Caroline A. Riely

Hepatic histopathologic condition does not correlate with laboratory abnormalities in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count)

OBJECTIVE Our objective was to categorize the histologic findings in the liver in patients with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) and to correlate these findings with the severity of clinical laboratory abnormalities. STUDY DESIGN Eleven patients with laboratory criteria for HELLP syndrome who required cesarean delivery underwent needle biopsy of the liver under direct visualization. RESULTS Eight patients had periportal hemorrhage, and six had fibrin deposition. Fatty infiltration was seen in four, one with large-droplet fat, three with microvesicular fat. There was no statistically significant correlation between the severity of the histologic findings of periportal hemorrhage and fibrin deposition and the clinical laboratory findings. Fatty infiltration did not correlate with the severity of the HELLP syndromes histologic condition, but, in contrast, did correlate with thrombocytopenia and aminotransferase elevations. CONCLUSIONS Laboratory abnormalities do not accurately reflect the severity of the underlying histopathologic condition in HELLP syndrome. We propose that all patients with HELLP syndrome, regardless of the degree of their laboratory abnormalities, be treated aggressively, primarily with delivery.

Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide.

The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria with crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.

Heritable urea cycle enzyme deficiency-liver disease in 16 patients.

The liver mitochondrial enzymes ornithine transcarbamylase and carbamyl phosphate synthetase I catalyze the first two steps in the Krebs-Henseleit pathway from ammonia to of either of these enzymes has been associated with severe and sometimes fatal hyperammonemia in infancy and childhood, but liver histology has usually been described as normal. The Reye syndrome also causes severe hyperammonemia and produces characteristic light microscopic changes in the liver. In addition, OTC and CPS activities have been shown to be depressed and it has been suggested that some cases of the Reye syndrome may reflect an inborn defect in OTC which predisposes the patient to the Reye syndrome. Review of the histopathology of 15 liver specimens from 13 patients with OTC deficiency and three liver specimens from three patients with CPS deficiency has disclosed the following: (1) hemizygous male infants with X-linked OTC deficiency had essentially normal liver histology, although fatally affected with extreme hyperammonemia; (2) in contrast, almost all heterozygous female children and adults had some histologic abnormalities, including nine with minor degrees of steatosis and eight with focal cell necrosis and inflammation, two of whom had piecemeal necrosis and stellate portal scarring; (3) livers from heterozygotes had discrete clusters of larger, pale-staining hepatocytes; (4) female heterozygotes had abnormal liver function, even after the hyperammonemia was controlled; (5) CPS deficient patients had essentially normal liver histology; and (6) neither OTC nor CPS deficiency was associated with a histologic picture which resembled that seen in the Reye syndrome.

Anterior Segment and Retinal Pigmentary Abnormalities in Arteriohepatic Dysplasia

Arteriohepatic dysplasia (AHD, Alagilles syndrome) is presumed to be one of the six known familial intrahepatic cholestatic syndromes, all of which present with neonatal jaundice or failure to thrive, or both. Accurate early diagnosis of the proper syndrome is important, as arteriohepatic dysplasia has a good prognosis, whereas the other syndromes usually lead to death in infancy or early adulthood. Posterior embryotoxon was found in all five of our patients and may be one of the hallmarks of this syndrome. Axenfelds anomaly was present in three of five patients, and retinal pigmentary abnormalities were found in four of five patients. Variable abnormalities were found in the cardiovascular system, bones, central nervous system, kidneys, endocrine system, and body habitus. Inheritance may be autosomal dominant as vertical transmission was documented in one family. Liver function improves during the first five years of life so that only the ocular and skeletal signs may be present in adults.

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. Although serum bile acid levels are elevated in these patients, the individual bile acids do not display a distinctive pattern and no abnormal bile acids are identified.

Biliary tract abnormalities in patients with arteriohepatic dysplasia.

Arteriohepatic dysplasia is a congenital syndrome associated with life-long cholestasis. Because of symptoms suggesting extrahepatic biliary tract obstruction, we studied three patients with this syndrome by endoscopic retrograde cholangiopancreatogram (ERCP). All patients showed a decrease in the number of intrahepatic ducts. In addition, the intrahepatic ducts show attenuation with focal areas of dilatation. In one subject, this latter finding appeared to be a localized process. The extrahepatic ducts were also narrowed. One patient in this series was found to have gallstones and another cirrhosis. Although the relationship of these anomalies to the cholestasis seen in these patients is unclear, arteriohepatic dysplasis can be added to the list of processes associated with biliary tract abnormalities.

Baking powder pica mimicking preeclampsia

We report a case of baking powder pica during pregnancy that was associated with maternal hypertension, hypokalemia, and elevated liver function tests. After discontinuation of baking powder ingestion and correction of electrolyte abnormalities, the blood pressure and the liver function tests normalized.

The effects of early treatment of hereditary tyrosinemia type I in infancy by orthotopic liver transplantation.

Two infants with hereditary tyrosinemia secondary to fumarylacetoacetate hydrolase (FAH) deficiency underwent orthotopic liver transplantation at 14 and 16 weeks of age due to poor clinical and biochemical response to medical therapy. Prompt clearance of abnormal metabolites with improved mental alertness and appetite occurred with minimal perioperative complications. Both infants tolerated rapid institution of normal diets and have shown progressive growth and development in the first 36 months after transplantation. Early liver transplantation should be considered as an option for infants with certain inherited metabolic disorders with poor prognosis, such as tyrosinemia type I, who fail to respond to medical therapy.

Cholangitis in a child due to biliary tract anomalies

A 29-month-old child with persistent cholangitis and steatorrhea complicating congenital hepatic fibrosis underwent radiographic evaluation of the biliary tree. Communicating intrahepatic cavernous ectasias were demonstrated by percutaneous transhepatic cholangiography, a procedure deemed safe in children of this age group. Unlike most patients with cholangitis, he had documented steatorrhea and growth failure which resolved following successful treatment with trimethoprim-sulfamethoxazole. Bacteriologic diagnosis was made by direct culture of liver tissue combined with duodenal intubation.

A Study of Inheritance in Progressive Intrahepatic Cholestasis: Hepatic excretory Function in Unaffected Family Members

Summary: In an attempt to identify the heterozygotes state for progressive intrahepatic cholestasis (PIC), hepatic excretory function (131I rose bengal half-life (t½) and bromosulpthalein-transport maximum (BSP-Tm) was studied in controls and in eight members of a family, two of whom are affected with PIC. Values for 131I rose bengal t½ varied over a wide range in normal controls and were normal in patients with the syndrome of cholestasis and peripheral pulmonic stenosis in whom BSP-Tm and 45 min % retention were abnormal. 131I rose bengal t½ was abnormal in seven of eight family members. Despite this, BSP studies, including Tm, percent retention at 45 min, clearance were normal in all unaffected family members with the exception of the mother who has a reduced BSP-Tm. Fasting serum bile acid studies were normal in all unaffected family members. These studies do not clearly define the inheritance in this syndrome and suggest that any of the following three possibilities exist: 1) that the methods employed were not sensitive enough to detect heterozygotes, 2) that the inheritance in this syndrome is heterogenous; for instance, compound heterozygotes or autosomal dominant, or 3) that the family studies here represents a syndrome different from PIC.Speculation: It has been suggested that the mode of inheritance of progressive intrahepatic cholestasis is autosomal recessive. The use of sensitive tests of hepatic excretory function (such as the t½ 131I rose bengal and the BSP-Tm may identify heterozygotes and confirm the type of inheritance.