Isabel Cirera

Prognostic significance of hepatic encephalopathy in patients with cirrhosis

BACKGROUND There are numerous studies concerning the natural history and prognostic factors in cirrhosis, the results of which are useful in selecting liver transplant candidates. However, little attention has been paid to the prognostic significance of hepatic encephalopathy despite the high frequency of this complication. METHODS We reviewed the charts of 111 cirrhotic patients who developed a first episode of acute hepatic encephalopathy to determine their survival probability and to identify prognostic factors. RESULTS During follow-up (12+/-17 months), 82 (74%) patients died. The survival probability was 42% at 1 year of follow-up and 23% at 3 years. With univariate analyses followed by a multivariate analysis, 7 out of 30 clinical and standard laboratory variables were significantly associated with poor prognosis: male sex, increased serum bilirubin, alkaline phosphatase, potassium and blood urea nitrogen, and decreased serum albumin and prothrombin activity. Patients were classified into two groups according to a prognostic index calculated from these 7 variables. Survival probability at 1 and 3 years was 73% and 38%, respectively, in patients with a low prognostic index, and 10% and 3% in patients with a high prognostic index. CONCLUSION Hepatic encephalopathy is associated with short survival in cirrhotic patients. Although these patients can be classified into several groups with a different prognosis, the survival probability in every group is lower than that currently expected after liver transplantation. Therefore, cirrhotic patients developing a first episode of acute hepatic encephalopathy should be considered as potential candidates for this therapeutic procedure.

Bacterial translocation of enteric organisms in patients with cirrhosis

BACKGROUND/AIMS The aim of the study was to investigate the prevalence and associated risk factors for bacterial translocation in patients with cirrhosis, a mechanism involved in the pathogenesis of bacterial infections in experimental cirrhosis. METHODS Mesenteric lymph nodes were obtained for microbiological culture from 101 patients with cirrhosis and from 35 non-cirrhotic patients. RESULTS Enteric organisms were grown from mesenteric lymph nodes in 8.6% of non-cirrhotic patients. In the 79 cirrhotic patients without selective intestinal decontamination, the prevalence of bacterial translocation significantly increased according to the Child-Pugh classification: 3.4% in Child A, 8.1% in Child B and 30.8% in Child C patients (chi2 = 6.106, P < 0.05). However, translocation by Enterobacteriaceae, the organisms commonly responsible for spontaneous bacteremia and peritonitis in cirrhosis, was only observed in 25% of the cases. The prevalence of bacterial translocation in the 22 cirrhotic patients undergoing selective intestinal decontamination, all Child-Pugh class B and C, was 4.5%. The Child-Pugh score was the only independent predictive factor for bacterial translocation (odds ratio 2.22, P = 0.02). CONCLUSIONS Translocation of enteric organisms to mesenteric lymph nodes is increased in patients with advanced cirrhosis and is reduced to the level found in non-cirrhotic patients by selective intestinal decontamination.

Diabetes mellitus after liver transplantation: prevalence and predictive factors.

AIMS/METHODS To investigate the prevalence and risk factors for the development of diabetes mellitus after orthotopic liver transplantation, we reviewed 27 variables (including previous history of diabetes mellitus, data related to pre-transplant liver disease, and postoperative events) in 102 patients who survived longer than 1 year after orthotopic liver transplantation. RESULTS Fourteen patients had diabetes mellitus prior to liver transplantation and all but one were alive 2 and 3 years after transplantation, with all survivors continuing to have diabetes mellitus 1, 2 and 3 years after transplantation. Among the 88 patients without pre-transplant diabetes mellitus, the prevalence of post-transplant diabetes mellitus was 27% at 1 year, 9% at 2 years and 7% at 3 years, probably related to a significant reduction in the daily prednisone dose (13 +/- 4 mg at 1 year, 7 +/- 6 mg at 2 years and 2 +/- 4 mg at 3 years, p < 0.001). Patients with post-transplant diabetes mellitus 1 year after transplantation had a higher number of rejection episodes during the first postoperative year than those without post-transplant diabetes mellitus (1.5 +/- 1.1 vs 1.1 +/- 0.7, p < 0.05) and also had higher, but not statistically significant, cumulative steroid dose and blood cyclosporine levels. Mortality of patients with post-transplant diabetes mellitus was significantly higher during the second postoperative year in comparison with patients without post-transplant diabetes mellitus: 4/24 vs 2/64 (17% vs 3%; p < 0.05). CONCLUSIONS Liver transplantation does not significantly modify pre-transplant diabetes mellitus. Diabetes mellitus frequently develops de novo after liver transplantation, although this complication is usually transient and probably related to immunosuppressive drug administration. The prognosis of patients with post-transplant diabetes mellitus is worse than that of those without this complication.

