HEPATOLOGY WATCH®
Timely
Information for Practicing Physicians
jANUARY 2001
Alcoholic Liver Disease (ALD)
Long-term follow-up after liver transplantation (LTx). An analysis by Ashok Jain and colleagues of patients
with ALD (n=185) vs. non-ALD (n=649) who underwent LTx identified upper airway
malignancies and age-related illnesses (i.e., cardiorespiratory and
cerebrovascular diseases), instead of recidivism or chronic allograft
rejection, to be the most common causes for lower patient and graft survival
beyond 5 years posttransplantation in patients with ALD. (Jain A, et al. Transplantation 2000;70:1335-1342)
Autoimmune Hepatitis (AIH)
Failure of budesonide therapy.
In a pilot study of 10 patients with AIH who were dependent on
continuous treatment to prevent exacerbation, Albert Czaja and Keith Lindor
observed that budesonide therapy was associated with a low remission rate, a
high recurrence rate, and frequent side effects. (Czaja A and Lindor KD. Gastroenterology 2000;119:1312-1318)
Liver transplantation (LTx).
David Reich and coworkers reviewed the clinical courses of 32 patients
with AIH treated with LTx and found the results to be generally excellent (81%
actuarial survival at 1 and 2 years).
However, AIH recipients had a high frequency of rejection (75%), often
requiring OKT3 (39% of rejection episodes), and recurrent AIH developed in 25%
of patients followed long-term, half of whom required retransplantation. (Reich DJ, et al. Hepatology 2000;32:693-700)
Chronic Hepatitis C Virus (HCV)
Peginterferon alfa-2a therapy.
Peginterferon alfa-2a (Hoffmann-LaRoche) is formed by the covalent
attachment of a 40-kd branched-chain polyethylene glycol moiety to interferon
alfa-2a. This alteration produces a
compound with a more sustained absorption, a slower rate of clearance, and a
longer plasma half-life than unmodified interferon alfa-2a. In this study conducted by Stefan Zeuzem et
al, 531 patients with chronic HCV infection were randomized to receive subcutaneously
either interferon alfa-2a (6 million units 3 times weekly for 12 weeks followed
by 3 million units 3 times weekly for 36 weeks) (n=264), or peginterferon
alfa-2a 180 ug once weekly for 48 weeks (n=267). Patients were assessed at week 72 and the peginterferon alfa-2a
treatment group had a higher rate of sustained virologic response (39% vs. 19%;
p=0.001) and a greater percentage of patients with sustained normalization of
serum alanine aminotransferase levels (45% vs. 25%; p=0.001). The frequency and severity of adverse events
were similar in the 2 treatment groups.
These results provide evidence that weekly peginterferon alfa-2a therapy
is more effective than a standard interferon alfa-2a for patients with chronic
HCV infection. (Zeuzem S, et al. N Engl J Med 2000;343:1666-1672)
Peginterferon alfa-2a in patients with cirrhosis. Jenny Heathcote and colleagues performed a
3-arm study (n=271) in which HCV patients with cirrhosis or bridging fibrosis
were randomized to receive subcutaneous treatment for 48 weeks with either
interferon alfa-2a 3 million units 3 times weekly, peginterferon alfa-2a 90 ug
once weekly, or peginterferon alfa-2a 180 ug once weekly. At week 72, the 180 ug peginterferon alfa-2a
treatment group had higher rates of sustained virological response (30% vs.
8%), normalization of serum alanine aminotransferase levels (34% vs. 15%), and
histological response (54% vs. 31%) compared to the interferon alfa-2a
group. These data indicate that
peginterferon alfa-2a 180 ug weekly is more effective than interferon alfa-2a
for the treatment of HCV patients with cirrhosis or bridging fibrosis. (Heathcote EJ, et al. N Engl J Med 2000;343:1673-1680)
Primary Biliary Cirrhosis (PBC)
Silymarin therapy. Paul Angulo
and coworkers did not find that treatment with silymarin, a potent antioxidant
with immunomodulatory and antifibrotic properties, provides benefit to patients
with PBC who have responded suboptimally to ursodeoxycholic acid therapy. (Angulo P, et al. Hepatology
2000;32:897-900)
Ursodeoxycholic acid (UDCA) effect on liver fibrosis progression. Christophe Corpechot and colleagues used a
Markov model to analyze the fibrosis progression rates in patients with PBC
randomized in a double-blind trial to receive either UDCA (13-15 mg/kg/day) or
placebo for 2 years (n=103). The UDCA
treatment group had a 5-fold lower rate of progression from early stage disease
to extensive fibrosis or cirrhosis than the placebo group (p<0.002). This study shows that UDCA therapy slows the
progression of hepatic fibrosis in patients with PBC. (Corpechot C, et al. Hepatology 2000;32:1196-1199)
Etidronate for osteoporosis.
In this randomized trial, Keith Lindor and his associates at the Mayo
Clinic compared the effects of therapy with the bisphosphonate, etidronate, to
placebo for osteoporosis in patients with PBC (n=67). Osteopenia was defined by bone mineral density criteria (T-score
< -2.0). Patients were administered
oral etidronate 400 mg/day for 14 days every 3 months for at least 1 year and supplemental
calcium was given on the days patients did not receive etidronate. Although etidronate significantly reduced
markers of bone turnover, no differences in bone mineral density in either the
lumbar spine (trabecular bone) or femur (cortical bone) were observed in
patients treated with etidronate compared to those who received placebo. Fractures developed in 4 patients in both of
the treatment groups. This trial demonstrates
that cyclical therapy with an early generation bisphosphonate administered
orally did not improve bone mineral density or prevent fractures in patients
with PBC. (Lindor KD, et al. J
Hepatol 2000;33:878-882)
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