Prediction of treatment outcome in patients with chronic hepatitis C: Significance of baseline parameters and viral dynamics during therapy

Abstract

In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-␣) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P < .0001), a low baseline gamma-glutamyltransferase (GGT) level (P < .0001), a high baseline alanine aminotransferase level (P ‫؍‬ .002), and a low baseline viral load (P ‫؍‬ .04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2-and 3-infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment. (HEPATOLOGY 2003;37:600-609.)

High Predictability of a Sustained Virological Response (87%) in Chronic Hepatitis C Virus Genotype 1 Infection Treatment by Combined IL28B Genotype Analysis and &#947;-Glutamyltransferase/Alanine Aminotransferase Ratio: A Retrospective Single-Center Study

“…The use of both the ratio of γ-GT/ALT and IL28B single nucleotide polymorphism factors enhances the predictability of antiviral combination therapy. In several studies using both uni- and multivariate analysis, a significant association with treatment outcome using the γ-GT level and the serum ALT for predicting an SVR has been shown [11,12,13]. In contrast to the reported studies, the present investigation focused on the role of the pretreatment γ-GT/ALT ratio.…”

“…Laboratory parameters such as the level of ALT and γ-GT are associated with treatment outcome after antiviral therapy irrespective of receiving either dual or triple therapy combinations [7,11,12,13,16]. None of these studies, however, reported a cutoff value for these two laboratory factors that define a successful treatment outcome.…”

“…In contrast, in retrospective studies using multivariate multinomial logistic regression analysis, high ALT activity was associated with treatment outcome [7,11,12]. In addition, low pretreatment serum γ-glutamyltransferase (γ-GT) activity was found to be significantly and independently related to SVR in multivariate regression analyses [12,13]. A low pretreatment serum γ-GT/ALT ratio was recognized as a simple predictive factor for therapeutic outcome in individuals infected with either genotype 1 or 3 both in retro- and prospective analyses [14,15].…”

Impact of HBV Infection on Outcomes of Direct-Acting Antiviral Therapy of Chronic Hepatitis C

“…Several factors have been identiied, including age, liver ibrosis, HCV genotype, HCV RNA levels, race, amino acid substitutions in the core and NS5A regions, and interleukin 28B polymorphisms have been reported as predictors of response to IFN therapy [26][27][28][29][30][31]. This study investigated whether HBV coinfection afects response to DAA therapy.…”

Outcome of Double-Filtration Plasmapheresis plus Interferon Treatment in Nonresponders to Pegylated Interferon plus Ribavirin Combination Therapy

“…Hemodialysis, hemofiltration and peritoneal dialysis given to chronic dialysis patients infected with HCV significantly lower HCV RNA levels in the blood [17]. The change in serum HCV RNA levels after starting therapy is an important predictor of treatment outcome [18,19,20]. Especially, a 2-log reduction in the HCV RNA viral load by week 4 is a prerequisite to achieving SVR with PEG-IFN/RBV combination therapy [21].…”