Chronic hepatitis C virus management: 2000-2005 update

OBJECTIVE: To review recent advances that have significantly changed the management of chronic hepatitis C virus (HCV) infection. DATA SOURCES: A MEDLINE search (2000-July 2005) was conducted using key words such as hepatitis C, interferon, pegylated interferon, and therapy. STUDY SELECTION AND DATA EXTRACTION: All articles pertaining to treatment of chronic HCV infection were identified. Studies evaluating HCV treatment in treatment-naive patients were considered for this review. DATA SYNTHESIS: Over the past several years, response to treatment for chronic HCV infection has significantly improved with the use of pegylated interferon and ribavirin therapy. Treatment response is influenced by HCV genotype and viral load, as well as patient-related factors, including adherence. CONCLUSIONS: Treatment of chronic HCV infection has improved, with overall response rates of approximately 55%. Identification and management of common adverse effects is important in maximizing adherence and response to therapy. Studies are needed to further delineate the optimum treatment of chronic HCV infection in specific patient populations.     

Treatment of hepatitis C in HIV-coinfected patients

OBJECTIVE: To review the current management of hepatitis C virus (HCV) in persons coinfected with HIV. DATA SOURCES: A MEDLINE search (1966-February 2006) was conducted, using key words such as HIV, human immunodeficiency virus, hepatitis C, interferon, pegylated interferon, and therapy. Article bibliographies and conference abstracts were also reviewed to identify relevant studies. STUDY SELECTION AND DATA EXTRACTION: Studies that examined HCV treatment in individuals coinfected with HIV and articles that focused on HCV/HIV coinfection were considered for this review. DATA SYNTHESIS: Coinfection with HIV leads to a more rapid and severe course of HCV-related liver disease. Treatment of HCV with pegylated interferon (PEG-IFN) and ribavirin therapy is relatively well tolerated in individuals coinfected with HIV, with overall sustained virologic response (SVR) rates of 27-40%. High relapse rates and poor response in HCV-genotype 1 contribute to the lower SVR in coinfected individuals compared with HCV monoinfection. Treatment of HCV is more complicated in HIV-infected persons due to increased risk of myelosuppression, drug interactions, hepatotoxicity of antiretroviral therapy, and the relative contraindication to interferon therapy in advanced HIV disease. Current guidelines recommend that all HIV-positive patients with chronic HCV infection be considered as treatment candidates for anti-HCV therapy due to the higher risk of liver disease progression. Further studies are needed, however, to define the appropriate dose and duration of therapy in HCV/HIV-coinfected individuals. CONCLUSIONS: Response to treatment with PEG-IFN and ribavirin is poorer in patients coinfected with HCV/HIV than in those infected with HCV alone. The benefits of anti-HCV therapy, including viral eradication, need to be weighed against the risks of adverse effects and drug-drug interactions between anti-HCV and antiretroviral medications.     

Combination therapy with interferon and ribavirin in the treatment of chronic hepatitis C infection

OBJECTIVE: To review and critique the medical literature regarding the combination of interferon and ribavirin in the initial treatment of chronic hepatitis C virus (HCV) infection. DATA SOURCES: A MEDLINE search (January 1966-June 1999) was conducted to identify human clinical trials regarding the combination of interferon and ribavirin therapy for the initial treatment of chronic HCV. Bibliographies were reviewed for relevant literature. STUDY SELECTION: Clinical trials of combination interferon and ribavirin for the treatment of chronic HCV in interferon-na?ve adults were reviewed. DATA SYNTHESIS: The combination of ribavirin and interferon in the treatment of chronic HCV has been beneficial in patients who are interferon-na?ve. Patients with predictors of poor response, such as baseline cirrhosis, male gender, age >40 years, high baseline viral loads (>2 x 10(6) copies/mL), and genotype 1 respond better to combination treatment when compared with those who receive interferon monotherapy. Patients with genotype 1 and/or high viral loads may benefit most from 48 weeks of combination therapy; however, adverse effects are of greater concern in these patients. Monitoring can limit these complications. CONCLUSIONS: Combination therapy is effective in the treatment of interferon-naive patients with chronic HCV infection. Patients should be evaluated for duration of treatment with combination therapy by determination of predictors of response. Further trials are needed to more closely evaluate the duration of treatment and to determine the best patient population to receive combination therapy.     

