M. Merli

Nutritional Supplementation With Branched-Chain Amino Acids in Advanced Cirrhosis: A Double-Blind, Randomized Trial

BACKGROUND & AIMS The role of oral supplementation with branched-chain amino acids (BCAA) in advanced cirrhosis is far from settled. A nutritional approach might prevent progressive liver failure and improve nutritional parameters and quality of life. METHODS A multicenter, randomized study comparing 1-year nutritional supplementation with BCAA against lactoalbumin or maltodextrins was performed in 174 patients with advanced cirrhosis. Primary outcomes were the prevention of a combined end point (death and deterioration to exclusion criteria), the need for hospital admission, and the duration of hospital stay. Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh score, anorexia, health-related quality of life, and need for therapy. RESULTS Treatment with BCAA significantly reduced the combined event rates compared with lactoalbumin (odds ratio, 0.43; 95% confidence interval, 0.19-0.96; P = 0.039) and nonsignificantly compared with maltodextrins (odds ratio, 0.51; 95% confidence interval, 0.23-1.17; P = 0.108). The average hospital admission rate was lower in the BCAA arm compared with control treatments (P = 0.006 and P = 0.003, respectively). In patients who remained in the study, nutritional parameters and liver function tests were, on average, stable or improved during treatment with BCAA and the Child-Pugh score decreased (P = 0.013). Also, anorexia and health-related quality of life (SF-36 questionnaire) improved. Long-term compliance with BCAA was poor. CONCLUSIONS In advanced cirrhosis, long-term nutritional supplementation with oral BCAA is useful to prevent progressive hepatic failure and to improve surrogate markers and perceived health status. New formulas are needed to increase compliance.

ESPEN guidelines for nutrition in liver disease and transplantation

clinical stage of chronic liver disease: When diagnosed by anthropometric criteria, PEM may be present in 20% of patients with well compensated liver cirrhosis and in more than 60% of patients with severe liver insufficiency (5). The prevalence is even higher when body composition is assessed by more sensitive methods (4, 6). The presence of muscle wasting indicates an advanced stage and apparently is associated with poorer survival (7) particularly following shunt surgery (8). The prevalence and degree of PEM do not appear to relate to the etiology of liver disease per se (4, 5). The higher prevalence of malnutrition in patients with alcoholic liver disease is generally restricted to skid row alcoholics and patients from low socioeconomic classes.

Incidence and natural history of small esophageal varices in cirrhotic patients

BACKGROUND/AIMS The incidence and natural history of small esophageal varices (EV) in cirrhotics may influence the frequency of endoscopies and the decision to start a pharmacological treatment in these patients. METHODS We prospectively evaluated 206 cirrhotics, 113 without varices and 93 with small EV, during a mean follow-up of 37+/-22 months. Patients with previous gastrointestinal bleeding or receiving any treatment for portal hypertension were excluded. Endoscopy was performed every 12 months. RESULTS The rate of incidence of EV was 5% (95%CI: 0.8-8.2%) at 1 year and 28% (21.0-35.0%) at 3 years. The rate of EV progression was 12% (5.6-18.4%) at 1 year and 31% (21.2-40.8%) at 3 years. Post-alcoholic origin of cirrhosis, Child-Pughs class (B or C) and the finding of red wale marks at first examination were predictors for the variceal progression. The two-years risk of bleeding from EV was higher in patients with small varices upon enrollment than in those without varices: 12% (95% CI: 5.2-18.8%) vs. 2% (0.1-4.1%); (P<0.01). Predictor for bleeding was the presence of red wale marks at first endoscopy. CONCLUSIONS In patients with no or small EV, endoscopy surveillance should be planned taking into account cause and degree of liver dysfunction.

Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites

The transjugular intrahepatic portosystemic shunt (TIPS) has been shown to be effective in the control of refractory or recidivant ascites. However, the effect of TIPS on survival as compared with that of large‐volume paracentesis plus albumin is uncertain. A multicenter, prospective, clinical trial was performed in 66 patients with cirrhosis and refractory or recidivant ascites (16 Child‐Turcotte‐Pugh class B and 50 Child‐Turcotte‐Pugh class C) randomly assigned to treatment with TIPS (n = 33) or with large‐volume paracentesis plus human albumin (n = 33). The primary endpoint was survival without liver transplantation. Secondary endpoints were treatment failure, rehospitalization, and occurrence of complications. Thirteen patients treated with TIPS and 20 patients treated with paracentesis died during the study period, 4 patients in each group underwent liver transplantation. The probability of survival without transplantation was 77% at 1 year and 59% at 2 years in the TIPS group as compared with 52% and 29% in the paracentesis group (P = .021). In a multivariate analysis, treatment with paracentesis and higher MELD score showed to independently predict death. Treatment failure was more frequent in patients assigned to paracentesis, whereas severe episodes of hepatic encephalopathy occurred more frequently in patients assigned to TIPS. The number and duration of rehospitalizations were similar in the two groups. In conclusion, compared to large‐volume paracentesis plus albumin, TIPS improves survival without liver transplantation in patients with refractory or recidivant ascites. (HEPATOLOGY 2004;40:629–635.)

