Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis worldwide. Up to 85% of individuals infected with HCV develop chronic infection, which can progress to cirrhosis and hepatocellular carcinoma. The primary goal in the treatment of HCV infection is to reduce the mortality by preventing liver-related deaths associated with the development of hepatocellular carcinoma and decompensated cirrhosis. Pegylated interferons together with ribavirin are currently the standard of care for patients with chronic hepatitis. Here, I discuss the goals of treatment, indication and treatment of chronic hepatitis C.
Antiviral Agents/*therapeutic use ; Drug Therapy, Combination ; Hepatitis C, Chronic/diagnosis/*drug therapy ; Humans ; Interferon Alfa-2a/*therapeutic use ; Interferon Alfa-2b/*therapeutic use ; Polyethylene Glycols/*therapeutic use ; Ribavirin/*therapeutic use

Chronic hepatitis B (CHB) is a serious health problem in Korea. The natural history of chronic HBV infection has been divided into 4 phases: immune tolerance, immune clearance, inactive HBsAg carrier state and reactivation. During the phases of immune tolerance and inactive HBsAg carrier state, no treatment is required. Patients in the immune clearance or reactivation phases are candidates for therapy. In the last years, treatment effects of CHB have considerably improved. Several agents are currently approved for the treatment of CHB: interferon alpha, pegylated interferon alpha, lamivudine, adefovir, entecavir, telbivudine and clevudine in Korea. The treatment recommendations from the 2004 Korean Association for the Study of the Liver guideline on the management of CHB have been updated to incorporate new therapeutic options. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Issues for consideration include efficacy, safety and incidences of resistance, and method of administration of antiviral therapy in treatment-naive patients.
Adenine/analogs & derivatives/therapeutic use ; Antiviral Agents/*therapeutic use ; Arabinofuranosyluracil/analogs & derivatives/therapeutic use ; Guanine/analogs & derivatives/therapeutic use ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon Alfa-2a/therapeutic use ; Interferon Alfa-2b/therapeutic use ; Korea ; Lamivudine/therapeutic use ; Phosphonic Acids/therapeutic use ; Polyethylene Glycols/therapeutic use ; Practice Guidelines as Topic

The wide use of lamivudine in chronic hepatitis B has produced a monotonic increase in patients with lamivudine resistance. Therefore, treating lamivudine resistance in chronic hepatitis B is a major concern in clinical practice for the treatment of hepatitis B virus (HBV). There is conflicting evidence on the outcome of pegylated interferon alpha (PEG-IFN alpha) therapy against lamivudine-resistant HBV, which is due to mutations in the YMDD motif. We experienced a patient with chronic hepatitis B who was successfully treated with PEG-IFN alpha-2a after the development of virologic and biochemical breakthrough during lamivudine therapy. Virologic breakthrough was associated with the emergence of YMDD mutants 48 months after starting lamivudine therapy. Treatment with PEG-IFN alpha-2a for 12 months resulted in an undetectable serum level of HBV DNA and the resolution of hepatitis, and the virologic response was maintained over 16 months after cessation of PEG-IFN alpha-2a.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis ; Drug Resistance, Viral ; Hepatitis B, Chronic/diagnosis/*drug therapy ; Humans ; Interferon Alfa-2a/*therapeutic use ; Lamivudine/*therapeutic use ; Liver/pathology ; Male ; Polyethylene Glycols/*therapeutic use

BACKGROUND/AIMS: The combination therapy with peginterferon and ribavirin is a standard treatment for patients with chronic hepatitis C. However, because of the long duration of the treatment and many complications, the reduction of adherence frequently occur. This study aimed to assess influences of reduced medication adherence in the combination therapy of chronic hepatitis C patients. METHODS: We retrospectively reviewed the medical records of 82 patients with chronic hepatitis C who received a combination therapy with peginterferon and ribavirin. The patients were categorized into 3 subgroups on the basis of medication adherence. Group 1 comprised patients who received > or =80% of the recommended dosage of both peginterferon and ribavirin. Group 2 comprised those patients who received > or =80% of the recommended dosage of only 1 drug. The patients of Group 3 received <80% of the recommended dosage of both the drugs. RESULTS: Sustained virologic response (SVR)s of patients in Group 1, 2 and 3 were 85.4% (41/48), 85.7% (18/21), and 38.5% (5/13), respectively (p=0.002). SVRs of genotype 1 patients in Group 1, 2 and 3 were 84.2% (16/19), 75% (9/12), and 14.3% (1/7) , respectively (p=0.003). SVRs of genotype non-1 patients in Group 1, 2 and 3 were 86.2% (25/29), 100% (9/9), and 66.7% (4/6), respectively (p=0.196). Furthermore are SVRs significantly differed with the degree of medication adherence to either peginterferon or ribavirin (p=0.003 and 0.021, respectively). In multivariate analysis, the peginterferon dose was a significant independent factor associated with SVR. CONCLUSIONS: Medication adherence of chronic hepatitis C patients to the combination therapy with peginterferon and ribavirin is very important for achieving SVR. In particular, we think that genotype 1 patients should maintain higher adherence than genotype non-1 patients.
Adult ; Antiviral Agents/*therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon Alfa-2a/*therapeutic use ; Male ; *Medication Adherence ; Middle Aged ; Polyethylene Glycols/*therapeutic use ; RNA, Viral/analysis ; Retrospective Studies ; Ribavirin/*therapeutic use

