Primary hepatocellular carcinoma after orthotopic liver transplantation for chronic hepatitis B infection.
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Biomedical subjects
Publications and source records attributed to R L Carithers.
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Recovery of hepatic function following orthotopic liver transplantation includes the ability to produce 'adequate' bile. What constitutes adequate bile flow, however, has not previously been defined. The present study was undertaken to characterize biliary water and electrolyte secretion following hepatic transplantation. Bile was sampled from nine liver transplant recipients for 15-25 consecutive days during chronic t-tube biliary drainage. Liver biopsies and t-tube cholangiograms were unremarkable in all patients. During the first post-operative day mean bile flow, bile salt concentration, [BS], and bile salt output (BSO) were 60.0 microliters/min, 6.8 mM and 0.41 mumol/min, respectively. [BS] increased over days 1-5 and then plateaued at 12.2 mM over days 6-25 post-transplant. BSO and bile flow increased over days 1-12 before achieving steady-state values of 4.52 mumol/min and 334.7 microliters/min, respectively. In each patient bile flow increased linearly with increasing BSO. Choleretic index (CI), varied from 36.9-77.1 microliters/mumol (mean: 50.7 +/- 8.8). The y-intercept for this relationship ranged from 52.4-156.9 microliters/min (mean: 95.9 +/- 81.8). Only primary bile salts (82% cholate and 17% chenodeoxycholate), were observed in the bile of each patient. Biliary electrolyte concentrations were similar to that observed in plasma. Each was relatively unaffected by changes in bile flow and BSO. Electrolyte outputs increased linearly with respect to both BSO and bile flow. We conclude that recovery of bile secretion following orthotopic liver transplantation occurs gradually over a 10-12 day period and is strongly dependent upon bile salt secretion.
Survival rates ranging from 70-80% have been documented over the past three years in liver transplant patients at the Medical College of Virginia. Survival declined in patients with numerous complications of chronic liver disease and with significant deterioration in hepatic synthetic function. Early referral was a major factor contributing to survival.
STUDY OBJECTIVE: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis. DESIGN: Randomized, double-blind, placebo-controlled multicenter trial. SETTING: Four university teaching hospitals. PATIENTS: We enrolled 66 patients with alcoholic hepatitis and either spontaneous hepatic encephalopathy or a discriminant function value greater than 32, calculated using the formula: 4.6 (prothrombin time - control time) + serum bilirubin [in mumol/L]/17.1. Fifty-nine patients (89%) completed the study. Two patients withdrew from the trial. The other 64 patients were hospitalized for the duration of the trial; however, treatment was discontinued in 5 patients because of potential drug toxicity. INTERVENTIONS: Patients were randomly assigned to receive either methylprednisolone (32 mg) or placebo within 7 days of admission. Treatment was given for 28 days. The doses were then tapered over 2 weeks and discontinued. MEASUREMENTS AND MAIN RESULTS: The endpoint of the study was death. Of the 31 recipients of placebo, 11 (35%) died within 28 days of randomization compared with 2 (6%) of the 35 patients given methylprednisolone (P = 0.006). The 95% CI for the difference in mortality was 12% to 70%. In the patients with spontaneous hepatic encephalopathy at entry, 9 of 19 recipients of placebo died (47%) compared with 1 (7%) of the 14 patients given methylprednisolone (P = 0.02). The 95% CI for the difference in mortality was 14% to 66%. The Cox proportional hazards regression model showed the advantage of methylprednisolone over placebo after adjustment for other potentially important prognostic variables (P = 0.004). CONCLUSIONS: Methylprednisolone therapy decreases short-term mortality in patients with severe alcoholic hepatitis manifested either by spontaneous hepatic encephalopathy or a markedly elevated discriminant function value.
Two young black male patients with seronegative rheumatoid arthritis and treated with nonsteroidal antiinflammatory agents developed fulminant hepatic necrosis following the institution of parenteral gold therapy. These cases, reported from different institutions, may represent a severe form of idiosyncratic gold hepatonecrosis. Awareness of the possible association between gold therapy and severe hepatic injury may become increasingly important as oral gold preparations become widely available.