Response to interferon-based therapies in HIV-infected patients with chronic hepatitis C due to genotype 4

BACKGROUND: The hepatitis C virus (HCV) genotype is the main predictor of response to interferon (IFN)-based therapies. HCV genotype 4 is spreading among European intravenous drug users, who are frequently coinfected with HIV. Information about treatment response in this subset of patients is scarce and conflicting results have been reported. METHODS: All HIV-infected patients treated for chronic hepatitis C at our institution with a minimum follow-up of 6 months after discontinuing therapy were retrospectively analysed. They had received one of three HCV treatment modalities: IFN monotherapy, IFN plus ribavirin (RBV) or pegylated interferon (PEG-IFN) plus RBV. Treatment responses were stratified according to HCV genotype. RESULTS: A total of 390 patients were analysed. Sustained virological response (SVR) to HCV therapy had been reached by 90 (23.1%): 22/119 (18.5%) with IFN monotherapy; 17/106 (16%) with IFN plus RBV; and 51/165 (30.9%) with PEG-IFN plus RBV. SVR was significantly higher among those with HCV genotypes 2 or 3 (40.4%; 61/151) than in patients with either HCV genotype 1 (11.2%; 22/197) or HCV genotype 4 (16.7%; 7/42) (P<0.0001). In contrast, there were no significant differences in the response rate comparing HCV genotypes 1 and 4 (P=0.53). CONCLUSIONS: Response to IFN-based therapies in HIV-positive patients with hepatitis C due to HCV genotype 4 is poor, similar to that obtained for HCV genotype 1 and much lower than for HCV genotypes 2 and 3. Therefore, HIV-infected patients with hepatitis C due to genotype 4 should be considered as a particular subset of difficult-to-treat patients. New treatment strategies and drugs for these patients are eagerly awaited.     

Antiviral treatment of hepatitis C: present status and future prospects

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis. A substantial proportion of patients with chronic hepatitis C eventually develop hepatocellular carcinoma (HCC), which is one of the leading causes of death worldwide. Therefore, efficient antiviral treatments for HCV have long been needed. A recently developed combination therapy of pegylated interferon and ribavirin has dramatically improved the outcome of antiviral therapy for HCV infection. In genotype 1b HCV infection, 48 weeks of the combination therapy achieved eradication of the virus in 50% of patients, and in genotype 2 HCV infection, 24 weeks of the therapy resulted in viral eradication in 80%–90% of patients. By this eradication, an improvement in the hepatic fibrosis, an inhibition of HCC development, and an improvement in life expectancy were attained. Patients who did not respond to the combination therapy may be treated with long-term interferon monotherapy, which is not intended to eradicate HCV, but will lower the serum alanine aminotransferase (ALT) level. Thus, the treatment for HCV infection has progressed significantly, but therapies with new modalities, such as inhibitors of viral protease or RNA polymerase, are still being awaited.     

Retreatment of patients who do not respond to initial therapy for chronic hepatitis C

Despite improvements in the treatment of chronic hepatitis C virus (HCV) infection, nearly half of all patients do not respond to initial therapy. Retreatment of these patients with pegylated interferon and ribavirin has been successful in only a limited percentage of cases. Factors associated with sustained virologic response (SVR) following retreatment include prior treatment with interferon monotherapy, HCV genotype 2 or 3, a low serum HCV RNA level, and the absence of cirrhosis. Fewer than 6% of nonresponders who were previously treated with interferon and ribavirin and who have cirrhosis, genotype 1, and a high viral load achieve SVR following retreatment with pegylated interferon and ribavirin. No therapy has been shown to yield SVR in patients who do not respond to pegylated interferon and ribavirin. Long-term maintenance therapy with pegylated interferon is currently being evaluated in nonresponders with advanced fibrosis and cirrhosis. Its use should be considered investigational at this time.     

Telaprevir and boceprevir in african americans with genotype 1 chronic hepatitis C: implications for patients and providers

ABSTRACT: Telaprevir and boceprevir have received US Food and Drug Administration approval for use as triple therapy with pegylated interferon and ribavirin in genotype 1 chronic hepatitis C virus (HCV) infection. Clinical trials of these agents included few African Americans, despite the overwhelming need for improved therapies in this racial group. Although African Americans are predicted to have improved response rates with this new treatment paradigm, clinical trials illustrate lower rates of sustained virologic response for this racial group versus whites. African Americans with genotype 1 HCV infection appear to require longer durations of therapy than do whites to achieve a sustained virologic response. Further investigation is required to adequately counsel African Americans with genotype 1 chronic HCV infection on the efficacy of telaprevir and boceprevir in their racial group. Increased participation of this racial group in HCV clinical trials is needed to improve therapies in this difficult-to-treat population.     

