Liver transplantation: who to refer and when.

Liver transplantation is a surgical procedure offered to individuals with irreversible, near fatal liver disease. The timing of both transplantation listing and surgical engraftment are critical factors in the success of this endeavour. To accomplish each and maintain surgical survival rates without prematurely transplanting individuals to achieve excellent outcome statistics is an art that requires knowledge about the procedure and the natural history of the specific liver disease in question. Herein are the views of the transplant team at Loyola University of Chicago as to how this can be accomplished within the framework of the American experience, and the rules and regulations governing donor organ procurement and allocation in the United States.

Chronic hepatitis C in patients with normal or near normal alanine aminotransferase levels: the role of interferon alpha 2b therapy.

BACKGROUND/AIMS: Interferon is the only approved therapy for chronic hepatitis occurring as a consequence of an infection with the hepatitis C virus. Because interferon is expensive, has a large number of untoward effects and its efficacy is not guaranteed, many physicians limit their use of this therapy to those with histologically advanced but not end-stage cirrhotic disease. Moreover, most cases are biopsied only after 6 months or more of abnormal alanine aminotransferase levels have been documented. The rationale for this approach to patients with hepatitis C virus infection has not been demonstrated. METHODS: In the present study, a total of 37 patients with alanine aminotransferase levels < 1.5 upper limits of normal (59 IU/l or less) who were HCV-RNA positive by reverse transcriptase polymerase chain reaction, were selected for interferon treatment, having been identified as having hepatitis C virus disease as the result of a screening Ab-HCV test confirmed with a positive radio immune blotting assay. Once identified, each subject underwent a percutaneous liver biopsy and was tested for the presence of HBsAg, Ab-HBs and HBV-DNA. All liver biopsies were read and graded according to the criteria of Knodell et al. Each subject was treated with interferon a2b at a dose of 5 MU administered daily until a response was achieved (a minimum period of 6 months) or until a full year had elapsed. A response was defined as HCV-RNA negativity in serum on three consecutive monthly determinations. The study population consisted of 21 males and 16 females ranging in age from 17 to 72 years (mean 46.7 +/- 2.2 years). Their mean serum alanine aminotransferase level at the initiation of therapy was 37.5 +/- 2.1 IU/l with a range of 10-59 (normal values being 40 IU/l or less). 54% of the subjects were presumed to have acquired their hepatitis C virus infection as a result of a blood transfusion; 32% as a result of prior intravenous drug abuse; and 13% had no identifiable risk factor for hepatitis C virus. Despite having normal or near normal serum alanine aminotransferase levels, 9 subjects had chronic persistent hepatitis, 13 had chronic active hepatitis and 15 had chronic active hepatitis + cirrhosis documented by histopathologic assessment of their liver biopsies. RESULTS: An interferon response was achieved in 5/9 with chronic persistent hepatitis, 11/13 with chronic active hepatitis and 8/15 with chronic active hepatitis + cirrhosis for an overall response rate of 65%. CONCLUSIONS: This study has demonstrated that individuals who: 1) are hepatitis C virus positive with serum alanine aminotransferase levels < 1.5 x upper limits of normal can have histologically advanced liver disease; 2) can respond to interferon therapy defined as clearance of detectable HCV-RNA in serum; and, 3) should be considered for interferon treatment.

Assessment of liver function: the current situation.

Hepatologists continue to search for a safe, accurate, and reliable method to quantify hepatic function similar in principle to the creatinine clearance for renal disease or spirometry for pulmonary disease. When evaluating patients with advanced decompensated chronic liver disease, there is little need for such tests and a decision for or against liver transplantation is all that is required. However, in patients with chronic compensated liver disease, an estimate of hepatic function based on objective criteria would be most valuable in establishing a prognosis and in determining a treatment plan. The best methods currently available for this purpose consist of the use of model drugs which are metabolized exclusively by the liver by cytochromes P-450 enzyme systems. The alterations in pharmacokinetic parameters (i.e., clearance rate of the parent compound or formation rate of one of its metabolites, etc.) produced as a result of liver disease can be quantitated. The results obtained can be utilized as a measure of hepatic function. The two drugs most commonly utilized for this purpose are lidocaine and caffeine. The advantages and disadvantages of each of these two drugs as probes of hepatic function are herein reviewed.

The incidence, timing, and management of biliary tract complications after orthotopic liver transplantation.

