A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome

Treatment of Chronic Hepatitis C with High Dose Interferon Therapy Experience From Pertamina Central Hospital Jakarta

Background: Until several years ago, interferon alfa was the only drug with proven benefit for the treatment of chronic Hepatitis C. Several therapy categories such as fixed-dose regimens, induction-dose regimens and escalation-dose regimens are already known. With standard dose interferon therapy of 3 MU, TIW for 6 months, a sustained response rate can ve achieved in only 10-20% of patients. This study reports the Results of treatment of chronic Hepatitis C with high dose interferon therapy of 6 MU, TIW for 6 months. Methods: From February 1996 to February 1998, 15 patients with Hepatitis C were treated with interferon alfa-2b 6 MU, TIW for 6 months. Ultrasound-guided liver-biopsy was performed using the Menghini-Technique (Hepafix). Virological and biochemical responses were assessed at the end of the treatment period at week 24 and at the end of follow-up period at week 48 and up to 2 years later. Virological and biochemical sustained responses were defined as the absence of HCV-RNA, and SGPT concentration within the normal range at both weeks 24 and 48. Histological response was assessed after the end of treatment. Side-effects were observed and noted. Results: Ten out of 15 patients (66.7%) were HCV-RNA negative and 11 out of 15 patients (73.3%) demonstrated ALT within the normal range at week 24. At the end of the follow-up, from week 48 until 2 years later, HCV-RNA negative and normal ALT were found in 6 patients (40%). Histological improvement was found in 4 out of 6 patients. Fever was the most common side-effect and was found in 13 patients, while fatigue was found in 12 patients, myalgia in 11, headache in 10, and anorexia in 11 patients. Conclusion: High dose interferon alfa-2b therapy for the treatment of chronic Hepatitis C can improve the rate of sustained response, but is associated with more side-effects

Raised serum transaminases during treatment with pegylated interferon for chronic hepatiti C

Introduction : Serum transaminases rose significantly in 7 patients with chronic hepatitis C, genotypes 2 and 3, who were treated with pegylated interferon and ribavirin. Methods : 219 patients with chronic hepatitis C, genotypes 2 and 3, were treated between 2005 and 2011 following the same protocol. For the 7 patients presented in this paper, the initial liver screen revealed chronic hepatitis C infection only. The same liver screen was repeated following the transaminase rise during the treatment period and failed to reveal additional comorbidity. Results : 5 male and 2 female patients with chronic hepatitis C experienced a rise in serum transaminases after commencement on treatment with pegylated interferon and ribavirin. They all achieved rapid and end of treatment virological responses. 3 of the patients achieved sustained virological response and 4 relapsed. There was no evidence to suggest that steatosis, development of autoimmunity or intercurrent illness was the cause of the liver injury. In 3 out of 7 patients, the level of transaminases exhibited a downward trend after pegylated interferon was changed to non pegylated interferon. Additionally, it is evident that in those patients whose treatment was temporarily or permanently aborted, the rise in transaminases rapidly improved and returned to baseline. Conclusion : Our experience suggests the possibility of a toxic reaction to polyethylene glycol in a small number of patients being treated with pegylated interferon, resulting in an acute hepatitic response which resolved when therapy was stopped or switched to non-pegylated interferon

Antioxidant status and glutathione metabolism in peripheral blood mononuclear cells from patients with chronic hepatitis C

BACKGROUND/AIMS: Oxidative stress could play a role in the pathogenesis of hepatitis C virus infection. We investigated the oxidant/antioxidant status in peripheral blood mononuclear cells from patients with chronic hepatitis C and controls. METHODS/RESULTS: Lipid peroxidation products and superoxide dismutase activity in peripheral blood mononuclear cells were higher in chronic hepatitis C patients than in healthy subjects while glutathione S-transferase activity was reduced in patients as compared to controls. Catalase, glutathione peroxidase and glutathione reductase were similar in chronic hepatitis C and normal individuals. No statistically significant differences were found between patients and controls with regard to glutathione levels in peripheral blood mononuclear cells, but 35% of patients with chronic hepatitis C showed values of glutathione and oxidized glutathione which were below and above, respectively, the limits of normal controls. Finally, the glutathione synthetic capacity of the cytosol of peripheral blood mononuclear cells was significantly higher in patients than in controls, indicating increased glutathione turnover in lymphocytes from patients with chronic hepatitis C. CONCLUSIONS: Oxidative stress is observed in peripheral blood mononuclear cells from chronic hepatitis C patients. This process might alter lymphocyte function and facilitate the chronicity of the infection

