Liver transplantation at the University of California, San Francisco.

The UCSF approach to liver transplantation is an attempt to balance academic advances and experimental protocols with personalized patient care. Equally important goals are lowered liver transplantation costs, expanded indications for transplantation, and improved results in specific disease entities.

Lipopeliosis: fat induced sinusoidal dilatation in transplanted liver mimicking peliosis hepatis.

A distinct peliosis-like lesion arose in the liver allograft of a 51 year old man. This lesion was caused by necrotic, fat-laden hepatocytes that released fat globules into the sinusoids. These then became strikingly distended with cysts, thus mimicking peliosis hepatitis.

Incidence and diagnostic features of macroregenerative nodules vs. small hepatocellular carcinoma in cirrhotic livers.

In Japan, the presence of a large regenerative nodule within a cirrhotic liver, referred to as a macroregenerative nodule or adenomatous hyperplasia, is thought to play a role in the pathogenesis of hepatocellular carcinoma. These lesions, however, have received little attention outside of Japan. We examined 110 sequentially explanted cirrhotic livers for the presence of such nodules.

Hepatitis C viral infection in liver transplant recipients.

In this study we examined multiple serial liver biopsy specimens from liver transplant recipients to determine the pathological features of hepatitis C virus-induced hepatitis. Hepatitis C virus infections acquired after transplantation and previous infections that recurred in patients after transplantation were confirmed by the results of the polymerase chain reaction. Of 43 patients infected with the hepatitis C virus, 18 had a mild form of chronic hepatitis.

Transjugular intrahepatic portosystemic shunts: preliminary results in 25 patients.

A retrospective study of transjugular intrahepatic shunts performed between June 1990 and June 1991 is reported. Twelve patients were actively bleeding at the time of the procedure; 12 other patients had had one to five bleeding episodes within the previous 2 weeks, and one patient had massive ascites from Budd-Chiari syndrome. Most patients had severe liver disease: 21 Child's class C, three Child's class B, and one Child's class A.

Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure.

Cerebral edema and intracranial hypertension, commonly present in fulminant hepatic failure, may lead to brainstem herniation and limit the survival of comatose patients awaiting liver transplantation before a donor organ becomes available. Also, they are likely responsible for postoperative neurological morbidity and mortality. Although intracranial pressure monitoring has been proposed to aid clinical decision making in this setting, its use in the prevention of brainstem herniation preoperatively, in the selection of patients for liver transplantation who have the potential for neurological recovery and in the maintenance of cerebral perfusion during liver transplantation has not been examined in detail.

Recurrent and acquired hepatitis C viral infection in liver transplant recipients.

To examine the postliver transplant recurrence of hepatitis C virus (HCV) infection in patients with pretransplant infection, as well as its acquisition in patients without prior infection, we used the polymerase chain reaction to amplify HCV RNA in serum and/or liver samples of 89 patients with alcoholic and cryptogenic cirrhosis undergoing liver transplantation. Results were correlated with histologic findings from posttransplant liver biopsies. Ninety-five percent of patients with pretransplant infection had posttransplant viremia.

Hepatitis B virus and apparent fulminant non-A, non-B hepatitis.

While there is evidence that hepatitis C virus (HCV) does not cause fulminant non-A, non-B hepatitis, the causal agent remains unknown. To evaluate the role of hepatitis B virus (HBV) in this disease, we used a two-step polymerase chain reaction (PCR) to amplify the surface and core regions of HBV DNA in serum and liver samples taken prospectively from twenty-six patients (mean age 36 years, range 1 to 64) with acute hepatic failure undergoing liver transplantation. HBV DNA was absent from the serum of all patients before transplantation.

Cell subsets responding to purified hepatocytes and evidence of indirect recognition of hepatocyte major histocompatibility complex class I antigen. II. In vitro-generated "memory" cells to class I+ class II- hepatocytes.