OBJECTIVE: This study analyzed the incidence and timing of biliary tract complications after orthotopic liver transplantation (OLTx) in 1792 consecutive patients. These results were then compared with those of previously reported series. Finally, recommendations were made on appropriate management strategies. SUMMARY BACKGROUND DATA: Technical complications after OLTx have a significant impact on patient and graft survival. One of the principal technical advances has been the standardization of techniques for biliary reconstruction. Nonetheless, biliary complications still occur. A 1983 report from the University of Pittsburgh reported biliary complications in 19% of all transplants, and an update in 1987 reported biliary complications in 13.2% of transplants. METHODS: The medical records of all patients who underwent liver transplantation and were hospitalized between January 1, 1988 and July 31, 1991 were reviewed. The case material consisted of the medical records of 217 patients treated for 245 biliary complications. RESULTS: Primary biliary continuity was established by either choledochocholedochostomy over a T-tube (C-C, n = 129) or a Roux-en-Y choledochojejunostomy with an internal stent (C-RY, n = 85). The overall incidence for biliary complication in this large series was 11.5%. Strictures (n = 93) and bile leak (n = 58) were the most common complications (69.6%). Most biliary complications (n = 143, 66%) occurred within the first 3 months after surgery. In general, leaks occurred early, and strictures developed later. Bile leaks were equally frequent in both C-C and C-RY (27.1% and 25.9%, respectively); strictures were more common after a C-RY type of reconstruction (36.4% and 52.9%, respectively). Twenty-one patients died, an incidence of 9.6%. Fifteen of the 21 biliary-related deaths were among patients treated for rejection before the recognition of biliary tract pathologic findings. CONCLUSIONS: Progress has been made on improving the results of biliary reconstruction after OLTx. Nonetheless, patients continue to experience biliary complications after OLTx, and these complications cause considerable loss of grafts and life. If significant additional improvement in patient and graft survival are to be obtained, the technical performance of OLTx must continue to improve.

Assessment of the estrogenic activity of phytoestrogens isolated from bourbon and beer.

Phytoestrogenic substances have previously been isolated and identified in two alcoholic beverages: bourbon and beer. To delineate the relative potencies of the estrogenic substances of plant origin thus far identified in these commonly consumed alcoholic beverages, we evaluated the ability of biochanin A, beta-sitosterol, genistein, and daidzein to bind to cytosolic estrogen receptor binding sites. The in vitro studies demonstrated that each of the contained substances was capable of effectively competing for cytosolic estrogen receptor binding sites of rat liver and uterus. Further, the two phytoestrogenic constituents of bourbon, beta-sitosterol and biochanin A, were less potent than those present in beer. Given the high concentration of beta-sitosterol in bourbon, we chose to evaluate the estrogenicity of beta-sitosterol in vivo using ovariectomized rats. beta-sitosterol was administered either daily or intermittently at 3 doses, based on amounts previously determined to be present in bourbon. The in vivo studies demonstrated that beta-sitosterol is capable of producing a weak estrogenic effect only at the lowest dose (6.2 micrograms/dl) administered intermittently. These responses suggest that beta-sitosterol may be weakly estrogenic at low doses, but is unable to maintain such an effect at higher doses.

Does previous abdominal surgery alter the outcome of pediatric patients subjected to orthotopic liver transplantation?

The medical, anesthesia, and surgical records of 89 consecutive pediatric patients who underwent an orthotopic hepatic transplantation procedure at the University of Pittsburgh from February 1981 to May 1984 were reviewed to evaluate the effect of prior abdominal surgery upon the morbidity and mortality of orthotopic liver transplantation in children. Fifty-seven children (group 1) had had prior abdominal surgery, whereas 32 (group 2) had not. The group 1 subjects were younger (p less than 0.001), had better prothrombin times (p less than 0.01), and better platelet counts (p less than 0.02) than did those in group 2. No difference in the duration of anesthesia or intraoperative use of fresh frozen plasma or platelets was evident between the two groups. However, group 1 patients were given more red blood cells intraoperatively than were the group 2 patients (p less than 0.01). The group 1 patients had more total postoperative infections (p less than 0.05), which was due solely to a greater number of abdominal infections (p less than 0.05), but similar total hospital and intensive care unit stays as did the group 2 patients. When those in group 1 were divided into those having a previous Kasai procedure versus those who did not, no differences between the two groups were apparent except for age. Based upon these data, we conclude that prior abdominal surgery does not affect mortality, the duration of hospital or intensive care unit stay, plasma or platelet requirements, and total anesthesia time required for orthotopic liver transplantation, but does enhance the number of red blood cell transfusions and infections, particularly abdominal infections, in children undergoing this procedure.

Neuropsychiatric assessment of liver transplantation candidates: delirium and other psychiatric disorders.

Forty consecutive liver transplantation candidates underwent a standard psychiatric evaluation as part of a multidisciplinary preoperative examination. Psychiatric diagnoses were determined using DSM-III criteria and correlations between the psychiatric diagnoses and the results of bedside cognitive examinations, biochemical measures of hepatic function, and EEG's were made. Half of the patients could not be given a specific psychiatric diagnosis despite the fact of their being in terminal stages of a severe medical illness and being stressed by the uncertainty of whether they would be accepted for possible liver transplantation. Of the twenty patients given a psychiatric diagnosis, 60 percent were found to be delirious and 35 percent had an adjustment disorder. Delirium was associated with a serum albumin less than 3.0 g/dl, grades 1 through 3 EEG dysrhythmias, a Mini Mental State score less than 24 or impairment on Trailmaking Tests. In addition, discriminant analyses were performed to determine which batteries of tests best differentiated the delirious patients. A unique pattern of psychosocial stressors was noted in these patients where the severity of overall stress and of occupational dysfunction was high in most, yet family and social relationships were reported as less affected.

Liver procurement for orthotopic transplantation: an analysis of the Pittsburgh experience.

The incidence of prospective organ donors in the United States and the techniques which are to used to guarantee their optimal use after identification are analyzed. Attitudes of the public and health professionals toward organ donation are discussed. The organization of the Pittsburgh Organ Procurement Agency and its relationship to other such agencies is described. Finally, the presently used techniques of liver salvaging and preservation are outlined.