Angels Escorsell

Incidence, Predictive Factors, and Prognosis of the Hepatorenal Syndrome in Cirrhosis With Ascites

BACKGROUND The aim of the study was to investigate the incidenc, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. METHODS The study is a follow-up investigation in 234 nonazotemic patients with cirrhosis and ascites. Thirty-nine variables obtained at inclusion were analyzed as possible predictors of hepatorenal syndrome occurrence (Kaplan-Meier method, Mantel-Cox test, and step-wise Cox regression procedure). RESULTS The probability of hepatorenal syndrome occurrence was 18% at 1 year and 39% at 5 years. Sixteen variables had predictive value for hepatorenal syndrome occurrence in the univariate analysis: history of ascites, hepatomegaly, nutritional status, blood urea nitrogen level, serum creatinine concentration, serum sodium and potassium concentration, serum and urine osmolality, urinary sodium excretion, free water clearance after a water load, glomerular filtration rate, arterial pressure, plasma renin activity, plasma norepinephrine concentration, and esophageal varices. Neither etiology (alcoholic vs. nonalcoholic) nor the Child-Pugh score had predictive value. A multivariate analysis disclosed only three independent predictors of hepatorenal syndrome occurrence: low serum sodium concentration, high plasma renin activity, and absence of hepatomegaly. CONCLUSIONS The hepatorenal syndrome is a relatively frequent complication in cirrhotic patients with ascites that is associated with an extremely short survival. Liver size, plasma renin activity, and serum sodium concentration are predictors of hepatorenal syndrome occurrence in these patients.

Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis

In patients with variceal bleeding as a complication of hepatic cirrhosis, propranolol therapy reduces the risk of recurrent variceal haemorrhage. However, the relation between portal pressure response to pharmacological treatment and clinical events has not been well defined. This relation was prospectively investigated in 69 cirrhotic patients receiving continued propranolol therapy after an episode of variceal bleeding. Hepatic venous pressure gradient (HVPG) was measured before and at 3 months of continued drug therapy. At 3 months HVPG had fallen by 20% or more in 25 patients. During follow-up of 28 (SD 17) months rebleeding occurred in 2 of these 25 patients compared with 23 of 44 who had lesser reductions in HVPG. Cumulative probability of rebleeding at 1, 2, and 3 years was 4%, 9%, and 9% in patients with a decrease in HVPG > or = 20%, and 28%, 39%, and 66% in patients with a decrease in HVPG < 20% (p < 0.001, log-rank test). On multivariate analysis, a decrease in HVPG > or = 20% was the only independent predictor of rebleeding (relative risk 0.09, 95% CI 0.02-0.41. Of the 8 patients in whom the HVPG fell to 12 mm Hg or less, none rebled. This study suggests that measurement of the HVPG response to pharmacotherapy will provide useful prognostic information on the long-term risk of variceal rebleeding.

Prognostic value of early measurements of portal pressure in acute variceal bleeding

BACKGROUND & AIMS Variceal bleeding is the most important complication of portal hypertension. However, the relationship between the increase in portal pressure and the outcome of variceal bleeding has not been well defined. METHODS We measured the hepatic venous pressure gradient (HVPG) of 65 cirrhotic patients with acute variceal hemorrhage, early after admission (20.6 +/- 15.6 hours). RESULTS Twenty-three patients had a poor evolution (failure to control bleeding or early variceal rebleeding), and 42 had an uneventful evolution. The only variable associated with outcome was the HVPG, which was higher in patients with a poor evolution (23.7 +/- 6.1 vs. 19.2 +/- 3.3 mm Hg; P < 0.0004). This was confirmed by multivariate analysis. HVPG was >/=20 mm Hg in 19 of 23 patients with poor evolution vs. 12 of 42 patients with uneventful evolution (P < 0.0001). An initial HVPG of >/=20 mm Hg was associated with a significantly longer intensive care unit stay (7 +/- 5 vs. 4 +/- 2 days; P < 0.02), longer hospital stay (19 +/- 10 vs. 14 +/- 6 days; P < 0.02), greater transfusion requirements (9.0 +/- 7.7 vs. 4.7 +/- 3.2 UU; P < 0.007), and a worse actuarial probability of survival (1-year mortality, 64% vs. 20%; P < 0.002). CONCLUSIONS Early measurement of HVPG in cirrhotic patients during acute variceal bleeding provides useful prognostic information on the evolution of the bleeding episode and long-term survival.

