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HEPATOLOGY WATCH® |
Editorial Board: Emmet B. Keeffe, MD
(Chair); John L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul
Martin, MD; Marion G. Peters, MD |
SEPTEMBER 2005
DRUG-INDUCED HEPATIC TOXICITY
Outcomes and prognostic markers. A literature review by Rostom and associates revealed that diclofenac
and rofecoxib caused higher rates of aminotransferase elevations than other nonsteroidal
anti-inflammatory drugs (NSAIDs) or placebo. However, no NSAID led to increased
rates of liver-related serious adverse events, hospitalizations, or deaths. In
a related article, Bjornsson and Olsson assessed outcomes and prognostic
markers in severe drug-induced liver disease. The authors noted that the
combination of high aminotransferase levels and jaundice has been reported to
lead to a 10% to 50% mortality with different drugs, a phenomenon known as
“Hy’s rule.” In this study, all reports of suspected hepatic adverse drug
reactions received by the Swedish Adverse Drug Reactions Advisory Committee
between 1970 and 2004 were reviewed. A total of 784 cases (hepatocellular
injury, 409; cholestatic injury, 206; mixed liver injury, 169) in which bilirubin
levels were two or more times the upper limit of normal (ULN) were analyzed. Here
the mortality/transplantation rate was 9.2%, and bilirubin levels were higher
in the deceased/transplanted patients than in the surviving patients (median,
5.5 × ULN). Using logistic regression analysis, age and aspartate
aminotransferase and bilirubin levels were found to independently predict death
or need for liver transplantation in the hepatocellular group whereas bilirubin
level was the only independent predictor in patients with cholestatic/mixed
liver injury. (Rostom A, et al. Clin
Gastroenterol Hepatol. 2005;3:489–498 and Bjornsson E and Olsson R. Hepatology. 2005;42;481–489.)
NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Natural history. Adams and colleagues at the Mayo Clinic reviewed the medical records of
420 patients from Olmsted County, Minnesota diagnosed with NAFLD between 1980
and 2000 to determine clinical outcomes to 2003 (mean follow-up, 7.6 years
[range, 0.1 to 23.5 years]). The survival of NAFLD patients was lower than
expected compared with the general population in
Sampling variability of liver biopsies. Ratziu and colleagues assessed
paired liver biopsies in 51 patients with NAFLD. Discordance of at least one
stage was found between the pairs in 41% of patients, suggesting that sampling
errors can result in inaccurate diagnosis and staging of NAFLD patients. (Ratziu
V, et al. Gastroenterology.
2005;128:1898–1906.)
AUTOIMMUNE HEPATITIS (AIH)
Long-term outcomes. Two recent studies investigated the long-term outcomes of patients with
AIH treated with standard immunosuppressive therapy. In a retrospective chart
review (n = 163) performed by Tan and others, multivariate regression analysis showed
that AIH patients who do not demonstrate a 50% improvement in serum
transaminase levels at 6 months of immunosuppressive therapy (early response) have
a poor prognosis and should be considered for alternative treatments or
referred for liver transplantation. In the second study, Seela and coworkers
reviewed the records of 42 AIH patients with a mean follow-up of 16 years
(range, 7 to 43 years). Their data indicate that AIH can be managed effectively
for up to four decades with low-dose immunosuppression. Liver transplantation
can be avoided for long periods in most of these patients. (Tan P,
et al. Liver Int. 2005;25:728–733 and
Seela S, et al. Liver Int. 2005;25:734–739.)
CHRONIC HEPATITIS B VIRUS (HBV) INFECTION
Adefovir resistance during 4 years of treatment. Lamivudine-resistant HBV has been
reported to emerge in 70% of HBV patients by 4 years of lamivudine therapy. In
the current investigation, Locarnini and others analyzed five studies in which
patients were treated with adefovir dipivoxil for 48 to 192 weeks. By 192
weeks, the cumulative probability of adefovir resistance was 15%. No
adefovir-resistant mutations were identified in patients who received
lamivudine plus adefovir. Logistic regression analyses identified only higher
serum HBV DNA levels at week 48 to predict for adefovir resistance. These data
indicate that the chance of developing resistance by 4 years of treatment is fourfold
lower with adefovir therapy than with lamivudine therapy. (Locarnini S, et al. EASL 2005; abstract 36.)
INTRAHEPATIC CHOLESTASIS OF PREGNANCY (ICP)
Ursodeoxycholic acid (UDCA) treatment. Zapata and coworkers retrospectively
analyzed a 12-year experience of treating ICP patients with UDCA at the
University of Chile School of Medicine. Compared with historical data, UDCA
treatment ameliorated pruritus (P
<0.05) and biochemical cholestasis (P
<0.05). In addition, infants born to UDCA-treated mothers weighed a mean of
500 g more than controls (P <0.01).
At 3 months all infants were observed to have developed normally. These
findings suggest that UDCA may be effective treatment for patients with ICP.
(Zapata R, et al. Liver Int.
2005;25:548–554.)
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