Asymptomatic primary biliary cirrhosis. A progress report on long-term follow-up and natural history.

Thirty-six patients presenting with asymptomatic primary biliary cirrhosis have been followed for a median period of 11.4 yr, extending by 5 yr a previously reported median follow-up study of 6 yr. Life table survival analysis indicates that the overall survival of this subgroup of patients with primary biliary cirrhosis continues to remain similar to that of the general population (p = 0.

Liver ultrastructure in mitochondrial urea cycle enzyme deficiencies and comparison with Reye's syndrome.

The liver ultrastructural findings in two girls with partial carbamyl phosphate synthetase I (CPS) deficiency and their heterozygote parents and two siblings with ornithine transcarbamylase (OTC) deficiency are described. Liver ultrastructure in the four patients with inherited deficiencies of urea cycle enzymes showed minimal alterations with essentially normal mitochondria when biopsy was performed during periods of good control of their hyperammonemia. Mitochondrial ultrastructure was also essentially normal in the heterozygotes for carbamyl phosphate synthetase I deficiency.

The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis.

To determine the life expectancy of patients with primary biliary cirrhosis, we analyzed survival data from 280 patients with either symptomatic (243) or asymptomatic (37) disease. Patients were followed for up to 19 years (mean, 6.9 years).

A prospective morphologic evaluation of hepatic toxicity of chenodeoxycholic acid in patients with cholelithiasis: the National Cooperative Gallstone Study.

A sample of 126 patients with cholelithiasis was treated with chenodeoxycholic acid (CDCA) (375 or 750 mg g.d.) for 2 years.

Arteriohepatic dysplasia: a benign syndrome of intrahepatic cholestasis with multiple organ involvement.

Arteriohepatic dysplasia (Alagille's syndrome) is presumed to be one of the familial intrahepatic cholestatic syndromes, all of which present with neonatal jaundice or failure to thrive, or both. We report the findings in five patients with this syndrome, four of whom have been followed into adulthood. In addition to hepatic dysfunction, patients had abnormalities of the cardiovascular system, eyes, bones, central nervous system, kidney, endocrine system, and habitus.

Enzymatic fluorometry for estimating serum total bile acid concentration.

Fasting serum total bile acid (SBA) levels were estimated by enzymatic fluorometry (EF) in 36 subjects without liver disease, 28 with hepatic lesions and impaired hepatic function, and 79 with hepatic lesions and normal function. Fasting and postprandial EF-SBA levels were compared in nine normal subjects and nine patients with cholestasis, and SBA assays by EF and gas-liquid chromatography (GLC) were compared in 28 patients with hepatic lesions and impaired function. Levels of SBA were below 9 mumole/L in all but two of the 36 subjects without liver disease, and above that level in all 28 with impaired hepatic function and 17 (24%) of the 70 with hepatic lesions and normal liver function.

Halothane hepatitis: benign resolution of a severe lesion.

Three patients with halothane hepatitis were studied during the acute phase of their illness and for 10 to 14 months thereafter. Clinical, biochemical, and histologic data were obtained initially and during the course of follow-up. Despite initially severe clinical and biochemical presentations, with extensive bridging hepatic necrosis on liver biopsy, all three patients resolved completely and had minimally abnormal liver biopsy appearances at last follow-up.

Hepatitis B in hemodialysis patients: significance of HBeAg.

Twenty-four HBsAg-positive (HBsAg+) hemodialysis patients were prospectively studied to assess (1) the prognostic value of HBeAg and its HBe1Ag and HBe2Ag components and (2) whether a difference in cellular immune status between HBeAg+ and HBeAg-negative (HBeAg-) patients could be defined. Sixteen patients were HBeAg+ and 8 were HBeAg- initially. After a mean follow-up period of 23.

A father and son with cholestasis and peripheral pulmonic stenosis: a distinct form of intrahepatic cholestasis.

We report a father and son with the syndrome of cholestasis and peripheral pulmonic stenosis. These cases demonstrate the clinical and biochemical features noted in previous reports of this entity and allows us to differentiate clearly this syndrome, with its benign course, from other more progressive forms of intrahepatic cholestasis. The vertical transmission supports a genetic etiology for this disease.

Elevations in skin tissue levels of bile acids in human cholestasis: relation to serum levels and topruritus.

To define the relationship of bile acid retention to the pruritus of cholestasis, we quantified individual bile acids in serum, acetone swabs of skin, and skin tissue in 13 patients with cholestasis undergoing laparotomy and in 8 controls. There was no consistent relationship between pruritus and concentrations of either total or individual bile acids in serum. Skin tissue concentrations of bile acids were elevated in patients with cholestasis, were linearly related to serum levels, and did not differentiate between those patients with and those without pruritus.

Identification of lymphocytes in percutaneous liver biopsy cores. Different T:B cell ratio in HB sAg-positive and -negative hepatitis.

