Autopsy Pathology Staff

Dr. Kleiner's section is responsible for administering the autopsies performed at the Clinical Center. Any patient seen on protocol at the NIH or who has a disease of significant clinical or research interest to a particular principal investigator may have an autopsy done by this section. The goal of the service is to answer clinical questions about the patient's disease, to determine the cause of death, to provide for hospital and protocol-related quality assurance, and to serve as a research support for investigators who would like to use tissue from autopsies or carry out autopsy-based studies. The section is also responsible for training pathology residents in autopsy pathology. A weekly CME-approved clinical-pathological correlation conference is held in the autopsy suite to review the gross and microscopic findings on our cases.

In addition to overseeing the autopsy service, Dr. Kleiner has significant service responsibilities as one of the full-time surgical pathologists. Although his area of expertise is in liver disease, he reviews all renal transplant biopsies and sees general surgical pathology material when on service. He reviews all liver biopsies are reviewed at the weekly liver biopsy conference. Dr. Kleiner's other service responsibilities include immunohistochemical QA and overseeing the clinical operation.

Chronic liver disease is a significant health problem both in the United States and worldwide. In particular, chronic hepatitis C (CHC) has become recognized as a potentially serious chronic disease in this country. Approximately 1 to 2 percent of the population is chronically infected with this virus and there is a wide variation in rate of disease progression. Some patients develop cirrhosis or hepatocellular carcinoma in less than 5 years while others may have chronic hepatitis for 40 years or more without significant morbidity. The focus of our research includes the objective evaluation of pathologic changes following therapy and prediction of disease outcome based on histological parameters. In collaboration with investigators in the National Institute of Diabetes and Digestive and Kidney Diseases, we are evaluating new treatment regimens for CHC. However, in the absence of an effective therapy or vaccine, it is of paramount importance to be able to predict not only which patients may expect to benefit from therapy but also which patients are likely to progress more quickly to cirrhosis. Using a multivariate regression model, we have determined histologic factors which predict short-term progression of fibrosis. These observations may be extended to other chronic liver diseases such as chronic hepatitis B and primary biliary cirrhosis.

Renal transplantation is the treatment of choice for end stage renal disease. However, the normal response of a host to a transplanted organ is rejection. Rejection is divided pathologically and clinically into acute and chronic phases and is controlled by complex multi-drug immunosuppression. Renal transplantation protocols at the NIH are directed at both understanding the cellular and molecular mechanisms of rejection and at designing regimens which induce tolerance of the transplanted organ. Renal biopsies taken from patients at specific protocol directed intervals are examined for evidence occult rejection and are studied with a panel of antibodies directed against the different immune cell populations. By careful correlation of the pathologic and immunophenotypic changes with clinical, biochemical and molecular analysis of cytokine expression, we hope to understand what factors are most important in directing both acute and chronic rejection.

Recent Publications
Kleiner, DE, et al. Mod Pathol 1997; 10:192-9.
Hoofnagle, JH, et al. J Viral Hepatitis 1996; 3:247-52.
Oliver, GW, et al. Analyt Biochem 1997; 244:161-6.
Corcoran, ML, et al. Enzyme Protein 1996; 49:7-19.

Collaborators
Stanley Pillemer, M.D.; Allan Kirk, M.D., Ph.D.; S. John Swanson, M.D.; Doug Hale, M.D.; Roslyn Mannon, M.D.; Mark Ghany, M.D.; H. Richard Alexander, M.D.; Jay H. Hoofnagle, M.D.; Stephen E. Straus, M.D.; and Phil Fox, D.D.S., NIH


Clinical Trials

• 02-DK-0022: Long-Term Efficacy of Leptin Replacement in Treatment of Lipodystrophy
• 02-DK-0065 Combination of Pegylated Interferon and Ribavirin as Therapy for Patients with Chronic Hepatitis C with and without Renal Disease
• 01-DK-0061 Renal Allotransplantation for Treatment of End Stage Renal Disease in the Setting of Human Immunodeficiency Virus (HIV) Infection
• 01-I-0239 Studies of the Addition of Adefovir Dipivoxil to Lamivudine for the Treatment of Chronic Hepatitis B: A Randomized, Double-Blind, Placebo Controlled Study in HIV-Infected Patients and an Open-Label Study in HIV-Negative Subjects
• 01-I-0194 A Non-Randomized, Open label, Study to Assess Hepatitis C Viral Kinetics in Predicting the Clinical Response in Patients with Hepatitis C Infection Coinfected with HIV-1 Treated with Peginterferon Alpha-2b and Ribavirin
• 01-I-0134 Adefovir Dipivoxil for the Treatment of Hepatitis B in Human Immunodeficiency Virus Infected Patients with Decompensated Hepatitis B Liver Disease and a Hepatitis B Viral Load of at Least 1.0 x 10(6) (copies/mL) Despite 52 Weeks of Lamivudine Therapy
• 01-DK-0247 Treatment of Chronic Delta Hepatitis with Pegylated Interferon
• 01-DK-0246 Combination of Lamivudine and Adefovir Dipivoxil for Treatment of Chronic Hepatitis B
• 01-CC-0045 Studies of Phlebotomy Therapy in Hereditary Hemochromatosis
• 01-DK-0130: Treatment of Nonalcoholic Steatohepatitis with Pioglitazone
• 00-DK-0186 The Hep C Antiviral Long-Term Tx Against Cirrhosis (HALT-C) Trial: A Randomized Controlled Trial to Evaluate the Safety & Efficacy of Long-Term Peginterferon Alpha-2A for Tx of Chronic Hep C in Patients Who Failed to Respond to Previous Interferon Thera
• 00-DK-0146: Efficacy of Leptin Replacement in Treatment of Lipodystrophy
• 00-DK-0196 Sirolimus Monotherapy to Optimize Activation Induced Cell Death (AICD) in Renal Transplants Following Lymphocyte Depletion Induction with Thymoglobulin
• 00-DK-0013 Tolerance Induction Following Human Renal Transplantation Using Treatment with a Humanized Monoclonal Antibody Against CD52 (Campath-1H)
• 99-DK-0042 Long-Term Therapy with Ribavirin for Chronic Hepatitis C
• 98-DK-0003 Combination of Alpha Interferon with Long Term Ribavirin Therapy for Patients with Chronic Hepatitis C
  
• 96-DK-0112 Alpha interferon for chronic hepatitis C
• 95-DK-0199 Lamivudine for chronic hepatitis B
• 94-D-0018 Salivary evaluation in normal volunteers
• 91-DK-0214 Evaluation of patients with liver disease
• 91-CC-0117 Epidemiology, infectivity and natural history of hepatitis C virus infection in a blood donor population
• 84-D-0056 Evaluation and treatment of salivary gland dysfunction