Purified hepatocytes stimulate the development of L3T4-, Ly2+ allospecific cytolytic T cells from naive splenocytes after 5 days in primary mixed lymphocyte-hepatocyte culture (MLHC). Previous studies indicate that the immunogenicity of purified hepatocytes relates to the expression of MHC class I antigen. The purpose of the following experiments was to identify the cell subsets that specifically recognize hepatocyte MHC class I antigen.

Cell subsets responding to purified hepatocytes and evidence of indirect recognition of hepatocyte major histocompatibility complex class I antigen. I. The role of L3T4+ T cells in the development of allospecific cytotoxicity in hepatocyte-sponge matrix allografts.

The purpose of this study was to determine the role of L3T4+, Ly2- T cells in the development of allospecific cytolytic T cells in response to purified allogeneic MHC class I+, class II- hepatocytes in vivo in hepatocyte-sponge matrix allografts (HC-SMA). In previous studies we have shown that 99% pure murine hepatocytes stimulate the development of allospecific cytolytic T cells in vitro in mixed lymphocyte-hepatocyte culture (MLHC) and in vivo in HC-SMA. Furthermore, depletion of L3T4+, Ly2- T cells from responder splenocytes inhibits the development of allo-CTLs in response to purified hepatocytes in mixed lymphocyte-hepatocyte culture.

Using transjugular intrahepatic portosystemic shunts to control variceal bleeding before liver transplantation.

Objective: To determine the safety and efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in controlling bleeding from esophageal varices in patients awaiting liver transplantation.

Design: Prospective, uncontrolled trial.

Setting: University medical center with an active liver transplant program.

Intragraft cytokine profile during human liver allograft rejection.

Forty-three human liver allograft biopsies and normal liver were directly analyzed for inflammatory and immunoregulatory cytokine gene expression by polymerase chain reaction (PCR). IL-5 gene expression was predominantly present in biopsies from liver allografts with histopathological evidence of acute rejection. IL-2 gene expression was rarely observed in rejecting allografts or allografts without evidence of rejection.

The potential supply of organ donors. An assessment of the efficacy of organ procurement efforts in the United States.

Objectives: To estimate the potential supply of organ donors and to measure the efficiency of organ procurement efforts in the United States.

Methods: A geographic database has been developed consisting of multiple cause of death and sociodemographic data compiled by the National Center for Health Statistics. All deaths are evaluated as to their potential for organ donation.

Azathioprine hepatotoxicity after liver transplantation.

We report the first two cases of apparent azathioprine hepatotoxicity occurring after liver transplantation. The two patients exhibited jaundice, elevated serum transaminase activities and histopathological features of sinusoidal congestion and centrilobular hepatocellular degeneration 17 and 61 days after transplantation. After withdrawal of azathioprine, liver test results improved immediately in both patients.

Histopathologic study of transjugular intrahepatic portosystemic shunts.

A detailed histopathologic analysis of intrahepatic portosystemic shunts was performed following liver transplantation in five patients. Gross examination revealed that all stents were patent and unchanged in size, shape, and position from initial placement. Histologic examination at 4 days revealed an irregular luminal surface with liver parenchyma protruding between the stent wires and a single, patchy layer of endothelial cells lining the shunt surface.

Evidence for direct and indirect pathways in the generation of the alloimmune response against pancreatic islets.

The role of the direct and indirect pathways of alloantigen presentation in the generation of the alloimmune response was dissected using the murine mixed lymphocyte-islet coculture system (MLIC). Stimulator DBA/2J (H-2d) pancreatic islet populations consisted of whole islets (MHC class I+, II+) or FACS-purified beta cells (MHC class I+, II-). Responding C57Bl/6 (H-2b) splenocyte populations were either: (1) untreated; (2) depleted of helper T cells with anti-L3T4 monoclonal antibody plus complement; (3) depleted of cytotoxic T lymphocytes with anti-Lyt2 mAb plus complement; or (4) depleted of antigen-presenting cells by passage through a Sephadex G-10 column.