Pegylated interferon treatment in HCV genotype 2 and 3 patients refractory to conventional interferon.

Abstract

HCV RNA detection and quantification, presence of coinfections and co-morbidity, liver biopsy to assess severity of disease and HCV genotype is recommended in patients with hepatitis C, prior to starting treatment. Transient elastography (TE) can also be used to assess cirrhosis in patients with chronic hepatitis C infection. 1 There are six genotypes of hepatitis C virus (HCV). Genotype 1, with subtypes 1a and 1b is the most prevalent worldwide. In USA and Europe, genotype 1a and 1b is common respectively. Genotype 2 is found in the Mediterranean region. Genotype 3a is seen in European intravenous drug users.2,3 Genotype 4 is prevalent in the Middle East. In Pakistan, genotype 3 is the most common. However, genotype 1, 2 and 4 have also been documented.3 Chronic infection with HCV is associated with hepatic inflammation, progressive fibrosis and HCC.4 The disease process is accelerated in the presence of comorbid conditions such as co-infection with hepatotropic viruses, HIV, diabetes mellitus etc. regardless of the genotype or viral load.5 Hence, before starting treatment in any patient, after a complete physical examination, preliminary investigations such as anti-HCV antibodies by enzyme immunoassays and HCV RNA detected by real-time polymerase chain reaction (PCR), which can quantify HCV RNA levels upto approximately 107 IU/mL HCV,6 as well as PT (prothrombin time), APTT (activated partial thromboplastin time), LFT (liver function test), complete blood picture, ultrasound abdomen (for hepato- splenomegaly), and co-morbid states such as co-existing infection with HBV and HDV need to be documented. Also, HCV genotype has to be assessed before starting treatment in order to determine the dose of ribavirin and decision regarding the treatment duration.1 To assess the grade of inflammation and stage of fibrosis (METAVIR, Scheuer, Ishak, and Knodell's), liver biopsy is regarded as a reference method to-date.7,8 Drawbacks of liver biopsy are well-known; therefore, recent alternative methods are being used such as the TE which perform better at diagnosing cirrhosis, rather than fibrosis. However, factors such as obesity, age and biochemical necroinflammatory factors may adversely affect TE. 9 The direct [ALT, AST, prothrombin time, platelets, APRI i.e. AST platelet ratio index, AST/ALT ratio [Forn's Index] and indirect biomarkers (α-2 globulin) are helpful in combination with TE for assessment of liver . 10 Patients infected with HCV genotypes other than genotype 1 who failed to respond to therapy with standard IFN-α and ribavirin can be treated with pegylated interferon (PEG-IFN) and weight based ribavirin.1 The first generation protease inhibitors i.e. teleprevir and boceprevir are not effective or licensed for non-1 genotypes. Retreatment should be considered, if they have significant fibrosis, evidence of inadequate exposure to PEG-IFN and ribavirin due to dose adjustment/ or poor adherence during the first course of therapy. Longer re-treatments of 48 weeks are advisable for genotypes 2 and 3, while 72 weeks for genotype 4.11 Patients relapsing after treatment with standard IFNbased regimens respond to re-treatment with pegylated IFN-α and ribavirin in 32-53% of cases.1,12 Maintenance