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Ira S. Goldman, MD; John L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul Martin, MD;
Marion G. Peters, MD |
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HEPATOLOGY WATCH® |
NOVEMBER 2003
NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Obesity associated with liver disease. Cross-sectional studies of
patients with chronic liver disease due to different causes have suggested a
correlation between obesity and the presence of fibrosis or cirrhosis. George Ioannou and colleagues analyzed data
from a cohort of 11,465 NHANES I (the first National Health and Nutrition
Examination Survey) participants who did not have evidence of cirrhosis at
baseline or during the first 5 years of follow-up. These subjects were 25 to 74 years of age and
were followed for a mean of 12.9 years. Analysis
of their data revealed a strong association between obesity or being overweight
and cirrhosis-related death or hospitalization among persons who consume little
or no alcohol. In a second study,
Stephen Harrison and coworkers conducted repeat liver biopsies in 22 patients
with nonalcoholic steatohepatitis (NASH) at a mean of 5.7 years (range, 1.4 –
15.7 years) after the first biopsy. They
found NASH to have a variable histological course in these patients; including
7 patients who had fibrosis progression (2 patients had rapid progression to
advanced fibrosis). Histological
progression correlated with higher serum AST levels at last biopsy. Samyah Shadid and Michael Jensen reported
that treatment of 20 NAFLD volunteers with the thiazolidinedione pioglitazone,
30 mg/day for 18 ± 0.4
weeks, resulted in improvement of insulin sensitivity and liver function
studies. Brent Neuschwander-Tetri et al
utilized rosiglitazone, another thiazolidinedione, 4 mg twice daily for 48
weeks, to treat 30 patients with NASH and found that improved insulin
sensitivity was associated with improved histological findings. Five patients (17%) did not complete 48 weeks
of treatment because of hepatotoxicity (increased ALT levels), bad dreams, or
personal reasons. ALT, aspartate
aminotransferase, alkaline phosphatase, and GGT levels all decreased during
rosiglitazone treatment. These 2
single-arm, uncontrolled studies of thiazolidinediones suggest that improving
insulin sensitivity may be of potential benefit in the treatment of NASH. Large, randomized, placebo-controlled studies
are needed to confirm these preliminary results. (Ioannou GN et al. Gastroenterology 2003;125:1053-1059. Harrison SA et al. Am J Gastroenterol 2003;98:2042-2047.
Shadid S, Jensen MD. Clin Gastroenterol
Hepatol 2003;1:384-387. Neuschwander-Tetri et al. Hepatology 2003;38:1008-1017.)
CHRONIC HEPATITIS C VIRUS (HCV) INFECTION
Treatment of HCV-related cirrhosis prior to liver
transplantation (LT). Xavier
Forns and others evaluated the safety and efficacy of antiviral therapy
(interferon alfa-2b 3 MU/d plus ribavirin 800 mg/d) in 30 patients with
HCV-related cirrhosis awaiting LT. The
median duration of treatment was 12 weeks and 9 patients (30%) achieved a
virological response. All 9 responders
underwent LT and 6 patients remained free of HCV after a median follow-up of 46
weeks. Side effects were frequent; dose reductions
were necessary in 19 patients; 11 patients required filgrastim because of neutropenia;
and 8 patients received erythropoietin because of anemia. In an accompanying editorial, Jean-Pierre
Zarski and Marie-Noelle Hilleret provided a brief review of the limited number
of small case series of the treatment of patients with decompensated
HCV-related cirrhosis before LT. They
emphasized that this therapy remains experimental and that prospective trials
are needed to confirm the usefulness of this strategy of anti-HCV therapy prior
to LT. (Forns X et al. J Hepatol
2003;39:389-396. Zarski J-P Hilleret M-N. J
Hepatol 2003;39:435-436.)
HCV and risk of
hepatocellular carcinoma. Adrian
Di Bisceglie and associates conducted a retrospective survey and found HCV to
be the most common risk factor for hepatocellular carcinoma in both African Americans
and Caucasians in the
MISCELLANEOUS
Natural history of the C282Y homozygote. Cory Yamashita and Paul Adams of
the London Health Sciences Centre in
Hepatic injury associated with herbal weight loss aids. Masayuki Adachi et al report
hepatic injury, including fulminant hepatic failure, in 12 patients who were
receiving herbal weight loss aids (chaso and onshido) that contained a variant
of the appetite-depressant fenfluramine (N-nitroso-fenfluramine). (Adachi M et
al. Ann Intern Med 2003:139:488-492.)
Recurrence of primary biliary cirrhosis (PBC)
after LT. Pamela Sylvestre and
coworkers at the Mayo Clinic in
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