Hepatitis Monthly
Volume:4 Issue: 4, Summer 2004

Hepatitis C is the main cause of chronic liver disease in many of countries, but since its discovery about 15 years ago through implantation of blood product screening there has been a constant decrease in the number of new cases of post transfusion acute hepatitis C (acute HCV). 1, 2, 3 This unfortunately did not translate to lower number of the end stage liver diseases caused by this virus and still in many countries it would be the most common indication of liver transplantation up to 2 more decades. 5, 6, 7 Despite blood screening, post transfusion acute HCV still occurs worldwide although it is becoming very rare. Other sources of HCV acquisition are rising and acute HCV is now a well established occupational hazard as well as nosocomial infection. 8, 9, 10Although the total number of acute HCV infection has decreased in many communities; there is now a growing number acute HCV especially among intravenous drug abusers (IVDs) and those who had occupational or nosocomial infection.11 There are some data indicating a good response of this group of acute HCV even to Interferon monotherapy, which is considered a suboptimal treatment in the cases of chronic HCV infection.12 In this article the current data on acute HCV infection and its management would be reviewed. It is especially important to have a guideline on the management of acute HCV in each institution especially considering those who get this infection nosocomially. We hope this review would help in developing such guidelines.

Pegylation of Interferon (IFN) prolongs the medication half-life, which has resulted in introducing Pegylated Interferon (PEG-IFN) as the new modality for treatment of chronic hepatitis C. This clinical trial was conducted to assess the efficacy and safety of Peg-INF in combination with ribavirin in a number of Iranian patients with chronic hepatitis C or cirrhosis. Fifty two patients with HCV RNA in serum, persistently elevated aminotransferase levels, and chronic hepatitis (n=45) or cirrhosis (n=7) on liver biopsy were enrolled to this study. The patients received PEG-IFN (40 kD) 180 micg per week plus ribavirin 10-15 mg/kg per day. Treatment lasted 48 weeks and was followed by a 24-week follow up period to assess sustained virologic response (SVR). The patients consisted of 46 males and 6 females with a mean age of 38.5 ± 10.9 years. In an intention-to-treat analysis HCV RNA was undetectable in 43 patients (83.7%) at week 48 and SVR was achieved in 28 patients (53.8%). SVR was achieved in 62.9% of naive patients, 35.3% of the patients who had a past failed treatment with IFN-based therapy, 60.0% of patients with chronic hepatitis and 14.3% of cirrhotic patients. In two patients (3.8%) adverse event led to treatment discontinuation and in eight patients (15.3%) dose modification of medication was required. This study showed that combination therapy with PEG-IFN plus ribavirin was associated with a promising SVR rate and acceptable tolerability in Iranian patients. This regimen may be effective for patients who failed prior IFN-based treatment.

Patients with inherited bleeding disorders who regularly receive clotting factors are frequently infected with hepatitis C virus (HCV). Liver biopsy in these patients is high-risk and not always performed. There is no report on pegylated interferon (PEG-IFN) and ribavirin in patients with bleeding disorders in whom no histologic data is available. To assess the safety and efficacy of combined PEG-IFN alfa-2a and ribavirin in patients with inherited bleeding disorders and hepatitis C. We studied 37 patients with inherited bleeding disorders and HCV infection. Patients where planned to receive pegylated interferon alfa 2a (PEG-IFN alfa-2a) 180micg weekly and ribavirin 800mg daily for 48 weeks. They were then followed for 24 weeks after the end of treatment. Early virologic response at week 12 of treatment was achieved in 31/34 patients (91%) and end-of-treatment response was achieved in 30/31 patients (97%). Sustained virologic response was 26/32 (81%) and 26/35 (74%) on per-protocol and intention-to-treat analysis respectively. Dose reduction due to adverse effects was necessary in 11 patients. The combination of PEG-IFN alpha 2a and ribavirin is safe and highly effective in patients with inherited bleeding disorders and HCV infection, even when histologic data is absent.

