Hepatology : official journal of the American Association for the Study of Liver Diseases
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Multicenter Study Clinical Trial
Model for end-stage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure.
Although it is often functional at presentation, acute renal failure has a poor prognosis in patients with cirrhosis. The role of inflammation, a key event in the outcome of cirrhosis, has never been studied in this setting. We aimed to investigate the predictive factors of mortality in patients with cirrhosis and acute functional renal failure, specifically in relation to inflammatory events. One hundred consecutive patients with cirrhosis from 5 French hospitals were prospectively included at the day of onset of acute renal failure. Medical history, treatments, and procedures during the month before inclusion were recorded. Physical examination, blood and urinary chemistries, and renal ultrasound examination were performed. The presence of systemic inflammatory response syndrome (SIRS), infection, and sepsis was assessed. The primary outcome was in-hospital mortality. The mechanism of renal failure was functional in 83 patients. Causes of renal failure were hypovolemia (34%), hepatorenal syndrome without ongoing infection (17%), hepatorenal syndrome with ongoing infection (16%), nephrotoxicity (2%), and multifactorial (31%). SIRS was observed in 41% of patients, 56% of them with infection. In-hospital mortality was 68% in patients with SIRS and 33% in patients without (P = 0.001). In multivariate analysis, only model for end-stage liver disease score and presence of SIRS, but not infection, remained associated with a poor outcome. ⋯ The presence of SIRS, with or without infection, is a major independent prognostic factor in patients with cirrhosis and acute functional renal failure. This suggests that preventing and treating SIRS could decrease mortality in patients with cirrhosis and acute renal failure.
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Randomized Controlled Trial Multicenter Study
Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial.
The hepatotoxic potential of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in patients with underlying chronic liver disease remains controversial. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that compared pravastatin (80 mg) to a placebo administered once daily to hypercholesterolemic subjects greater than 18 years of age with at least a 6-month history of compensated chronic liver disease and with a low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL and a triglyceride (TG) level lower than 400 mg/dL. The efficacy was determined by the percentage change in LDL-C [along with the total cholesterol (TC), high-density lipoprotein cholesterol, and TG] from the baseline to week 12. The safety was analyzed by the proportion of subjects who developed at least 1 alanine aminotransferase (ALT) value greater than or equal to 2 times the upper limit of normal for those with normal ALT at the baseline or a doubling of the baseline ALT for those with elevated ALT at the baseline during 36 weeks of treatment. A total of 630 subjects were screened, and 326 subjects were randomized; nonalcoholic fatty liver disease was present in 64%, and chronic hepatitis C was present in 23%. In the intent-to-treat population, pravastatin (80 mg/day) significantly lowered the mean LDL-C, TC, and TG values at week 12 and at other times (weeks 4, 8, 24, and 36) in comparison with the placebo. The incidence of subjects who met the primary prespecified ALT event definition was lower in the pravastatin group at all times over the 36 weeks of therapy in comparison with the placebo group, although the difference was not statistically significant. No differences were seen on the basis of the baseline ALT values or among the different liver disease groups. ⋯ High-dose pravastatin (80 mg/day) administered to hypercholesterolemic subjects with chronic liver disease significantly lowered LDL-C, TC, and TGs in comparison with the placebo and was safe and well tolerated. The concern over an increased potential for statin-induced hepatotoxicity in patients with chronic liver disease appears to be lessened on the basis of these results.
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Multicenter Study
Prospective evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver transplantation.
The hepatopulmonary syndrome (HPS) occurs in a subgroup of patients with cirrhosis and results from intrapulmonary vasodilatation, which may cause significant hypoxemia. Liver transplantation has emerged as a therapeutic option for patients with HPS based on retrospective case series and reports. However, morbidity and mortality appear to be increased after transplantation for HPS, and no prospective studies evaluating clinical features that may predict poor surgical outcome are available. ⋯ A preoperative arterial oxygen tension (PaO(2)) of /= 20% were the strongest predictors of postoperative mortality. In conclusion, we found that mortality is increased after liver transplantation for HPS, particularly in patients with more severe hypoxemia and significant intrapulmonary shunting. Preoperative testing for the severity of HPS can be used to stratify patients according to the risk for postoperative mortality.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal bleeding in cirrhosis: a randomized multicenter trial. Gruppo Italiano Studio TIPS (G.I.S.T.).
Transjugular intrahepatic portosystemic shunt (TIPS), a new technique for the treatment of portal hypertension, has been successful in preliminary studies to treat acute variceal hemorrhage and to prevent variceal rebleeding. The purpose of this multicenter, randomized controlled trial is to compare the efficacy of TIPS with that of endoscopic sclerotherapy in the prevention of variceal rebleeding in cirrhosis. Eighty-one cirrhotic patients, with endoscopically proven variceal bleeding, were randomized to either TIPS (38 patients) or endoscopic sclerotherapy (43 patients). ⋯ A separate analysis of the three strata showed that TIPS was significantly more effective than sclerotherapy (P = .026) in preventing rebleeding only in stratum I patients. TIPS is significantly better than sclerotherapy in preventing rebleeding only when it is performed shortly after a variceal bleed; however, TIPS does not improve survival and is associated with a significantly higher incidence of HE. The overall performance of TIPS does not seem to justify the adoption of this technique as a first-choice treatment to prevent rebleeding from esophageal varices in cirrhotic patients.
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Randomized Controlled Trial Multicenter Study Clinical Trial
A randomized controlled trial of thymosin-alpha1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody--and hepatitis B virus DNA--positive chronic hepatitis B.
It has recently been shown that thymosin-alpha1(T-alpha1), a synthetic polypeptide of thymic origin, is able to promote disease remission and inhibition of hepatitis B virus (HBV) replication in patients affected by hepatitis B e antigen (HBeAg)-positive chronic active hepatitis. We evaluated the efficacy and safety of T-alpha1 treatment in patients with hepatitis B e antibody (anti-HBe) and HBV-DNA-positive chronic hepatitis. Thirty-three patients were randomly assigned to receive either T-alpha1 900 microg/m2 body surface area twice weekly (17 patients) or 5 MU of interferon alfa (IFN-alpha) three times weekly (16 patients) for 6 months. ⋯ Furthermore, compared with IFN-alpha, T-alpha1 is better tolerated and seems to induce a gradual and more sustained ALT normalization and HBV-DNA loss. In conclusion, T-alpha1 appears to be a safe and effective alternative treatment for anti-HBe-positive chronic hepatitis. The benefit of this agent in producing long-term inhibition of HBV replication must be confirmed by future trials.