Treatment options for nonresponders and relapsers to initial therapy for hepatitis C

As treatment for chronic hepatitis C virus (HCV) infection has advanced over the past decade, efforts have evolved to retreat patients who did not achieve a sustained virologic response to previous antiviral regimens. Retreating nonresponders to interferon alfa monotherapy with a combination of interferon and ribavirin yields a sustained virologic response in 9% to 32% of patients, whereas retreatment with peginterferon alfa plus ribavirin yields a sustained virologic response in up to 30% to 40% of patients. Sustained virologic response is more likely in retreated patients with HCV genotype 2 or 3, low serum HCV RNA levels, and lack of response to prior interferon monotherapy. Retreatment of nonresponders to interferon-ribavirin combination therapy is associated with lower response rates (< or = 20%). Despite treatment advances, the efficacy of current antiviral regimens for nonresponders remains inadequate. The next few years will see more-targeted antiviral regimens for these patients and therapies focused on slowing the progression of liver disease rather than viral eradication.     

New therapies for chronic hepatitis C infection: a systematic review of evidence from clinical trials

Introduction: Hepatitis C virus (HCV) affects approximately 3% of the world population. The current standard of care for treatment of HCV is a combination of pegylated interferon and ribavirin. Approximately 10% of patients will stop treatment and 30% of patients require dose reduction because of side effects. For genotype 1 HCV‐infected patients, only 40% of patients will achieve undetectable viral load 26 weeks posttreatment. Aims: The objectives of this review were to identify new treatments that are in clinical trials. These include boceprevir and telaprevir which are in routine clinical use and form part of the American Association for the Study of Liver Diseases (AASLD) 2011 guidelines as well as drugs based on observational studies, improving/modifying ribavirin or interferon‐based therapies, modifying the host response and finally the use of direct‐acting antiviral agents (DAA). Materials and methods: MEDLINE and EMBASE databases were searched from 2008 to 2011 for treatments for hepatitis C. Furthermore, abstracts and poster presentations for the annual European Association Study of the Liver, AASLD, Digestive Disease Week and Asian Pacific Association for the study of the Liver were searched for relevant material. Results: All four classes of DAA; NS3/NS4a serine protease inhibitors, cyclophilin inhibitors, NS5b polymerase inhibitors and NS5a inhibitors, show good success rates. Trials have been performed without ribavirin or interferon and demonstrate good antiviral activity with a decreased side effect profile. Combinations of DAA are a promising area of research with a high success rate. Conclusions: Clinical trials show that future HCV therapy could be personalised, achieve higher success rates with decreased adverse incidents.     

丙型肝炎患者基因分型与干扰素治疗疗效分析

目的讨本地区丙型肝炎病毒基因型与干扰素疗效的关系。方法156例慢性丙型肝炎（CHC）患者,HCVRNA采用荧光定量PCR试剂盒,RFLP分析进行HCV基因分型,57例慢性丙型肝炎患者采用IFN—alb治疗,疗程24周。全自动生化分析仪检测血清ALT。结果156例抗HCV阳性患者HCVRNA检出率82．05％（128／156）,HCVⅠ型、Ⅱ型、Ⅲ型、Ⅳ型、Ⅱ＋Ⅲ型分别为0、21．15％、55．13％、0,5．78％。干扰素治疗病例中,HCVⅡ型、Ⅲ型、Ⅱ＋Ⅲ型感染的应答率分别为28．95％、53．33％、25．00％,有显著性差异（P〈0．05）。HCV基因型与血清ALT水平无相关性。结论鲁北地区HCV感染以Ⅱ、Ⅲ型感染为主,干扰素对HCVⅢ型感染的疗效优于HCVⅡ型,ALT与HCVRNA水平可作为干扰素疗效的参考指标,HCV基因分型有预测干扰素疗效的意义。     

