Weight Reduction May Improve Fibrosis, ALT, Insulin & Triglycerides in Chronic HCV

     Andrew D Clouston, Julie R Jonsson, Univ of Queensland, Brisbane Australia; Ingrid Hickman, Claudia Shorthouse, Princess Alexandra Hosp, Brisbane Australia; Trevor Mori, Univ of Western Australia, Perth Australia; John Prins, Princess Alexandra Hosp, Brisbane Australia; Graeme Macdonald, Elizabeth E Powell, Univ of Queensland, Brisbane Australia

The results of this small study in 12 individuals ( with pre and post liver biopsies) suggest that weight reduction may reduce fat around the liver (steatosis), lower ALT, improve fibrosis, and triglycerides & serum insulin.

Steatosis is a common histological finding in chronic hepatitis C (HCV) and is associated with increased hepatic fibrosis. Steatosis is more common in patients with HCV genotype 3 and in patients with an increased body mass index (BMI). We studied 12 patients (9M, 3F, mean age: 424.5 [range 30-52]) with chronic HCV, steatosis, and BMI 25  to determine the effect of weight reduction on hepatic steatosis, necroinflammatory activity and fibrosis, and lipid peroxidation. Patients received a calorie-controlled diet and increased their daily exercise during a 12-week intervention period, and were seen weekly by a nutritionist. The goal was a 0.5kg weight loss per week.

Liver function tests were performed monthly during the study and a liver biopsy was obtained prior to and 3-6 months following the intervention. Steatosis was graded from 1-3 and HAI/fibrosis scored by modified Knodell. Urinary F2-isoprostanes (a marker of in vivo lipid peroxidation) were measured by gas chromatography/mass spectrometry in paired urine samples from 5 patients taken prior to and at completion of the intervention. Fasting lipids, glucose and insulin were measured. Initial BMI (mean 303.9) ranged from 25.2-34.4kg/m2. Waist (cm) was 1028.8 (range 90-129). 7 patients had genotype 1 and 4 had genotype 3. 

Mean weight loss was 7.6 kg, (reduction in BMI [range 1.1-4.2] 2.4 kg/m2). Body weight reduced mean 8.0% (range 4.4-12.7). All patients reported subjective increase in energy & well being. In 8 of 12 patients there was a progressive reduction in ALT (p=0.02) that paralleled their weight loss (p<0.001). Pre-treatment and post- liver biopsies were available at this time from 7 patients. The grade of steatosis decreased in all 7 patients. The Knodell Fibrosis score was reduced in 3 of 7 patients. These improvements were seen in patients with genotype 1 or 3. The 3 patients with improved fibrosis had their pre- biopsy just prior to the 12 week intervention and unfortunately the post biopsy was performed around 6 months following the 12 week intervention. There was a mean reduction in grade of steatosis of 1.3, necroinflammatory activity of 0.4, fibrosis of 0.7 and urinary F2-isoprostanes of 11%. The mean ALT loss was from 120 to 85 over the 12 week study period. The authors concluded that these results demonstrate that weight reduction in patients with chronic HCV is achievable and reduces hepatic steatosis irrespective of viral genotype. Preliminary results show a reduction in lipid peroxidation and an improvement in Knodell necroinflammatory and fibrosis score. These results support the need for larger studies to assess the place of weight loss in the management of chronic hepatitis C.

Weight loss was also accompanied by significantly reduced fasting serum insulin (p=0.004) and triglycerides (p=0.04).