MELD score is better than Child-Pugh score in predicting 3-month survival of patients undergoing transjugular intrahepatic portosystemic shunt

BACKGROUND/AIMS Patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) are at risk of early death due to end-stage liver failure. The aim of this study was to compare model of end-stage liver disease (MELD) and Child-Pugh scores as predictors of survival after TIPS. METHODS We studied 140 cirrhotic patients treated with elective TIPS. Concordance (c)-statistic was used to assess the ability of MELD or Child-Pugh scores to predict 3-month survival. The prediction of overall survivals was estimated by comparing actuarial curves of subgroups of patients stratified according to either Child-Pugh scores or MELD risk scores. RESULTS During a median follow-up of 23.7 months, 55 patients died, 14 underwent liver transplantation and seven were lost to follow-up. For 3-month survival, the discrimination power of MELD score was superior to Child-Pugh score (0.84 vs. 0.70, z=2.07; P=0.038). Unlike Pugh score, MELD score identified two subgroups of Child C patients with different overall survivals (P=0.027). The comparison between observed and predicted survivals showed that MELD score overrates death risk. CONCLUSIONS MELD score is superior to Child-Pugh score as predictor of short-term outcome after TIPS. Its accuracy, however, decreases for long-term predictions.

Cirrhotic Patients Are at Risk for Health Care–Associated Bacterial Infections

BACKGROUND & AIMS Bacterial infections are a frequent and serious burden among patients with cirrhosis because they can further deteriorate liver function. We assessed the epidemiology, risk factors, and clinical consequences of bacterial infections in hospitalized cirrhotic patients. METHODS In a cohort of hospitalized cirrhotic patients (n = 150) referred to a tertiary care setting, all episodes of bacterial infections were recorded prospectively. Infections were classified as community-acquired (CA), health care-associated (HCA), or hospital-acquired (HA). Site of infection, characteristics of bacteria, and prevalence of antibiotic resistance were reported; consequences for liver function and patient survival were evaluated. RESULTS Fifty-four infections were observed among 50 patients (12 CA, 22 HCA, and 20 HA). Bacterial resistance was more frequent among patients with HCA or HA infections (64% of isolates). Mortality was 37% from HA, 36% from HCA, and 0% from CA infections. Independent predictors of infection included a previous infection within the past 12 months (P = .0001; 95% confidence interval [CI], 2.2-10.6), model of end-stage liver disease score ≥ 5 (P = .01; 95% CI, 1.3-6.1), and protein malnutrition (P = .04; 95% CI, 1.5-10). Infectious episodes worsened liver function in 62% of patients. Patients with infection more frequently developed ascites, hepatic encephalopathy, hyponatremia, hepatorenal syndrome, or septic shock. Child class C (P = .006; 95% CI, 1.67-23.7), sepsis (P = .005; 95% CI, 1.7-21.4), and protein malnutrition (P = .001; 95% CI, 2.8-38.5) increased mortality among patients in the hospital. CONCLUSIONS In hospitalized cirrhotic patients, the most frequent infections are HCA and HA; these infections are frequently resistant to antibiotics. As infections worsen, liver function deteriorates and mortality increases. Cirrhotic patients should be monitored closely for infections.

