Decompensated liver disease associated with chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation. It was shown previously that greater pretransplantation ...HCV titers are associated with relatively poor patient and graft survival. The tolerability and efficacy of antiviral therapy in patients with decompensated liver disease are not known. We conducted a pilot study to determine the likely tolerability and efficacy of pretransplantation antiviral therapy with interferon alfa-2b, with or without ribavirin. HCV RNA–positive patients at or near the top of their respective waiting lists were randomly assigned to one of three treatment regimens until the time of liver transplantation: (1) group A, interferon alfa-2b, 1 × 106 U/d; (2) group B, interferon alfa-2b, 3 × 106 U three times weekly; or (3) group C, interferon alfa-2b, 1 × 106 U/d, plus ribavirin, 400 mg twice daily. Less than half the patients screened met entry criteria, with thrombocytopenia and leukopenia the most common reasons for exclusion. Fifteen patients were administered antiviral therapy; three patients in group A and six patients each in groups B and C. Loss of detectable HCV RNA was seen in 33% of patients, whereas 55% had a decrease in viral titers on therapy. Twenty-three adverse events occurred, including 20 serious adverse events. Thrombocytopenia was the most common adverse event. Two infectious complications occurred; one of these had a fatal outcome. We conclude that although pretransplantation antiviral therapy may reduce HCV titers in a minority of patients who meet treatment initiation criteria, adverse events associated with therapy are frequent and often severe in patients with Child's class B and C cirrhosis. (Liver Transpl 2002;8:350-355.)
Because acute liver failure is rare, related data have been sparse. Studies have suggested that viral hepatitis is the most common underlying cause of this condition.
To describe the clinical ...features, presumed causes, and short-term outcomes of acute liver failure.
Prospective cohort study.
17 tertiary care centers participating in the U.S. Acute Liver Failure Study Group.
308 consecutive patients with acute liver failure, admitted over a 41-month period.
Detailed clinical and laboratory data collected during hospitalization, including outcome 3 weeks after study admission.
73% of patients were women; median age was 38 years. Acetaminophen overdose was the most common apparent cause of acute liver failure, accounting for 39% of cases. Idiosyncratic drug reactions were the presumptive cause in 13% of cases, viral hepatitis A and B combined were implicated in 12% of cases, and 17% of cases were of indeterminate cause. Overall patient survival at 3 weeks was 67%. Twenty-nine percent of patients had liver transplantation, and 43% survived without transplantation. Short-term transplant-free survival varied greatly, from 68% for patients with acetaminophen-related liver failure to 25% and 17% for those with other drug reactions and liver failure of indeterminate cause, respectively. Coma grade at admission appeared to be associated with outcome, but age and symptom duration did not.
Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure. Apparent cause and coma grade at admission were associated with outcome. Although transplantation may improve patient survival, it was unavailable or unnecessary for most patients.
Hepatitis C virus (HCV)‐induced cirrhosis is the commonest indication for orthotopic liver transplantation, but HCV recurrence is nearly universal and may worsen patient / graft outcomes. The ...frequency and severity of HCV recurrence has apparently increased in recent years, raising concern about a possible role for newer immunosuppression regimens in this increase, including potentially tacrolimus. We randomized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation. A pathologist blinded to treatment reviewed serial liver biopsies. Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus‐ and cyclosporine‐treated patients were .38 and .54 (P = .19) and failure / death were .25 and .28, respectively (P = .789). Although cyclosporine‐treated patients had significantly larger increases in median serum HCV RNA levels (months 1, 6, and 12), no significant differences were observed between the two treatment arms in histologically‐diagnosed HCV recurrence / survival rates. In conclusion, choice of calcineurin inhibitors does not impact severity of recurrent HCV. (Liver Transpl 2004;10:1258–1262.)
The optimal embolic agent for transhepatic arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been identified. This study reports outcomes of TACE for HCC with Gelfoam ...powder and polyvinyl alcohol (PVA).
Eighty-one patients underwent 152 TACE sessions with Gelfoam powder (n = 41) or polyvinyl alcohol (PVA) and Ethiodol (n = 40) as the embolic agent. Chemotherapeutic drugs were the same for all patients (50 mg cisplatin, 20 mg doxorubicin, 10 mg mitomycin-c). The groups were compared based on number of TACE sessions, maximum tumor size, bilirubin level, aspartate and alanine aminotransferase levels, Child-Pugh score, Model for End-stage Liver Disease score, and hepatitis B or C virus positivity. The number of cases of each Child class in each group was also evaluated. Survival starting from the first TACE session was calculated according to Kaplan-Meier analysis. Forty-eight patients died during the study period, 19 received transplants, and 14 were alive at the end of the study period.
