Interleukin-28b CC genotype predicts early treatment response and CT/TT genotypes predicts non-response in patients infected with HCV genotype 3.

Response to antiviral therapy for hepatitis C virus (HCV) depends upon the genotype and host immune response. IL28b gene mutations have been shown to modulate host antiviral immune response against genotype 1. However, the predictive value of IL28b polymorphism in genotype 3 HCV patients is largely unknown. The association of IL28b polymorphism with virological response was studied in 356 patients with genotype 3 chronic HCV undergoing treatment with peg-interferon and ribavirin and was compared with matched controls. IL28b genotyping followed by DNA sequencing was performed to identify the CC, CT, or TT genotypes. Two log reduction of HCV RNA at Day 7 (Quick Viral Response, QVR) and HCV RNA negativity at Day 28 (Rapid Viral Response, RVR) were analyzed with CC and non-CC genotypes in addition to other predictors of response. The associations of alleles with the response patterns were predicted. Sustained viral response was seen in 250 (70.2%) patients and the IL28b genotype CC/CT/TT distribution was 61.1%; 30.5%; and 8.4%, respectively. The non-CC genotypes were significantly higher in non-responders when compared to responders (67.6% vs. 38.9%, P < 0.001). Interestingly, the rapid viral response in responders was observed in 72.7% with the CC genotype and in 27.2% with the non-CC genotype (P < 0.001). Multivariate analysis showed CC genotype as an independent factor predicting the sustained viral response in patients infected with HCV genotype 3. In conclusion, the IL28b CT/TT genotype strongly correlates with treatment non-response in patients infected with HCV genotype 3 and CC genotype of IL28b is associated with higher quick viral response.

Comparison of low-dose pegylated interferon versus standard high-dose pegylated interferon in combination with ribavirin in patients with chronic hepatitis C with genotype 3: an Indian experience.

BACKGROUND AND AIMS: In chronic hepatitis C virus (HCV) infection with genotype 3, therapy with pegylated interferon (peg-IFN) alfa-2b in a dose of 1.5 mug/kg/week and ribavirin (800-1000 mg/day) is recommended for 24 weeks. Reduced doses of peg-IFN may increase compliance and decrease cost and adverse events. This study aimed to assess the safety and efficacy of two different regimens of peg-IFN alfa-2b, in combination with ribavirin, in genotype 3 patients. METHODS: A total of 103 liver biopsy-proven chronic HCV patients with genotype 3, having alanine aminotransferase levels >1.2 x ULN and positive HCV-RNA were randomized into two groups: group I (n = 76; age, 43.1 +/- 11.4 years; male/female, 67/9) received peg-IFN 1.0 mug/kg/week + ribavirin 10.6 mg/kg/day, while group II (n = 27; age, 37.3 +/- 11.6 years; male/female, 21/6) received peg-IFN 1.5 microg/kg/week + ribavirin 10.6 mg/kg/day. Patients in both groups were treated for 24 weeks. End of treatment viral response (ETVR) and sustained viral response (SVR) after a 6-month follow-up period were assessed. RESULTS: In both groups I and II, one patient was lost to follow-up, while one patient in group II withdrew due to side-effects. ETVR was seen in 72/76 (94.7%) of patients in the low dose group and 24/27 (88.9%) of patients in the high dose group (P = 0.375). SVR was seen in 60/76 (78.9%) of patients in the low dose group and 25/27 (92.6%) of patients in the high dose group (P = 0.145). Age (Pearson correlation coefficient = 0.263; P = 0.008) and fibrosis (correlation coefficient, 0.263; P = 0.008) showed a significant correlation with the SVR. CONCLUSION: In patients with genotype 3, peg-IFN at 1.0 microg/kg/week with ribavirin is as effective as peg-IFN at 1.5 mug/kg/week with ribavirin.

Combination of pegylated interferon and lamivudine for patients with chronic hepatitis B who have failed treatment.

