Clinicians are required to assess abnormal liver chemistries on a daily basis. The most common liver chemistries ordered are serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin. These tests should be termed liver chemistries or liver tests. Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels. Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels. The majority of bilirubin circulates as unconjugated bilirubin and an elevated conjugated bilirubin implies hepatocellular disease or cholestasis. Multiple studies have demonstrated that the presence of an elevated ALT has been associated with increased liver-related mortality. A true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females and levels above this should be assessed. The degree of elevation of ALT and or AST in the clinical setting helps guide the evaluation. The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency. In addition, a history of prescribed and over-the-counter medicines should be sought. For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken. Total bilirubin elevation can occur in either cholestatic or hepatocellular diseases. Elevated total serum bilirubin levels should be fractionated to direct and indirect bilirubin fractions and an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible.
Biliary cast syndrome (BCS), the presence of biliary casts and debris causing biliary obstruction, occurs in 4%-18% of orthotopic liver transplant (OLT) recipients. Potential consequences include cholangitis and graft damage or loss. Limited data exist regarding the etiology and outcomes of BCS. The purpose of this study was to evaluate donor and recipient risk factors and determine the impact of BCS. A retrospective review of 355 OLT cases identified 9 BCS patients (2.5%) diagnosed by cholangiography. Twenty-six matched controls were also identified. The warm ischemic time was significantly longer in BCS patients. Other recipient and donor preoperative and intraoperative characteristics, including the donor risk index, revealed no significant differences. Overall patient survival showed a trend toward worse outcomes at 6, 12, and 18 months and end of follow-up in the BCS group. Overall graft survival was also worse in the BCS group at all time periods, with statistical significance demonstrated at 18 months and end of follow-up. The number of therapeutic biliary procedures and hospital readmissions was significantly higher in the BCS group. Twenty-two percent of the BCS patients required repeat OLT versus none of the control patients. In conclusion, BCS is an uncommon complication of OLT. Except for a longer warm ischemic time, recipient and donor factors did not predict the occurrence of BCS. BCS patients showed a significantly worse graft survival, as well as a trend toward worse patient survival. Given the negative impact of BCS on liver transplant outcomes, further studies appear justified.
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