IL28B rs12979860 polymorphism and zinc supplementation affect treatment outcome and liver fibrosis after direct-acting antiviral hepatitis C therapy.

BACKGROUND: Impact of interleukin 28B (IL28B) rs12979860 polymorphism on response to direct-acting antivirals agents in HCV genotype 4-infected patients is under investigation. Zinc may have an advantage in improvement of liver damage and treatment outcome. We aimed to evaluate IL28B polymorphism and zinc administration impact on patient response to treatment and amelioration of liver fibrosis. RESULTS: Three hundred patients on anti-HCV treatments were equally categorized into patients treated with dual therapy (sofosbuvir/ribavirin) for 24 weeks, triple therapy (sofosbuvir/ribavirin+pegylated interferon-alpha) for 12 weeks, dual therapy plus oral zinc and with triple therapy plus oral zinc. All patients were genotyped for IL28B. Sustained virologic response (SVR) was achieved in 100% of patients with CC genotypes while 15.5% of CT/TT carriers did not attain SVR. After treatment, patients with CC genotype showed improvement in liver-related parameters compared with CT/TT genotypes. Zinc supplementation was associated with improved SVR in CT/TT genotypes and liver parameters in both CC and CT/TT genotypes. Hepatic fibrosis was improved in higher percent of CC genotype (16.7%) compared with CT/TT genotypes (5.8%). Interestingly with zinc administration, improved fibrosis increased to 60.9% in CC genotype vs. 15.4% in CT/TT genotypes. CONCLUSION: Absolute SVR rates in patients with IL28B CC genotype support their selection for shorter treatment duration and therefore associated with high economic value. IL28B polymorphism is associated with improvement of hepatic functions and fibrosis after antiviral treatments. Zinc is powerful supplement not only to increase SVR in non-responders but also to improve hepatic functions and fibrosis.

Influence of virologic response on disease progression in patients with compensated hepatitis B cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of sustained virologic response on disease progression and the development of hepatocellular carcinoma (HCC) in patients with compensated hepatitis B cirrhosis receiving antiviral therapy with nucleos(t)ide analogues (NAs). MethodsA total of 542 patients with compensated hepatitis B cirrhosis who attended Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 1 to December 31, 2013, received antiviral therapy, and were followed up for more than 5 years were enrolled, and according to the status of virologic response during follow-up, they were divided into a sustained virologic response cohort with 496 cases and a non-sustained virologic response cohort with 46 cases. With disease progression as the outcome event, general information and examination data were collected during the 5-year follow-up period. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was performed; relative risk and 95% confidence interval (CI) were used to investigate the degree of correlation of factors measured with the progression of liver cirrhosis. The life-table method was used to calculate the 1-, 3-, and 5-year progression-free survival rates, and the Kaplan-Meier method was used to plot survival curves; the log-rank test was used for univariate analysis, and the Cox regression model was used for multivariate regression analysis. ResultsFor the 542 patients, the mean progression-free survival time was 62.50 months (95% CI: 61.01-63.92), and the 1-, 3-, and 5-year progression-free survival rates were 94%, 82%, and 71%, respectively. The sustained virologic response cohort had a significantly longer mean progression-free survival time than the non-sustained virologic response cohort ［63.10 months (95% CI: 61.65-64.55) vs 55.95 months (95% CI: 50.19-61.71), χ2=12.058, P=0.001］. Compared with the non-sustained virologic response cohort, the sustained virologic response cohort had significantly lower 5-year cumulative incidence rate of HCC than (20.6% vs 34.8%, χ2=5.759, P=0.016) and 5-year cumulative incidence rate of decompensated cirrhosis (5.0% vs 15.2%, χ2=8.239, P=0.004). Virologic response was an independent risk factor for disease progression (hazard ratio=232, 95% CI: 1.45-3.72). ConclusionSustained virologic response can reduce the incidence rates of complications and HCC, improve long-term prognosis, and prolong survival time in patients with compensated hepatitis B cirrhosis.

Glycemic Control after Initiating Direct-Acting Antiviral Agents in Patients with Hepatitis C Virus and Type 2 Diabetes Mellitus Using the United States Integrated Healthcare System.