BACKGROUND: Treatment of chronic hepatitis B (CHB) alone with interferon or lamivudine alone or in combination is effective in only a small proportion of patients. Treatment of patients in whom antiviral therapy fails is challenging. This study was made to determine the efficacy of combined pegylated interferon alpha (peg-IFN) and lamivudine in patients with CHB who had failed to respond to antiviral treatment. METHODS: Twenty patients with CHB proven by liver biopsy, with ALT levels >1.5 X ULN, HBV DNA levels>141,500 copies/ml, and previous treatment failure with an adequate regimen were treated with a combination of peg-IFN 1.5 microg/kg and lamivudine 100 mg/day for 52 weeks and followed up for a further 24 weeks. Biochemical response was defined as normalization of ALT and DNA response as HBV DNA<141,500 copies/ml. Secondary efficacy measures included HBsAg loss, HBeAg loss and appearance of anti-HBe (in cases of HBeAg-positive patients). RESULTS: Twenty patients were treated, of whom 16 were HBeAg positive. At 52 weeks, normal ALT was seen in 10 (50%) (8 of 16 HBeAg+ and 2 of 4 HBeAg-), HBV DNA response in 5 (25%) (5 of 16 in HBeAg+ and none in HBeAg-), and HBeAg loss with appearance of anti-HBe in 5 (31.3%) of the 16 HBeAg positive patients. At 76 weeks, 8 (80%) of the 10 patients with normal ALT at 52 weeks relapsed, with normal ALT only in 2 (10%) (1 of 16 HBeAg+ and 1 of 4 HBeAg-), and all 5 patients who had a DNA response at 52 weeks relapsed at 76 weeks and had no DNA response. HBeAg loss with appearance of anti-HBe was seen in 1 (6.3%) of 16 HBeAg-positive patients. None of the patients lost HBsAg. CONCLUSIONS: The combination of peg-IFN and lamivudine for 52 weeks is not effective for treatment of CHB patients with a failed treatment. New treatment strategies need to be developed.

Treatment of chronic hepatitis C with pegylated interferon plus ribavirin in treatment-naïve 'real-life' patients in India.

PURPOSE/AIM: Results of treatment of chronic hepatitis C (CHC) with pegylated interferon plus ribavirin (PEG-RBV) are mainly available from well-designed clinical trials, and only few 'real-life' studies which give a true picture of success of therapy are available. Such data in Indian patients is scarce. This prospective study aimed to evaluate the efficacy, safety, and factors associated with sustained virological response (SVR) in Indian CHC patients treated with PEG-RBV in 'real-life' setting. MATERIAL AND METHODS: All treatment-naïve patients with CHC/compensated cirrhosis treated with PEG-RBV between January 2004 and December 2010 were included. RESULTS: Of 592 patients started on treatment, 524 (88.5 %) completed therapy (mean ± SD age-42.0 ± 12.1 years; 74.3 % males). Genotype 3 (73.6 %) was the commonest, followed by genotype 1 (19.3 %). In intention to treat analysis, SVR rates for 'all' patients, genotype 1 and genotype 3 patients were 72.3 % (428/592), 57 % (65/114), and 78.2 % (341/436), respectively (in per-protocol analysis-81.7 %, 69.1 %, and 85.3 %, respectively). Noncirrhotics had better SVR rates compared to cirrhotics treated for the same duration. About 20 % patients had both low viral load and achieved rapid virological response (RVR). Factors significantly associated with SVR were age <40 years, absence of cirrhosis, RVR, and no reduction in interferon dose. CONCLUSION: SVR rates in CHC patients treated in 'real-life' setting in India were better than those reported in western population. Therapy should be prolonged for patients with cirrhosis, while one-fifth of patients may qualify for abbreviated therapy. Factors significantly associated with SVR were age <40 years, absence of cirrhosis, RVR, and no reduction in interferon dose.

Prevalence of hepatitis C virus in a selected geographical area of northern India: a population based survey.

BACKGROUND AND AIM: Epidemiological data on hepatitis C virus (HCV) infection from India are scanty. We conducted a population-based seroepidemiologic survey to estimate the prevalence of hepatitis C in Punjab state of northern India. METHODS: A house-to-house survey was conducted in a defined population of 26,273 subjects. Information was gathered according to a predesigned questionnaire with socio-demographic characteristics (age, gender and substance abuse), family history of HCV infection, general health status, associated co-infection, immunization history and potential risk factors for HCV transmission. At the time of clinical evaluation, blood was tested for anti-HCV and those found positive were tested for HCV RNA. RESULTS: Among 5,258 subjects screened, 272 were found to be anti-HCV positive (prevalence rate of 5.2 %); highest prevalence being noticed in 41-60 years age group. Anti-HCV positive rate were not different among males and females. Sixty-seven subjects (1.3 %) were found to be HBsAg positive; four of these being co-infected (5.9 %). Various risk factors for acquiring HCV infection identified were history of surgery, dental treatment and unprotected sex. Other associations were strong family history of HCV positivity, alcohol consumption and diabetes mellitus. CONCLUSION: Chronic HCV infection is a major health problem in Punjab; it appears to be more common than HBV infection. Exercising safe health care related procedures should be emphasized in our country as main modes of transmission of infection identified were related to these.