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C

Background Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C

Chronic Hepatitis C

The goal of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection is to attain a sustained virologic response (SVR), which is defined as undetectable serum HCV-RNA levels at 6 months after the cessation of treatment. Major improvements in antiviral therapy for chronic hepatitis C have occurred in the past decade. The addition of ribavirin to interferon-alfa therapy and the introduction of pegylated interferon (PEG-IFN) have substantially improved SVR rates in patients with chronic hepatitis C. The optimization of HCV therapy with PEG-IFN and ribavirin continues to evolve. Studies are ongoing that use viral kinetics to tailor therapy to an individual's antiviral response and determine the ideal length of treatment to maximize the chance of SVR. Improved SVR can be achieved with new specific inhibitors that target the HCV NS3/4A protease and the NS5B polymerase. Several long-term follow-up studies have shown that SVR, when achieved, is associated with a very low risk of virologic relapse. Furthermore, antiviral therapy can reduce the morbidity and mortality rates associated with chronic hepatitis C by reducing fibrosis progression, the incidence of cirrhosis, and hepatocellular carcinoma

Hepatitis C and Kidney Disease

Multiple extrahepatic manifestations have been associated with chronic hepatitis C, the most important among them being cryoglobulinemia, glomerulonephritis, porphyria cutanea tarda, lichen planus, seronegative arthritis, and lymphoproliferative disorders as in the sudies of Bonkovsky and Mehta (2001) and El-Serag et al. (2002). We will discuss in this paper chronic hepatitis C- related kidney disease and course and management of patients with chronic hepatitis C in special circumstances like hemodialysis and kidney transplantation

Hepatitis C prevalence in Denmark -an estimate based on multiple national registers

Background: A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare. Methods: Patients with a diagnosis of chronic hepatitis C were identified from four national registers: a laboratory register, the Hospital Discharge Register, a clinical database of chronic viral hepatitis and the Register of Communicable Diseases. The total population diagnosed with hepatitis C was estimated by capture-recapture analysis. The population with undiagnosed hepatitis C was derived from the national register of drug users by comparing diagnosed and tested persons. Results: A total of 6,935 patients diagnosed with chronic hepatitis C were identified in the four registers and the estimated population diagnosed with the disease was 9,166 persons (95% C.I. interval 8,973 – 9,877), corresponding to 0.21% (95% CI 0.21%-0.23%) of the Danish population over 15years of age. The prevalence was highest among persons 40–49years old (0.39%) and males (0.28%). It was estimated that 40% of the diagnosed patients lived in the capital region, and 33.5% had attended specialised healthcare. It was estimated that 46% of hepatitis C patients had not been diagnosed and the total population with chronic hepatitis C in Denmark was 16,888 (95% C.I. 16,474-18,287), corresponding to 0.38% (95% CI 0.37-0.42) of the population over 15years of age. Conclusions: The estimated prevalence of chronic hepatitis C in Denmark was 0.38%. Less than half of the patients with chronic hepatitis C in Denmark have been identified and among these patients, one in three has attended specialised care

Treatment of chronic hepatitis C genotype 1 with triple therapy comprising telaprevir or boceprevir.

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. Two first-generation protease inhibitors, telaprevir and boceprevir, have recently been approved for the treatment of chronic hepatitis C genotype 1. Triple therapy comprising pegylated interferon-α, ribavirin and telaprevir or boceprevir increases sustained virological response rates to ~70% and allows to shorten treatment duration in ~½ of treatment-naïve patients with chronic hepatitis C genotype 1. Sustained virological response rates in treatment-experienced patients depend on the response to previous treatment, ranging from &gt;80% in previous relapsers to ~30% in previous null responders. These advances come at the expense of new adverse effects and increased cost. In addition, treatment of chronic hepatitis C will become more complex. In these times of changing medical practice, the present expert opinion statement by the Swiss Association for the Study of the Liver shall provide guidance on the treatment of chronic hepatitis C with triple therapy comprising telaprevir or boceprevir

Relation of IL28B Gene Polymorphism with Biochemical and Histological Features in Hepatitis C Virus-Induced Liver Disease

BACKGROUND/AIMS: Polymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV-induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma. METHODS: We have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma. The distribution of the analysed SNP in hepatocellular carcinoma patients was compared with that found in untreated chronic hepatitis C patients. All patients were white and most were Spaniards. RESULTS: In multivariate analysis ALT values were higher (P = 0.001) and GGT values were lower (P<0.001) in chronic hepatitis C patients homozygotes for the major rs12979860C allele as compared with carriers of the mutated rs12979860T allele. Steatosis was more frequent (Odds ratio = 1.764, 95% C.I. 1.053-2.955) and severe (P = 0.026) in carriers of the rs12979860T allele. No relation was found between the analysed SNP and METAVIR scores for necroinflammation and fibrosis, and there were no differences in the distribution of the analysed SNP between hepatocellular carcinoma and untreated chronic hepatitis C patients. CONCLUSION: The IL28B rs12979860 polymorphism correlates with the biochemical activity and the presence and severity of liver steatosis in chronic hepatitis C