The lymphocytes infiltrating the liver were isolated and characterized as T or B cells in three groups of patients: 20 patients with hepatitis B surface antigen (HB sAg)-positive acute and chronic hepatitis, 8 patients with HBsAg-negative chronic hepatitis with prior evidence for hepatitis B virus (HBV) infection, and 5 patients with HBsAg-negative chronic hepatitis without prior evidence for HBV infection. The predominant cell infiltrating the liver was shown to be a T cell in all categories; however, the ratio of T:B cells was significantly lower (1.96) in the patients without evidence for HBV infection than in the patients who were HBsAg-positive at (7.

Serum alpha-fetoprotein in patients with massive hepatic necrosis.

Serum concentrations of alpha-fetoprotein (AFP) were measured by radioimmunoassay in 12 patients with massive hepatic necrosis, 11 of whom died. Levels were significantly elevated after the 8th day of illness in 8 of the 9 patients who died between the 10th and 60th day, and in the 1 patient who survived. All 9 patients with increased levels of serum AFP exhibited histological evidence of hepatic regeneration.

Nonhuman primate-associated viral hepatitis type A. Serologic evidence of hepatitis A virus infection.

Since 1961, viral hepatitis has been recognized as an occupational hazard among handlers of newly imported chimpanzees and other nonhuman primates. To determine whether previously reported cases were caused by human viral hepatitis type A, we tested paired serum samples from two outbreaks for antibody to hepatitis A antigen (anti-HA) by immune adherence hemagglutination (IAHA), recently available test. In both outbreaks, one of hepatitis transmitted from chimpanzee to man (Michigan, 1964), the second from chimpanzee to chimpanzee, man, and woolly monkey (Connecticut, 1971), serologic data documented recent hepatitis A virus infection among contacts-human and nonhuman primate-of implicated chimpanzees.

Serum bile acids in alcoholic liver disease. Comparison with histological features of the disease.

Fasting serum bile acids were measured by gas-liquid chromatography in 64 patients with alcoholic liver disease and compared with histological features in their percutaneous liver biopsy specimens. Total bile acid concentrations were normal (less than 2 mug/ml) or minimally increased in 6 patients in whom fatty infiltration was the only hepatic lesion. In the remaining 58 patients with more severe histological lesions, levels were increased in 93%, whereas serum bilirubins were elevated in only 43%.

Inhibitory effects of scillaren and dinitrophenol on bilirubin excretion by the isolated perfused rat liver.

The effects of scillaren and dinitrophenol on bilirubin excretion by the perfused rat liver were studied. Both compounds inhibited bile flow, scillaren by 20 to 40%, and dinitrophenol by 60 to 80%. Bilirubin excretion was also impaired.

Serum bile acids in primary biliary cirrhosis.

Fasting serum bile acid levels were measured by gas-liquid chromatography in 56 patients with primary biliary cirrhosis. Of these, 52 (93%) had increased levels (greater than 2mug/ml), including 14 of the 18 with normal serum bilirubin concentrations. The four patients with normal bile acid levels had early lesions as judged by histological and clinical criteria.

Hepatic granulomata: problems in interpretation.

Granulomata occur in the liver not only in patients with systemic granulomatous disease, but also in a variable number with underlying liver disease and in a heterogeneous group of disorders that appear to be neither hepatic nor granulomatous in nature. The hepatic granulomata found in association with liver disease are rarely attributable to complicating systemic granulomatous disease, and probably represent a nonspecific response to the underlying hepatic disease. In the heterogeneous group of diseases that appear to be neither hepatic nor granulomatous in nature, hepatic granulomata may (in some instances) represent a nonspecific response to such conditions as intraabdominal malignancy and ulcerative bowel disease.

Acute granulomatous hepatitis. Occurrence in cytomegalovirus mononucleosis.

Two previously healthy adults with acute granulomatous hepatitis attributable to cytomegalovirus (CMV) monucleosis had prolonged fever, heterophil-negative lymphocytosis with numerous atypical forms, minor alterations in hepatic function, and evidence on biopsy, of a nonspecific acute hepatitis with granulomata. Infection with CMV was corroborated by a rising titer of complement-fixing antibody in case 1 and by a high titer of antibody that later fell in case 2. It is important to exclude CMV ivfection as an etiologic factor in cases of acute granulomatous hepatitis and fever of unknown origin.

alpha-fetoprotein in noneoplastic hepatic disorders.

Serum alpha-fetoprotein levels were measured by radioimmunoassay in 473 patients with biopsy-proved noneoplastic hepatic disorders; 22% had values greater than 40 ng/ml, whereas only 1 of 350 patients with nonhepatic benign diseases had a value greater than this. Levels exceeded 40 ng/ml in more than 30% of patients with various types of hepatitis, and in 0% to 15% with inactive postnecrotic cirrhosis, primary biliary cirrhosis, biliary tract obstruction, and alcoholic liver disease. Values greater than 500 mg/ml were observed solely in viral subacute hepatic necrois.