HEPATOLOGY WATCH®
Timely
Information for Practicing Physicians
FEBRUARY
2000
Chronic Hepatitis C Virus (HCV) Infection
Characteristics of patients with persistently normal ALT levels. M. Mazen Jamal and colleagues conducted a
case-control study to assess the clinical features of chronic HCV patients with
persistently normal serum ALT levels (³ 4 consecutive normal ALT values within 12 months) (n=75)
compared to those of chronic HCV patients with abnormal serum ALT levels
(n=200). Patients were previously
untreated with interferon, and all patients were found to have significant
liver disease. Mean serum ferritin and
HCV RNA levels were lower in the persistently normal ALT group (P=0.017 and
0.02, respectively). The normal ALT
group had a lower prevalence of cirrhosis (P=0.007) and less fibrosis,
piecemeal necrosis, and severe portal and lobular inflammation
(P<0.05). In addition, a slower
fibrosis progression rate was observed in the normal ALT patients
(P<0.001). These data show that
chronic HCV patients with persistently normal ALT levels have a lower level of
viremia and less severe hepatitis than patients with abnormal ALT levels. (Jamal MM, et al. Hepatology 1999; 30: 1307-1311)
Autoimmune Hepatitis (AIH)
Ursodeoxycholic acid (UDCA) adjunctive therapy. AIH patient responses to standard
corticosteroid therapy are variable and relapses are frequent following drug
withdrawal. Albert Czaja and coworkers
conducted a study in which AIH patients who were suboptimal responders to
corticosteroid treatment were randomized in a double-blind fashion to receive
UDCA (13-15 mg/kg) (n=21) or placebo (n=16) daily x 6 months in addition to
corticosteroid therapy. Although UDCA
treated patients more commonly experienced decreases in serum ALT and alkaline
phosphatase levels, the frequencies of clinical improvement and corticosteroid
dose reduction or withdrawal were similar in the placebo group compared to the
UDCA group. The results of this small
study indicate that a 6-month adjunctive course of UDCA can improve laboratory
tests but does not affect the clinical outcome of this subgroup of AIH patients
with a suboptimal response to corticosteroid therapy. (Czaja AJ, et al. Hepatology
1999; 30: 1381-1386)
Primary Biliary Cirrhosis
Mitochondrial antigens in saliva.
PBC is primarily a disease of intrahepatic bile ducts; however, recent
studies have noted pathologic findings within the epithelium of pancreatic,
salivary, and lacrimal glands. Sandra
Reynoso-Paz et al. evaluated saliva samples from PBC patients to search for the
presence of mitochondrial autoantigens in mucosal compartments. Antimitochondrial autoantibodies (AMA) were
detected in 92% (45/49) of the PBC saliva samples, and 80% of these AMAs were
IgA against PDC-E2 (the major autoantigen in PBC). In addition, saliva from PBC patients was found to inhibit pyruvate
dehydrogenase, and a 74 kd molecule (the same molecular weight as PDC-E2) was
found in PBC saliva but not in control saliva.
These results show that mitochondrial autoantigens are present in the
saliva of PBC patients and that a locally initiated mucosal immune response may
be responsible for the pathologic findings present in the secretory tissues of
PBC patients. (Reynose-Paz S, et
al. Hepatology 2000; 31: 24-29)
Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Gastric variceal bleeding/predictors of outcome after TIPS. TIPS is an effective therapeutic procedure
for the complications of portal hypertension.
Karl Barange and coworkers evaluated the use of TIPS in 32 consecutive
patients with bleeding gastric varices unresponsive to sclerotherapy, infusion
of vasoactive agents and tamponade.
Hemostasis was achieved in 18 of 20 actively (requirement for ³ 2-unit blood transfusion)
bleeding patients, and rebleeding rates were 14%, 26% and 31% at 1 month, 6
months, and 1 year, respectively. A second
study by Naga Chalasani and colleagues determined prognostic factors for
survival of patients with cirrhosis who underwent TIPS placement (n=129). 30-day and 1-year survival rates were 81%
and 25%, respectively. Multivariate
analysis identified variceal hemorrhage requiring emergent TIPS placement and a
serum bilirubin level >3.0 mg/dL to be predictors of 30-day mortality. These 2 predictors of 30-day mortality plus
a serum ALT >100 IU/L and pre-TIPS
encephalopathy independently predicted an increased risk of death during
long-term follow-up. TIPS is an
effective therapy for cirrhotic patients with gastric variceal bleeding
refractory to standard treatments, and prognostic variables have been
identified to evaluate the appropriateness of a TIPS procedure for individual
patients. (Barange K, et al. Hepatology
1999; 30: 1139-1143 and Chalasani N, et al.
Gastroenterology 2000; 118: 138-144)
Hepatocellular Carcinoma (HCC)
Surgical resection. Jean-Marc Regimbeau et al. compared the outcomes of HCC patients
who underwent liver resection for small tumors (<5 cm in diameter) (n=121)
to those who had large tumors (>8 cm in diameter) (n=94) resected. They found that short-term in-hospital
mortality, long-term survival, and disease-free survival were similar in
patients undergoing resection for large HCCs compared to those with small
HCCs. A greater risk of death and
recurrence in patients with large HCCs was found only in a subgroup of patients
with chronic underlying liver disease (P=0.02 at 2 years postoperatively). Thus, patients with large HCCs, if
resectable, should not be left untreated but considered for resection. (Regimbeau J-M, et al. J Hepatol
1999; 31: 1062-1068)
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