Improving anti-hepatitis C virus therapy

The estimated prevalence of hepatitis C virus (HCV) infection is 2%, representing 123 million infected individuals worldwide. HCV infection burdens public health in relation to hepatic (cirrhosis and its complications in 20% of patients) and extrahepatic (vasculitis) complications, and lessens quality of life. Major progress has been made in the last two decades for the diagnosis and treatment of HCV, including more appropriate screening strategies for HCV infection (improved sensitivity of serological and virological tests); a better evaluation of the impact of chronic HCV infection on the liver (semi-quantitative scoring systems of necro-inflammation and fibrosis on liver biopsy, non-invasive evaluation of fibrosis with biochemical markers and elastometry); and improved therapeutic regimens. This progress provides a better definition of who to treat (clinical impact or significant fibrosis); how to treat; tailoring therapies for doses and durations of the pegylated interferon plus ribavirin combination according to virological (mainly genotype and early viral kinetics, but also baseline viral load) and hosts factors (fibrosis, immune status, weight); and how to monitor efficacy and tolerance of therapy. The progress has now resulted in a 50% rate of complete HCV eradication, ranging 45 - 90% according to the genotype and especially in those patients with early viral response. New therapies, specifically HCV protease or polymerase inhibitors, in combination with pegylated interferon, or more potent and less toxic new formulations of interferons or ribavirin, will increase these encouraging results in the future.     

Response to combined interferon and ribavirin is better in patients infected with hepatitis C virus genotype 6 than genotype 1 in Hong Kong

Data on the treatment efficacy of interferon (IFN)-alpha and ribavirin in patients with chronic hepatitis infected with hepatitis C virus (HCV) of genotype 6 are lacking. A study has been reported from Hong Kong which compared the treatment efficacy of IFN-alpha and ribavirin in the treatment of chronic HCV infection with genotypes 1 and 6. Twenty-four patients with HCV genotype 1 and 16 patients with HCV genotype 6 were studied. The baseline demographic data including median age, gender ratio, alanine aminotransferase levels, bilirubin levels, HCV RNA levels and histological scores were comparable between the two groups of patients. All patients received IFN-alpha 5 million units three times per week and ribavirin (1,000 mg for those weighing 75 kg) for 1 year. Patients infected with HCV genotype 6 achieved virological response significantly higher than those with HCV genotype 1 (67 vs. 33% at week 24, p = 0.02; 75 vs. 42% at the end of treatment, p = 0.05; 63 vs. 29% at 6 months after completion of treatment, p = 0.04). Histological improvement in inflammatory activity and fibrosis in the liver were observed in 25% and 25% of patients infected with HCV genotype 6 in contrast to only 13 and 8% in patients infected with HCV genotype 1; however, the differences were not statistically significant. In conclusion, patients with HCV genotype 6 gain a better response to combined treatment with IFN-alpha and ribavirin than those with HCV genotype 1 and achieve a significantly higher rate of sustained virological response.     

Improving anti-hepatitis C virus therapy

The estimated prevalence of hepatitis C virus (HCV) infection is 2%, representing 123 million infected individuals worldwide. HCV infection burdens public health in relation to hepatic (cirrhosis and its complications in 20% of patients) and extrahepatic (vasculitis) complications, and lessens quality of life. Major progress has been made in the last two decades for the diagnosis and treatment of HCV, including more appropriate screening strategies for HCV infection (improved sensitivity of serological and virological tests); a better evaluation of the impact of chronic HCV infection on the liver (semi-quantitative scoring systems of necro-inflammation and fibrosis on liver biopsy, non-invasive evaluation of fibrosis with biochemical markers and elastometry); and improved therapeutic regimens. This progress provides a better definition of who to treat (clinical impact or significant fibrosis); how to treat; tailoring therapies for doses and durations of the pegylated interferon plus ribavirin combination according to virological (mainly genotype and early viral kinetics, but also baseline viral load) and hosts factors (fibrosis, immune status, weight); and how to monitor efficacy and tolerance of therapy. The progress has now resulted in a 50% rate of complete HCV eradication, ranging 45 – 90% according to the genotype and especially in those patients with early viral response. New therapies, specifically HCV protease or polymerase inhibitors, in combination with pegylated interferon, or more potent and less toxic new formulations of interferons or ribavirin, will increase these encouraging results in the future.     

Sofosbuvir (GS-7977), a pan-genotype,direct-acting antiviral for hepatitis C virus infection

Given the global importance of chronic hepatitis C virus infection as a major health burden, there is still a need for treatment options that are more efficient, safer, simpler, more convenient and preferably interferon-free. Sofosbuvir (GS-7977; formerly PSI-7977) is a direct-acting antiviral agent that has met many of these attributes. This novel nucleotide analogue has demonstrated a consistently potent antiviral activity across several hepatitis C virus genotypes, and has been found to be safe and well tolerated when administered alone or with ribavarin +/? pegylated interferon. The clinical data evaluating the safety, tolerability and antiviral activity of sofosbuvir in various treatment regimens are presented in this article. Sofosbuvir is a major breakthrough in the care of HCV infection, making it possible that thousands of HCV infected patients around the world achieve cures, and preventing HCV associated morbidity and mortality.     

