Orthotopic liver transplantation for Wilson's disease: a single-center experience.

BACKGROUND: Wilson's disease is an inherited disorder of copper metabolism characterized by reduced biliary copper excretion, which results in copper accumulation in tissues with liver injury and failure. Orthotopic liver transplantation (OLT) can be lifesaving for patients with Wilson's disease who present with fulminant liver failure and for patients unresponsive to medical therapy. The aim of this study is to review our experience with OLT for patients with Wilson's disease. METHODS: Between 1988 and 2000, 21 OLTs were performed in 17 patients with Wilson's disease. Patient demographics, pre-OLT laboratory data, operative data, and early and late postoperative complications were reviewed retrospectively. One-year patient and graft survival was calculated. RESULTS: Eleven patients had fulminant Wilson's disease; in six patients the presentation was chronic. Mean patient age at presentation was 28 years (range 4-51 years); mean follow-up was 5.27 years (range 0.4-11.4 years). Neurologic features of Wilson's disease were not prominent preoperatively and did not develop post-OLT except in one patient who developed acute neuropsychiatric illness and seizure. Renal failure, present in 45% of patients with fulminant Wilson's disease, resolved post-OLT with supportive care. One-year patient and graft survivals were 87.5% and 62.5%, respectively. Fifteen survivors have remained well with normal liver function and no disease recurrence. CONCLUSION: Liver transplantation for hepatic complications of Wilson's disease cures and corrects the underlying metabolic defect and leads to long-term survival in patients who present with either acute or chronic liver disease. Acute renal failure develops frequently in patients with fulminant Wilsonian hepatitis and typically resolves postoperatively.

Outcome of hepatitis C patients with and without hepatocellular carcinoma undergoing liver transplant.

OBJECTIVE: Hepatitis C virus (HCV) infection is associated with development of hepatocellular carcinoma (HCC). The aim of this study was to examine clinical characteristics and outcome of patients with HCV with or without HCC undergoing liver transplant. METHODS: We reviewed the charts of all 55 patients transplanted between November 1990 and December 1996 for HCV cirrhosis with HCC and compared them with a control group of HCV patients without HCC. Patients with a history of alcohol abuse or HBsAg positivity were excluded. There were 37 men and 18 women, with a mean age of 57.6 yr (range, 19-70 yr) in the HCC group. RESULTS: There was no significant difference between the HCC and nonHCC groups regarding Child's class or United Network for Organ Sharing (UNOS) status at the time of transplant. Twenty-six (45%) patients were diagnosed or suspected of having HCC before transplant. Twenty-five patients (45.5%) had a single focus of HCC. Fourteen percent (seven of 50) of the patients with HCC had been treated with interferon, whereas 12% (six of 52) of patients in the nonHCC group had received interferon. Duration of interferon therapy ranged from 1 to 9 months. All interferon treatment occurred within 5 yr of transplant. A history of intravenous drug use or transfusion was identified in 37 (67%) of HCC patients. Thirty-two patients (58%) without HCC had a parenteral exposure. There was no significant difference in patient or graft survival rates between the patients with and without HCC. CONCLUSION: Approximately one-half of HCC was not detected before liver transplant. There was no significant difference in the mode of transmission, clinical status at the time of transplant, or outcome between the HCV patients with and without HCC.

Modulation of abnormal colonic epithelial cell proliferation and differentiation by low-fat dairy foods: a randomized controlled trial.

CONTEXT: Before the development of human colonic neoplasms, colonic epithelial cells showed altered growth and differentiation. These alterations characterized mucosa at risk for cancer formation and were termed intermediate biomarkers of risk. Modifications of the mucosa toward more normal features by nutrients or drugs are putative approaches to chemoprevention of colon cancer. OBJECTIVE: To determine whether increasing calcium intake via dairy products alters colonic biomarkers toward normal. DESIGN: Randomized, single-blind, controlled study. SETTING: Outpatient clinic. PARTICIPANTS: Seventy subjects with a history of polypectomy for colonic adenomatous polyps. INTERVENTION: Low-fat dairy products containing up to 1200 mg/d of calcium. Subjects were randomized to 4 strata by diet (control vs higher calcium) and age (<60 vs > or = 60 years). MAIN OUTCOME MEASURES: Changes in total colonic epithelial cells and number and position of thymidine-labeled epithelial cells and changes in the ratio of sulfomucins (predominantly secreted by distal colorectal epithelial cells) to sialomucins and expression of cytokeratin AE1, 2 markers of colonic cell differentiation. RESULTS: During 6 and 12 months of treatment, reduction of colonic epithelial cell proliferative activity (P<.05), reduction in size of the proliferative compartment (P<.05), and restoration of acidic mucin (P<.02), cytokeratin AE1 distribution (P<.05), and nuclear size (P<.05) toward that of normal cells occurred. Control subjects showed no differences from baseline proliferative values at 6 and 12 months (P>.05). CONCLUSION: Increasing the daily intake of calcium by up to 1200 mg via low-fat dairy food in subjects at risk for colonic neoplasia reduces proliferative activity of colonic epithelial cells and restores markers of normal cellular differentiation.

