tacrolimus and Hepatitis--Chronic

To study the outcomes of patients who underwent liver transplantation for the primary diagnosis of chronic active hepatitis secondary to hepatitis C virus (HCV).. Retrospective review within a university medical center.. Seventy-four adult recipients who received 78 orthotopic liver allografts for the primary diagnosis of chronic active hepatitis secondary to HCV between January 1990 and December 1994. Sixty-seven patients (91%) survived more than 2 months and were analyzed further for recurrent HCV infection.. Recurrence of HCV infection, hepatitis, or cirrhosis and survival rates for patients who were undergoing orthotopic liver transplantation for chronic active hepatitis secondary to HCV.. Actuarial survival rates for the entire group were 79.3%, 70.9%, and 64.5% at 1,2, and 3 years, respectively. Four patients (5% underwent retransplantation with an actuarial survival rate of 14.3% at 1 year (P<.05). Thirty-eight patients (57%) had evidence of posttransplant HCV infection, 31 patients (46%) showed histologic evidence of viral hepatitis, and 11 patients (16%) experienced portal fibrosis or cirrhosis. Seven (33%) of the deaths and all retransplantations were secondary to recurrent HCV infection. There were no significant differences in age, sex, United Network of Organ Sharing status, associated diagnoses, intraoperative packed red blood cell requirements, OKT3 use, or 1-, 2-, and 3-year survival rates in the recurrent vs nonrecurrent HCV infection groups. A higher incidence of posttransplant cirrhosis was observed in patients who were treated with tacrolimus (FK 506) (31.8% vs 8.9%, P<.05). Twenty-one patients (70%) received interferon alfa antiviral therapy with a significant benefit in the liver function test results during therapy (P<.01).. Despite recurrence of HCV infection in most patients after transplantation, survival following primary orthotopic liver transplantation for chronic active hepatitis secondary to HCV infection remains favorable, and these patients should continue to be candidates for liver transplantation. In contrast, survival following retransplantation for HCV infection is poor and should be reconsidered. There is an apparent association between the intensity of immunosuppression and recurrent HCV infection and cirrhosis that warrants continued evaluation. Interferon therapy appears to afford benefit to patients in whom recurrent HCV hepatitis develops after transplantation.

Topics: Actuarial Analysis; Adult; Aged; Female; Hepatitis C; Hepatitis, Chronic; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Medical Records; Middle Aged; Retrospective Studies; Survival Analysis; Tacrolimus; Treatment Outcome

Autoimmune chronic active hepatitis (CAH-A) is a chronic liver disease of unknown etiology that is believed to have an autoimmune pathogenesis. The disease is slowly progressive until hepatic failure and portal hypertension develop and either death or liver transplantation occur. Currently, the only widely recognized therapy is the administration of glucocorticoids, which have both anti-inflammatory and immunosuppressive actions. Many patients cannot tolerate such therapy because of the psychiatric, osteoporotic, and weight-enhancing actions of steroids. Tacrolimus (FK 506) is a new macrolide antibiotic that has an immunosuppressive activity that is estimated to be 10-200 times greater than that of cyclosporine. Because of its greater immunosuppressive activity, we have used it in the treatment of 21 patients with autoimmune chronic active hepatitis. Before each subject was treated, a liver biopsy and a panel of hematological, serological, and biochemical parameters were assessed. The Tacrolimus was administered orally at 12-h intervals, and the dose was controlled by monitoring plasma FK trough levels. After 3 months of therapy at an oral dose of 3 mg twice a day, having achieved a median blood level of 0.5 ng/ml, the serum ALT level was reduced by 80%, and the AST level was reduced by 70%. Modest change in the white blood cell count and platelet count were noted. The median BUN level increased from a level of 12 to 18 mg/dl, and the serum creatinine increased from 0.9 to 1.3 mg/dl. These preliminary data demonstrate that: 1) Tacrolimus can be used to successfully treat CAH-A; 2) the response of CAH-A to Tacrolimus treatment is rapid and sustained; and 3) a minor increase in the serum BUN and creatinine levels occurs as a consequence of Tacrolimus treatment. It is anticipated that with continued treatment for periods of 1-2 yr, the natural history of CAH-A will be changed such that hepatic failure and the requirement for liver transplantation may be averted.

Topics: Adult; Autoimmune Diseases; Female; Hepatitis, Chronic; Humans; Male; Tacrolimus

Topics: Aged; Alanine Transaminase; Antiviral Agents; Graft Rejection; Hepatitis E; Hepatitis E virus; Hepatitis, Chronic; Humans; Immunocompromised Host; Immunoglobulin M; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Polycystic Kidney Diseases; Polymerase Chain Reaction; Ribavirin; RNA, Viral; Tacrolimus; Viral Load

Topics: Diagnosis, Differential; Graft Rejection; Hepatitis, Chronic; Humans; Immunosuppressive Agents; Liver Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Myelinolysis, Central Pontine; Pons; Tacrolimus

Previously described neurologic damage induced by immunosuppressive treatments includes transient or reversible central nervous system involvement. We describe a 57-year-old man who underwent liver transplantation and was started on immunosuppressive therapy with tacrolimus (FK506). Six months later, he started complaining of a progressive motor and sensory impairment of the left side, together with cognitive impairment. Brain MRI showed an enlarging lesion of the white matter with peripheral contrast enhancement. PET study indicated severe hypometabolism in the right hemisphere and spectroscopic MRI showed a peak of choline and relative reduction of other metabolites. Findings of CSF examinations and cultures, serology, and molecular techniques were normal. Tacrolimus treatment was stopped. A cerebral biopsy of the lesion showed a sub acute necrotizing process. In the following months, cognitive status of the patient tended to improve although he remained hemiplegic, while serial MRI confirmed the tendency to the recovery of the lesion that was still present 1 year after. The present observation describes a progressive encephalopathy associated with immune suppression with an unusual feature and permanent brain damage.

Topics: Brain; Brain Diseases; Disease Progression; Follow-Up Studies; Hepatitis, Chronic; Humans; Immunosuppressive Agents; Liver Transplantation; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Necrosis; Positron-Emission Tomography; Tacrolimus; White People