Radioimmunoassays for the determination of the relative amounts of hepatitus B viral pre-S proteins present in serum samples have been developed which utilize antibodies against synthetic peptides corresponding to the amino termini of these proteins. The assays were shown to be sensitive and specific. These assays have been used to examine hepatitis B surface antigen positive human plasma samples for the presence and relative amounts of pre-S proteins. Contrary to previously published data, it was found that there is no correlation between the presence of the pre-S proteins and the HBeAg status of the plasma, but that the ability to detect the pre-S proteins is only a function of the hepatitis surface antigen titre of the plasma. It is concluded that the pre-S proteins would not serve as a useful marker for active viral replication.
Commercial assays for serum bile acids (SBA) have made this measurement practical. The purpose of this study was to examine the utility of SBA measured every 30 min after a standardized meal in controls and in patients with acute viral hepatitis, cholestasis, and anicteric cirrhosis. In five controls, repeated examination of the area under the bile acid curve (AUC) was not statistically different, whereas the fasting and 2-hr postprandial levels were significantly different. In the group of patients with anicteric cirrhosis, AUC identified disease in 18/20 using total serum bile acids (TSBAs) and in 15/20 using cholylglycine (CG). AUC can be calculated from three samples obtained at 0, 60, and 120 min without losing the sensitivity achieved with seven serial samples. SGOT, alkaline phosphatase, and serum albumin were compared for sensitivity to the total SBA response curve in 20 patients with anicteric cirrhosis. SGOT and alkaline phosphatase identified only 50% and 55% as abnormal and serum albumin was less sensitive. Using total SBA, combining the fasting level and AUC identified 100% as abnormal; using CG, 85% of these patients were detected. As a stepwise cost-effective approach, the fasting level of SBAs can identify most patients with anicteric liver disease. In cases with normal fasting levels where liver disease is suspected, the three-point AUC determination may identify additional patients.
Liver biopsies from patients with alcoholic hepatitis, chemical hepatitis, or viral hepatitis types A, B, or non-A, non-B were examined by electron microscopy. Circular, fused, cytoplasmic membranes were observed in hepatocytes of 17% of patients with hepatitis type B and 92% of patients with hepatitis type non-A, non-B. The membrane alterations were not observed in hepatocytes of patients with the other types of hepatitis. The greater frequency of altered cytoplasmic membranes in hepatocytes of patients with non-A, non-B hepatitis was shown to be statistically significant (p less than 0.05) when compared to that in patients with viral hepatitis type B.
A sonographic-anatomic correlation study was undertaken to define the sonographic appearance of regenerating nodules in cirrhotic livers. Three cirrhotic livers with multiple regenerating nodules were obtained from patients undergoing liver transplantation. Sonograms of the resected livers were made and correlated directly with the anatomic specimens. Using a 3-MHz transducer, no discrete alterations in the echo texture of the livers were seen to correspond to the regenerating nodules. With a 7.5-MHz transducer, discrete islands of liver parenchyma were identified corresponding to regenerating nodules anatomically. The nodules were recognized because of visualization of thin, slightly more echogenic borders, which corresponded pathologically to fibrous and fatty connective tissue surrounding and separating the nodules.
Hepatitis A is spread by fecal-oral transmission and accounts for 25% of the cases of sporadic hepatitis in this country; fatal cases have been documented but are unusual, and chronic hepatitis A has not been documented. Hepatitis B is spread by varied routes of transmission, fecal-oral being the least important, and accounts for half the cases of sporadic hepatitis in this country; fatal cases are well documented and chronic hepatitis B is common. The only documented route of transmission of non-A, non-B hepatitis is parenteral; fatal and chronic cases have been documented, and a quarter of the cases of sporadic hepatitis are non-A, non-B. Diagnosis of the etiology of viral hepatitis cannot be determined on clinical grounds but must be made through serologic tests.