatic fibrosis, and carriers showed higher levels of steatosis, higher levels of hepatitis C virus (HCV) RNA and advanced fibrosis. The aim of this study was to study MTP expression pattern in HCV patients and impact of the MTP polymorphism on the response to antiviral therapy.

Methods

One hundred consecutive naive HCV genotype 4 patients were recruited to receive antiviral therapy, and 40 control subjects were also recruited. Demographic, laboratory, and histopathology data were collected. DNA was isolated, and the samples were subjected to polymerase chain reaction analysis and genotyping for MTP by restriction fragment length polymorphism analysis.

Results

Patients and controls were age- and sex-matched (male/female, 56/44, age, 39.2±7.8 years for patients with HCV; male/female, 18/22, age, 38.1±8.1 years for controls). MTP single nucleotide polymorphisms (SNPs) (GG, GT, TT) and alleles (G, T) in the patients versus the controls were 70%, 21%, 9% & 80.5%, 19.5% versus 10%, 87.5%, 2.5% & 53.8%, 46.3%, respectively (p=0.0001). The sustained viral response (SVR) of the patients was 60%. SNPs in MTP genotypes (GG, GT, and TT) and alleles (G and T) in the responders and nonresponders were 71.7%, 25%, 3.3% & 84.2%, 15.8% versus 67.5%, 15%, 17.5% & 75%, 25% (p=0.038 and p=0.109, respectively). A multivariate analysis showed that the GT genotype was an independent predictor of SVR (area under the curve 90% and p=0.0001).

Conclusions

MTP could be a new predictor for SVR to antiviral therapy in patients with HCV genotype 4 infection.     

Quasispecies as Predictive Response Factors for Antiviral Treatment in Patients with Chronic Hepatitis C

The object of this study was to evaluate the viral factor, especially the quasispecies, as predictive of sustained virologic response. We studied the quasispecies, genotype, viral load, and hepatitis C (HCV) cAg in 41 patients with chronic hepatitis C treated with interferon and in 84 with interferon and ribavirin. In the interferon group, responders presented a lower viral load. From logistic regression analysis of patients treated with interferon plus ribavirin, independent predictors for sustained virologic response were genotype 3a, a low baseline viral load and ≤3 bands quasispecies. Genotype and viral load presented higher specificity and positive predictive value than did quasispecies. In patients with genotype 1, viral load ≤5 × 10⁵ IU/mL and ≤3 quasispecies were predictive for sustained virologic response. In conclusion, the predictive factors of virologic response are genotype, viral load, and quasispecies. Quasispecies did not improve on the genotype or the viral load as predictors of virologic response.     

Occult Hepatitis B Virus Infection in Patients With Chronic Hepatitis C Treated With Antiviral Therapy

Background

Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver and/or in the serum of patients with negative results of hepatitis B s antigen (HBsAg) test with or without serological markers of previous viral exposure. The impact of OBI in patients with chronic hepatitis C (CHC) is still unclear.

Objectives

The Aim of this study was to assess OBI prevalence and its potential implications on treatment outcome in a cohort of patients with CHC underwent standard antiviral therapy.

Patients and Methods

Baseline serum samples from 137 HBsAg-negative CHC patients treated with pegylated-interferon and ribavirin (73 Responders/74 Non Responders),were retrospectively analyzed for HBV status.

Results

Seventy-three patients (53.3%) showed markers of previous exposure to HBV. HBV DNA was detected in 2 of 137 serum samples (1.5%), both carrying HBV antibodies. Liver biopsies and post-therapy sera were available for 35 patients (12 Responders/23 Non Responders). HBV DNA sequences were found in 13 of 35 specimens (37.1%), all of patients with HBV DNA negativity in basal and post-therapy serum samples. Among OBI-positive patients, 5 (38.5%) carried serological markers of HBV infection. Regarding therapy outcome, in the OBI-positive group there were 5 of 13 (38.5%) sustained virological responders (SVR) compared to 7 of 22 (31.8%) in the OBI-negative one.

Conclusions

Despite the high prevalence rate of liver HBV DNA in patients with CHC, SVR was not affected by occult HBV infection.     

Utilization and Antiviral Therapy in Patients with Chronic Hepatitis C: Analysis of Ambulatory Care Visits in the US

Background  

Studies on mostly veterans found the majority of chronic hepatitis C (CHC) patients were not treated. Little information exists on a broad-based population.     

A Review on Extrahepatic Manifestations of Chronic Hepatitis C Virus Infection and the Impact of Direct-Acting Antiviral Therapy

Extrahepatic manifestations are a feature of chronic hepatitis C virus (HCV) infection. In the course of chronic HCV infection, about 70% of patients have one or more extrahepatic manifestations. The latter are often the first and only clinical sign of infection. Experimental and clinical data support a causal association for many extrahepatic manifestations and HCV infection, which include mixed cryoglobulinemia, non-Hodgkin lymphomas (NHL), cardiovascular disease, insulin resistance, type 2 diabetes, neurological and psychiatric disease and other rheumatic diseases. All these extrahepatic conditions influence the morbidity, quality of life and mortality of HCV-infected patients. Currently, interferon-free therapeutic regimens with direct-acting antiviral agents (DAA) offer the possibility of treatment to almost the entire infected population, irrespective of stage of cirrhosis and associated serious comorbidities, always maintaining a high efficacy and tolerability. Several studies have shown a close association between HCV clearance by DAAs and an improvement or reduction in the risk of extrahepatic manifestations. Patients with HCV after a sustained virologic response (SVR) by DAA treatment have a lower risk than non-responders of developing cryoglobulinemic vasculitis and B-cell non-Hodgkin’s lymphomas. Furthermore, the SVR by DAA also reduces the risk of acute coronary syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, and it improves atherosclerosis. HCV clearance by DAA also improves the quality of life and survival of patients with chronic HCV infection with associated extrahepatic diseases. Thus, DAAs should be initiated as early as possible in HCV patients with extrahepatic manifestations.     

Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

Background/AimsThis study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence.MethodsA total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results.ResultsAmong the 100 patients, 88% achieved a sustained virological response (SVR) 12 weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR 3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively).ConclusionsDAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy. (Gut Liver 2021;15-419)     

Fas Antigen Expression on Hepatocytes Predicts the Short- and Long-term Response to Interferon Therapy in Patients with Chronic Hepatitis C

Background: Interaction between Fas antigen on hepatocytes and Fas ligand on cytotoxic T cells induces apoptosis, a major mechanism of hepatitis C virus (HCV)-induced hepatocyte injury. We investigated the usefulness of Fas expression on hepatocytes as a predictor of short- and long-term response to interferon (IFN) therapy in 72 patients with chronic hepatitis C. Methods: