Michael R. Lucey

Biliary casts after orthotopic liver transplantation: clinical factors, treatment, biochemical analysis

OBJECTIVES:Biliary casts develop in up to 18% of liver transplant recipients. Casts are associated with morbidity, graft failure, need for retransplantation, and mortality. Proposed etiological mechanisms include acute cellular rejection, ischemia, infection, and biliary obstruction. We aimed to identify clinical features associated with biliary cast formation, review treatments, and analyze the biochemical composition of casts at a single, large, liver transplant center.METHODS:Patient records were reviewed retrospectively to identify patients who developed casts. Data were collected with attention to ischemia, rejection, obstruction, infection, immunosuppression, postoperative biliary drain use, and cast-directed management, and were compared with data from controls. Cast specimens, retrieved at cholangiography, were analyzed with chromatography techniques.RESULTS:Ischemic factors were noted in 70% (7/10) of cast patients versus 15% (6/40) of controls (OR = 13.2; 95% CI = 2.7–66.0; p = 0.001). Biliary strictures were present in 50% of cast patients versus 10% of controls (OR = 9.0; 95% CI = 1.8–45.2; p = 0.01). Differences in cold ischemia time, acute cellular rejection, cyclosporin use, infection, and postoperative biliary drain use were not significant. Casts were successfully treated by endoscopic and percutaneous methods in 60% of patients. One patient died of cast-related complications (mortality 10%). Four casts were in satisfactory condition for biochemical analysis. Bilirubin was the main component (∼10–50%). Bile acid synthesis products and cholesterol comprised smaller percentages, and protein comprised only 5–10%.CONCLUSION:Biliary casts are more likely to develop in the setting of hepatic ischemia and biliary strictures. Endoscopic and percutaneous cast extraction might achieve favorable results and should be attempted before surgical therapy.

Drinking behavior and motivation for treatment among alcohol-dependent liver transplant candidates

Abstract Alcohol misuse is the second most common indication for liver transplantation in the United States. Our post-transplant alcoholism treatment trial suggested that current interventions might not be transferable to liver transplantees. We sought to identify differences between patients awaiting liver transplantation and alcoholics entering treatment without severe liver disease. Thirty transplant patients were compared to thirty naltrexone study patients on medical status, alcohol and drug use, alcohol craving, motivation for treatment, psychiatric symptoms, and psychosocial problems. Lifetime alcohol consumption was greater for transplant patients compared to naltrexone patients. In contrast to the naltrexone group, transplant patients denied craving for alcohol and showed little motivation for alcoholism treatment. Groups did not differ on other psychosocial measures. Liver transplant patients differ from patients in alcoholism treatment trials on measures of alcohol consumption, alcohol craving and motivation for treatment. Alcoholism interventions should accommodate their medical condition and boost motivation for continued abstinence.

Hepatitis C transmission and infection by orthotopic heart transplantation

BACKGROUNDnThe transmission and clinical consequences of hepatitis C viral (HCV) infection acquired by orthotopic heart transplantation (OHT) from an HCV-infected donor to an HCV-naive recipient have not been well described. We report our experience in 5 HCV-naive patients who were transplanted with hearts from HCV-positive donors. All transplants occurred within a 1-year period.nnnMETHODSnAfter cardiac transplantation we retrospectively examined the recipients clinical course, liver-associated enzymes, HCV-antibody serology, quantitative HCV RNA level, and HCV genotype.nnnRESULTSnFive subjects with rapidly deteriorating heart failure and negative serum antibodies to HCV received an emergent OHT from a donor known to be infected with HCV. Liver-associated enzymes peaked at 2 to 6 weeks post-transplant: mean peak alanine aminotransferase was 180 U/L (normal, 9 to 52) and aspartate aminotransferase was 111 U/L (normal, 14 to 36). Liver enzymes had returned to normal limits by 6 and 12 months post-OHT. At a mean 15 months after transplantation, only 1 of 5 patients has developed antibodies to HCV, but 4 of 5 have evidence of infection, as shown by serum HCV RNA. No patient has developed evidence of liver failure.nnnCONCLUSIONSn(1) Transmission of HCV from an HCV-positive donor to an HCV-naive recipient at the time of OHT is likely. (2) Antibodies to HCV post-OHT may remain negative for more than 1 year in these patients. (3) Hepatitis C viral RNA using polymerase chain reaction should be the test of choice for diagnosis of HCV infection post-OHT. (4) Hepatitis C viral donor hearts should be limited to critically ill patients in extremis until the long-term consequences of acquisition of HCV by an OHT recipient are known.

Helicobacter pylori infection is not associated with subclinical hepatic encephalopathy in stable cirrhotic patients.

The importance of ammonia-producing Helicobacter pylori infection as a cause of subclinical encephalopathy in cirrhosis was investigated. In addition, a single psychometric test that can reliably detect subclinical hepatic encephalopathy was sought. Out-patients with cirrhosis and no overt encephalopathy underwent [14C]urea breath testing once and psychometric testing on two separate occasions, with an intervening course of clarithromycin/omeprazole if they had subclinical encephalopathy (two of four psychometric tests abnormal). Subclinical encephalopathy was present in 27 of 69 patients (39%), and Helicobacter pylori infection in 14 of 69 (20%). There was no association between the two conditions (P = 0.769). Subclinical encephalopathy resolved in 75% of treated Helicobacter pylori-positive patients and 37.5% of treated Helicobacter pylori-negative patients (P = 0.285). Number connection test-B had high reproducibility among untreated patients (R = 0.655) and high correlation (P ≤ 0.01) with three surrogate gold standards. In stable cirrhotic patients, subclinical hepatic encephalopathy was found to: (1) have a high prevalence, (2) not be associated with Helicobacter pylori infection, and (3) be readily detected with the number connection test-B alone.