Incidence and etiology of hepatic dysfunction in heart transplant recipients receiving a cyclosporine-based triple immunosuppressive therapy.
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Biomedical subjects
Publications and source records attributed to H I Wright.
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A case report of rheumatoid arthritis developing during alpha-interferon therapy of chronic hepatitis C is reported. The rheumatoid arthritis was severe, being non-responsive to the use of nonsteroidal anti-inflammatory drugs, and persisted despite discontinuation of the interferon therapy. The literature relative to this case suggesting an association between rheumatoid arthritis and interferon therapy is presented. This case suggests that interferon therapy may precipitate subclinical rheumatoid arthritis in an individual without pre-existing clinical arthritis.
A 10-year-old girl with acute influenza B virus disease was given repetitive doses of acetaminophen by her mother to reduce the child's fever. When finally seen by trained medical personnel, the child was experiencing abdominal pain, nausea, and vomiting, which are classic signs of acetaminophen hepatotoxicity. Despite these findings, the child was given additional acetaminophen and experienced lethal hepatotoxicity.
The authors describe a rare case of Campylobacter fetus occurring in a patient who showed no overt evidence of immune incompetence. The patient presented with severe cellulitis of the legs, a chronic low grade fever, and a history of recent exposure to sick calves.
Our procedure for donor harvesting and preserving intestinal grafts has matured. In 27 consecutive cases, a protocol was established whose essentials consist of (a) selecting hemodynamically stable donors, (b) antibiotic pretreatment of the donor, and (c) short warm ischemic times (< 40 minutes). Assessment of graft quality can be achieved by daily inspection of stomas, inspection for diarrhea > 2.5 1/day in adults or > 300 ml in children, and weekly protocol or clinically directed endoscopic biopsies. Edema and microscopic separation of the mucosal surface and sloughing are routinely found during the first few post-engraftment days, but the crypt cells remain and regenerate a normal mucosa within a week. Recovery of a normal mucosal surface took place in all cases.
Upper gastrointestinal endoscopy is a widely practiced clinical procedure that has become routine in even the most remote medical environments. Its application at a liver transplant center represents the use of this particular technology at the opposite extreme of medical practice and its use in a unique and severely ill group of patients. The following is a description of the author's experience with upper gastrointestinal endoscopy at the University of Pittsburgh's liver transplant center. Despite the severity of illness of the patients seen at this center, documented by the high frequency of patients seen with abnormal prothrombin times and low platelet counts, upper gastrointestinal endoscopy performed either for diagnostic or therapeutic procedures has been found to be safe. The disease processes that affect transplant patients both before and after transplantation are not seen frequently in the general practice of gastroenterology. Thus the endoscopist at a transplant center has to be able to recognize, identify, and treat the unique problems seen in a transplant population.
Chronic hepatic encephalopathy is highly responsive to changes in diet, to antibiotic therapy and to ingestion of nondigestible disaccharides. The precise pathophysiology of chronic hepatic encephalopathy in individual cases is highly variable, although ammonia toxicity and production of neurotransmitterlike substances in the gut have been proposed to contribute to the overall syndrome of chronic hepatic encephalopathy. The support for this hypothesis is based on the empiric observation that reduction in protein intake, a catharsis or both are effective treatments for chronic hepatic encephalopathy. This study was performed to evaluate the effect of mild subclinical and low-grade (grade 0 to 1) chronic hepatic encephalopathy on gastric emptying and oral-cecal transit times. Thirty patients were studied. Ten had no evidence of chronic hepatic encephalopathy, as determined with a battery of neuropsychiatric studies (group 1); 10 had subclinical hepatic encephalopathy, as judged on the basis of abnormal neuropsychiatric test performance but normal neurological examination (group 2); and 10 had grade 1 hepatic encephalopathy. Each underwent a liquid gastric emptying study and a lactulose oral-cecal transit time study. No significant differences between groups were evident in the results of the gastric emptying studies. In contrast, the time required for a lactulose load to reach the cecum was significantly greater in the patients with hepatic encephalopathy (p < 0.01) and increased as a function of the hepatic encephalopathy grade.(ABSTRACT TRUNCATED AT 250 WORDS)
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An overview is given of current practice in deciding which patients can undergo a major abdominal operative procedure involving the hepatobiliary system. The criteria developed for individuals with normal and diseased livers are presented, and the unique circumstances of liver transplantation are also addressed.
Liver transplantation (OLTx) has become a common life-saving procedure for individuals with chronic advanced liver disease. It is also used in the clinical treatment of patients with fulminant hepatic failure and those with primary neoplastic disease of the liver. Despite its overall success in restoring meaningful life to those who undergo the procedure, the posttransplant life of a liver allograft recipient is not without hazard. A common problem following liver transplantation is the finding of abnormal liver injury tests reflecting a "hepatitis" that can not be ascribed to allograft rejection. The majority of such cases are a consequence of either a technically flawed operation, drug-induced liver injury, or one or another form of viral hepatitis. Each of these problems is discussed in the following clinical review.
