Liver transplantation has revolutionized the care of patients with end-stage liver disease. Liver transplantation is indicated for acute or chronic liver failure from any cause. Because there are no randomized controlled trials of liver transplantation versus no therapy, the efficacy of this surgery is best assessed by carefully comparing postoperative survival with the known natural history of the disease in question. The best examples of this are in primary biliary cirrhosis and primary sclerosing cholangitis, for which well-validated disease-specific models of natural history are available. There are currently relatively few absolute contraindications to liver transplantation. These include severe cardiopulmonary disease, uncontrolled systemic infection, extrahepatic malignancy, severe psychiatric or neurological disorders, and absence of a viable splanchnic venous inflow system. One of the most frequently encountered contraindications to transplantation is ongoing destructive behavior caused by drug and alcohol addiction. The timing of the surgery can have a profound impact on the mortality and morbidity of patients undergoing liver transplantation. Because of the long waiting lists for donor organs, the need to project far in advance when transplantation might be required has proven to be one of the greatest challenges to those treating patients with end-stage liver disease. Three important questions must be addressed in a patient being considered for liver transplantation: (1) when should the patient be referred for possible transplantation? (2) when should the patient be listed for transplantation? and (3) when is the patient too sick to have a reasonable chance of surviving the perioperative period?

Hepatitis frequently recurs after liver transplantation for early recurrence is associated with a higher risk of disease progression. (HEPATOLOGY 1997;26:1646-1652.) hepatitis C. However, the histological progression of disease, predictors of recurrence and disease severity, and patient survival remain uncertain. Fifty-five patients with cirrhosis Hepatitis C virus (HCV) infection has become the leadcaused by chronic hepatitis C underwent liver transplantation ing indication for orthotopic liver transplantation (OLT) between January 1990 and December 1993. Hepatitis C geno-in the United States. Approximately 50% to 60% of patients type was determined, and liver biopsies were performed at develop recurrent liver disease in the first few years after frequent intervals posttransplantation. The median follow-up transplantation, whereas the remaining patients remain distime was 40.4 months. The cumulative rate of survival was ease-free despite persistent viremia. [1][2][3][4][5][6] Although recurrent no different in liver transplant recipients for hepatitis C than disease is often clinically mild, early graft failure and morin liver transplant recipients for other chronic liver diseases tality have been reported. 4,7 The reasons for the variation (P Å .62). Histological recurrent hepatitis C developed in 33 in disease expression remain uncertain. Studies of the relaof 50 patients assessable for disease recurrence; the median tionship between circulating viral levels and recurrent herecurrence-free survival time was 13.4 months. Histological patocellular injury have yielded conflicting results. [8][9][10][11][12] Paactivity and stage were mild in most cases. Only 2 patients tients infected with genotype 1b have been reported to have developed cirrhosis, and no patient required a second trans-a greater incidence of recurrent hepatitis and more severe plantation for recurrent disease. Patients with acute cellular liver disease. 3,11,13 It also has been suggested that immunorejection had a shorter recurrence-free survival (P Å .0141). In suppression for cellular rejection may play a role in disease patients with recurrent hepatitis, rejection also was correlated recurrence.14 Finally, a correlation between donor-recipiwith increased histological grade 2 years after transplantation ent matching and recurrent hepatitis has been shown in (P Å .0061). Recurrence-free survival was decreased in pa-some, but not all, studies (Unpublished data, September tients infected with genotype 1 (1a and 1b combined) com-1996). 13 Reports on rates of patient survival have also been pared with genotypes 2 and 3 combined (P Å .02), whereas conflicting. Although short-term survival appears to be there was no difference between genotypes 1a and 1b (P ú good, 2,5 preliminary data from one U.S. center suggest de-.80). Only patients infected with genotype 1a or 1b developed creased survival rates among patients undergoing liver bridging fibrosis or cirrhosis. In addition, patients who had an transplantation for HCV. 15 To date, only two centers ha...

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1 Duplex scanning was used to measure liver blood flow (hepatic artery and main branches of the portal and hepatic veins) in six healthy subjects, five cirrhotic patients, and six hepatitis patients. Antipyrine clearance and formation clearances to its metabolites were also measured. 2 Compared with healthy control subjects, cirrhotic patients had a lower hepatic vein blood flow (-76%, P < 0.05). This was due primarily to a lower portal vein blood flow (-36%, NS). A statistically significant difference in liver blood flow between patients with hepatitis and normal subjects was not detected. 3 Antipyrine half-life, clearance, and the area under the serum drug concentration vs time curve were significantly different in cirrhotic patients compared with the healthy subjects (mean ± s.d.-healthy controls: t, 2 = 13.7 ± 3.0 h, CL = 30.0 ± 8.6ml h-' kg-', AUC = 549 ± 139 mg 1-1 h; cirrhotic patients: ti,2 = 32.4 ± 1.7 h, CL = 12.3 ± 2.1 ml h-1 kg-', AUC = 1061 ± 218 mg 1-1 h; P < 0.008). Antipyrine halflife, clearance, and the area under the serum drug concentration vs time curve were not significantly different in hepatitis patients compared with the healthy subjects (hepatitis patients: tb = 14.3 ± 3.7 h, CL = 29.3 ± 8.5 ml h-1 kg-I, AUC = 498 ± 142 mg I1-h). The volume of distribution of antipyrine was similar in all three groups of subjects. 4 Formation clearances to 3-OH-methylantipyrine, 4-OH-antipyrine, and norantipyrine were all lower (P < 0.009) in cirrhotic patients compared with normal subjects and hepatitis patients. However, only the formation clearance to norantipyrine was lower (P < 0.002) in hepatitis patients when compared with normals. 5 There were strong correlations between the logarithmic transformations of the formation clearances for all antipyrine metabolites (r = 0.88-0.93, P < 0.0001). However, the only orthogonal regression line with a slope not significantly different from one was that for norantipyrine and 3-OH-methylantipyrine indicating that these two metabolites may be metabolized by a common enzyme(s). 6 Weak correlations were found between the logarithmic transformations of hepatic vein blood flow and antipyrine clearance and the logarithmic transformations of hepatic vein blood flow and formation clearances to antipyrine metabolites (r= 0.54-0.62, P < 0.05). 7 Cirrhotic patients may have difficulty metabolizing drugs with high hepatic extraction ratios or drugs that are eliminated by the same liver enzyme systems which produce the three major metabolites of antipyrine. Hepatitis patients may have difficulty metabolizing drugs that share the same hepatic enzyme system responsible for the formation of norantipyine from antipyrine.

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