Serum and ascitic fluid bacterial DNA: A new independent prognostic factor in noninfected patients with cirrhosis

We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/μL, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of large‐volume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12‐month follow‐up period. BactDNA was detected in 48 patients. The most prevalent identified bactDNA corresponded to Escherichia coli (n = 32/48 patients, 66.6%). Patients were followed for 12 months after inclusion and in this period 34 patients died: 16 of 108 (15%) bactDNA negative versus 18 of 48 (38%) bactDNA positive (P = 0.003). The most frequent cause of death was acute‐on‐chronic liver failure in both groups (7/16 and 9/18 in patients without or with bactDNA, respectively), although more prevalent in the first month of follow‐up in patients with presence of bactDNA (0 versus 4/7). When considering patients with model for end‐stage liver disease (MELD) score less than 15, mortality was significantly higher in those with presence of bactDNA. Spontaneous bacterial peritonitis developed similarly in patients with or without bactDNA at admission. Conclusion: The presence of bactDNA in a patient with cirrhosis during an ascitic episode is an indicator of poor prognosis. This fact may be related to the development of acute‐on‐chronic liver failure at short term and does not predict the development of spontaneous bacterial peritonitis. (HEPATOLOGY 2008;48:1924‐1931.)

Hemodynamic Effects of Acute Changes in Intra-abdominal Pressure in Patients With Cirrhosis

BACKGROUND Changes in intra-abdominal pressure (IAP) have significant circulatory effects. However, whether this may influence the gastroesophageal collateral blood flow in patients with cirrhosis has not been studied. METHODS In 14 portal hypertensive cirrhotics, serial hemodynamic measurements were obtained in baseline conditions 30 minutes after the mechanical increase of IAP by 10 mm Hg and 30 minutes after returning IAP to baseline levels. RESULTS Increasing IAP caused similar increases in free and wedged hepatic venous pressures (+10.3 mm Hg and +11.0 mm Hg, respectively; P < 0.005), without changing the hepatic venous pressure gradient (HVPG). However, there were significant decreases in cardiac output (-18%; P < 0.005) and hepatic blood flow (-20%; P < 0.05), whereas azygos blood flow, an index of gastroesophageal collateral blood flow, increased markedly (+23%; P < 0.005). The opposite occurred after releasing the high IAP. CONCLUSION In portal hypertensive cirrhotics, acute changes in IAP did not change HVPG but markedly modified splanchnic and systemic hemodynamics. Brief elevations of IAP may have deletereous effects, as shown by the increase in azygos blood flow and the decrease in cardiac output and hepatic blood flow, whereas reduction of a high IAP causes the opposite changes and may be beneficial.

Ascites after liver transplantation

Massive ascites after liver transplantation, although uncommon, usually represents a serious adverse event. The pathogenesis of this complication has not been adequately investigated. To determine the incidence, characteristics, and pathogenic factors of massive ascites after liver transplantation (ascitic fluid > 500 mL/d for >10 days), the charts of 378 liver transplant recipients were reviewed. Massive ascites occurred in 25 patients (7%). Mean ascitic fluid production was 960 mL/d (range, 625 to 2,350 mL/d), and the duration of ascites was 77 days (range, 15 to 223 days). The ascitic fluid had a high protein content (36 ± 7 g/L; range, 25 to 50 g/L). When patients who did and did not develop massive ascites were compared, significant differences were found in receptor sex (men, 88% v 60%, respectively; P < .01) and surgical technique (inferior vena cava preservation with piggyback technique, 72% v 41%P < .01). Significantly increased wedged and free hepatic venous pressures and gradients between hepatic vein and right atrial pressures were found in patients who developed ascites, suggesting a difficulty in graft blood outflow. Massive ascites was associated with renal impairment, increased incidence of abdominal infection, prolonged hospitalization, and a tendency toward reduced survival. In conclusion, massive ascites after liver transplantation is relatively uncommon but associated with increased morbidity and mortality and is predominantly related to difficulties of hepatic venous drainage. Measurement of hepatic vein and atrial pressures to detect a significant gradient and correct possible alterations in hepatic vein outflow should be the first approach in the management of these patients.

Propranolol versus sclerotherapy in preventing variceal rebleeding: a randomized controlled trial.

