Liver Cirrhosis

Aim: Non-insulin-dependent diabetes mellitus (type 2 diabetes) not responding to dietary treatment alone in patients with non-alcoholic liver cirrhosis is characterized by high postprandial hyperglycaemia. The control of postprandial hyperglycaemia in such patients, is generally achieved by the means of progressively higher doses of insulin, with an increasing risk of hypoglycaemia in the late postprandial period. The aim of this study was to evaluate the use of acarbose for the control of postprandial hyperglycaemia in 100 patients with wellcompensated liver cirrhosis and type 2 diabetes treated with insulin. Methods: The study was double blind with randomization of treatments into acarbose (52 patients) vs. placebo (48 patients) with parallel branches over a period of 28 weeks. Results: All patients tolerated the treatments well and no signi®cant variations in liver function tests were observed (< 5% vs. pretreatment). A signi®cant reduction of several parameters was observed only after acarbose treatment: fasting glycaemia (173 T 28 vs. 146 T 19 mg/dl; p < 0.01), postprandial glycaemia (230 T 24 vs. 148 T 20 mg/dl; p < 0.01), mean glycaemia (206 T 20 vs. 136 T 13 mg/dl; p < 0.01), mean variation (180 T 14 vs. 51 T 10 mg/dl; p < 0.01), HbA 1c (8.9 T 0.8 vs. 7.2 T 0.5; p < 0.05), C-peptide 2 h after a standard meal (4.5 T 1.9 vs. 2.8 T 1.7 ng/ml; p < 0.05), whereas the parameters did not change signi®cantly after the placebo. After acarbose treatment a signi®cant increase of intestinal voiding/week (+ 116% vs. + 10%; p < 0.01) and a parallel reduction of blood ammonia levels (± 52 T 9% vs. ± 9 T 5%; P < 0.01) were observed. Conclusions: The results clearly document the good tolerability and the absence of toxic effects of acarbose on liver, due to the lack of both intestinal absorption and hepatic metabolism of the drug at doses in the therapeutic range. In fact, acarbose increases the peristalsis movements of the gut, stimulates the proliferation of the saccarolytic bacteria and simultaneously reduces the proliferation of proteolytic bacteria, thus resulting active in the reduction of blood ammonia levels. These effects of acarbose may be advantageously exploited in the treatment of type 2 diabetic patients with well-compensated non-alcholic liver cirrhosis.

Endoscopy plays a major role in the management of gastrointestinal varices in portal hypertension. It is used for the prophylaxis of the fi rst bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding. Today not only nonselective betablockers, but also endoscopic band ligation is an option in the primary prophylaxis of the fi rst bleeding episode in patients with large esophageal varices. Acutely bleeding varices should be treated by ligation, pharmacological and antibiotic therapy. Prophylaxis of recurrent bleeding despite endoscopic and pharmacologic treatment is patient dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A). In patients with refractory ascites and a bilirubin level below 3 mg/dl, TIPS is a good option. Nevertheless, the fi rst-line treatment in most patients in Germany is endoscopic band ligation. Bleeding from ectopic varices and due to hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.

Hepatitis C virus (HCV) is not directly cytopathic to the hepatocytes; however, host immune response against the virus does cause hepatic injury. Production of the HCV antibody is a host immune response to a viral antigen. The currently used HCV antibody assay is a qualitative, not quantitative, assessment. In this study, we sought to quantitatively estimate HCV antibody levels in patients who had undergone liver transplantations at the University of Rochester Medical Center, Rochester, New York, and correlate these levels with HCV RNA viral load, genotype, severity of recurrence, and anti-HCV treatment. From 39 liver transplantation patients, we obtained 141 blood samples for quantitative HCV RNA to measure HCV antibody levels quantitatively. Most antibody levels were within a narrow range with a mean of 32.9+/-5.1. Samples with undetectable RNA had a mean antibody level of 31.4+/-8.0, and samples with a positive RNA had mean level of 33.0+/-4.6. The mean antibody levels were signi...

