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HEPATOLOGY WATCH® |
Editorial Board: Emmet B. Keeffe, MD
(Chair); M. Eric Gershwin, MD; Ira S. Goldman, MD; John L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul
Martin, MD; Marion G. Peters, MD |
JUNE
2005
PRIMARY
BILIARY CIRRHOSIS (PBC)
Combination
budesonide and ursodeoxycholic acid (UDCA) therapy. Henna Rautiainen
and colleagues conducted an open, multicenter study to assess the effects of
UDCA and budesonide treatments on liver histology in patients with PBC. In total, 77 patients were randomized to
receive either combination budesonide 6 mg/day and UDCA 15 mg/kg/day (treatment
arm A) or UDCA alone (treatment arm B). Liver histology was assessed at
baseline and 3 years later at the end of the study. Paired liver biopsy specimens were available
for 69 patients (37 patients in arm A and 32 patients in arm B). Results showed
that hepatic inflammation decreased in both study arms; fibrosis decreased in
25% of group A patients and increased in 70% of group B patients (P=0.0009). Overall, histologic stage
improved in 22% of patients in arm A and deteriorated in 20% of patients in arm
B (P=0.009). These findings showed
that combination therapy with budesonide and UDCA, but not treatment with UDCA
alone, improved liver histology in patients with PBC. Further studies with
larger numbers of patients and longer follow-up are warranted. (Rautiainen H,
et al. Hepatology. 2005;41:747–752)
Chemical
xenobiotics: possible etiologic role. The etiology of
PBC remains elusive, but emerging evidence has suggested that environmental
factors may be causative agents in its pathogenesis. One theory is that the AMA
response is initiated by a chemical exposure that leads to modification or
alteration of mitochondrial autoantigens. In fact, PDC-E2, the major AMA
reactive antigen, contains lipoic acid and is easily chemically altered. In the
current study, a chemical found in cosmetics, food additives, and perfumes
(2-octynoic acid) was found to react with sera from patients with PBC. The
implication of this work is that a post-translational modification of a
self-protein may lead to loss of tolerance and development of autoimmunity in
genetically susceptible hosts. (Amano K,
et al. J Immunol. 2005;174:5874–5883)
HEPATOCELLULAR
CARCINOMA (HCC)
Coffee
consumption reduces HCC risk. Umberto Gelatti
and others performed a case-control study in a high-incidence region in
CIRRHOSIS
Banding
vs propranolol to prevent initial variceal hemorrhage. Rome Jutabha and
colleagues randomized 62 patients with cirrhosis and high-risk esophageal
varices to receive either propranolol (dose titrated to reduce resting pulse
rate
by ≥25%) or endoscopic banding (performed monthly until varices were
eradicated) for prevention of the first variceal hemorrhage. Mean duration of
follow-up was 15 months. The trial was stopped early because an interim
analysis showed a significantly worse failure rate for propranolol than for
banding (6/31 vs 0/31; P=0.0098). In
addition, the cumulative mortality rate in the propranolol group was greater
than that in the banding group (P=0.0443).
In an accompanying editorial, Thomas Boyer expresses concern about the value of
the statistical differences observed in this study, because the number of
patients was small, the follow-up period was short, and the number of events
(variceal bleeding and deaths) was also small. He reviews the 6 studies
comparing variceal banding to b-blockers, including this study, with only
2 studies showing reduced risk of bleeding in patients treated with banding.
Further studies with sufficient statistical power are needed to define the
respective roles of propranolol therapy and endoscopic banding as prophylaxis
for variceal hemorrhage in cirrhosis. (Jutabha R, et al. Gastroenterology. 2005;128:870–881; Boyer TD. Gastroenterology. 2005;128:1120–1122)
CHRONIC
HEPATITIS C VIRUS (HCV) INFECTION
Peginterferon
alfa-2b plus ribavirin in children. Peginterferon alfa-2b plus ribavirin is standard therapy for adults with
chronic HCV. In the current study, Stefan Wirth and associates evaluated the efficacy and
safety of combination sub-cutaneous peginterferon (1.5 mg/kg weekly) and
oral ribavirin (15 mg/kg/day) in 62 children (ages 2–17 years) with chronic HCV
infection. Therapy was administered for 48 weeks; 61 children completed the
study. Treatment was tolerated with acceptable adverse events: leukopenia
occurred in 83% of patients (only 3 patients required dose reduction), and
10.3% of patients developed thyroid autoantibodies and thyroid dysfunction. Sustained
viral responses were achieved in 47.8% (22/46) of patients with genotype 1
infection, in 100% (13/13) of patients with genotype 2 or 3 infection, and in 1
of 2 patients with genotype 4 infection. These results demonstrated the
efficacy and tolerability of combination peginterferon plus ribavirin therapy
in children with chronic HCV. (Wirth S,
et al. Hepatology. 2005;41:1013–1018)
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