BACKGROUND Sclerotherapy has been widely recommended as initial treatment for prevention of variceal rebleeding. The present study was aimed at comparing the efficacy of endoscopic sclerotherapy and long-term administration of propranolol in the prevention of rebleeding and long-term survival in patients who had bled from varices. METHODS One hundred sixteen consecutive cirrhotic patients admitted because of variceal bleeding were randomly allocated to either continuous administration of propranolol to reduce the resting heart rate by 25% (58 patients) or weekly intravariceal sclerotherapy sessions using 5% ethanolamide oleate until varices disappeared (58 patients). Results were analyzed on an intention-to-treat basis. RESULTS Rebleeding occurred in 37 patients of the propranolol group and in 26 patients of the sclerotherapy group (RR = 1.45; 95% CI, 1.03-2.03). The actuarial probability of rebleeding was lower in the sclerotherapy group (P = 0.02). No differences were found in rebleeding index, hospitalization requirements, survival, and causes of death. Complications were significantly more frequent and severe in the sclerotherapy group. CONCLUSIONS Despite the higher efficacy of sclerotherapy decreasing the probability of rebleeding when compared with propranolol, no beneficial effects were observed on other parameters also reflecting the efficacy of therapy. Moreover, complications of sclerotherapy were more frequent and severe than those of propranolol, which probably shall restrict the use of long-term elective sclerotherapy.

Severe portopulmonary hypertension after liver transplantation in a patient with preexisting hepatopulmonary syndrome.

BACKGROUND Portopulmonary hypertension and hepatopulmonary syndrome have been considered mutually exclusive pulmonary vascular disorders in liver disease states. METHODS This current report describes a middle-aged patient, a candidate for liver transplantation, diagnosed with hepatopulmonary syndrome on the basis of clinical, echocardiographic and gas exchange criteria. Unusually high pulmonary pressures were observed at liver transplantation, performed 6 months after the initial diagnosis of hepatopulmonary syndrome. Three months later, the patient developed severe pulmonary hypertension and died of right ventricular failure during a second attempted liver transplantation. Postmortem histologic findings in the lung confirmed the presence of plexogenic pulmonary arteriopathy. CONCLUSION This case illustrates the potential occurrence of hepatopulmonary syndrome and portopulmonary hypertension in the same patient, suggesting that the presence of hepatopulmonary syndrome may not preclude the development of portopulmonary hypertension.

Surgical resection and survival in western patients with hepatocellular carcinoma

In a retrospective study the survival of 28 patients with hepatocellular carcinoma, 25 of them with underlying cirrhosis, submitted to surgical resection was compared with the survival of 28 untreated patients, matched for variables known to bear independent prognostic value and therefore sharing the same baseline prognosis. Diagnosis was made in the same time period for both groups of patients. In addition, to further evaluate the effects of tumor resection on survival, the outcome of operated patients was also compared to their expected survival. This was derived from a mathematical model which takes into account the regression coefficients of the variables previously shown to be independently related to the survival of untreated patients with hepatocellular carcinoma. The median survival for resected patients was 27.1 months, which was significantly better than untreated controls (12.4 months; p less than 0.003). Median survival for patients submitted to resection and with tumors smaller than 5 cm was 35.8 months, while the median survival for untreated cases was 14.6 months p less than 0.0005. The comparison of observed survival (82% at one year and 73% at two years) and statistically expected survival (58% and 34%, respectively) further indicated that surgical resection effectively improves prognosis in Western patients with hepatocellular carcinoma. Thus, early detection of small tumors in the population at risk appears to be justified.

Long-term clinical course of decompensated alcoholic cirrhosis: a prospective study of 165 patients.

Background: Prognosis of decompensated alcoholic cirrhosis is based mainly on studies that included patients with different severities of liver disease and did not recognize either hepatitis C virus epidemic or changes in clinical management of cirrhosis. Aim: To define the long-term course after the first hepatic decompensation in alcoholic cirrhosis. Methods: Prospective inclusion at the start point of decompensated cirrhosis of 165 consecutive patients with alcoholic cirrhosis without known hepatocellular carcinoma hospitalized from January 1998 to December 2001 was made. Follow-up was maintained until death or the end of the observation period (April 1, 2010). Results: The patients were followed for 835.75 patient years. Median age was 56 years (95% confidence interval: 54-58). Baseline Child-Pugh score was 9 (95% CI: 8-9), and model for end-stage liver disease (MELD) was 13.8 (95% CI: 12.5-14.7). Ascites was the most frequent first decompensation (51%). During follow-up, 99 (60%) patients were abstinent, hepatocellular carcinoma developed in 18 (11%) patients, and 116 patients died (70%). Median overall survival was 61 months (95% CI: 48-74). Median survival probability after onset of hepatic encephalopathy (HE) was only 14 months (95% CI: 5-23). Age, baseline MELD, albumin, development of HE, and persistence of alcohol use were independently correlated with mortality. Conclusions: Patients with alcoholic cirrhosis show a high frequency of complications. The low mortality rate in our cohort of patients probably reflects the improvement in the management of patients with cirrhosis; it is mainly influenced by baseline MELD, age, HE development, and continued abstinence. Patients who develop HE should be considered for hepatic transplantation.