Amaranthin lectin binding in the rat colon: response to dietary manipulation.

BACKGROUND: In human colon, binding of the lectin Amaranthus caudatus has been considered to be a marker of cellular proliferation and malignant progression. We studied regional amaranthin binding in rat colon and correlated this with physiologic manipulations of proliferation. METHODS: Binding of amaranthin in segments of proximal and distal colon was studied in starved, refed, and control Wistar rats and was compared to tritiated thymidine labeling and proliferating cell nuclear-antigen expression. RESULTS: Amaranthin bound mainly to cells in the lower crypt of distal colon and midcrypt of proximal colon, paralleling the distribution of proliferative markers. Binding occurred in the supranuclear region in distal colon and the pericellular membrane in proximal colon. Starvation/refeeding was associated with a change in amaranthin binding intensity in distal colon, but not in proximal colon. CONCLUSION: The pattern of amaranthin binding during starvation/refeeding seems to reflect physiologic changes in several areas of the colon.

Coexistence of hereditary hemorrhagic telangiectasia and fibropolycystic liver disease.

This is a case report of a 43-year-old woman who received a transplant for end-stage liver disease due to hereditary hemorrhagic telangiectasia and fibropolycystic liver disease. This is an uncommon association of two autosomal-dominant conditions with defined genetic and molecular defects. The liver showed extensive vascular malformations of arteries and veins as well as telangiectasia and fibrosis. In addition, there were cystically dilated ducts containing inspissated bile and extensive von Meyenburg complexes. This case raises interesting questions about the possible relationship of these genes and their gene products, both of which are related to cell-matrix interactions and are strongly associated with blood vessels, one of them being expressed on endothelial cells and the other being developmentally important in blood vessels.

Reassessing the role of medical therapy in the management of hepatic vein thrombosis.

Hepatic venous outflow obstruction caused by hepatic vein thrombosis (HVT) is a manifestation of a hypercoagulable state, most commonly a myeloproliferative disorder (MPD). In the past, HVT was thought to have a poor prognosis unless treated surgically with portosystemic shunt or orthotopic liver transplantation (OLT). The aim of this study was to assess whether early diagnosis of the underlying hematologic disorder and institution of appropriate medical therapy have altered outcome. We reviewed the charts of 22 patients with HVT evaluated at our center from January 1986 to January 1995. The median age was 32 years (range, 14 to 59 years). Underlying etiologies were MPD, 13 (polycythemia vera, 8; essential thrombocythemia, 4; undefined, 1); dysfibrinogenemia, 1; anticardiolipin antibody, 1; oral contraceptive use, 3; and idiopathic, 4. All patients had ascites, hepatomegaly, and/or abdominal pain. Two underwent mesocaval shunting, and 1 had a peritoneal-venous shunt. Seven patients, including 1 with a mesocaval shunt, underwent OLT. The median duration of symptoms before transplantation was 6 months (range, 1.5 to 11 months). Six transplant patients are alive on long-term anticoagulation therapy at a mean post-OLT follow-up of 42 months (range, 2 to 77 months), without recurrence. Of 13 patients treated medically, 10 (77%) are alive at a median follow-up of 40 months (range, 17 months to 14 years 8 months), 1 has died, and 2 have been lost to follow-up. In a majority of patients, symptoms improve with prompt treatment of the underlying hematologic disorder, with a favorable long-term prognosis. Patients with decompensated liver disease can successfully undergo OLT with a low risk of recurrence on long-term oral anticoagulation.