Interferon monotherapy is currently the only approved treatment for chronic hepatitis C (CHC) infection in transfusion dependent thalassemic patients, in whom ribavirin has limited use because of its hematologic complications. Our aim was to evaluate the efficacy and safety of pegylated Interferon monotherapy for the treatment of HCV infection in transfusion dependent thalassemic patients. The trial was a multicenteric, open label, single treatment prospective study of Peginterferon alfa-2 a (PEGASYS, 180 micg per week) for a period of 48 weeks. 32 subjects, 18 to 42 years old (mean ± SD: 24.1 ± 9.44 years), whose serum HCV RNA was positive and mean ALT remained greater than 1.5 times upper limit of normal were enrolled. A percutaneous liver biopsy was performed before treatment and all patients underwent monthly assessment of any adverse events and were monitored for serum ALT. Efficacy was assessed by measuring serum HCV RNA following 24 week treatment-free period. One patient missed follow up and another died due to a drug unrelated cause and 30 patients were evaluated. Liver biopsy showed mild fibrosis in 31.2%, moderate fibrosis in 53.1% and cirrhosis in 15.6% of patients. Siderosis was severe in 16 patients (50%). In 26 out of 30 patients (86.6%) HCV RNA was negative at the end of treatment (ETR response). Data about 24 weeks post treatment was available in 23 patients, which showed a sustained virological response (SVR) of about 14/23 (60.8%). Two patients had an elevated end of treatment serum ALT instead of negative HCV RNA but their ALT returned to normal as soon as the treatment stopped. These 2 patients were considered to have INF toxicity. Our experience indicates that the cure of HCV-related liver disease in thalassemic patients is not an unrealistic aim and may be reached with Peginterferon alfa-2 a monotherapy in a sizable portion of cases.

Peginterferon alpha-2a is a known standard therapy for patients with chronic HCV infection. However efficacy and safety of this treatment is still unclear in regional settings. This study was designed to clarify efficacy and safety of peg-interferon based therapy in Iranian patients. 23 patients were treated with Peginterferon alpha-2a in combination with ribavirin for 48 weeks. The patients were observed for adverse effects and response to therapy during treatment and 24 weeks after the end of therapy. Early virologic response, end of treatment response, and sustained virologic response rates were 86.9 % (20/23), 82.6 % (19/23), and 78.3 % (18/23) respectively. The most common adverse effects in descending order were flue-like symptoms (74%), mood changes (48%), and weight loss (43%). Combination therapy with Peginterferon alpha-2a and ribavirin for 48 weeks is an effective treatment with minimal adverse effects.

Pegylation of interferon alfa-2a is a new modality for treatment of chronic hepatitis C. This clinical trial was conducted to evaluate the efficacy and safety of PEG IFN in combination with ribavirin in CHC patients. Fifty seven patients with HCV RNA in serum, persistently elevated ALT and chronic C hepatitis on liver biopsy enrolled to this study. The patients received PEG IFN 180 micg per week plus ribavirin 10-15 mg/kg per day. HCV RNA was negative in 37 patients (74%) after three months of beginning of study (EVR) and SVR occurred in 50% of all patients. Peginterferon alfa-2a plus ribavirin is safe and effective in treatment of naïve patients and relapsers.

Hearing loss has been reported on interferons therapy. Combination therapy of pegylated (PEG)-IFN alfa2a plus ribavirin is the current optimal therapy for hepatitis C infection. PEG-INF side effect profile is reported similar in different studies, but with the increasing long-term use of PEG-INF several new adverse effects have been recognized. However, hearing loss has only been recorded once. We report a case of sensorineural hearing loss occurring in a patient with chronic hepatitis C treated with PEG-IFN plus ribavirin and recovered partially one month after the discontinuation of PEG-INF. The ototoxicity would be more serious with the use of PEG-INF. Patients on therapy with this drug should be monitored for auditory disability. The ototoxicity is reversible with discontinuation of drug if the diagnosis is made early in the course.