High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C

Abstract

The aim of this study was to determine if body mass index (BMI) was an independent predictor of response to antiviral treatment in patients with chronic hepatitis C. A retrospective review was performed of all patients at a single center with chronic hepatitis C treated with antiviral medication from 1989 to 2000. A sustained response was defined as either negative hepatitis C virus (HCV) RNA by polymerase chain reaction and/or normal alanine aminotransferase (ALT) level (only in those treated before availability of HCV RNA testing) 6 months following completion of therapy. All patients were classified into one of 3 groups according to BMI (normal, <25 kg/m 2 ; overweight, 25-30 kg/m 2 ; obese, >30 kg/ m 2 ). A total of 253 patients were treated with either interferon (IFN) monotherapy or IFN in combination with ribavirin. Patients were excluded if predetermined clinical characteristics were unavailable. Using logistic regression, and after adjusting for the examined variables (age, sex, history of alcohol consumption >50 g/d, cirrhosis on pretreatment biopsy, and BMI), likelihood ratio tests showed significant differences in response to treatment according to BMI group (P ‫؍‬ .01), genotype (P < .01), and cirrhosis (P < .01). Those with genotypes 2 or 3 had an odds ratio (OR) for success of 11.7 compared with those with genotype 1, cirrhotic patients had an OR of 0.15 compared with noncirrhotic patients, and obese patients had an OR of 0.23 compared with normal and overweight patients. Hepatic steatosis was not an independent risk factor for response to antiviral treatment. In conclusion, obesity, only when defined as a BMI greater than 30 kg/m 2 , is an independent (of genotype and cirrhosis) negative predictor of response to hepatitis C treatment. (HEPATOLOGY 2003;38:639-644.)

Steatosis: Co-factor in other liver diseases

“…However, in subjects with viral genotype 3, steatosis does not negatively affect the outcome of treatment, suggesting that steatosis per se may not intrinsically impair antiviral efficacy. Other investigators found that obesity is a negative predictor of treatment response, 60 and in an earlier study, interferon blood levels and 2Ј5Ј-oligoadenylatesynthetase induction were lower in obese patients after a dose of interferon-␣. 61 Because obesity and steatosis are inter-related, whether their effects are independent and whether weight-based dosing can improve the treatment response remain unclear.…”

“…8 The development of cirrhosis in patients with HCV may be associated with regression of steatosis, 21 as has previously been documented in non-alcoholic steatohepatitis (NASH). 22,23 The mechanisms leading to a reduction in steatosis in the liver with cirrhosis remain Mihm et al 99 Yes Ratziu et al 18 Yes Fartoux et al 19 Yes Czaja et al 9 Yes Yes Yes Hourigan et al 10,11 Yes Yes Yes Adinolfi et al 12 Yes Yes Yes Yes Westin et al 13 Yes Weak Yes Yes Castera et al 14 Yes Yes Monto et al 15 Yes Yes Yes Kumar et al 100 Yes Camps et al 101 Yes (BMI) Kaserer et al 102 Yes Bressler et al 60 Yes (BMI) Rubbia-Brandt et al 28 Yes Yes Poynard et al 16 Yes Yes Yes Yes Yes Patton et al 17 Yes Yes Yes Yes Yes Nair et al 70 No* Marrero et al 103 Yes Ohata et al 74 Yes *Steatosis was a risk for HCC in alcoholic and cryptogenic cirrhosis only. Abbreviation: BMI, body mass index.…”

Steatosis and Chronic Hepatitis C Infection: Mechanisms and Significance

“…Data suggest that fixed, rather than weight-based dosing, irrespective of the type of interferon, leads to a decreased response to therapy in obese patients. Bressler et al 37 showed in a retrospective trial that BMI was associated independently with a decreased SVR in patients, although only a small number of patients received peginterferon alfa-2a at standard dose, and none of these patients were given ribavirin. However, pharmacokinetic studies of peginterferon alfa-2a have shown that serum levels of drug are higher at all time points than the weight-based peginterferon alfa2b.…”

Pharmacogenomic perspectives of chronic hepatitis C virus (HCV) infection

“…Thus, the majority of SR patients are under 40 years old and have normal BMI and low baseline HCV RNA level, along with non-1 HCV genotypes and accelerated viral decay in the early periods of therapy. [2][3][4][5] In addition to the various factors enumerated above, documentation of higher SR rate in European Americans than African Americans has highlighted the ethnic differences, most likely due to genetic heterogeneity or increased occurrence of HCV genotype 1 in black people. Pharmacogenetic studies should be useful in elucidating such individual and ethnic disparities in response to HCV therapy.…”