Extensive Liver Disease Research Articles

Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-fu and interferon-alpha-2b

A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5-FU) and subcutaneous recombinant interferon-alpha-2b (rIFN-alpha-2b) in the treatment of hepatocellular carcinoma (HCC) and to define factors that might be predictive of a response to treatment. Twenty-nine patients were registered on the protocol. 5-FU was administered as a continuous intravenous (i.v.) infusion (dose = 750 mg/m2) for 5 consecutive days. rIFN-alpha-2b was administered subcutaneously (SC) (dose = 5 x 10(6) um/m2) once a day on days 1, 3, and 5 of the 5-FU infusion. The treatment was repeated at 14-day intervals. Responses were assessed at the end of one course of therapy, which was equivalent to four treatments. Of the 28 patients evaluable for response, 5 (18%) had a partial response, and 1 (4%) had a minor response. Responses lasted from more than 2 to more than 24 months (median, 11.5 months). Ten (36%) patients experienced no response, and 12 (43%) had progressive disease. The 6 responders were part of a group of 16 patients who had pretreatment levels of serum alpha-fetoprotein (AFP) of 50 ng/ml or less and a group of 8 whose tumors involved 50% or less of the liver parenchyma. Mucositis, which occurred in 54% of the patients, was the most common toxicity associated with the treatment regimen. Diarrhea and dermatitis were observed in 16% and 17% of the patients, respectively; fatigue, thrombocytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen. The regimen of i.v. 5-FU and SC rIFN-alpha-2b was well tolerated and induced durable partial response in 31% (5 of 16) of patients with HCC who had low levels of serum AFP and in those with 50% or less of liver replacement. In contrast, the treatment regimen was ineffective in patients with HCC who had high levels of serum AFP or extensive liver disease.

Immunocytochemical diagnosis of alpha-1-antitrypsin deficiency Review of eight cases

Eight cases of liver disease associated with alpha-1-antitrypsin deficiency are described. Six of the cases, including the only childhood case, showed no evidence of lung disease. An occult but variable clinical course is defined in this disorder. A spectrum in the severity of tissue change was noted, and in some instances, extensive liver disease was correlated with relatively minor derangement in liver function. While this form of liver disease is uncommon, it should be included in the differential diagnosis of adult liver disease. Screening for alpha-1-antitrypsin globules in periodic acid-Schiff stained liver tissue sections should be considered in certain cases of cryptogenic liver disease in adults, particularly when advanced disease presents suddenly, where micronodular (portal) cirrhosis is unrelated to excessive alcohol use, or where tissue changes exceed those anticipated from serum biochemical abnormalities. In most of these cases, tissue findings from liver biopsy or autopsy, rather than clinical suspicion, led to the diagnosis. The availability of a simple and reliable immunoperoxidase technique, applicable to routinely processed tissue samples, allowed for rapid and specific diagnosis in all cases. This immunocytochemical method has proven its usefulness in the prospective and retrospective tissue diagnosis of alpha-1-antitrypsin deficiency and associated liver disease.

Chronic Hypervitaminosis A

A case of chronic hypervitaminosis A in a 51-year-old female is discussed. The patient was ingesting 27,500--35,000 international units of vitamin A daily for 30 years. The patient displayed the classic symptoms of the disease, including skin and hair changes, esophageal varices and extensive liver disease. Vitamin A products were discontinued and the patient's dietary intake of the vitamin was minimized. Previous reports and studies of hypervitaminosis A are reviewed. Social factors causing increased consumption of vitamin A and regulations governing the sale of vitamin A are discussed. By being aware of the factors influencing vitamin A consumption, hypervitaminosis A can be detected and prevented more readily.

Formula omitted] acid : Asialoglycoprotein sialic acid transferase activity in liver and serum of patients with juvenile hepatic cirrhosis and α-1-antitrypsin deficiency

The molecular basis for the accumulation of a substance which displays the immunological reactivity of α-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum α-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with α-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 2.4.99.1) an enzyme which transfers sialic acid from cytidine-5′-monophosphate-N- acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with α-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with α-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients withliver disease. However, serum from family members homozygous for α-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialyltransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with α-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialyltransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuais with α-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of α-1-antitrypsin rather than the enzyme deficiency being the primary cause of the hepatic cirrhosis and α-1-antitrypsin deficiency.