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

Pegylated interferon and ribavirin combination therapy is accepted as the standard antiviral treatment for chronic hepatitis C regardless of HCV genotype. This combination therapy achieves higher response rates than previous therapy, but, nevertheless, a large proportion of patients suffer from treatment failure or adverse events. Recent clinical studies of viral kinetics during antiviral treatment have led to the introduction of response-guided therapy, the concept of 'customized therapy depending on viral response', which focuses on modulation of the treatment period depending on the viral response to create a sustained viral response without unnecessary medication and costs. New upcoming direct-acting antivirals (DAAs) maximize response rate, and triple therapy including DAAs along with pegylated interferon and ribavirin combination therapy could soon be the standard therapy. In this article, we reviewed the factors affecting treatment, response guided treatment, retreatment after failure of standard treatment, management of adverse events during treatment, and new treatment options.
Anemia, Hemolytic/drug therapy/etiology ; Antiviral Agents/adverse effects/*therapeutic use ; Erythropoietin/therapeutic use ; Hepatitis C, Chronic/*drug therapy ; Humans ; Individualized Medicine ; Interferon-alpha/adverse effects/therapeutic use ; Polyethylene Glycols/adverse effects/therapeutic use ; Protease Inhibitors/therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/adverse effects/therapeutic use ; Ribavirin/adverse effects/therapeutic use

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

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

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: 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

OBJECTIVETo compare the efficacy and safety of a double therapy containing pegylated interferon and ribavirin to a triple therapy (with addition of a protease inhibitor) for untreated chronic hepatitis C with genotype 1 infection.

METHODSWe searched Pub med, EMBASE, OVID, the Cochrane Library Clinical Trials Registry and included relevant randomized controlled trials for comparing the efficacy and safety of the triple therapy to the double therapy in HCV genotype 1 untreated patient, using terms: protease inhibitor, hepatitis C, genotype 1. The primary endpoints were composed of the rates of SVR, the rates of relapse, the rates of anemia, and the rates of discontinuation due to severe adverse events, respectively.

RESULTSFive trials (involving a total of 3200 patients) were included. Data showed the triple therapy with either telaprevir or boceprevir significantly increased the SVR rate and decreased the relapse rate compared with the double therapy [for SVR rate, 65.4% vs. 40.9%, OR=2.92, 95% CI 2.5 to 3.42, P less than 0.01, and for relapse rate, 11.3% vs. 24.8%, OR=0.42, 95% CI 0.26 to 0.68, P less than 0.01], but the triple therapy associated with higher side effects and intolerability [ higher anemia rate, 44.1 % vs. 26.2%, OR=2.25, 95% CI 1.9 to 2.65, P less than 0.01 and higher discontinuation rate owing to severe adverse events, 12.4% vs. 7.7%, OR=1.66, 95% CI 1.19 to 2.32, P less than 0.01]. Subgroup analysis found that the rates of SVR were still higher and the relapse rates were lower in all triple treatment groups [composed by 24 (or 28) -week groups, 48-week groups, and response-guided therapy groups] than that of the double therapy.

CONCLUSIONA triple therapy with peginterferon-ribavirin plus either boceprevir or telaprevir significantly increased the rate of sustained virologic response among untreated patients infected with hepatitis C genotype 1. Both the incidence of adverse events and the frequency of discontinuation owing to severe adverse events were higher in patients receiving the triple therapy than those receiving the standard double therapy.

