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To investigate the natural history of compensated cirrhosis, 293 consecutive patients without previous major complications (ascites, jaundice, encephalopathy or gastrointestinal hemorrhage) were studied in terms of morbidity (probability of developing decompensated cirrhosis during follow-up) and survival. Patients were diagnosed by liver histology between 1968 and 1980. Median follow-up was 63 months. Decompensation of cirrhosis was considered when a patient first developed one of the major complications of the disease. Ten years after diagnosis, the probability of developing decompensated cirrhosis and the survival probability rate were 58 and 47%, respectively. A multivariate survival analysis (Cox's regression model) using clinical, biochemical and histological data obtained at diagnosis disclosed seven factors that predicted prognosis: serum bilirubin; serum gamma-globulin concentration; hepatic stigmata; prothrombin time; sex; age, and alkaline phosphatase. According to the contribution of each one of these factors to the final model, a prognostic index was constructed that allows calculation of the estimated survival probability. The predicting value of this index was validated by a split sample testing technique.

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The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope ؊0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope ؊0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT. (HEPATOLOGY 2002;35: 680-687.) C irrhosis caused by hepatitis C virus (HCV) infection is the main indication of liver transplantation (LT) in most transplant programs. Infection of the liver graft after transplantation is almost universal and persistent infection leading to chronic hepatitis, cirrhosis, and graft failure is common. 1,2 In our geographic area, 30% of patients undergoing LT for HCV-related liver disease are already cirrhotic 5 years after transplantation. 3 Regretfully, prophylaxis of HCV infection of the graft is not feasible because no specific anti-HCV immune globulin is available. In addition, antiviral treatment in patients on waiting lists for LT appears to be poorly effective and may cause severe adverse effects. 4,5 Currently, treatment of hepatitis C infection after LT seems the most feasible strategy to eradicate HCV. 6-8 Treatment of HCV infection after LT can be initiated before liver damage occurs or once liver disease is already established. Treatment in the early phase of LT seems a reasonable approach because eradication of HCV would prevent liver damage. 9-11 However, there are only a few studies analyzing the efficacy of antiviral therapy in the early posttransplantation period. Interferon monotherapy is not effective in achieving sustained virologic response in ...

Although spontaneous bacterial peritonitis is considered a precipitating factor of renal impairment in cirrhosis, no study specifically addressing this problem has been reported. This study was aimed at assessing the incidence, clinical course, predictive factors and prognosis of renal impairment in cirrhotic patients with peritonitis. Therefore, 252 consecutive episodes of spontaneous bacterial peritonitis in 197 patients were analyzed. Clinical and laboratory data obtained before and after diagnosis of peritonitis were considered as possible predictors of renal impairment and hospital mortality. Renal impairment occurred in 83 (33%) episodes, and in every instance it fulfilled the criteria of functional kidney failure. Renal impairment was progressive in 35 episodes, steady in 27 and transient in 21. Blood urea nitrogen and serum sodium concentration before peritonitis and band neutrophils count in blood at diagnosis were independent predictors for the development of renal impairment. Renal impairment was the strongest independent predictor of mortality during hospitalization. Other independent prognostic factors were blood urea nitrogen level before peritonitis, age, positive ascitic fluid culture and serum bilirubin level during infection. These results indicate that renal impairment is a frequent event in cirrhotic patients with spontaneous bacterial peritonitis that occurs mainly in patients with kidney failure before infection. Renal impairment is the most important predictor of hospital mortality in cirrhotic patients with spontaneous bacterial peritonitis.

Eighty cirrhotic patients who had recovered from an episode of spontaneous bacterial peritonitis were included in a multicenter, double-blind trial aimed at comparing long-term norfloxacin administration (400 mg/day; 40 patients) vs. placebo (40 patients) in the prevention of spontaneous bacterial peritonitis recurrence. At entry, both groups were similar with respect to clinical and laboratory data, ascitic fluid protein and polymorphonuclear concentrations, number of previous episodes of spontaneous bacterial peritonitis and causative organisms of the index spontaneous bacterial peritonitis. Norfloxacin administration produced a selective intestinal decontamination (elimination of aerobic gram-negative bacilli from the fecal flora without significant changes in other microorganisms) throughout the study in six patients in whom the effect of norfloxacin on the fecal flora was periodically assessed. Fourteen patients from the placebo group (35%) and five from the norfloxacin group (12%) developed spontaneous bacterial peritonitis recurrence during follow-up (chi 2 = 5.97; p = 0.014) (mean follow-up period = 6.4 +/- 0.6 mo; range = 1 to 19 mo). Ten of the 14 spontaneous bacterial peritonitis recurrences in the placebo group and only one of the five spontaneous bacterial peritonitis recurrences in the norfloxacin group were caused by aerobic gram-negative bacilli (chi 2 = 8.87; p = 0.0029). The overall probability of spontaneous bacterial peritonitis recurrence at 1 yr of follow-up was 20% in the norfloxacin group and 68% in the placebo group (p = 0.0063) and the probability of spontaneous bacterial peritonitis recurrence caused by aerobic gram-negative bacilli at 1 yr of follow-up was 3% and 60%, respectively (p = 0.0013).(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

Immunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as 'operationally' tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter 'fingerprint' of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for c d T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4 + CD25 + T-cells and Vd1 + T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and † Deceased 12/9/2005 constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.