Effect of ribavirin on the hepatitis C virus (JFH-1) and its correlation with interferon sensitivity

BACKGROUND: The consensus therapy for chronic hepatitis C infection is based on a synergistic combination of pegylated interferon and ribavirin. The therapy leads to a sustained virological response in around 60% of infected patients. The mechanism by which this synergy occurs has not yet been elucidated. Several mechanisms of action have been proposed; one suggests that ribavirin, which is a nucleoside analogue, is incorporated into the RNA strand and generates an increase in the error rate. Such an accumulation of mutations would threaten the integrity of the virus's genetic information. METHODS: The effects of ribavirin on the new infectious hepatitis C virus cell culture (HCVcc) system were investigated using Huh-7 cells. Cells were cultured for 1 month in either 0 microM, 20 microM or 50 microM ribavirin. The HCV interferon sensitivity and the NS5A quasispecies were analysed. RESULTS: An increase in the mutation rate in the HCV NS5A gene was observed when the infected cells were treated with 50 microM ribavirin for 1 month. Amino acid sequence analysis revealed that ribavirin exerts an increase in G to A transition events as predicted by its mutagenic effect and a selective pressure on the HCV NS5A sequence. Furthermore, ribavirin treatment modified the efficacy of interferon (IFN) treatment. The IFN half-inhibition concentration (IC50) was significantly lower for viruses obtained after 1 month's exposure to 50 microM ribavirin than for viruses cultured in the absence of ribavirin. CONCLUSIONS: Ribavirin's mutagenic effect could explain in part its synergistic action with interferon.     

Recent advances of basic research and clinical application of lactoferrin as an antiviral reagent against chronic hepatitis C

Hepatitis C virus(HCV), discovered in 1989, is the major causative agent of chronic viral hepatitis. Most patients progress to liver cirrhosis and hepatocellular carcinoma. In the therapy of hepatitis C, only interferon has been used effectively as an anti-HCV reagent in Japan, but its effectiveness is limited to about 30% of cases. Using human hepatocyte cell line which could support efficient HCV replication, we previously found that lactoferrin inhibited HCV infection, and demonstrated that this inhibiting activity was due to the interaction of lactoferrin with HCV. Further analysis found that the carboxyl region of lactoferrin, which partially shows amino acid sequence homology to human CD81, specifically bound to the HCV E2 envelope protein, and identified a 33 amino acids as a critical binding domain of lactoferrin. On the other hand, it has been shown that bovine lactoferrin was effective in some patients with chronic hepatitis received an 8-week course of lactoferrin treatment. Further clinical trials showed that lactoferrin is a promising candidate for adjuvant therapy with interferon in patients with chronic hepatitis C.     

Genotype does not affect pattern of HCV RNA decrease among responders during interferon treatment of chronic hepatitis C. Consensus Interferon Study Group

We assessed differences in the pattern of HCV RNA decrease for HCV genotypes 1, 2, and 3 during interferon treatment to determine if the lower response rates observed among genotype 1 patients were related to a slower decrease in HCV clearance. Serum HCV RNA values of 472 chronic hepatitis C patients treated with either consensus interferon (CIFN) or interferon alfa-2b (IFN alfa-2b) were evaluated. Neither virological sustained responders nor relapsers differed in the pattern of serum HCV RNA decrease based on genotype. Virological sustained responders infected with genotype 1 cleared HCV RNA as rapidly as sustained responders who were infected with genotype 2 or 3. Relapsers had a slower rate of serum HCV RNA decrease than did virological sustained responders. Nonresponders differed in the pattern of serum HCV RNA decrease based on genotype: HCV genotype 3 patients had the greatest decrease in serum HCV RNA; genotype 2 patients had an intermediate decrease; and genotype 1 patients had the least serum HCV RNA decrease. HCV genotype 1 patients treated with CIFN had a greater decrease in serum HCV RNA during therapy than did patients treated with IFN alfa-2b. However, there was no difference in the magnitude of serum HCV RNA decrease between the two interferon treatments for patients infected with genotype 2 or 3. In summary, both genotype and ultimate response to treatment are determinants of the pattern and rate of serum HCV RNA change during interferon therapy of chronic hepatitis C.     