OBJECTIVE: Hepatitis C virus (HCV) has an increased risk of Type 2 diabetes mellitus (T2DM). Prior studies found that the eradication of HCV with direct-acting antiviral (DAA) agents led to improved glycemic control in patients with T2DM. We aimed to identify the association between HCV eradication and glycemic control in patients diagnosed with HCV and T2DM. METHODS: A retrospective observational study was conducted to identify adult patients diagnosed with HCV from January 1, 2014, to August 31, 2017. Patients were included if they were initiated on one of the following DAA agents within the study period: Sofosbuvir/velpatasvir, sofosbuvir/ledispavir, elbasvir/grazopevir. Patients were also required to have the diagnosis of T2DM. The primary outcome of this study was the average change in glycosylated hemoglobin (HbA1c) pre- versus post-DAA agents. FINDINGS: Our final cohort consisted of 996 patients diagnosed with HCV and T2DM: Patients who achieved sustained virologic response (SVR) (n = 937, 94%) and those who did not achieve SVR (n = 59, 6%). In the SVR group, there was a 0.3950% reduction in HbA1c (P < 0.0001) and in those who did not achieve SVR group, there was 0.3532% reduction in HbA1c (P = 0.0051). In the overall study population, SVR group had 0.04% more reduction in HbA1c but was not statistically significant (P = 0.7441). CONCLUSION: Both groups had statistically significant reductions in HbA1c when comparing the mean change in average HbA1c pre-versus post-DAA agent. Patients who achieved SVR had a greater absolute reduction in HbA1c by 0.04%; however, this was not statistically significant.

Outcomes of Direct-Acting Antiviral Treatment of Psychiatric Patients with Comorbid Hepatitis C Virus Infection.

BACKGROUND: The highest burden of hepatitis C virus (HCV) infection is seen in patients with psychiatric disorders who have been excluded from traditional treatments with Interferon due to treatment-emergent neuropsychiatric adverse effects. The goal of this study is to determine the tolerability, treatment retention, and efficacy of direct-acting antivirals with psychiatric disorders and comorbid substance use disorders in real-life settings. METHODS: This is a retrospective cohort observational study of HCV patients treated with direct-acting antivirals between January 2016 and December 2018. Patients were stratified and sub-stratified based on their psychiatric diagnosis and substance use. The primary assessment was the sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS: Among the 291 patients analyzed, patients with psychiatric diagnosis and non-psychiatric patients made up 51.2% (n = 149) and 48.8% (n = 142) respectively. Majority of the patients included in the study were African-Americans (68.7%, n = 200). Overall, 95.3% (142/149) and 94.4% (134/142) of psychiatric and non-psychiatric patients, respectively, achieved SVR12 and treatment response was similar between the groups (p = 0.72). Among psychiatric patients, only the prior treatment status was identified as a predictor of treatment response (OR 0.153, 95% CI 0.03-0.79; p = 0.05). No statistical difference was observed among the patients with SVR12 based on their primary psychiatric diagnoses or by comorbid substance abuse. CONCLUSION: The results of our study show that direct-acting antiviral treatments are well tolerated in psychiatric patients, and an overwhelming majority of patients achieved SVR12. Our study highlights the need to integrate HCV screening with treatment linkage in psychiatry and primary care practice.

Effects of vitamin D supplements in patients with chronic hepatitis C: a randomized, multi-center, open label study.

BACKGROUND/AIMS: We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC). METHODS: Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). RESULTS: One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverse effects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). CONCLUSION: Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.

Sustained virologic response with 6 weeks or less of direct-acting antiviral therapy for chronic hepatitis C: Experience at a veterans affairs healthcare system.

BACKGROUND AND AIM: Duration of treatment for chronic hepatitis C infection has been shortened since the introduction of highly effective direct-acting antivirals (DAAs). Presented is our experience in successful treatment of veterans with chronic hepatitis C infection, with a shorter than currently recommended duration of therapy. METHODS: Retrospective chart review of veterans with chronic hepatitis C infection who received more than 1 week and up to 6 weeks (8-42 days) of DAA therapy with the initiation day between January 1, 2015, and October 15, 2018, at Bay Pines Veterans Affairs Healthcare System. Successful treatment was defined by a sustained virologic response at 12 weeks (SVR-12) since the end of treatment. RESULTS: Of the 1841 veterans treated, 27 met the criteria for this review. Overall, SVR-12 was achieved in 92.6% of veterans treated for a duration of more than 1 week and up to 6 weeks. Amongst those who completed only 4 weeks of therapy, 93.3% achieved SVR-12. All four veterans (100%) treated for a duration of more than 4 weeks and up to 6 weeks achieved SVR-12. CONCLUSIONS: Amongst the chronically infected hepatitis C population, a subpopulation who could achieve SVR with a shorter course of treatment than currently recommended does exist. A prospective study of a larger scale will likely provide helpful data in this regard. Our findings could be an impetus for further work.

Integrating comprehensive hepatitis C virus care within a residential substance use disorder treatment program.