From January 1986 through December 1991, a total of 221 patients with alcoholic liver disease received liver transplantation. In 147 of these cases, complete pretransplant histopathologic, demographic, and laboratory data (minimum of CBC, AST, ALT, total bilirubin, albumin, and prothrombin time) were available for review. Forty-five (30%) of the 147 recipients had alcoholic hepatitis plus cirrhosis (AH), whereas 70% had cirrhosis (CIRR) alone. Age and sex were similar in the subgroups, but the patients with CIRR had a greater AST/ALT ratio, longer protime, and lower platelet count (all p < 0.01). Coexistent hepatitis B (4.7%) or hepatitis C (4.1%) was similar in both groups. Current survival is 80% for patients with AH and 84% for those with CIRR (NS). Overall, survivors were younger (43.4 +/- 1.7 years) than nonsurvivors (53.6 +/- 3.2) (p < 0.01), an age influence that was significant in the CIRR group (p < 0.01) but not in the AH group. Inexplicably, the AST/ALT ratio was greater in AH survivors (1.5 +/- 0.2) than it was in nonsurvivors (0.4 +/- 0.1) (p < 0.01). In patients with CIRR, the platelet count was greater in survivors (252 +/- 29 vs. 86 +/- 11 x 10(9) cells/liter). The data support the clinical impression that patients with chronic decompensated cirrhosis referred for liver transplantation had more severe complications of their liver disease than did those with AH. Survival in both subgroups was similar, but overall the survivors are nearly a decade younger than the nonsurvivors.(ABSTRACT TRUNCATED AT 250 WORDS)
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The preceding discussion has characterized the various types of viral hepatitis, both common and unusual, that can lead to subfulminant hepatic failure. Whenever specific medical therapy exists, it is preferred. If the disease has progressed sufficiently to prohibit survival inspite of medical therapy, OLT is indicated under the umbrella of continuing specific medical therapy. Conversely, if no medical therapy exists, OLT is the only possible therapy but should be used only if extrahepatic disease processes do not prohibit survival. Hopefully, with better and more effective means of immunosuppression, immunosuppression monitoring and the development of additional medical therapies for viruses, OLT will be used less often in cases of subfulminant viral hepatitis in the future.
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Currently, alpha interferon is the only recognized therapy for chronic viral hepatitis. As a result of its success in several multicenter trials, the agent was approved recently by the FDA for use in the clinical management of patients with chronic hepatitis C. FDA approval for its use in chronic hepatitis B is anticipated. Based upon this experience in nonimmunosuppressed individuals, the efficacy of alpha interferon therapy in patients who are recipients of liver allografts and are receiving chronic immunosuppression was assessed in a preliminary trial of the agent in 30 patients (13 with HBV, 11 with HCV, and 6 with hepatitis non A, non B, non C). Therapy was initiated at a dose of 3 X 10(6) units three times per week and continued for 6 months. Dose reduction in the amount of the alpha interferon administered was determined by a preestablished protocol. Nine percent of those with HCV and 18% of those with hepatitis non A, non B, non C experienced a full response to alpha interferon therapy. No full responses to alpha interferon therapy. No full responses were seen in those with HBV disease. Partial responses were common in all three groups but were most frequent in those with hepatitis non A, non B, non C and least frequent in those with HCV-related disease. This preliminary experience demonstrates the following: 1. Viral hepatitis following OLTx can be treated with alpha-2b-interferon. 2. The complications of alpha-2b-interferon therapy utilized prior to OLTx can be avoided by giving the therapy following successful OLTx. 3. The high rate of partial responses noted suggests that future studies should utilize either higher doses or longer durations of therapy or both. 4. The response rate was greatest for those having non A, non B, non C hepatitis and least for those with HCV hepatitis. 5. In this small preliminary series, no episodes of liver graft rejection could be ascribed to the use of alpha-2b-interferon in the patients so treated.
Recipients of solid organ allografts require lifelong immunosuppression in order to prevent graft rejection and to maintain graft function. In general, such immunosuppression greatly impairs the cellular immune system, as this level of the immune system is principally responsible for self and non-self recognition. The consequences of allograft transplantation in terms of patient and graft survival when transplants are given to individuals who have a preexisting humoral immune deficiency characterized by a deficiency of the serum levels of one or more of the major Ig classes have not yet been reported. From February 1, 1981 through December 31, 1990, a total of 43 adult patients with a deficiency of 1 or more Ig classes received a ABO-matched liver allograft at this institution. This sample represents 2.5% of a total of 1684 adults transplanted during this interval. These 43 liver graft recipients could be divided into 3 major groups based upon the presence of an IgG, IgM, or IgA deficiency. IgG deficiencies were defined as levels less than 50 mg/dl. Patient and graft survival for the IgA-deficient group was significantly reduced (P less than 0.04 and P less than 0.009, respectively) compared with both the IgG- and IgM-deficient groups. The latter two groups did not differ from controls without an Ig deficiency for these same two endpoints. The major causes of death in the IgA-deficient group were sepsis and opportunistic infection. A third of the deaths in the IgA-deficient group occurred in the perioperative period (first 30 days) while greater than 50% of the deaths occurred within the first 3 months, and all deaths occurred before the first year. Based upon these data, the following conclusions can be made: (1) serum IgA deficiency but not IgG or IgM deficiency is associated with an increased post-OLTx death and graft loss rate; (2) the majority of these deaths are due to sepsis or an opportunistic infection; and (3) most of the deaths occur early. These data suggest that recognition of a deficiency of IgA prior to organ grafting necessitates meticulous attention to the prevention of infection in the immediate perioperative period if patient and graft survival of these patients is to be improved.
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