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Biomedical subjects

E B Keeffe

Publications and source records attributed to E B Keeffe.

At least 109 records · Page 6Linked to original sources
PubMed1994

Treatment of hepatic failure secondary to isoniazid hepatitis with liver transplantation.

Two patients with liver failure secondary to isoniazid hepatotoxicity were successfully treated with orthotopic liver transplantation. A 49-year-old man received isoniazid prophylaxis for a positive tuberculin test, and a 60-year-old woman was treated for active pulmonary tuberculosis with isoniazid, rifampin, and pyrazinamide. Both patients developed hepatic failure 4 and 1.5 months after initiation of antituberculous drug therapy, respectively. Liver transplantation was performed for progressive hepatic failure and was successful in both patients. The patient with active pulmonary tuberculosis was successfully treated with a modified antituberculous drug regimen while taking standard doses of immunosuppressive drugs after transplantation. In conclusion, liver transplantation is feasible and effective therapy for patients with isoniazid-induced hepatic failure, and active pulmonary tuberculosis may represent a relative rather than absolute contraindication to transplantation.

Chemical and Drug Induced Liver Injury↗
PubMed1994

Pulmonary varices presenting as a solitary lung mass in a patient with end-stage liver disease.

A man undergoing evaluation for liver transplantation was found to have an asymptomatic chest mass, which further evaluation revealed to be pulmonary varices. The left hilar lesion was discovered on a screening chest x-ray film and confirmed by a computed tomographic scan of the thoracic cavity. Bronchoscopy was nondiagnostic, and a thoracotomy was required to diagnose the vascular lesion and exclude carcinoma. The pathophysiology of this pulmonary venous anomaly appeared to be related to portal hypertension, since esophagogastric and colonic varices also were present and the pulmonary varices resolved after liver transplantation. This is the first reported case of pulmonary varices caused by portal hypertension.

Diagnosis, Differential↗
PubMed1994

Liver transplantation at California Pacific Medical Center, San Francisco, California.

A number of modifications in patient selection, operative technique, and immunosuppressive management have greatly contributed to the success of the liver transplant program at CPMC. Graft rejection and the timely detection of EBV infection are ongoing problems in hepatic transplantation that are foci of active research in our field. To address these issues, our group is investigating the activity of cytokines and adhesion molecules using sophisticated molecular techniques, and we are developing a sensitive assay for EBV markers in blood. These and other projects currently in progress will continue when we move our liver transplant program to Stanford University Medical Center in January 1995.

Actuarial Analysis↗
PubMed1994

Liver transplantation for uncontrollable variceal bleeding.

OBJECTIVES: A small number of liver transplant candidates experience variceal bleeding that cannot be controlled by standard medical therapy. The objective of this study was to analyze the role of urgent liver transplantation for this subset of patients with acute, refractory, portal hypertensive bleeding. METHODS: Retrospective review of data from 416 patients undergoing 449 liver transplantations between March, 1988 and February, 1993 revealed seven patients (1.7%) with endstage liver disease who underwent transplantation for uncontrollable variceal bleeding. All patients failed therapy with intravenous pitressin, endoscopic sclerotherapy, balloon tamponade, and/or transjugular intrahepatic portosystemic shunt and continued to bleed. Patients ranged in age from 6 months to 56 years. All patients were Child's class C. Two patients were listed for transplantation with the United Network for Organ Sharing as status 3, and five patients were listed as status 4. RESULTS: All patients underwent successful liver transplantation with immediate control of bleeding. One patient expired on the 26th postoperative day from multiple organ failure, and another patient expired with recurrent hepatocellular carcinoma on the 110th postoperative day. No patients experienced late rebleeding from varices after transplantation. CONCLUSIONS: Urgent liver transplantation is effective and feasible for the small subset of patients with uncontrollable variceal bleeding and endstage liver disease. Prompt and complete evaluation of the potential recipient and availability of a donor organ are critical to the success of this approach.

Acute Disease↗
PubMed1994

Outcome of liver transplantation in patients with hemochromatosis.