BACKGROUND/AIMS: Various predictive factors for peginterferon alpha and ribavirin therapy in chronic hepatitis C have been reported, but the effect of adherence to therapy has not been established. We investigated how adherence affects the sustained virologic response (SVR). METHODS: We analyzed 92 chronic hepatitis C patients receiving peginterferon alpha and ribavirin combination therapy. Patients were first identified as having either genotype 1 or genotype non-1 infection and then categorized into three groups according to their adherence to the treatment protocol: (1) patients who received > or =80% of the recommended dosage of both peginterferon alpha and ribavirin for > or =80% of the intended duration of therapy, (2) patients who received <60% of the recommended dosage of both peginterferon alpha and ribavirin for <60% of the intended duration of therapy, and (3) patients who were not included in either group 1 or 2. RESULTS: The rates of early virologic response, end of treatment response, and SVR differed significantly with the degree of adherence to the treatment. The SVRs of genotype 1 patients were 86.7%, 26.7%, and 66.7% in groups 1, 2, and 3, respectively (P=0.003), and those of genotype non-1 were 100%, 16.7%, and 88.9%, respectively (P<0.001). CONCLUSIONS: Adherence to therapy is a key factor in achieving an SVR. Supportive strategies to improve adherence will increase overall SVR rates.
Adult ; Aged ; Antiviral Agents/*therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon Alfa-2a/*therapeutic use ; Interferon Alfa-2b/*therapeutic use ; Male ; Middle Aged ; *Patient Compliance ; Polyethylene Glycols/*therapeutic use ; RNA, Viral/analysis ; Ribavirin/*therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: Pegylated interferon plus ribavirin combination therapy has been the standard of therapy for patients with chronic hepatitis C. Although previous studies have reported long term durability after the sustained virologic response (SVR) with standard therapy for chronic hepatitis C, it is still unclear in Korea. The aim of this study was to evaluate the relapse rate and related factors after SVR to pegylated interferon therapy in Korean patients with chronic hepatitis C. METHODS: A total of 119 chronic hepatitis C patients were treated with pegylated interferon plus ribavirin, and 73 patients achieved SVR (61.3%). Among 73 patients who achieved SVR, 68 patients (genotype 1, n=40; genotype non-1, n=28) were evaluated for virological response after SVR. RESULTS: SVR rate in genotype 1 and genotype non-1 were 52.5%, and 65.1%, respectively. Relapse after SVR occurred in 5 patients (7.4%) with genotype 1, and the median time to relapse from SVR was 10 months. Univariate analysis revealed that the dose reduction of pegylated interferon (p=0.005) and cirrhosis (p=0.03) were significantly associated with relapse. CONCLUSIONS: These results suggested that the relapse could occur even after SVR achievement in Korean patients with chronic hepatitis C, and the dose reduction of pegylated interferon during treatment or having cirrhosis may increased the risk for relapse.
Adult ; Aged ; Antiviral Agents/*therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis C, Chronic/complications/*drug therapy ; Humans ; Interferon Alfa-2a/*therapeutic use ; Interferon Alfa-2b/*therapeutic use ; Liver Cirrhosis/complications ; Logistic Models ; Male ; Middle Aged ; Polyethylene Glycols/*therapeutic use ; RNA, Viral/blood ; Recurrence ; Ribavirin/*therapeutic use ; Risk Factors

