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H Conjeevaram

Publications and source records attributed to H Conjeevaram.

12 recordsLinked to original sources
PubMed2000

Modern immunosuppression.

The current treatment of posttransplant lymphoproliferative disease (PTLD) includes prophylaxis at the time of transplant, decreasing or stopping immunosuppresion and initiation of antiviral therapy in patients with polymerase chain reaction or clinical evidence of PTLD, and judicial reintroduction of immunosuppression in patients who have cleared their PTLD and have begun to have rejection. The pharmacology, pharmacokinetics, notable side effects, and toxicities of the immunosuppressive agents are described in this article. At the conclusion of each section the author's current practice with these agents and treatment strategies are described.

Antibodies↗
PubMed2000

A multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis c: pretreatment stratification by viral burden and genotype.

OBJECTIVES: The aim of this study was to determine prospectively whether an intensive regimen of daily, high-dose interferon would improve the response rate for the treatment of chronic hepatitis C in patients with unfavorable virological characteristics. METHODS: A total of 104 patients with chronic hepatitis C were randomized at eight centers to receive interferon alfa-2b at a dose of 5 million units (MU) daily or 3 MU t.i.w. for a period of 24 wk. Patients were prospectively randomized by low or high viral burden and stratified by genotype. HCV RNA was measured by quantitative polymerase chain reaction, and response rates were compared between the dosage regimens. RESULTS: HCV RNA levels dropped more rapidly to lower levels in the group treated with 5 MU daily. In this group, the initial virological response (IR) at wk 12 and the end-of-treatment response (ETR) at wk 24 were double that of patients treated with standard interferon (66% vs 33% and 48% vs 24%, p < 0.01). Sustained response rates were low for both dose groups (14% vs 4%, p = 0.08). Genotype-related differences in initial response rates were present in the standard dose group (63% non-1 genotype vs 24% genotype 1; p = 0.005) but not in those treated with 5 MU daily (66% vs 67%, p = NS). Using multivariate analysis, only the interferon dose was associated with IR and ETR (p = 0.002). CONCLUSIONS: Daily, high dose interferon rapidly dropped HCV RNA and increased initial and end-of-treatment response rates when compared to t.i.w. regimens. This effect, independent of viral burden and genotype, suggests that patients with unfavorable viral characteristics might benefit from an intensive regimen that promotes rapid viral clearance. These data support further study of the use of high-dose induction regimens. However, improvements in sustained response rates will require additional therapeutic maneuvers such as prolonged therapy or the adjunctive use of ribavirin.

Adult↗
PubMed1999

Liver transplantation at the University of Chicago.

Since our 1995 report, improvements in patient survival after liver transplantation have widened indications for liver transplantation and led to a greater imbalance between donor supply and need. The organ shortage is the major barrier to liver transplantation at this time. Despite expanded donor criteria, there has been only a marginal increase in the number of liver transplants performed nationally. We have used several approaches to decrease the demand for organs in both adults and children. Our center was one of the first institutions to use reduced-size, living-donor, and split liver transplants routinely. The use of reduced-size liver transplants has decreased as the use of split liver transplantation has increased. Both split liver transplantation and living donor transplantation play an important role in caring for pediatric and adult patients with end-stage and fulminant liver disease. We have concentrated our recent efforts to optimizing the technical aspects of living donor transplantation in order to decrease the need for retransplantation and further organ use. These efforts have dramatically increased graft survival. We have also focused attention on treating patients prior to transplantation in an attempt to eventually abrogate the need for traditional transplantation in some disease processes. With the use of hepatocytes and liver assist devices, we have demonstrated that we can provide a level of metabolic support not achieved with traditional medical therapy for patients with fulminant hepatic failure. As further advances in these therapies are made over the next several years, a concerted effort to bridge patients to recovery will be made. As liver transplantation has become more standardized, it has opened the door to more challenges. We have used liver transplantation in combination with cardiac transplantation to care for selected patients with end stage disease of both organs. This has been remarkably successful for the 3 patients transplanted at the University of Chicago. The immunologic benefit of this combination appears to be a decreased incidence of cardiac rejection. We have standardized the technical components of this combined operation to allow for optimal organ function and patient survival.

Adult↗
PubMed1998

Night blindness secondary to vitamin A deficiency in a patient with bile duct strictures after liver transplantation.