BACKGROUND AND AIMS: Although central to the hepatitis C virus (HCV) epidemic, many patients with both substance use disorders (SUD) and HCV have difficultly engaging in treatment for either condition. To facilitate HCV care in Veterans with active SUD, a comprehensive HCV screening, education, referral, and treatment program was integrated into a VA residential SUD treatment program. METHODS: Evaluation of HCV screening, education, referral, and treatment initiative among admissions to a residential SUD treatment program from December 2014 to April 2018. RESULTS: To date, 97.49% (582/597) of admissions to the program have been screened for HCV infection, with 12.71% (74/582) of the cases confirmed HCV-positive, and 100% (74/74) of the positive cases being connected or re-connected to the infectious disease clinic for further evaluation and, if appropriate, to begin HCV pharmacotherapy. Importantly, 18.92% (14/74) of the HCV-positive cases were newly diagnosed and would have likely gone undetected without this program. Of the HCV-positive cases, 78.38% (58/74) have received pharmacotherapy, with a sustained virologic response rate of 82.76% (48/58). CONCLUSIONS: Integrating comprehensive HCV care within a residential SUD treatment program using a collaborative care model can substantially increase the detection of previously undiagnosed infections, facilitate linkage to care, and promote HCV treatment uptake among HCV-infected Veterans with SUD.

Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia.

INTRODUCTION: In the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes. PATIENTS AND METHODS: This is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014-2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed. RESULTS: All patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose. CONCLUSION: HCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.

Early Successes in an Open Access, Provincially Funded Hepatitis C Treatment Program in Prince Edward Island.

INTRODUCTION: The availability of curative hepatitis C therapies has created an opportunity to improve treatment delivery and access. Local providers, government, industry, and community groups in Prince Edward Island developed an innovative province-wide care model. Our goal was to describe the first year of program implementation. MATERIAL AND METHODS: Using a communitybased prospective observational study design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded in a database. Primary analysis assessed the time from referral to assessment/treatment, as well as the number of referrals, assessments, and treatment initiations. Secondary objectives included: (1) treatment effectiveness using intention-to-treat analysis; and (2) patient treatment experience assessed using demographics, adverse events, and medication adherence. RESULTS: During the study period 242 referrals were received, 123 patients were seen for intake assessments, and 93 initiated direct-acting antiviral therapy based on medical need. This is compared to 4 treatment initiations in the previous 2 years. The median time from assessment to treatment initiation was 3 weeks. Eighty-two of 84 (97.6%, 95% CI 91.7 - 99.7%) patients for whom outcome data were available achieved sustained virologic response at 12 weeks post-treatment; 1 was lost to follow-up and 1 died from an unrelated event. In the voluntary registry, 39.7% of patients reported missed treatment doses. CONCLUSION: In conclusion, results from the first 12 months of this multi-phase hepatitis C elimination strategy demonstrate improved access to treatment, and high rates of safe engagement and cure for patients living with chronic hepatitis C genotype 1 infections.

25-Vitamin D levels in chronic hepatitis C infection: association with cirrhosis and sustained virologic response.

BACKGROUND: Low serum 25-Vitamin D levels are associated with advanced fibrosis in hepatitis C infection. Vitamin D supplementation has been hypothesized to augment response rates to interferon-based therapy. To date, no investigation has evaluated vitamin D levels during direct-acting antiviral therapy. We aimed to evaluate the prevalence of vitamin D deficiency in cirrhotic and non-cirrhotic cohorts, the predictive value of pretreatment levels for a sustained virologic response, and the changes in 25-OH vitamin D levels during direct-acting antiviral therapy. METHODS: Two hundred eighteen patients with chronic hepatitis C who completed direct-acting antiviral therapy were consecutively enrolled. Vitamin D levels were measured using chemiluminescence immunoassay, prior to initiation and at completion of therapy. Advanced liver fibrosis (cirrhosis) was determined by biopsy, FibroSURE blood test, or imaging. RESULTS: A sustained virologic response was achieved in 79% (n=172) of patients, with 19% (n=44) relapsing. A total of 123 (56.4%) patients were cirrhotic. The prevalence of Vitamin D deficiency (10-20 ng/mL) and severe deficiency (<10 ng/mL) was significantly higher in cirrhotic patients (P=0.04). Pre-treatment vitamin D levels in cirrhotic patients were negatively correlated with Model for End-Stage Liver Disease score, total bilirubin and INR (P<0.05). Neither pretreatment vitamin D level nor the change during therapy was associated with an increased rate of sustained virologic response. CONCLUSIONS: The prevalence of vitamin D deficiency is higher in hepatitis-C-related cirrhotic cohorts compared to non-cirrhotic patients and correlates with components of hepatic function. Neither pretreatment vitamin D level nor the change during therapy was associated with an increased rate of sustained virologic response.