BACKGROUND/AIMS: The combination therapy of peginterferon (PEG-IFN) and ribavirin is the standard treatment for hepatitis C virus (HCV) infection. However, few trials have involved patients with cirrhosis. The purpose of this study was to elucidate the efficacy and safety of treatment with PEG-IFN and ribavirin in patients with cirrhosis associated with HCV infection. METHOD: A total of 65 patients were treated with PEG-IFN alpha-2a/ribavirin (n=32) or PEG-IFN alpha-2b/ribavirin (n=33). PEG-IFN alpha-2a and PEG-IFN alpha-2b were administered at doses of 180 microg/week and 1.5 microg/kg/week, respectively, and ribavirin was administered orally at doses of 800-200 mg. Patients with HCV genotype 1 and genotype non-1 were treated for 48 and 24 weeks, respectively. The treatment response was assessed based on the sustained virologic response (SVR). RESULTS: The early virologic response (EVR), end-of-treatment response (ETR), and SVR were 70.0%, 52.0%, and 24.0%, respectively, in genotype 1 (n=50). In genotype non-1 (n=15), the ETR was 53.3% and the SVR was 33.3%. The overall SVR did not differ with genotype (1 vs non-1, 24.0% vs. 33.3%; P=0.471) or between decompensated cirrhosis and compensated cirrhosis (20.0% vs. 27.3%, P=0.630). Ten patients developed cirrhotic complications during the treatment, and 11 stopped treatment due to treatment-related adverse events. CONCLUSION: The combination therapy of PEG-IFN and ribavirin exhibited a low efficacy in cirrhotic patients with HCV infection and was associated with frequent serious complications. However, with careful management of complications, the therapy may have a considerable efficacy in some patients with cirrhosis and HCV infection.
Aged ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; Hepatitis C, Chronic/complications/*drug therapy ; Humans ; Interferon Alfa-2a/adverse effects/*therapeutic use ; Interferon Alfa-2b/adverse effects/*therapeutic use ; Liver Cirrhosis/*complications ; Male ; Middle Aged ; Neutropenia/etiology ; Platelet Count ; Polyethylene Glycols/adverse effects/*therapeutic use ; RNA, Viral/blood ; Retrospective Studies ; Ribavirin/adverse effects/*therapeutic use ; Severity of Illness Index ; Treatment Outcome

BACKGROUND/AIMS: The treatment response to interferon could differ with mutations in the interferon-sensitivity-determining region (ISDR) in patients infected with hepatitis C virus (HCV) genotype-1b (HCV-Ib). We examined the pattern of ISDR mutations and analyzed whether the number of amino acid substitutions influences the treatment response to peginterferon plus ribavirin in chronic hepatitis or cirrhotic patients infected with HCV-Ib. METHODS: The study population comprised 52 patients who visited Seoul Asan Medical Center and Seoul National University Bundang Hospital from January 2006 to December 2008 and who received peginterferon alpha-2a (n=37) or -2b (n=15) plus ribavirin, and whose serum was stored. We analyzed the early virologic response, end-of-treatment response, and sustained virologic response (SVR), and examined the ISDR using direct sequencing. RESULTS: The proportions of patients with ISDR mutation types of wild (0 mutations), intermediate (1-3 mutations), and mutant (> or =4 mutations) were 50.0%, 42.3%, and 7.7%, respectively, and the corresponding SVR rates were 63%, 50%, and 67% (p>0.05). The SVR rates were 59.4% and 50.0% in patients with <2 and > or =2 mutations, respectively (p>0.05). On univariate analysis, age was the only predictive factor for SVR (p=0.016). The pretreatment HCV RNA titer tended to be lower in those with SVR, but without statistical significance (p=0.069). CONCLUSIONS: The frequency of ISDR mutations was low in our cohort of Korean patients infected with HCV-Ib. Therefore, ISDR mutations might not contribute to the response to treatment with peginterferon plus ribavirin.
Adult ; Aged ; Amino Acid Sequence ; Antiviral Agents/*therapeutic use ; Drug Resistance, Viral/genetics ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/*genetics ; Hepatitis C, Chronic/*drug therapy/virology ; Humans ; Interferon Alfa-2a/*therapeutic use ; Interferon Alfa-2b/*therapeutic use ; Male ; Middle Aged ; Molecular Sequence Data ; *Mutation ; Polyethylene Glycols/*therapeutic use ; Republic of Korea ; Ribavirin/therapeutic use

No abstract available.
Antiviral Agents/*administration & dosage/therapeutic use ; Drug Therapy, Combination ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon Alfa-2a/administration & dosage/therapeutic use ; Interferon Alfa-2b/administration & dosage/therapeutic use ; Polyethylene Glycols/administration & dosage/therapeutic use ; Ribavirin/administration & dosage/therapeutic use ; Time Factors ; Treatment Outcome

No abstract available.
Drug Therapy, Combination ; Hepacivirus ; Hepatitis C, Chronic/complications/*diagnosis/therapy ; Humans ; Interferon Alfa-2a/therapeutic use ; Liver Cirrhosis/*diagnosis/mortality/virology ; *Liver Transplantation ; Living Donors ; Polyethylene Glycols/therapeutic use ; Ribavirin/therapeutic use ; Severity of Illness Index ; Treatment Outcome