Recent preliminary reports suggest a poor outcome of orthotopic liver transplantation for patients with hemochromatosis. We analyzed an institutional experience with orthotopic liver transplantation for hemochromatosis, focusing on factors contributing to increased morbidity and mortality. Between March 1988 and October 1992, nine of 249 adults (3.6%) undergoing orthotopic liver transplantation had hemochromatosis. Mean age was 53 yr (range, 42 to 62 yr), and eight of nine patients were men. The diagnosis of hemochromatosis was based on transferrin saturation > 62% and hepatic iron index > 2.0. Only two patients were known to have hemochromatosis before liver transplantation. All nine patients underwent standard cardiac evaluation before transplantation, and no patient had detectable pre-existing cardiac disease. One patient had a major operative cardiac complication as a result of pulmonary embolism and made a full recovery. Postoperatively, congestive heart failure developed in three patients and four patients had arrhythmias. One patient is undergoing phlebotomy for post-transplant cardiac complications from hemochromatosis. Two patients had primary hepatic tumors in the explant liver. There were four deaths caused by multiorgan failure with congestive heart failure (1), infection (2), and/or malignancy (2). Five patients are alive 3 to 25 mo post-transplant. The actuarial survival of the nine patients was 53% at 25 mo vs. 89% for 18 age- and sex-matched control transplant recipients (p = 0.1) and 81% for all other adult liver transplant recipients (p < 0.01). In five of seven patients, post-transplant liver biopsies revealed hepatic iron accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1993

Immunogenicity of two recombinant hepatitis B vaccines in older individuals.

PURPOSE: Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-micrograms or 20-micrograms doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. PATIENTS AND METHODS: In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. RESULTS: Seroprotection rates for subjects receiving the 20-micrograms dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-micrograms dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p < 0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 micrograms were significantly greater than that for the group receiving Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001). CONCLUSIONS: Immunization with the 20-micrograms dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-micrograms dose. The latter data suggest that the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs titers.

Adult↗
PubMed1993

Variation in antibody reactivity to the hepatitis C virus by comparative immunoscreening and enzyme immunoassay.

The detection of antibody to the hepatitis C virus C100-3 antigen from the nonstructural region (NS3/NS4) of the viral genome was the first useful marker developed to detect past or potentially active infection with the hepatitis C virus. A systematic epitope survey of the nonstructural region has uncovered other immunogenic antigens. In order to assess the possible diagnostic utility of these antigens, their reactivity against a limited panel of sera from patients with chronic liver disease due to hepatitis C virus and other etiologies was tested. Antibody assays were performed using an immunoblot plaque assay and an enzyme-linked immunosorbent assay (ELISA). In a study of 16 C100-3-reactive individuals, all 16 patients were reactive using the plaque assay for the NS3 3' (409-1-1) and NS3 5' (C33u). In this same group of patients, antibodies by ELISA were reactive to NS3 3' in 12 of 16 patients (75%), NS3 5' in 15 of 16 patients (93%), and a capsid antigen (NC450) in 14 of 16 patients. In a group of five patients who were diagnosed with cryptogenic liver disease (C100-3 negative), 4 of 5 patients were reactive for antibody to all of the above epitopes. In a survey of 23 patients with other forms of chronic liver disease (nonviral liver disease, hepatitis B, alcoholic liver disease, cholestatic liver disease, and autoimmune hepatitis), only 1 of 23 patients was reactive for antibody to the C100-3 and 4 of 23 patients were reactive for antibodies to structural and nonstructural regions of the virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Primary sclerosing cholangitis and Hodgkin's disease.

Three patients with primary sclerosing cholangitis and Hodgkin's disease, a previously unrecognized association, are reported. All three patients were men, and one patient had Crohn's disease of the colon. Primary sclerosing cholangitis was diagnosed 2, 11 and 17 yr before diagnosis of Hodgkin's disease in the three patients, and all three had advanced biliary cirrhosis prompting referral for liver transplantation. The symptoms of Hodgkin's disease were often masked by similar manifestations of primary sclerosing cholangitis, particularly symptoms of recurrent biliary sepsis. Hodgkin's disease is another disorder that may occur in patients with primary sclerosing cholangitis, particularly in the setting of advanced disease, and may be masked by the underlying hepatobiliary disease.

