The impact of renal transplantation on the course of hepatitis B liver disease.

To establish the impact of transplantation on the course of chronic hepatitis B liver disease we performed a prospective study of the clinical and pathological sequelae of hepatitis B disease in all 22 patients who had renal allografts that functioned for more than 1 year and who were hepatitis B surface antigen (HBsAg)-positive following transplantation. No patient converted to HBsAg-negative. During a mean follow-up of 83 months serial liver biopsies were performed in 20 patients and 1 liver biopsy was available in the remaining 2 patients. Eleven patients died of liver disease, 5 of whom died of hepatic failure, 3 with hepatoma, 2 of gastrointestinal hemorrhage, and 1 of ascites with pleuroperitoneal fistula. Aggressive liver disease was observed in the vast majority of patients: 12 ultimately developed cirrhosis, (mean follow-up 81 months), 6 chronic active hepatitis (mean follow-up 93 months), 3 chronic persistent hepatitis (mean follow-up 89 months), and in 1 patient the presence of HB virus in hepatocytes was the sole morphologic alteration (follow-up 42 months). There was a marked tendency to progression in that 82% of patients with virus only, reactive hepatitis, or chronic persistent hepatitis on initial biopsy subsequently developed chronic active hepatitis or cirrhosis. For comparison, 10 HBsAg-positive patients whose renal failure had been treated by hemodialysis were also studied over a comparable period. Four patients converted to the negative state. Biochemical evidence of persistent liver dysfunction occurred in only 1 patient and no patient has died from complications of liver disease. We conclude that in the immunosuppressed renal transplant patient HB infection often results in the development of cirrhosis, leading to death from hepatoma and hepatic failure. This course is worse than that in dialysis patients. Renal transplantation of HBsAg-positive patients with end-stage renal failure may be inadvisable.

Diazoxide in the management of chlorpropamide overdose.

Three cases of chlorpropamide overdose are reported. Plasma levels of chlorpropamide, diazoxide, glucose, and insulin are presented for each patient during treatment. The simultaneous analysis of chlorpropamide, hydrochlorothiazide, and diazoxide in plasma by high pressure liquid chromatography (HPLC) is also reported. Although all three cases presented at hospital with potentially lethal plasma levels of chlorpropamide, each was successfully treated with intravenous diazoxide and glucose. Plasma diazoxide concentrations between 50-100 microgram/mL appear to be optimal in achieving therapeutic control of chlorpropamide induced hypoglycemia.

Chronic hepatitis in end-stage renal disease: comparison of HBsAg-negative and HBsAg-positive patients.

To determine the outcome of chronic hepatitis in ESRD we studied all 358 renal transplant recipients and 295 hemodialysis patients treated for greater than 1 year since 1970. The incidence of chronic hepatitis (elevated SGOT for greater than 1 year) was 15% (N = 54) in transplanted and 3.4% (N = 10) in dialysis patients. Forty-eight percent (26) of transplanted and 50% (5) of dialysis patients were HBsAg positive. In the transplanted group, the clinical outcome of chronic hepatitis was significantly better in HBsAg-negative compared to HBsAg-positive patients; 11% died, none from liver disease, and 32% remitted after a mean follow-up from start of liver disease of 77.3 +/- 8.2 months, whereas in the HBsAg-positive group 54% (14) died, nine from liver disease, and one remitted after a follow-up of 90.2 +/- 8.9 months. Adverse prognostic factors (age, duration of diabetes, and heart disease) present before ESRD treatment began were similar in both groups, as was duration of follow-up. Only 14% (2/14) of HBsAg-negative patients progressed to chronic active hepatitis on liver biopsy compared to 71% (15/21) of HBsAg-positive patients. Histological stability in those with serial biopsies occurred in 66% (4/6) of HBsAg-negative patients, but in only 18% (13/16) of HBsAg-positive patients with a similar duration of follow-up. No dialysis patients died from liver disease. We conclude that chronic hepatitis occurs more frequently in transplanted than dialyzed patients, and that HBsAg-negative chronic hepatitis has a more benign, clinical, and histological outcome than chronic HBsAg-positive hepatitis in renal transplant recipients.