Clinical events after transjugular intrahepatic portosystemic shunt: Correlation with hemodynamic findings

BACKGROUND & AIMS Transjugular intrahepatic portosystemic shunt (TIPS) procedures are increasingly being used, but the relationship between the hemodynamic effects of TIPS and the clinical events on follow-up remains undefined. Hence, we have investigated the hemodynamic correlations of portal hypertension-related events after a TIPS procedure. METHODS Prospective follow-up of 122 cirrhotic patients who had a TIPS procedure performed because of variceal hemorrhage was conducted. RESULTS The portacaval pressure gradient (PPG) significantly decreased after the TIPS procedure (from 19.7 +/- 4.6 to 8.6 +/- 2.7 mm Hg; P > 0.001), but increased thereafter and at rebleeding (n = 25) was > 12 mm Hg in all patients (18.4 +/- 4.6 mm Hg). Twenty-six patients developed ascites; the PPG (measured in 19) was always > 12 mm Hg. Increasing the PPG to > 12 mm Hg occurred very frequently (83% at 1 year). Within 1 year, 77% of patients underwent balloon angioplasty or restenting. However, 80% had again a PPG of > 12 mm Hg 1 year after reintervention. Hepatic encephalopathy developed in 31% of patients at 1 year; 21 of 23 patients had a PPG of < 12 mm Hg. CONCLUSIONS Total protection from the risk of recurrent complications of portal hypertension after a TIPS procedure requires that the PPG be decreased and maintained < 12 mm Hg. However, reintervention will be required in most patients within 1 year and again the second year. On the other hand, such portal decompression is associated with an increased risk of hepatic encephalopathy.

Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival

Relative adrenal insufficiency is frequent in patients with severe sepsis and is associated with hemodynamic instability, renal failure, and increased mortality. This study prospectively evaluated the effects of steroids on shock resolution and hospital survival in a series of 25 consecutive patients with cirrhosis and septic shock (group 1). Adrenal function was evaluated by the short corticotropin test within the first 24 hours of admission. Patients with adrenal insufficiency were treated with stress doses of intravenous hydrocortisone (50 mg/6 h). Data were compared to those obtained from the last 50 consecutive patients with cirrhosis and septic shock admitted to the same intensive care unit in whom adrenal function was not investigated and who did not receive treatment with steroids (group 2). Incidence of adrenal insufficiency in group 1 was 68% (17 patients). Adrenal dysfunction was frequent in patients with advanced cirrhosis (Child C: 76% vs. Child B: 25%, P = .08). Resolution of septic shock (96% vs. 58%, P = .001), survival in the intensive care unit (68% vs. 38%, P = .03), and hospital survival (64% vs. 32%, P = .003) were significantly higher in group 1. The main causes of death in group 1 were hepatorenal syndrome or liver failure (7 of 9 patients). In contrast, refractory shock caused most of the deaths in group 2 (20 of 34 patients). In conclusion, relative adrenal insufficiency is very frequent in patients with advanced cirrhosis and septic shock. Hydrocortisone administration in these patients is associated with a high frequency of shock resolution and high survival rate. (HEPATOLOGY 2006;44:1288–1295.)

Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis

BACKGROUND/AIMS A total of 213 patients with compensated cirrhosis, portal hypertension and no varices were included in a trial evaluating beta-blockers in preventing varices. Predictors of the development of hepatocellular carcinoma (HCC), including hepatic venous pressure gradient (HVPG) were analyzed. METHODS Baseline laboratory tests, ultrasound and HVPG measurements were performed. Patients were followed prospectively every three months until development of varices or variceal bleeding or end of the study in 09/02. The endpoint was HCC development according to standard diagnostic criteria. Univariate and multivariate Cox regression models were developed to identify predictors of HCC. RESULTS In a median follow-up of 58 months 26/213 (12.2%) patients developed HCC. Eight patients were transplanted and 28 patients died without HCC. Twenty-one (84%) HCC developed in patients with HCV. On multivariate analysis HVPG (HR 1.18; 95%CI 1.08-1.29), albumin (HR 0.34; 95%CI 0.14-0.83) and viral etiology (HR 4.59; 95%CI 1.51-13.92) were independent predictors of HCC development. ROC curves identified 10 mmHg of HVPG as the best cut-off; those who had an HVPG above this value had a 6-fold increase in the HCC incidence. CONCLUSIONS Portal hypertension is an independent predictor of HCC development. An HVPG >10 mmHg is associated with a 6-fold increase of HCC risk.