Incidence, natural history, and risk factors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stent grafts

BACKGROUND AND AIMS:The aim of this study was to assess the incidence, natural history, and risk factors of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) with the new polytetrafluoroethylene (PTFE)-covered stent grafts in cirrhotic patients.PATIENTS AND METHODS:Seventy-eight cirrhotic patients treated by TIPS with PTFE-covered stent grafts and followed by the same medical team—according to a prospective protocol for diagnostic workup and surveillance strategy—were reviewed. The follow-up was 19.9 ± 20.6 months.RESULTS: At least one episode of HE occurred in 35 of 78 (44.8%) patients. The probability of remaining free of HE was 53.8% (95% confidence interval [CI] 41.4–66.2] at 1 yr and 50.9% at 2 yr (95% CI 38.2–63.8%). The total number of HE episodes was 89. Fifty-five percent of the episodes were grades III–IV. The occurrence of HE tended to be constant during the follow-up, probably because of the very low incidence of shunt dysfunction (13.6% at 2 yr). Moreover, in six patients, a refractory HE required the reduction of the shunt diameter. One patient died due to variceal bleeding after this procedure. At a multivariate analysis, an older age, high creatinine levels, and low serum sodium and low albumin values were shown to be independent factors for the occurrence of HE. Serum creatinine level was the only variable related to the development of refractory HE at the logistic multivariate analysis.CONCLUSIONS: HE after TIPS with PTFE-covered stent grafts is frequent; its incidence is not confined to the first post-TIPS period, but it has the tendency to be frequent over time. Refractory HE occurred in 8% of patients and may be successfully managed by reducing the stent diameter. The selection of patients undergoing TIPS placement should be very accurate, especially for those subjects with abnormal creatinine level.

Branched-chain amino acids vs lactulose in the treatment of hepatic coma

A controlled study was carried out in two groups of 20 patients with cirrhosis of the liver and deep coma in order to compare the efficacy of intravenous branched-chain amino acid solutions in 20% glucose (group A) vs lactulose plus glucose in isocaloric amount (group B). There were 3 drop-outs from each group. Plasma amino acids and ammonia were assayed at fixed intervals throughout the 10-day observation period. Routine tests were assayed daily. Complete mental recovery was obtained in 70% of patients in group A and in 47% in group B. The difference was not significant, likely due to the lack of placebo group. With the exception of free tryptophan/all competing amino acids ratio, the modifications in plasma amino acid levels showed no correlation with the clinical course under either treatment. Ammonia, like free tryptophan, decreased significantly upon mental recovery, paralleling the clinical course throughout the study. In conclusion, branched-chain amino acids are at least as effective as lactulose in deep hepatic coma. It is suggested that branched-chain amino acids may reverse coma either by competing with brain entry of the aromatic amino acid or by metabolically decreasing free tryptophan and ammonia.

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunt (TIPS) has been used for more than 20 years to treat some of the complications of portal hypertension. When TIPS was initially proposed, it was claimed that the optimal calibration of the shunt could allow an adequate reduction of portal hypertension, avoiding, at the same time, the occurrence of hepatic encephalopathy (HE), a neurologic syndrome. However, several clinical observations have shown that HE occurred rather frequently after TIPS, and HE has become an important issue to be taken into consideration in TIPS candidates and a problem to be faced after the procedure.

Modification of cardiac function in cirrhotic patients with and without ascites

OBJECTIVES: Abnormalities in cardiac function have been reported in liver cirrhosis, suggesting a latent cardiomyopathy in these patients. In this study we investigated cardiac function in cirrhotic patients and in controls. METHODS: A total of 20 cirrhotic patients without previous or ongoing ascites, 20 cirrhotic patients with moderate-to-severe ascites, and 10 healthy controls were studied by two-dimensional Doppler echocardiography. Cardiac dimensions and left and right ventricular function were evaluated. The left ventricular geometric pattern was calculated according to Ganau’s criteria. Diastolic function was evaluated by the peak filling velocity of E wave and A wave, E/A ratio, and deceleration time of E wave. The pulmonary systolic arterial pressure was also estimated in patients with tricuspid insufficiency. RESULTS: Right and left atrium and right ventricle diameters were significantly enlarged in cirrhotic patients versus controls. E/A ratio was decreased (p < 0.05) in patients with ascites (0.9 ± 0.2) versus those without ascites (1.3 ± 0.4) and controls (1.3 ± 1). The estimated pulmonary systolic arterial pressure was slightly elevated in patients with ascites (35 ± 5 mm Hg, six patients) versus those with no ascites (28 ± 5, 10 patients) and controls (27 ± 8, 6 controls, analysis of variance, p < 0.05). The pattern of left ventricular geometry was normal in the majority of patients. Nitrite and nitrate levels were increased in cirrhotics irrespective of the presence of ascites. CONCLUSIONS: Liver cirrhosis is associated with enlarged right cardiac chambers. Diastolic dysfunction and mild pulmonary hypertension are evident in cirrhotic patients with ascites. These changes do not depend on variations in the left ventricular geometry.