Antiviral Agents ; adverse effects ; therapeutic use ; Drug Therapy, Combination ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; adverse effects ; therapeutic use ; Polyethylene Glycols ; administration & dosage ; adverse effects ; therapeutic use ; Protease Inhibitors ; administration & dosage ; adverse effects ; therapeutic use ; Ribavirin ; adverse effects ; therapeutic use ; Treatment Outcome

Combination therapy of pegylated interferon alpha and ribavirin has been associated with various adverse effects, but sudden-onset hearing loss is uncommon. We report a 60-year-old male patient who developed sudden-onset hearing loss during combination therapy with pegylated interferon alpha and ribavirin for chronic hepatitis C. This patient had been diagnosed with chronic hepatitis C (genotype Ib) and early-stage liver cirrhosis 3 years previously, and had been treated with conventional interferon-alpha and ribavirin for 12 months. However, 6 months from the end of the treatment course the patient relapsed and received combination retreatment with pegylated interferon alpha-2b and ribavirin. He developed sudden-onset right-side hearing loss and tinnitus 42 weeks after the start of this retreatment. Pure-tone audiometry revealed a right-side hearing loss of 60~90dB. The patient consequently immediately discontinued the pegylated interferon therapy and was given prednisone 60 mg/day for 10 days, after which the hearing loss had almost completely recovered.
Anti-Inflammatory Agents/therapeutic use ; Antiviral Agents/*adverse effects/therapeutic use ; Audiometry, Pure-Tone ; Drug Therapy, Combination ; Hearing Loss, Sudden/chemically induced/*diagnosis ; Hepatitis C, Chronic/diagnosis/*drug therapy ; Humans ; Interferon Alfa-2b/*adverse effects/therapeutic use ; Liver Cirrhosis/diagnosis ; Male ; Middle Aged ; Polyethylene Glycols/*adverse effects/therapeutic use ; Prednisone/therapeutic use ; Ribavirin/*adverse effects/therapeutic use

Combined pegylated interferon and ribavirin therapy for chronic hepatitis C infection cause a wide range of side effects, including flu-like syndrome, hematological abnormalities, cardiovascular symptoms, gastrointestinal symptoms, pulmonary dysfunction, depression, and retinopathy. Interferon-alpha has been shown to be related to the development of various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroid disease, and type 1 diabetes mellitus (DM). Type 1 DM and thyroid disease respectively develop in 0.08~2.61% and 10~15% of patients treated with combined interferon-alpha and ribavirin for chronic hepatitis C. The coexistence of type 1 DM and autoimmune thyroiditis was rarely reported. We report a case of a 33-year-old female patient with chronic hepatitis C who simultaneously developed diabetic ketoacidosis and autoimmune thyroiditis after treatment with pegylated interferon-alpha 2b and ribavirin.
Adult ; Antiviral Agents/*adverse effects/therapeutic use ; Diabetic Ketoacidosis/drug therapy/*etiology ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/*drug therapy ; Humans ; Insulin/therapeutic use ; Interferon Alfa-2b/*adverse effects/therapeutic use ; Polyethylene Glycols/*adverse effects/therapeutic use ; Ribavirin/*adverse effects/therapeutic use ; Thyroiditis, Autoimmune/drug therapy/*etiology ; Thyroxine/therapeutic use

Vogt-Koyanagi-Harada (VKH) disease is a multisystem syndrome characterized by ocular (uveitis and retinal detachment), neurological (headache, tinnitus, and meningitis), and integumentary (vitiligo, alopecia, and poliosis) involvement. Although the pathogenesis of VKH disease is not well understood, an autoimmune T-cell response to a melanocyte-associated antigen is considered to be a cause of VKH disease. The complex immunological response to interferon and ribavirin may induce or exacerbate the autoimmune condition; however, VKH disease is a very rare complication associated with interferon therapy in chronic hepatitis C. We report a case of VKH disease occurring during pegylated interferon-alpha2b and ribavirin combination therapy for chronic hepatitis C.
Anti-Inflammatory Agents/therapeutic use ; Antiviral Agents/*adverse effects/therapeutic use ; Drug Therapy, Combination ; Female ; Fluorescein Angiography ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon Alfa-2b/*adverse effects/therapeutic use ; Magnetic Resonance Imaging ; Middle Aged ; Polyethylene Glycols/*adverse effects/therapeutic use ; Prednisolone/therapeutic use ; Ribavirin/*adverse effects/therapeutic use ; Tomography, X-Ray Computed ; Uveomeningoencephalitic Syndrome/*diagnosis/drug therapy/etiology