There has been an increase in the number of patients treated with pegylated interferon (PEG-IFN) and ribavirin due to the better antiviral efficacy. The main serious adverse events of PEG-IFN plus ribavirin combination therapy are bone marrow suppression and hemolytic anemia. However, there are few reports of vasculitis occurring during PEG-IFN therapy. We describe a patient who developed vasculitis during the treatment of chronic hepatitis C with PEG-IFN and ribavirin.
Antiviral Agents/*adverse effects ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon Alfa-2a/*adverse effects ; Liver Function Tests ; Middle Aged ; Polyethylene Glycols/*adverse effects ; Ribavirin/*adverse effects ; Skin/drug effects ; Vasculitis/*chemically induced

Anemia ; chemically induced ; Hepatitis C, Chronic ; drug therapy ; genetics ; Humans ; Polymorphism, Genetic ; Pyrophosphatases ; genetics ; Ribavirin ; adverse effects ; therapeutic use

Chronic hepatitis C manifests with many extrahepatic features including renal involvement. However, less commonly, interferon therapy for chronic hepatitis C can also result in renal involvement and we describe a case when interferon therapy resulted in minimal change glomerulopathy, a form of involvement which, carries a good prognosis. Our patient developed nephrotic syndrome while on interferon therapy and HCV RNA levels were undetectable at that time. The disease showed excellent response to steroid therapy.
Antiviral Agents/*adverse effects ; Drug Therapy, Combination ; Hepatitis C, Chronic/*drug therapy ; Interferons/*adverse effects ; Liver Function Tests ; Nephrotic Syndrome/*chemically induced ; Ribavirin/administration & dosage

Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Drug Therapy, Combination ; Female ; Hearing Disorders ; chemically induced ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Middle Aged ; Recombinant Proteins ; adverse effects ; therapeutic use ; Ribavirin ; adverse effects ; therapeutic use

BACKGROUND/AIMS: Combination therapy with peginterferon and ribavirin is a standard therapy for western patients with chronic hepatitis C; however, its efficacy remains unclear in East Asian patients. We evaluated the efficacy and safety of administering peginterferon alfa-2a plus ribavirin in native Korean patients with chronic hepatitis C. METHODS: Seventy-five patients with detectable HCV RNA (52.0% male, median age: 50.8 years) were eligible for the study. The patients were treated with peginterferon alfa-2a 180 mcg/week plus ribavirin 800 mg/day for 24 weeks (for genotype non-1, n=46) or 1000-1200 mg/day for 48 weeks (for genotype 1, n=29). The early virologic response (EVR), the end of treatment virologic response (ETVR), the sustained virologic response (SVR), the biochemical response and the adverse event were analyzed. RESULTS: EVR was seen in 86.2% of the patients with genotype 1. The ETVR was 58.6% in the genotype 1 group and 84.8% in the genotype non-1 group (P=0.02). The overall SVR was 70.7%: 55.2% in the genotype 1 group and 80.4% in the non-1 group (P=0.04). The sustained biochemical response was 64.0%. Multivariate analysis showed that the baseline HCV RNA level (Odds ratio: 0.045, 95% CI: 0.011-0.183, P<0.001) and genotype (Odds ratio: 0.247, 95% CI: 0.063-0.969, P=0.045) had an independent effect on the SVR. Neutropenia, anemia, flu-like symptoms and itching were the common adverse events. Aggravated liver function led to discontinuation of therapy for six patients. Dose modification in twenty-nine patients was effective without producing a significant reduction of the SVR. CONCLUSIONS: Our data suggest that the efficacy of peginterferon plus ribavirin therapy in Koreans is comparable to those from studies on Western patients as an initial treatment for chronic hepatitis C patients. The baseline HCV RNA level and the genotype can be significant factors influencing the SVR.
Ribavirin/*administration & dosage/adverse effects ; Polyethylene Glycols/*administration & dosage/adverse effects ; Middle Aged ; Male ; Korea ; Interferon Alfa-2a/*administration & dosage/adverse effects ; Humans ; Hepatitis C, Chronic/*drug therapy/virology ; Female ; Drug Therapy, Combination ; Antiviral Agents/*administration & dosage/adverse effects ; Adult

BACKGROUND/AIMS: The effectiveness of combination therapy with conventional or pegylated interferon alpha and ribavirin in patients with chronic hepatitis C is well understood. However, the profound investigation about complications of the treatment has been rarely reported in Korea, where patients have broader spectrum of disease manifestations. The aim of this study was to evaluate the effectiveness and complications of the combination therapy of interferon alpha and ribavirin in patients with chronic hepatitis C. METHODS: Two hundred and forty patients with chronic hepatitis C were included. All patients were treated with interferon alpha (3 million units thrice a week) in combination with ribavirin (800-1,200 mg, depending on body weight). Patients were treated for 6 or 12 months according to the genotypes (genotype 1; 12 months, non-1; 6 months). We retrospectively evaluated ETR (end of treatment response) and SVR (sustained virologic response) on the basis of intent-to-treat in patients completing the therapy. RESULTS: In 154 patients who had completed the therapy, ETR was 79.2% and SVR was 61.0%. Multivariate analysis showed that genotype and early virologic response at 3 months of treatment were indepedent predictive factors of SVR. Due to insufficient response, 11.3% of the patients discontinued the therapy. In addition, 24.5% of the patients prematurely discontinued the therapy due to adverse events including aggravated liver function (15.4%), failure to return (7.9%), and others (1.2%). Dose modifications of interferon alpha or ribavirin were required due to anemia (15.4%), neutropenia (8.8%), or thrombocytopenia (4.6%). CONCLUSIONS: The overall SVR of patients who had completed the combination therapy with interferon alpha and ribavirin was 61.0%. However, about one third of the patients discontinued the therapy prematurely due to insufficient response, adverse events and/or noncompliance.
Adult ; Aged ; Antiviral Agents/*adverse effects/therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/*drug effects/genetics ; Hepatitis C, Chronic/*drug therapy/virology ; Humans ; Interferon-alpha/administration & dosage/*adverse effects ; Male ; Middle Aged ; Ribavirin/administration & dosage/*adverse effects

Combination therapy with interferon alpha (IFN- alpha) and ribavirin for 24 or 48 weeks according to HCV genotype has improved the overall sustained virological response (SVR) rates to approximately 40%. The aim of this study was to investigate the long-term efficacy of combination therapy with IFN-alpha and ribavirin for chronic hepatitis C in Koreans. One hundred thirty-eight patients with chronic hepatitis C who received this combination therapy between 1995 and 2003 were analyzed retrospectively. All patients were treated with IFN-alpha 3-6 million units three times weekly in combination with 900-1200 mg/day of ribavirin for 24 weeks. The overall SVR rate was 41.3%. Patients were followed up for a median of 41 months (range, 12-105 months) after completion of therapy. In all of the SVR patients (57 patients), SVR was conserved during the follow-up period. None of the patients progressed to decompensated liver disease or hepatocellular carcinoma (HCC). However, 5 of the 81 non-SVR patients (6.2%) progressed to decompensated liver disease or HCC. In conclusion, combination therapy with IFN-alpha and ribavirin shows good long-term efficacy in patients with chronic hepatitis C in Korea, one of the highest endemic areas of hepatitis B virus (HBV) infection.
Ribavirin/adverse effects/*therapeutic use ; Retrospective Studies ; Middle Aged ; Male ; Korea ; Interferon-alpha/adverse effects/*therapeutic use ; Humans ; Hepatitis C, Chronic/*drug therapy/immunology/virology ; Follow-Up Studies ; Female ; Drug Therapy, Combination ; Antiviral Agents/adverse effects/*therapeutic use ; Adult

Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Hepacivirus ; drug effects ; genetics ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; adverse effects ; Ribavirin ; administration & dosage ; Treatment Outcome

OBJECTIVETo analyze the frequency of thyroid dysfunction and determine its influencing factors in chronic hepatitis C (CHC) patients treated with pegylated-interferon alpha (peg-IFNa)-2a and ribavirin (RBV) combination therapy.

METHODSA total of 194 CHC patients were treated with peg-IFNa-2a and RBV for 48 weeks. Development of thyroid dysfunction was recorded. Clinical and biological factors from pre-treatment (baseline) to post-treatment were statistically analyzed to determine correlation with thyroid dysfunction in this patient population.