Adult↗
PubMed1993

Controversies in patient selection for liver transplantation.

A variety of specific conditions often stimulate controversy regarding candidacy for liver transplantation. We review the published experience with liver transplantation for alcoholic liver disease, fulminant and chronic hepatitis B, and hepatocellular carcinoma and transplantation in older subjects. Liver transplantation for alcoholic liver disease and in subjects older than 60 years is becoming less controversial because recent data demonstrate that these patients have excellent survival and good quality of life after transplantation. Only 10% to 15% of persons with alcoholism return to drinking after transplantation, and most do so only transiently. Liver transplantation for patients with hepatitis B virus infection or primary liver cancer is more problematic because recurrent disease is common in both conditions. After transplantation for chronic hepatitis B, 80% to 90% of patients have reinfection of the allograft and long-term survival is 45% to 50%. Patients receiving transplants for hepatocellular carcinoma have only 20% to 30% long-term survival, but these survivors are cured of malignancy. Data are presented to support continued liver transplantation for chronic hepatitis B and hepatocellular carcinoma; however, patients must be selected based on factors that predict a favorable outcome, and experimental therapies should be employed to explore ways to improve the existing survival rates.

Age Factors↗
PubMed1993

Liver transplantation for patients with alcoholism and end-stage liver disease.

Liver transplantation for alcoholic cirrhosis remains controversial. In particular, criteria for the selection of patients who will remain recovered from alcoholism post-transplant require better definition. We analyzed the long-term predictive value of categorizing transplant referral patients with alcoholism and end-stage liver disease into risk groups for recidivism and noncompliance. Forty-seven patients with the diagnosis of alcoholism and advanced liver disease were evaluated and placed into predefined risk groups (low-, moderate-, and high-risk) for recidivism and noncompliance. No absolute period of abstinence from alcohol was required. All patients were asked to sign a contract not to drink alcohol and comply with a rehabilitation program before and after transplantation. Compliance with alcohol rehabilitation, abstinence, functional level, employment, and survival were assessed. Patients who were not compliant with the rehabilitation program or consumed alcohol were scored as failures. Thirty-one patients were ranked as low risk, and were accepted for liver transplantation; 27 patients were transplanted. Five of 31 patients (16%) drank alcohol. One patient drank before and four patients drank transiently after transplantation. Ten patients were categorized as moderate risk, and were deferred for transplantation; two patients underwent later transplantation. All 10 patients (100%) were noncompliant or drank alcohol, including two patients who drank after transplantation after a period of abstinence and rehabilitation. Six patients were ranked as high risk, and were denied liver transplantation. Five patients (83%) drank alcohol and were noncompliant. Minimum follow-up was 12 months (mean, 24 months; range, 12-41 months). The mean Karnofsky performance score was 34 before and 84 after liver transplantation. Actuarial survival of alcoholic patients undergoing transplantation was 93%. We conclude that categorization of transplant referral patients with alcoholism and liver failure into predefined risk groups for recidivism and noncompliance accurately predicts pre- and post-transplant behavior. As defined, only low-risk alcoholic patients are good candidates for liver transplantation.

Actuarial Analysis↗
PubMed1992

Transjugular liver biopsy.

Although transjugular liver biopsy requires the availability of trained personnel, takes more time than percutaneous biopsy and is moderately expensive, it is a safe alternative technique for obtaining adequate liver tissue for diagnosis in special clinical situations. The usual indications for transjugular rather than percutaneous liver biopsy are (a) coagulation disorder (prothrombin time greater than 3 sec over control value and/or platelet count less than 60,000/cm3), (b) massive ascites and (c) desire to perform ancillary procedures, such as measurement of pressures or opacification of the hepatic veins and inferior vena cava. Less common indications for transjugular liver biopsy include failed percutaneous biopsy, massive obesity, small cirrhotic liver (increased risk and lower success rate) and suspected vascular tumor or peliosis hepatis. Results from several centers indicate that adequate or diagnostic liver tissue is obtained in 81% to 97% of cases. The typical length of the biopsy core ranges from 0.3 cm to 2.0 cm. Modification of the classic technique, particularly the adaptation of a Tru-Cut needle, shows promise in yielding longer cores of tissue with less fragmentation. Transjugular liver biopsy is performed with an acceptable complication rate that ranges 0% to 20%. The reported mortality of transjugular liver biopsy was 0 in three major centers and ranged from 0.1% to 0.5% in three other centers. Transjugular liver biopsy may be useful in obtaining diagnostic liver tissue not only in advanced chronic liver disease with coagulopathy, ascites or both, but also in patients with fulminant hepatic failure to better determine prognosis and the need for liver transplantation.