Effects of Fractionated Plasma Separation and Adsorption on Survival in Patients With Acute-on-Chronic Liver Failure

BACKGROUND & AIMS Fractionated plasma separation and adsorption (FPSA) is an extracorporeal procedure that supports liver function by removing endogenous toxins that cause complications from acute-on-chronic liver failure (AOCLF). We performed a randomized trial to investigate survival of patients with AOCLF treated with FPSA. METHODS Patients with AOCLF were randomly assigned to groups given a combination of FPSA and standard medical therapy (SMT) (FPSA group, n = 77) or only SMT (SMT group, n = 68). The Prometheus liver support system was used to provide 8 to 11 rounds of FPSA (minimum of 4 hours each) for 3 weeks. Primary end points were survival probabilities at days 28 and 90, irrespective of liver transplantation. RESULTS Baseline clinical parameters and number of transplant patients were similar between study arms. Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Baseline factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects. CONCLUSIONS Among all patients with AOCLF, extracorporeal liver support with FPSA does not increase the probability of survival. Further studies are needed to assess whether therapy might be beneficial in specific subsets of patients.

Epidemiology of primary sclerosing cholangitis in Spain

The incidence of primary sclerosing cholangitis has been estimated on the basis of its frequent association with ulcerative colitis, but direct epidemiologic studies have not yet been carried out. In the current study we report a survey of clinical and epidemiological aspects of primary sclerosing cholangitis in Spain. A questionnaire was circulated to physicians in 33 hospitals throughout Spain to ascertain the number and the clinical, biochemical and immunologic characteristics of patients with primary sclerosing cholangitis from January 1, 1984 to December 31, 1988. Twenty-three centers, from 12 Spanish regions, covering a population of 19.23 million answered the questionnaire. Forty-three patients (60.5% males) with a mean age of 42.3 years (range 12 to 75 years) were seen during the 5-year period. At presentation, 16% of the cases were asymptomatic. Ulcerative colitis was present in 44.2% of cases, and one patient had Crohns disease. The overall annual incidence ranged from 0.16 to 0.68 cases/million from 1985 to 1988, and the annual prevalence increased from 0.78 cases/million in 1984 to 2.24 cases/million in 1988. No geographical differences were found, but there was a trend to detect more cases in industrialized regions. In conclusion, there was a continuing rise in the annual incidence and prevalence of primary sclerosing cholangitis in Spain over a 5-year period.

Acute liver failure in Spain: Analysis of 267 cases

The cause of acute liver failure (ALF) is a major determinant of its outcome. Acetaminophen (paracetamol) overdose is a leading cause of ALF in some developed countries, whereas in others, such as Spain, it is extremely rare. To analyze the etiology, characteristics, and outcome of ALF in Spain, we performed a retrospective analysis of 267 patients whom we observed from 1992 to 2000. Seventeen tertiary‐care hospitals with active liver transplantation (LT) programs contributed data. Causes of ALF were viral hepatitis in 98 (37%; hepatitis B virus in 75 patients), unknown in 86 (32%), drug or toxic reactions in 52 (19.5%; acetaminophen overdose in 6), and miscellaneous in 31 (11.6%). Overall survival was 58%. LT was performed in 150 patients, with a survival of 69%. Despite fulfilling criteria, 51 patients were not transplanted because of contraindications; their survival was only 7.8%. Forty‐seven (85.5%) of 55 patients without transplant criteria survived. Hepatitis B virus is the most common cause of ALF in Spain, although the origin of 30% of cases remains undetermined. Acetaminophen overdose represents a very rare cause of ALF. LT was performed in >50% of cases. Patients without transplant criteria had a very good prognosis; those who fulfilled these criteria but who had contraindications for transplantation had a high mortality rate. Liver Transpl, 2007.

Incidence, Prevalence, and Clinical Significance of Abnormal Hematologic Indices in Compensated Cirrhosis

BACKGROUND & AIMS Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance. METHODS We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, < or =13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, < or =4000/mm3), or thrombocytopenia (platelet counts, < or =150,000/mm3). The primary end points were death or transplant surgery. RESULTS Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = -0.35, P < .0001; white blood cell count, r = -0.31, P < .0001). CONCLUSIONS Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality.