Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection #

Abstract

In hepatitis C virus (HCV) genotypes 2 and 3 patients, the high rate of relapse after 12 to 16 weeks of antiviral therapy is the main concern for shortening treatment duration. This study was undertaken to delineate predictors of relapse after short treatment in patients with undetectable HCV RNA at treatment week 4 (RVR), and to report in RVR patients with relapse the sustained virological response (SVR) after a second 24-week course of therapy. RVR patients received pegylated interferon (Peg-IFN) alfa-2b (1.5 g/kg) and ribavirin (1000-1200 mg/day) for 12 weeks; those who relapsed were retreated with the same drug doses but for the extended standard duration of 24 weeks. Logistic regression analysis was applied to delineate predictors of relapse by using age, sex, route of transmission, body mass index ( I n patients with chronic hepatitis C virus (HCV) genotype 2 and 3 infection, a combination of pegylated interferon (Peg-IFN) with ribavirin attained sustained virological response (SVR) rates of up to 88% when administered for the standard duration of 24 weeks. [1][2][3][4] In the event the infection was cleared at treatment week 4, length of treatment may be shortened to 12 to 16 weeks without compromising SVR rates. [5][6][7][8] The major concern about the implementation of short treatment in clinical practice is the relapse rate. 9 In our original investigation, in which truncated treatment was offered only to patients with rapid virological response (RVR), relapse amounted to 10%, 5 a figure not different from the 10% to 12% values reported in other studies that used short treatment duration. 6,8 At a variance, when genotype 2 and 3 infected patients were treated for 16 weeks, irrespective of the RVR status, the rate increased to 31%. 9 Defining efficacy of re-treating patients who relapse after a shortened course of therapy is of paramount relevance, but only limited information on this aspect is available: 9 of 10 relapsers after short therapy who agreed to be re-treated for 24 weeks eventually cleared the infection. 5

Association of Amino Acid Substitution Pattern in Core Protein of Hepatitis C Virus Genotype 2a High Viral Load and Virological Response to Interferon-Ribavirin Combination Therapy

“…Previous reports indicated that viral factors (e.g., viral load, aa substitutions in the NS5A region, early viral kinetics, and periods from the start of treatment to initial point of undetectable HCV-RNA) and host factors (e.g., body mass index, fibrosis stage, and level of soluble interleukin-2 receptor) might be important predictors of treatment response to 24-week IFN + ribavirin combination therapy in patients infected with HCV genotype 2a, in addition to treatment-related factors (e.g., treatment duration and ribavirin dose) [6][7][8][9][23][24][25][26][27][28] . Using multivariate analysis, the present study identified viral-(viral load and substitution of aa 4) and host-related factors (age and serum albumin levels as surrogate markers of liver fibrosis [3,11] ) that influenced the virological response to 24-week combination therapy in patients with genotype 2a infection and a high viral load.…”

“…IFN + ribavirin combination therapy carries potential serious side effects and is costly, especially when used long enough to achieve a high SVR. For these reasons, especially in genotype 2 infection, it is necessary to identify those patients who could achieve SVR with a shorter treatment course ( ^ 16 weeks) to free them of unnecessary side effects and reduce costs, preferably as early as possible [6][7][8] . Identification of these viral and host factors before the start of combination therapy should help design better therapeutic regimens.…”

“…For these reasons, especially in genotype 2 infection, it is necessary to identify those patients who could achieve SVR with a shorter treatment course ( ^ 16 weeks) to free them of unnecessary side effects and reduce costs, preferably as early as possible [6][7][8] . Furthermore, we also sometimes encounter treatment-resistant patients infected with genotype 2a [3,10] .…”

Extending Combination Therapy with Peginterferon plus Ribavirin for Genotype 2 Chronic Hepatitis C Virological Responders: A Pilot Study of 7 Cases

“…body mass index, fibrosis stage, and hepatocyte steatosis) might be important predictors of treatment response to IFN-related therapy in patients infected with HCV genotype 2a, in addition to treatment-related factors (e.g. treatment duration, and ribavirin dose) [6][7][8][9][10][11][21][22][23][24][25][26][27] . One of the lim- itations to this study is that due to the small number of patients we were not able to investigate treatment-resistant factors.…”

“…Intervirology 2010;53: [188][189][190][191][192] 189 especially in genotype 2 infection, it is necessary to identify those patients who could achieve SVR with a shorter treatment course (16 weeks or less) to free them of unnecessary side effects and reduce costs, preferably as early as possible [6][7][8] . However, we also sometimes encounter treatment-resistant patients infected with genotype 2 [3,10,11] .…”