The groups were statistically similar in all categories regarding liver function, Child-Pugh score, tumor size, hepatitis status, and percentage of patients with Child class A, B, and C disease. The number of TACE sessions was significantly greater for the Gelfoam powder group (mean, 2.2) versus the PVA group (mean, 1.6; P = .01). Overall survival was similar between groups whether patients who received transplants were included in the analysis (mean, 659 days +/- 83 with Gelfoam powder vs 565 days +/- 71 with PVA; P = .42) or were excluded (mean, 519 days +/- 80 with Gelfoam powder vs 511 days +/- 75 with PVA; P = .93).
In similar patient groups, survival after treatment of HCC with TACE with Gelfoam powder or PVA and Ethiodol was similar.
Non‐alcohol‐induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to ...cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH. Forty patients were diagnosed with NASH based on a compatible liver biopsy with other causes of liver disease, including alcohol abuse, excluded by history, serum tests, and use of ultrasound. Twenty‐four patients received 13 to 15 mg/kg/d of UDCA for 12 months. Sixteen patients with hypertriglyceridemia were placed on clofibrate, 2 g/day for 12 months. Twenty‐five women and 15 men entered the study. Six of 40 patients (15%) withdrew because of side effects. Four additional patients were withdrawn because of noncompliance; one of them later required liver transplantation. In the UDCA group, the decreases in mean serum levels of alkaline phosphatase, alanine transaminase (ALT), and γ‐glutamyl transpeptidase (GGT) as well as histological grade of steatosis were significant. Among the patients treated with clofibrate, no change from baseline was found in mean ALT, aspartate transaminase (AST), GGT, bilirubin, triglycerides, and cholesterol, or in histological grade of steatosis, inflammation, or fibrosis after 12 months of treatment as compared with entry. Alkaline phosphatase activities decreased significantly from baseline. Despite the known lipid‐lowering effects of clofibrate, it did not appear to be of clinical benefit in the treatment of NASH in this 1‐year pilot study. However, treatment of NASH with UDCA for 12 months resulted in significant improvement in alkaline phosphatase, ALT, GGT, and hepatic steatosis. The possible benefit of UDCA therapy should be further investigated in the context of a randomized, controlled trial.
Unless they maintain Medicare status through disability or age, kidney transplant recipients lose their Medicare coverage of immunosuppression 3 years after transplantation. A significant transplant ...survival advantage has previously been demonstrated by the extension of Medicare immunosuppressive medication coverage from 1 year to 3 years, which occurred between 1993 and 1995.
The United States Renal Data System (USRDS) was analyzed for recipients of kidney transplants from 1995 to 1999. Using a Markov model, we estimated survival and costs of the current system of 3‐year coverage compared with lifetime immunosuppression coverage. Results were calculated from the perspectives of society and Medicare.
Extension of immunosuppression coverage produced an expected improvement from 38.6% to 47.6% in graft survival and from 55.4% to 61.8% in patient survival.
The annualized expected savings to society from lifetime coverage was $136 million assuming current rates of transplantation. Medicare would break‐even compared with current coverage if the fraction of patients using extended coverage was <32%. The extension would be cost‐effective to Medicare if this fraction was <91%.
Extended Medicare immunosuppression coverage to the life of a kidney transplant should result in better transplant and economic outcomes, and should be considered by policy makers.
To compare the value of the Child-Pugh and Model for End-stage Liver Disease (MELD) scores to predict patient survival rates after transarterial chemoembolization (TACE) for hepatocellular carcinoma ...(HCC).
Eighty-seven patients underwent 169 TACE sessions. Child-Pugh and MELD values were calculated before initial treatment. Survival length was tracked from the date of the first TACE procedure. Transplant recipients were censored from the study at the time of surgery. Child-Pugh and MELD scores as well as bilirubin and albumin levels and International Normalized Ratio were placed in high and low categories defined by their respective medians. Patient survival was compared at 3 months, 6 months, 12 months, and 24 months, and patterns were tested with chi2 or Fisher exact tests. Survival over the entire period was examined with Kaplan-Meier analysis and differences were tested with log-rank tests.
