Factors predictive of a beneficial response to therapy of hepatitis C

Abstract

disease. 2 Many of these studies identified pretreatment paAlpha interferon is the only drug that has been shown to tient characteristics that are associated with a greater or lesser be effective in the treatment of chronic hepatitis C, but only likelihood of response to interferon ( Table 1). The most clinihalf of patients respond, either transiently or permanently.cally important of these factors were the level of serum HCV Pretreatment features that are associated with a greater likeli-RNA, viral genotype, and the histology of the pretreatment hood of response to short courses of interferon include low liver biopsy specimen. [3][4][5] Indeed, each of these factors has hepatitis C virus (HCV) RNA levels, viral genotypes 2 or 3, been shown by multivariate analysis to be independently and the absence of fibrosis or cirrhosis on liver biopsy. Each associated with response by the end of the course of interof these features is more predictive of sustained response feron treatment, known as end-of-treatment response (ETR; (SR) than the end-of-treatment response (ETR). However, the previously termed complete response), and sustained reaccuracy of these features in predicting response in individual sponse (SR; response persisting for at least 6 months after patients is poor. Furthermore, there are several limitations to the discontinuation of treatment). The clinical application of using these factors in the clinical management of patients.these predictive factors has taken several forms. First, and Most importantly, they were identified in 6-month treatment most importantly, it has allowed clinical investigators to detrials. Longer treatment or combination of interferon with sign better studies by stratifying for these factors that influribavirin reduces relapses and will therefore lessen the associence response. It has also allowed investigators to understand ation of these factors with long-term response. In addition, differences in response rates in studies conducted in different changes in the definition of treatment end points and the populations. However, it has also led to changes in treatment technology used to measure HCV RNA might change the assopatterns. In an attempt to improve response rates and reduce ciation between these predictive factors and response. The the cost of interferon treatment, some have suggested exclubest predictor of a treatment response is the early normalizasion of patients from treatment if they have one or more of tion of the serum alanine aminotransferase (ALT) level during the pretreatment markers that have been associated with a interferon treatment. HCV RNA loss during treatment may reduced likelihood of response. Some physicians routinely also be helpful in predicting response, but it is probably no exclude patients with cirrhosis from treatment and some clinbetter than serum ALT levels and is expensive. In summary, ical trials have excluded them to increase response rates. 6 several clinical and virological features are associated with Furthermore, commercial advertisements ...

Effect of interferon therapy on hepatitis C virus RNA in whole blood, plasma, and peripheral blood mononuclear cells

“…11 Additionally, there was a trend for genotypes other than 1a and 1b to be preferentially found in patient groups responding to interferon, similar to previous reports. 11 Figure 1 shows representative profiles of the serum ALT Abbreviations: n, Total number of patients; ALT, alanine aminotransferase (normal levels are male Ͻ35 U/L and female Ͻ25 U/L); NT, non-typeable. *Number of patients in each genotype, with percent of total in each genotype in parenthesis.…”

“…Some favorable pretreatment variables include low serum viral RNA levels, young patient age, early histological grade of chronic hepatitis, and viral genotypes other than type 1a or 1b. 11 The possibility of a favorable outcome is enhanced if normalization of serum transaminase levels and clearance of serum viral RNA occur within the first 3 months after initiation of therapy. 12,35 The identification of laboratory parameters that are useful in predicting a sustained response has been elusive.…”

“…6,7 Although the reasons responsible for relapse are unclear, variables such as length of treatment, HCV genotype, and histological evidence of inflammation and fibrosis at the start of therapy appear to correlate with treatment outcomes. 3,[8][9][10][11] Reverse-transcription (RT) polymerase chain reaction (PCR) techniques to detect HCV RNA during interferon therapy have been widely employed and are considered to be important for optimum management. 12,13 A high level of HCV RNA in serum before treatment is a poor prognostic sign for sustained response; unfortunately, clearance of virus from serum or plasma at the end of treatment as determined by qualitative RT-PCR test does not reliably predict a sustained response.…”

Efficacy and Safety of Pegylated (40–Kd) Interferon α–2A Compared With Interferon α–2A in Noncirrhotic Patients With Chronic Hepatitis C

“…Patients with HCV genotype non-1 had better responses compared with patients with HCV genotype 1, across all treatment arms, as has been observed in other trials of IFN-based therapy. 1,2,6,[9][10][11] This study demonstrated that PEG(40kd) IFN ␣-2a is superior to IFN ␣-2a in the treatment of patients with CHC. The 180-g PEG(40kd) IFN ␣-2a dose was associated with the highest sustained virological and biochemical responses (36% and 38%, respectively).…”

Mutations in nonstructural protein 5A gene and response to interferon in hepatitis C virus genotype 2 infection

“…Pretreatment serum HCV-RNA levels in HCV-2a and -2b and patient' s age in HCV-2b were confirmed to be factors affecting the interferon response as previously described. 51 Recently, we found a significant association between the mutation in the NS5A2209-2248 of HCV-1b (ISDR) and the response to interferon alfa 13 or beta. 39 ISDR mutations are also shown to be related to the serum HCV-RNA levels.…”