Adolescent↗
PubMed1992

Management of biliary complications after liver transplantation.

Biliary tract complications after liver transplantation are common, and the evaluation of newer treatment options compared with standard surgical treatment is important. In 62 liver transplants performed in 55 adult patients, the biliary tract was reconstructed with choledochocholedochostomy (CC) in 52 (84%) and Roux-en-Y choledochojejunostomy (RYCJ) in 10 (16%). Seventeen biliary tract complications occurred in 16 patients (29%). The incidence of complications was the same after CC and RYCJ. Eight complications (47%) occurred within the first month and nine (53%) thereafter. Only 6 of 17 (35%) biliary tract complications required operation. One patient died of a biliary tract complication. No other allografts were lost due to biliary tract complications. Four patients transplanted at other centers were also treated, for a total of 21 biliary tract complications. Overall, there were nine bile leaks, eight bile duct strictures, two Roux loop hemorrhages, one choledocholithiasis, and one ampullary dyskinesia. Temporary or permanent stents were used successfully in seven of eight strictures. Five bile leaks were managed without operation. Nonsurgical management is appropriate for a selected majority of patients with late bile leaks, biliary tract strictures, or choledocholithiasis after liver transplantation.

Biliary Tract Diseases↗
PubMed1992

Prolonged cholestasis due to trimethoprim sulfamethoxazole.

Drug-induced liver injury due to trimethoprim sulfamethoxazole is rare and classified as an unpredictable or idiosyncratic type of hepatotoxic reaction. Early reports suggested that the pattern of liver injury in the majority of cases is mixed hepatocellular-cholestatic. The current report describes two cases of severe, prolonged cholestasis after treatment with trimethoprim sulfamethoxazole; intractable pruritus and abnormal liver test results lasted for 1-2 years after discontinuation of the drug. Liver biopsy specimens showed a cholestatic pattern of liver injury and only minimal hepatocellular necrosis or inflammation. Recent case reports suggest that cholestasis alone may occur after the use of trimethoprim sulfamethoxazole; these two additional cases show that cholestasis may be quite prolonged.

Adult↗
PubMed1992

Fibrosing cytolytic liver failure secondary to recurrent hepatitis B after liver transplantation.

Four patients who underwent transplantation for hepatitis B virus-related liver disease developed rapidly progressive liver failure attributable to recurrent hepatitis B disease typified by hyperbilirubinemia and distinctive hepatocyte ballooning and progressive fibrosis consistent with recently reported fibrosing cholestatic hepatitis. Among these four patients, the mean interval from transplantation to redocumentation of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) was 5 months, to development of malaise and jaundice 6 months, to histological diagnosis 7 months, and to graft failure 8 months. The only patient who underwent retransplantation had accelerated recurrence of the same syndrome with biopsy documentation 1 month later and graft failure 2 months later. Distinctive histological features included confluent hepatocellular ballooning and progressive periportal fibrosis followed by lobular collapse over 4-6 weeks without significant inflammation. Immunohistochemical staining showed marked HBsAg and hepatitis B core antigen (HBcAg) immunoreactivity. The rapid development of cytolytic hepatocellular necrosis and lobular collapse with prominent HBcAg immunoreactivity without significant inflammation suggests a cytolytic rather than immune pathogenesis for this unique and devastating form of recurrent hepatitis B that might better be termed "fibrosing cytolytic hepatitis."

Adult↗