HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians
JUNE 1998
BENIGN LIVER TUMORS
Focal nodular hyperplasia in pregnancy. Focal nodular hyperplasia (FNH) and hepatocellular adenoma are two benign liver tumors that occur predominately in women. FNH is associated with a benign clinical course while patients with adenoma are treated surgically because of the risk of hemorrhage and hepatocellular carcinoma. Dr. Weimann and coworkers have reviewed the cases of 10 women with FNH who became pregnant and were followed at their institution between the years 1980 and 1996 to determine the clinical course of these patients during pregnancy. No increase in tumor size was observed and all children were healthy at delivery. In contrast, 3 of 47 adenoma patients having surgery during the same period had complicated pregnancies (including 2 stillbirths). The authors conclude that while life threatening tumor rupture may occur during pregnancy in patients with adenomas, no substantial risk has been found in cases of FNH. (Weimann A, et al. Lancet 1998; 351: 1251-1252)
CHRONIC HEPATITIS B
Interferon-a for chronic hepatitis B in children. Dr. Sokal and colleagues have performed an open-label, randomized trial of 24 weeks of interferon-a2b (Intron A 6 megaunits/m2 three times weekly) versus no therapy in children with chronic hepatitis B infection (144 evaluable patients; 70 treated and 74 controls). Twenty-six percent of treated children compared to 11% of untreated children became negative for HBV DNA and lost HBeAg (P=0.029) and HBsAg became undetectable in 10% of interferon patients versus 1% of controls (P=0.03). Among the responders, serum aminotransferase levels normalized and liver histology improved. Interferon treatment was generally well tolerated as therapy was discontinued early or doses were reduced in only 4% and 24% of children, respectively. The authors conclude that a 6-month course of interferon-a therapy is safe in children and promotes loss of markers of viral replication. (Sokal ME, et al. Gastroenterology 1998; 114: 988-993)
CHRONIC CHOLECYSTITIS
Isolation of Helicobacter species from bile. Gallbladder carcinoma is the number one cause of cancer mortality in Chilean women. Incidence rates for cancer of the gallbladder vary widely throughout the world suggesting that environmental factors, including infectious microorganisms, play a role in its pathogenesis. Dr. James Fox and colleagues recently examined bile or resected gallbladder tissue from 46 Chileans undergoing cholecystectomy by polymerase chain reaction analysis to determine whether Helicobacter species is associated with chronic cholecystitis. Thirteen of 23 bile samples and 9 of 23 tissue samples were positive for Helicobacter. Eight amplicons were fully sequenced and bile resistant Helicobacter species were identified. The authors conclude that their data support an association of bile resistant Helicobacter species with gallbladder disease. (Fox JG, et al. Gastroenterology 1998; 114: 755-763)
HEMOCHROMATOSIS
Heterogeneity of hemochromatosis in Italy. Patients with hereditary hemochromatosis (HHC) show a widely variable degree of iron overload. Dr. Alberto Piperno and coworkers studied genotype-phenotype correlation in a series of 188 Italian patients with iron overload in the range of homozygous HHC. HHC gene analysis by polymerase chain reaction restriction assay found the frequency of homozygosity for the C282Y mutation to be 64%. C282Y homozygotes showed more severe iron overload than other genotypes. In addition, among the C282Y homozygotes, the ancestral haplotype (HLA-A3 linked) was associated with a more severe phenotype. Acquired factors (e.g., thalassemia, alcohol intake, viral hepatitis) may favor the development of a mild hemochromatosis phenotype in patients nonhomozygous for C282Y. The authors conclude that HHC in Italy is a heterogenous disorder influenced by genetic and acquired factors. (Piperno A, et al. Gastroenterology 1998; 114: 996-1002)
Screening for hemochromatosis. Dr. Claus Niederau and colleagues prospectively screened 3,012 asymptomatic employees and 3,027 outpatients by determining serum ferritin levels and transferrin saturation to estimate the frequency of iron overload and iron deficiency. Gross iron overload indicated by elevated transferrin saturation and ferritin levels was proven by liver biopsy or phlebotomy treatment in 28 study subjects and 6 of their siblings. Thirty of these 34 subjects were precirrhotic. Among male employees, gross iron overload was almost as common as iron deficiency (0.4% and 0.5%, respectively). The authors conclude that the prevalence of hemochromatosis is high and that screening for hemochromatosis in asymptomatic people should be established. (Neiderau C, et al. Ann Intern Med 1998; 128: 337-345)
ALTERNATIVE THERAPY
Milk thistle therapy for liver disease. Dr. Kenneth Flora and colleagues at the Oregon Health Sciences University review the history and pharmacological properties of milk thistle extract as well as the clinical trials investigating their use as therapy for liver disease. Silymarin, the active extract of the milk thistle plant, is a mixture of several compounds including flavonoids and silybin. The flavonoids act as free radical scavengers and silybin may function as an antioxidant. Silymarin has been utilized for centuries, however well designed clinical trials with adequate numbers of patients have yet to be performed. (Flora K, et al. Am J Gastroenterol 1998; 93: 139-143)
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