HEPATOLOGY WATCH®
Timely
Information for Practicing Physicians
july 2000
Refractory
Ascites
Transjugular intrahepatic
portosystemic shunt (TIPS). Martin Rossle and colleagues conducted a prospective
study in which patients with cirrhosis and refractory (no response to at least
300 mg of spironolactone or 120 mg of furosemide per day for ³4 weeks) or recurrent
(³3
times in one year) tense ascites were randomized to receive TIPS (n=29) or large
volume paracentesis (n=31). Patients
with grade 2 or higher hepatic encephalopathy, a serum bilirubin >5 mg/dL, a
serum creatinine >3 mg/dL, or portal vein thrombosis were excluded. At 1 and 2 years, the probability of
survival without transplantation was greater in the TIPS (69% and 58%,
respectively) than in the paracentesis group (52% and 32%, respectively), but
not significantly so (p=0.11). However,
at 3 months 61% of the TIPS patients compared to 18% of the paracentesis
patients had no ascites (p=0.006), and multivariate analysis showed TIPS to
have an independent effect on survival without transplantation (p=0.02). There was no difference between the groups
in the incidence of hepatic encephalopathy.
Thus, in selected patients with refractory/recurrent ascites, TIPS is
associated with a greater response rate and a trend towards improved
survival. (Rossle et al. N Engl J Med 2000;342:1701-1707)
Liver
Transplantation
Living donor liver
transplantation (LDLT). The shortage of organs has stimulated the
investigation of adult-to-adult LDLT utilizing the right hepatic lobe as a
source of functioning liver tissue. The
first series of adult patients treated with LDLT were reported in 1999, and
both donors and recipients did well, generating enthusiasm for LDLT. Amadeo Marcos and coworkers compared the
results of the first 20 adults to the results of the second 20 adults at their
institution who underwent LDLT.
Modifications in patient selection (United Network for Organ Sharing
criteria IIA patients excluded), surgical management (uniform systemic stenting
of bile ducts), and postoperative care (more rapid tapering of
immunosuppressive drugs) instituted in the second cohort of 20 patients
improved outcomes with respect to infectious and biliary complications and
mortality in recipients. The morbidity
in donors was minimal in both groups.
(Marcos. Liver Transpl
2000;6:3-20 and Marcos et al. Liver
Transpl 2000;6:296-301)
PRIMARY BILIARY CIRRHOSIS (PBC)
Long-term effects of
ursodeoxycholic acid (UDCA) therapy. The administration of UDCA to patients with
cholestatic liver disease increases secretion of bile acids, may improve bile
flow, and may reduce immune-mediated liver damage. Kris Kowdley concluded in a recent review that the role of UDCA
in patients with miscellaneous cholestatic liver diseases is pending the
outcome of more randomized trials, but UDCA shows promising effects in PBC,
cystic fibrosis and intrahepatic cholestasis of pregnancy. Subsequently, Albert Pares et al. reported
the results of a double-blind trial (n=192) in which patients with PBC were
randomized to receive UDCA (14-16 mg/kg/day) or placebo. The median follow-up was 3.4 years (range,
0.3 to 6.1 years). UDCA-treated
patients had decreases in biochemical liver tests of cholestasis and did not
experience histological progression of disease, while the histological stage
progressed in placebo patients.
However, times to death, liver transplantation, and clinical
complications were similar between the two groups, likely because >70% of
patients were in stages I and II with survival times expected to be longer than
the study follow-up period. (Kowdley. Am J Med 2000;108:481-486 and Pares et
al. J Hepatol 2000;32:561-566)
Hepatic
Veno-Occlusive Disease (VOD)
UDCA prophylaxis. K. Ohashi and
associates conducted a prospective, multicenter trial in which 132 patients who
had undergone stem cell transplantation were randomized to receive UDCA therapy
as prophylaxis for hepatic VOD or no prophylactic therapy. VOD occurred in 3% of the patients treated
with UDCA compared to 18.5% of the control patients (p=0.0043). This result is consistent with those of a
previous study reported by James Essell et al., which demonstrated that
ursodiol prophylaxis following bone marrow transplantation was found to
effectively prevent VOD (p=0.03).
(Ohashi et al. Am J Hematol 2000;64:32-38 and Essell et
al. Ann Intern Med 1998;128:975-981)
Hepatitis
C Virus (HCV)
Interferon alfa (IFN) and
depression. In a recent article, Darko Zdilar and colleagues
reviewed the association of depression with IFN therapy of patients with
HCV. Psychiatric side effects,
including depression, occur in at least 20% of IFN-treated patients with HCV. IFN-induced depression is an important
challenge because it has a negative impact on quality of life, interferes with
treatment compliance, and can have serious complications, including
suicide. The pathophysiology of
IFN-induced depression is unknown.
Selective serotonin reuptake inhibitors have been used to treat the depression. A suggested practical approach for the
assessment and management of IFN-induced depression is provided. The authors conclude that studies directed
at the mechanism of this IFN-induced psychiatric disorder are needed. (Zdilar et al. Hepatology 2000;31:1207-1211)
Liver
Fibrosis
Association with obesity. Vlad Ratziu et al
studied 93 consecutive overweight patients (body mass index [BMI] >25 kg/m2)
referred for investigation of abnormal liver function tests. All patients had a complete evaluation
including liver biopsy. Septal fibrosis
was found in 28 patients (30%) and cirrhosis in 10 patients (11%). Septal fibrosis was strongly associated with
necroinflammatory activity.
Multivariate analysis identified age ³50 years, BMI ³28 kg/m2, triglycerides ³1.7 mmol/L and ALT ³2 x normal to be
independently correlated with septal fibrosis.
These data show that septal fibrosis frequently occurs in overweight
patients with abnormal liver function tests.
(Ratziu et al. Gastroenterology 2000;118:1117-1123)
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