Lack of rapid virological response predicts interferon-alpha2b/ribavirin therapy failure in HCV genotype 2 patients: a single-centre study

BACKGROUND: A minority of patients with HCV-2 chronic hepatitis does not attain a sustained virological response to interferon-based therapies. Registration trials have failed to identify the real proportion of HCV-2 non-responders, and predictors of non-response. The analysis of 'real-life' HCV-2 patients might help define the effectiveness of anti-HCV therapy and the role of response moderators. METHODS: A re-analysis of all treatment-naive HCV-2 patients who consecutively received weight-dosed ribavirin with either 3 MU three times a week standard interferon-alpha2b or 1.5 microg/kg/week pegylated interferon-alpha2b. RESULTS: The 94 interferon-treated patients and the 136 pegylated-interferon-treated patients were comparable for demography, prevalence of cirrhosis (25%) and adherence to therapy (74%). By intention-to-treat analysis, the overall sustained virological response rate was 80% (82% interferon versus 78% pegylated interferon). Overall, sustained virological rates were 83% for the 182 patients who cleared HCV RNA at week 4 (rapid virological response) and 52% for the 48 who did not (P < 0.001). The corresponding week 12 figures of HCV RNA clearance were 90% and 32%, respectively (P < 0.001). Sustained response was independent of gender, age, body mass index, modality of infection, duration and severity of liver disease, adherence to therapy and interferon type. After stratification for interferon type, the only treatment failure predictor was persistence of HCV RNA at week 4 and 12. CONCLUSIONS: Despite the prevalence of moderators of treatment outcome, HCV-2 patients showed as high sustained virological response rates as those reported in registration trials for HCV-2 and HCV-3 pooled patients; pegylated interferon therapy failure was predicted by lack of rapid virological response.     

Development and exacerbation of oral lichen planus during and after interferon therapy for hepatitis C

Oral lichen planus (OLP) is frequently seen in patients with hepatitis C virus (HCV) infection. To clarify the role of HCV in OLP pathogenesis, we investigated the occurrence and progression of oral lesions in chronic hepatitis C patients treated with interferon. Oral surgeons examined 24 hepatitis C patients (15 men, nine women; mean age 48.1 years) for oral lesions before, during and after interferon (IFN) treatment. OLP was observed in 16.7% (4/24). Two patients had OLP before treatment, one during and one after treatment. Those who developed OLP during or after treatment had neither improvement nor disappearance of OLP even when serum HCV RNA became negative. Leucoplakia was seen in four patients before treatment and oral cancer in one patient 6 months after completing treatment. OLP can occur, exacerbate and persist during IFN treatment for hepatitis C, even when serum HCV RNA becomes negative. The present study suggested that OLP pathogenesis in hepatitis C is due to host factors induced by HCV infection rather than direct HCV participation. Treating physicians should be aware of OLP occurrence or exacerbation by IFN treatment with hepatitis C patients, but IFN therapy is not necessarily contraindicated in these patients.     

Combined interferon and ribavirin therapy for chronic hepatitis C in Taiwan

Chronic hepatitis C virus (HCV) infection, including its sequelae, is an important healthcare problem in Taiwan. The seroprevalence of HCV infection in first-time blood donors in Taiwan is 1.2% and an estimated 2-5% in the general population, with a great geographic variation. Genotype 1b is the most prevalent HCV genotype in Taiwan, with a prevalence rate of 50-70%. An increasing incidence of hepatocellular carcinoma (HCC) is mainly attributed to HCV infection, while the declining role of HBV is observed in Taiwan. The seroprevalence of hepatitis B surface antigen among patients with HCC was 90% three decades ago, while recently, chronic HCV infection accounts for more than 30% of HCC patients in the National Taiwan University Hospital. With the advent of a combined conventional interferon (IFN)-alpha and ribavirin therapy, to which Taiwan has contributed in the early study phase, the sustained virological response rate has been greatly improved compared with IFN monotherapy. The sustained virological response rate in Taiwanese patients treated with the combination therapy for 6 months has reached up to 50-60%, which is higher than that reported in patients from the Western countries receiving a 12-month regimen. It is necessary to search for the underlying mechanisms for the better treatment outcome with IFN plus ribavirin combination therapy in Taiwanese patients. Whether long-term effects of IFN plus ribavirin therapy can reduce the incidence of HCC needs to be established.