|
Ira S. Goldman, MD; John L. Gollan, MD, PhD; Kris V. Kowdley, MD; Paul Martin, MD;
Marion G. Peters, MD |
|
HEPATOLOGY WATCH® |
AUGUST 2003
PRIMARY BILIARY CIRRHOSIS (PBC)
Estrogen therapy to prevent bone loss. Although
estrogen replacement therapy is useful in the treatment of postmenopausal
osteoporosis, there are concerns about its potential for worsening cholestasis
in women with PBC. K.V. Menon and coworkers at the Mayo Clinic (Rochester, MN)
measured bone mineral density of the lumbar spine using dual energy X-ray
absorptiometry in 46 unselected postmenopausal women with PBC. The mean
duration of follow-up was 4.8 ± 0.4 years. Compared to 46 age-matched women
with PBC not receiving estrogen replacement therapy, treatment with estrogens
resulted in a lower rate of bone loss (0.002 ± 0.028 vs. 0.009 ± 0.020
g/cm2/year; p = 0.05). In addition, worsening cholestasis related to estrogen
therapy was not reported in any patient. These findings show that estrogen
replacement therapy is safe in postmenopausal women with PBC and that it may
effectively decrease the rate of bone loss. (Menon KVN, et al. Am J Gastroenterol 2003;98:889-892)
Effect of ursodeoxycholic acid (UDCA) on histologic
progression. Renee Poupon et al. analyzed histologic progression
data obtained from 4 clinical trials investigating UDCA therapy for PBC. They
selected 367 patients who had available paired liver biopsy specimens with a
time interval of approximately 36 months between biopsies for study (200
patients treated with UDCA and 167 patients treated with placebo). While there
was no difference in the progression of the histologic stage between treatment
groups overall, PBC patients with initial stages I-II (n = 177) treated with
UDCA had a decrease in histological stage progression compared to those treated
with placebo (p = 0.03). For all UDCA-treated patients, there was also a delay
in the progression of periportal necroinflammatory lesions (p = 0.03) and an
improvement in the degree of ductular proliferation (p = 0.02) vs the
placebo-treated patients. This analysis supports the early initiation of UDCA
to prevent these histologic features of PBC. An accompanying editorial by
Gustav Paumgartner briefly summarizes previous investigations, which have
indicated that the effect of UDCA on the histologic progression of PBC is
questionable. The editorial emphasizes the importance of UDCA studies that
include an adequate duration and dose of UDCA therapy. (Poupon RE, et al. J Hepatol 2003;39:12-16 and Paumgartner
G. J Hepatol 2003;39:112-114)
HEPATITIS C VIRUS (HCV) INFECTION
Viral dynamics. Jennifer Layden-Almer and others
compared viral kinetics between African-American (n = 19) and white (n = 16)
patients with HCV genotype 1 treated with interferon (IFN)-a2b (10 MU
daily with or without ribavirin for 1 month followed by 3 MU IFN-a2b 3 tiw
with ribavirin 1,000-1,200 mg/d). Nine patients (3 whites and 6 African-Americans)
stopped treatment prior to the end of 48 wk. The median HCV RNA decrease in the
first 24 hr of IFN therapy was 1.74 log copies/mL in white patients compared to
0.94 log copies/mL in African-American patients. Whites also had a higher loss
rate of infected cells. At wk 48 the number of African-American patients (7 of
19 patients) with a treatment effectiveness >90% (log decrease of HCV RNA
>1) was less than that for white patients (13 of 15 patients). However,
viral negativity rates were not different between the 2 groups when controlling
for treatment effectiveness > 90% or < 90%. These data show that the
lower effectiveness of IFN in African-American patients with HCV is due largely
to an impaired ability to inhibit viral production. (Layden-Almer JE, et al. Hepatology 2003;37:1343-1350)
Acute hepatitis C. J. Tilman
Gerlach et al. observed spontaneous viral clearance to occur within 12 weeks in
24 (52%) of 46 patients with acute symptomatic HCV. All asymptomatic HCV
patients (n = 9) developed chronic HCV. The initiation of antiviral therapy
>12 weeks after the onset of acute hepatitis in symptomatic patients who
continued to have detectable HCV RNA levels induced sustained viral clearance
in 80% of patients. These findings showed that treatment of only those
symptomatic patients who remained HCV RNA-positive for >12 weeks after the
acute onset of disease was effective and avoided unnecessary therapy for the
large percentage of patients with spontaneous viral clearance. Patients with
asymptomatic acute HCV infection appear unlikely to undergo spontaneous viral
clearance and should be treated early. (Gerlach JT, et al. Gastroenterology 2003;125:80-88)
CHRONIC HEPATITIS B VIRUS (HBV) INFECTION
Serum HBV DNA as a marker for treatment efficacy. Herve
Mommeja-Marin and coworkers reviewed the literature to investigate the
relationship of treatment-induced changes in serum HBV DNA levels to the
activity of chronic HBV infection. The
literature review included 26 prospective studies with 33 evaluable treatment arms.
Consistent and statistically significant correlations between viral load and
histological, biochemical, and serologic evidence of disease activity were
observed. More specifically, the authors observed that a treatment-induced
reduction in the serum HBV DNA level of >1 log10 was associated with disease
response. Moreover, the authors found that analyses of serum HBV DNA levels had
a broader dynamic range than histology and demonstrated stronger results in
studies using nucleoside regimens to treat HBeAg-positive patients. This review
indicates that HBV DNA is potentially a useful and easily measured alternative
marker to histology of HBV disease activity. (Mommeja-Marin H, et al. Hepatology 2003;37:1309-1319)
VARICEAL BLEEDING
Propranolol plus isosorbide-5-mononitrate. Juan
Carlos Garcia-Pagan et al. performed a multicenter, randomized, double-blind,
placebo-controlled study that showed propranolol plus isosorbide-5-nitrate
therapy did not further decrease the risk of a first variceal bleed in cirrhotic
patients with varices compared to propranolol alone. (Garcia-Pagan JC, et al. Hepatology 2003;37:1260-1266)
Hepatology Watch is produced through
educational grant from 
Hepatology Watch is a registered trademark of Market Development Group