Mean and median survival times for all patients were 24 and 17 months, respectively. Sixteen patients were censored for transplantation at a mean of 12.9 months. MELD and Child-Pugh scores correlated well with each other (r = 0.68). Child-Pugh score (r = -0.35, P = .04) correlated more strongly with 12-month survival than did MELD score (r = -0.26, P = .12). After high/low score category division, a significantly greater survival difference was predicted by Child-Pugh score (27.2 months vs 10.3 months; P = .03) versus MELD score (27.5 months vs 15.8 months; P = .19). An albumin level greater than 3.4 g/dL was also associated with significantly improved survival (29.3 months vs 10.1 months; P = .0032). Survival differences between high-risk and low-risk groups at the 3-, 6-, 12-, and 24-month intervals were significant for low Child-Pugh scores and for albumin levels greater than 3.4 g/dL. Statistical significance was not approached at any of the time lengths with MELD scores.
Child-Pugh score correlates better than MELD score to overall patient survival and is a better predictor than MELD score of survival at specific time points. Of the components of the Child-Pugh and MELD systems, albumin level is the most useful predictor of survival.
Non-alcohol-induced steatohepatitis (NASH) is characterized by elevated serum aminotransferase activities with hepatic steatosis, inflammation, and occasionally fibrosis that may progress to ...cirrhosis. No established treatment exists for this potentially serious disorder. Our aim was to conduct a pilot study to evaluate the safety and estimate the efficacy of ursodeoxycholic acid (UDCA) and clofibrate in the treatment of NASH. Forty patients were diagnosed with NASH based on a compatible liver biopsy with other causes of liver disease, including alcohol abuse, excluded by history, serum tests, and use of ultrasound. Twenty-four patients received 13 to 15 mg/kg/d of UDCA for 12 months. Sixteen patients with hypertriglyceridemia were placed on clofibrate, 2 g/day for 12 months. Twenty-five women and 15 men entered the study. Six of 40 patients (15%) withdrew because of side effects. Four additional patients were withdrawn because of noncompliance; one of them later required liver transplantation. In the UDCA group, the decreases in mean serum levels of alkaline phosphatase, alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) as well as histological grade of steatosis were significant. Among the patients treated with clofibrate, no change from baseline was found in mean ALT, aspartate transaminase (AST), GGT, bilirubin, triglycerides, and cholesterol, or in histological grade of steatosis, inflammation, or fibrosis after 12 months of treatment as compared with entry. Alkaline phosphatase activities decreased significantly from baseline. Despite the known lipid-lowering effects of clofibrate, it did not appear to be of clinical benefit in the treatment of NASH in this 1-year pilot study. However, treatment of NASH with UDCA for 12 months resulted in significant improvement in alkaline phosphatase, ALT, GGT, and hepatic steatosis. The possible benefit of UDCA therapy should be further investigated in the context of a randomized, controlled trial. (Hepatology 1996 Jun;23(6):1464-7)
The time progression of allograft damage in patients with recurrent hepatitis C after orthotopic liver transplantation (OLT) is not precisely determined. The aim of this analysis is to study the ...progression of disease recurrence and its impact on patient and graft survival. Data for 300 patients who underwent OLT for hepatitis C were analyzed regarding the incidence of histological recurrence, risk factors, immunosuppressive regimen, rejection episodes, and survival. For patients with histological recurrence, the timing and risks for disease progression were analyzed. Data for 30 patients who underwent retransplantation were studied. Histological recurrence occurred in 40.3% of patients, 27.2% of whom progressed to bridging fibrosis or cirrhosis. Eighty-seven percent of the patients experienced recurrence of disease within 24 months of OLT. Patients with histological recurrence within 6 months of OLT had an increased risk for progression to cirrhosis compared with patients with recurrence later than 6 months (risk ratio, 2.3). Recurrence within 1 year was associated with decreased patient and graft survival rates at 1 and 5 years (65.1% and 56.4% versus 80.6% and 78.4%; P = .004 andP = .0008, respectively). Patients with histological recurrence had a greater incidence of acute cellular rejection, as well as multiple episodes of rejection, steroid-resistant rejections, and greater cumulative doses of corticosteroids. Histological recurrence after OLT for hepatitis C is common and usually occurs within 2 years of OLT. Early recurrence negatively affects patient and graft survival. Host factors impacting on recurrence need further study. A relation between the hepatitis C virus, allograft rejection, and immunosuppression exists and needs investigation. (Liver Transpl 2000;6:553-561.)
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