RESULTSFifty-two (26.80%) of 194 peg-IFNa-2a/RBV-treated patients developed thyroid dysfunction. Dysfunction severity ranged from hyperthyroidism (n = 1, 0.52%) and hypothyroidism (n = 10, 5.15%) to subclinical hyperthyroidism (n = 4, 2.06%) and subclinical hypothyroidism (n = 37, 19.07%). The dysfunction rate was significantly higher after peg-IFNa-2a/RBV treatment (26.80% vs. 12.37% at baseline, x2 = 12.829, P less than 0.05, odds ratio (OR) = 0.386, 95% confidence interval (CI): 0.226-0.657), in females (33.00% vs. 20.21% in males, P less than 0.05, 95% CI: 1.016-3.040), and in thyroid auto-antibody positive patients (64.29% vs. 23.89% in negative patients, P less than 0.05, 95% CI: 1.681-36.183). Early virological response did not have any significant effect on dysfunction rate (23.00% vs. 30.85% no early virological response, x2 = 1.522, P more than 0.05) nor did end of treatment response (27.19% vs. 26.25% no response at end of treatment, x2 = 0.021, P more than 0.05). Patients who developed thyroid dysfunction had higher interleukin (IL)-6 at baseline (i.e. before peg-IFNa-2a/RBV treatment) (27.08+/-14.90 vs. 11.65+/-5.46 in patients who maintained normal thyroid function, t = 3.127, P less than 0.05, 95% CI: 5.28-25.58). IL-6 levels were not significantly different between the two groups at 24 weeks (6.30+/-2.47 vs. 6.81+/-2.80, t = 0.352, P more than 0.05). IL-6 levels before and after 48 weeks of treatment in normal thyroid function patients were 27.08+/-14.90 and 6.30+/-2.47, t = 3.632, P less than 0.05, and in thyroid dysfunction patients were 11.65+/-5.46 and 6.81+/-2.80, t = 1.997, P more than 0.05.

CONCLUSIONPeg-IFNa-2a/RBV combination therapy may cause thyroid dysfunction, especially hypothyroidism, in CHC patients. Female sex and thyroid auto-antibody positivity may put CHC patients at higher risk of developing thyroid dysfunction during peg-IFNa-2a/RBV therapy. Elevated IL-6 may be a predictive marker of peg-IFNa-2a/RBV-induced thyroid dysfunction.

Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic ; drug therapy ; physiopathology ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Recombinant Proteins ; adverse effects ; therapeutic use ; Retrospective Studies ; Ribavirin ; adverse effects ; therapeutic use ; Thyroid Diseases ; chemically induced ; physiopathology ; Thyroid Gland ; drug effects ; physiopathology ; Treatment Outcome

BACKGROUND/AIMS: Thyroid dysfunction (TD) is more likely to occur in patients with chronic hepatitis C (CHC) and is particularly associated with interferon (IFN) treatment. The purpose of this study was to investigate the incidence, outcomes, and risk factors for TD during pegylated interferon (PEG-IFN) and ribavirin (RBV) combined therapy in patients with CHC. METHODS: A total of 242 euthyroid patients with CHC treated with PEG-IFN/RBV were included. Thyroid function and autoantibodies were measured at baseline, and virologic response and thyroid function were assessed every 3 months during therapy. RESULTS: TD developed in 67 patients (27.7%) during the PEG-IFN/RBV treatment. The types of TD were subclinical hypothyroidism (50.7%), hypothyroidism (14.9%), thyroiditis (11.9%), subclinical hyperthyroidism (10.4%), and hyperthyroidism (10.4%). Most of the patients with TD recovered spontaneously; however, seven patients (10.4%) needed thyroid treatment. The sustained virological response rate was higher in patients with TD than those without (65.7% vs. 49.1%, p = 0.02). Baseline thyroid stimulating hormone (TSH) concentrations (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.96 to 8.77; p < 0.001), presence of the thyroid peroxidase antibody (OR, 8.81; 95% CI, 1.74 to 44.6; p = 0.009), and PEG-IFNalpha-2b (OR, 3.01; 95% CI, 1.43 to 6.39; p = 0.004) were independent risk factors for the development of TD. CONCLUSIONS: TD developed in 27.7% of patients with CHC during PEG-IFN/RBV treatment, and 10.4% of these patients needed thyroid treatment. TD is associated with a favorable virologic response to PEG-IFN/RBV. Assessment of TSH and thyroid autoantibodies at baseline and close monitoring of thyroid function during PEG-IFN/RBV therapy are necessary for early detection and management of IFN-induced TD.
Adult ; Aged ; Antiviral Agents/*adverse effects ; Autoantibodies/blood ; Biomarkers/blood ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnosis/*drug therapy ; Humans ; Incidence ; Interferon-alpha/*adverse effects ; Male ; Middle Aged ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Republic of Korea ; Retrospective Studies ; Ribavirin/*adverse effects ; Thyroid Diseases/*chemically induced/diagnosis/epidemiology/immunology/physiopathology ; Thyroid Gland/*drug effects/immunology/physiopathology ; Time Factors ; Treatment Outcome