A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan.
ABSTRACT The long-term benefit for chronic hepatitis C (CHC) patients treated with interferon (IFN)/ribavirin (RBV) combination therapy remains unclear. We aimed to evaluate the long-term effects of IFN monotherapy and IFN/RBV combination therapy on reducing hepatocellular carcinoma (HCC) and mortality in patients with chronic hepatitis C virus (HCV) infection, adjusting for risk factors.
A total of 1,619 patients with biopsy-proven CHC, including 1,057 receiving IFN-based therapy (760 on IFN/RBV combination therapy) and 562 untreated controls from three medical centres and one regional core hospital in Taiwan were enrolled in this retrospective-prospective cohort study.
The incidence of HCC and survival during a follow-up period of 1.0-15.3 (mean 5.18) and 1-16 (mean 5.15) years in treated and untreated patients, respectively, was analysed using Cox proportional hazards regression. The cumulative incidence of HCC was 35.2% and 12.2% for untreated and treated groups, respectively (P=0.0013). The cumulative survival rate was 93.1% and 96.2% for untreated and treated groups, respectively (P=0.3928). Significantly lower incidences of HCC and mortality were observed in sustained virological responders (both for IFN monotherapy and IFN/RBV combination) but not in nonresponders when compared with untreated patients. HCV genotype 1 patients had significantly higher incidences of HCC than genotype non-1 patients. In multivariate analysis, pre-existing cirrhosis, non-response, HCV genotype-1 and age were associated with HCC; pre-existing cirrhosis and non-response correlated to mortality.
A sustained virological response secondary to IFN monotherapy or IFN/RBV combination therapy could reduce the risk for HCC and improve survival of CHC patients.
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ABSTRACT: Background& Aims Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR. Methods A total of 642 patients with an SVR after peginterferon/ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6–133 months). Results Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI. 2.32-10.71, P<0.001), followed by age (HR 1.06, 95% CI. 1.02-1.11, P=0.005) and r-GT levels (HR 1.008, 95% CI. 1.004-1.013, P<0.001). The incidence of HCC did not differ between patients with high and low baseline r-GT levels among patients with cirrhosis (P=0.53), but the incidence of HCC was significantly higher in non-cirrhotic patients with high r-GT levels compared with those with low r-GT levels (P=0.001). Cox regression analysis revealed that the strongest factors associated with HCC development in non-cirrhotic sustained responders were baseline r-GT levels (HR 6.44, 95% CI. 2.20-18.89, P=0.001) and age (HR 3.68, 95% CI. 1.33-10.17, P=0.012). The incidence of HCC was not different between older non-cirrhotic patients with high r-GT levels and cirrhotic patients (P=0.34). Conclusions HCC remains a threat in non-cirrhotic patients with an SVR. Serum r-GT levels helped to identify potential patients at high risk.Journal of Hepatology 07/2014; DOI:10.1016/j.jhep.2014.02.022 · 10.40 Impact Factor
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ABSTRACT: Accuracy for monitoring of the concentration of hepatitis C virus (HCV) RNA represents a major challenge throughout the management of patients with chronic hepatitis C. To investigate the genotype-independent efficiency and the accuracy of two real-time detection reverse transcription-polymerase chain reaction (RT-PCR) assays; the Cobas Ampliprep/Cobas TaqMan (CAP/CTM); and the Abbott RealTime HCV (ART), a total of 184 samples with different HCV subtypes were examined; 1b (n=58), 2a (n=39), 2b (n=26), 3a (n=20), and 4 (n=41). A robust linear correlation was observed between the two assays applied to genotypes 1b, 2a, 2b, and 3a [the correlation coefficient (R) ranged from 0.99 to 0.98], but not to genotype 4 specimens (R=0.78). A significant difference in measurements of HCV RNA using CAP/CTM and ART in serum samples with genotypes 1b and 4 was observed (0.72, -0.53 log IU/ml, P<0.0001, 0.01, respectively). A robust correlation was observed between the HCV core antigen and HCV RNA values by either of the HCV RNA quantitation assays applied to all genotypes with exception of genotype 4, for which R was higher with ART (R=0.95) than with CAP/CTM (R=0.80). The lower limit of detection of CAP/CTM and ART were 41.4 and 28.5 IU/ml using the WHO standards, respectively. In conclusion, two RT-PCR assays had a high efficiency and accuracy for quantitation of HCV RNA of genotypes 2a, 2b, and 3a, but the mean values of HCV RNA differed for genotype 1b and 4.Journal of Medical Virology 11/2010; 82(11):1878-88. DOI:10.1002/jmv.21911 · 2.22 Impact Factor
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ABSTRACT: Evidence on the efficacy of antiviral treatment in chronic hepatitis C (CHC) patients with hepatocellular carcinoma (HCC) after curative treatment is scarce. We aimed to evaluate the efficacy and safety of pegylated interferon-alpha plus ribavirin (pegIFN/RBV) combination therapy in these patients, compared to cirrhotic patients. This prospective, multicenter, case-control study recruited 82 consecutive CHC patients with HCC after curative management and 87 sex/age-matched cirrhotic patients. All patients received pegIFN-alpha-2a and weight-based RBV according to current treatment recommendations. The primary outcome measurement was sustained virological response (SVR, seronegative of hepatitis C virus RNA throughout the 6-month post-treatment follow-up period). The SVR rate was significantly lower in the HCC group compared to the cirrhosis group (48.8% vs 64.4%, p=0.04). However, the significantly lower rate of SVR in the HCC group was observed among genotype-1 patients (33.3% vs 60.7%, p=0.005) but not among genotype-2/3 patients (70.6% vs 71.0%, p=0.88). In patients who achieved 80/80/80 adherence, there was no significant difference of SVR rate between groups (50.7% vs 64.2%, p=0.12) Multivariate logistic regression analysis demonstrated that rapid virological response (viral clearance during the first 4 weeks of treatment, odds ratio=22.1, p<0.001) and adherence (odds ratio=3.1, p=0.05) were predictive factors associated with SVR, whilst previous occurrence of HCC was not associated with SVR (Odds ratio=0.4, p=0.09). The incidence of severe adverse events did not differ between the two groups. The study proved the feasibility of pegIFN/RBV therapy with current treatment guidelines in CHC patients after successful eradication of HCC, with careful monitoring.Journal of Hepatology 09/2010; 54(2):219-26. DOI:10.1016/j.jhep.2010.07.011 · 10.40 Impact Factor