Vitamin A deficiency and resulting night blindness have previously been reported in patients with chronic liver disease before undergoing liver transplantation. Because early identification of patients with vitamin A deficiency can lead to the relief of symptoms and the prevention of irreversible retinal degeneration, vitamin A deficiency should always be considered in the differential diagnosis of visual disturbances in patients with liver disease. We describe a case of night blindness due to vitamin A deficiency resulting from bile duct strictures in a post-orthotopic liver transplant patient and its successful resolution with vitamin A supplementation.

Cholestasis↗
PubMed1998

Clinical course and management of inflammatory bowel disease after liver transplantation.

BACKGROUND: Previous reports investigating the clinical course and management of inflammatory bowel disease (IBD) after orthotopic liver transplant (OLT) have revealed conflicting results. METHODS: To determine the natural history and course of therapy for liver transplant patients with IBD, we reviewed the records of 35 patients, who underwent OLT between 1985 and 1996 and who had a history of either IBD (29 patients) or primary sclerosing cholangitis (PSC) without evidence of IBD before OLT (6 patients). Of 29 patients with IBD before OLT, 25 had a history of ulcerative colitis (UC) and 4 had Crohn's disease. Six patients had undergone total colectomy, one subtotal colectomy, and three partial colectomy before OLT. Mean follow-up after OLT was 37+/-6.4 months. Immunosuppression included cyclosporine, prednisone, and azathioprine in 34 patients and tacrolimus and prednisone in 1 patient. RESULTS: After OLT, 17 patients (49%) had quiescent disease and were receiving no additional medications other than standard immunosuppression to prevent organ rejection. Five patients (14%) had mild flares controlled with initiation of 5'-aminosalicylates (5'-ASA), and two patients (6%) required an increase in oral prednisone. Only one patient with PSC, without evidence of IBD before OLT, developed IBD after OLT. No patients required intravenous steroids or surgical intervention for active IBD. CONCLUSIONS: (1) Standard postOLT immunosuppressive agents in patients undergoing OLT with IBD were able to adequately control disease activity after OLT in the majority of patients. (2) IBD flares after OLT were generally well controlled with aminosalicylates or oral steroids. (3) Aminosalicylates were helpful in the clinical management of IBD, even when patients were taking standard doses of steroids, azathioprine, and cyclosporine.

Adult↗
PubMed1996

Prolonged therapy of chronic hepatitis C with ribavirin.

Therapy with ribavirin for 6-12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000-1200 mg of ribavirin daily for 24 months. Serum aminotransferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long-term side-effects.

Adult↗
PubMed1995

Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B.

BACKGROUND: We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection. METHODS: Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. RESULTS: During the 13th week lactic acidosis and liver failure suddenly developed in one patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function despite the discontinuation of fialuridine. Three other patients had mild hepatotoxicity. Several patients also had pancreatitis, neuropathy, or myopathy. Of the seven patients with severe hepatotoxicity, five died and two survived after liver transplantation. Histologic analysis of liver tissue revealed marked accumulation of microvesicular and macrovesicular fat, with minimal necrosis of hepatocytes or architectural changes. Electron microscopy showed abnormal mitochondria and the accumulation of fat in hepatocytes. CONCLUSIONS: In patients with chronic hepatitis B, treatment with fialuridine induced a severe toxic reaction characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. This toxic reaction was probably caused by widespread mitochondrial damage and may occur infrequently with other nucleoside analogues.

Acidosis, Lactic↗
PubMed1994

Animal models of hepatic encephalopathy and hyperammonemia.

Animal models of chronic liver disease with hyperammonemia are currently available to investigators. Two in particular have been utilized extensively. Carbon tetrachloride induced (CCl4) cirrhosis in the rat and portacaval shunt in the same species and other animals particularly the dog. In regards to hepatic encephalopathy, however, the CCl4 cirrhosis rat model seems to display few behavioral changes unless very advanced decompensated cirrhosis is produced. Further work should be done on this model to verify the development of encephalopathy and to improve reproducibility. The portacaval shunt rat on the other hand clearly has a consistent albeit subtle set of behavioral changes. Recent improvements in detecting these changes and more importantly showing reversal or improvement by neomycin or a low protein diet are a major advance. Hopefully, more laboratories will be able to reproduce this reversible change in behavior. Experiences gained from 7 years of using the portacaval shunt rat and other models of liver disease are described.

Ammonia↗