With the global pandemic of hepatitis B and C infections, the incidence of Hepatocellular carcinoma (HCC) is rapidly increasing world wide. We identified glypican-3 (GPC3), a novel oncofetal gene over-expressed specifically in human HCC, as based on data of cDNA microarrays. As GPC3 is a GPI-anchored membrane protein and could be secreted, we attempted to detect secreted GPC3 protein in sera from HCC patients using Western blotting and ELISA. GPC3 protein was positive in sera of 40.0% (16/40) of HCC patients, and negative in sera from subjects with liver cirrhosis (LC) (0/13), chronic hepatitis (CH) (0/34), and healthy donors (0/60). All subjects were Japanese. Although 12 of 40 HCC patients were negative for both a-fetoprotein (AFP) and PIVKA-II well known tumor markers of HCC, four of these were GPC3-positive in the sera. We also observed vanishing GPC3 protein in the sera of three patients after the surgical treatment for HCC. On the other hand, immunohistochemical analysis revealed that HCC expressed GPC3 protein in all 14 HCC patients tested. In conclusion, GPC3, as defined in this study was shown to be a useful tumor marker for cancer-diagnosis for large numbers of patients with HCC.

Haydée Marina do Valle PEREIRA(1), Norma de Paula CAVALHEIRO(2), Fátima Mitiko TENGAN(2), Carlos Eduardo MELO(2), Evandro Sobroza de MELLO(3) & Antônio Alci BARONE(2) SUMMARY Hepatitis C virus infection evolves progressively persisting in the majority of patients (85%). Most patients have high ALT (alanine aminotransferase) levels and approximately 25% normal ALT. The latter are usually female and there is no association between genotype and severity of hepatic lesion. Histologic analysis usually shows small lesion and absence or low amount of fibrosis, despite cirrhosis having been reported. Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we have carried out a study of 68 chronic hepatitis C patients between January 1997 and April 2000. There was a prevalence of 13.8% chronic hepatitis C patients with normal ALT levels, 45.6% of which were male and 54.4% female, the mean age being 38 +/-13 years. We found a predominance of genotype 1 in 84.7% of the patients, genotype 2 in 6.8% and genotype 3 in 10.7%. In 52.9% of the cases liver biopsies revealed liver reaction, periportal activity score 0-1 was observed in 85.3% of the patients and score 2-4 was seen in 14.7%. Structural activity score 0-1 was seen in 73.5% of the patients and score 2-4 in 26.5% of them. Periportal activity ≥ 2 and structural activity > 1 was seen in 29%, but steatosis was not seen in 73.5%. Our results suggest the need to revisit for liver biopsy practice in patients with Chronic Hepatitis C and normal transaminases.

SYNOPSIS A method for the differential determination of plasma antithrombins, antithrombin III and U macroglobulin, is described. The method is based on the selective inactivation of plasma (x2 macroglobulin by treatment with 01 M methylamine for 10 minutes at 37°C and on the observation that antithrombin III and a2 macroglobulin inhibited in defibrinated plasma low concentrations of thrombin without mutual interference and according to pseudo-first order reaction. In healthy subjects antithrombin III was shown to account for about 70% of the total antithrombin activity. But in patients with liver cirrhosis, where low levels of total antithrombin activity were observed, the relative contribution of antithrombin III was found to be noticeably lower.

Introduction. Cirrhosis predisposes to the development of hepatocellular carcinoma (HCC), demanding that these patients undergo follow-up with imaging methods for the early detection of neoplastic nodules. Morphologic study of the explanted livers allows identification of lesions not detected pre-operatively. Objective. To assess the frequency and to characterize the HCC found incidentally at pathological evaluation of explanted cirrhotic livers. Material and methods. Thirty patients had HCC diagnosed in explanted cirrhotic livers. The livers were sectioned at intervals of 0.5 cm. Each detached nodule was selected for microscopic study according to size, color and/or consistency. Retrospective analysis of the clinical records was performed comparing available data from various imaging methods. Results. In 11 patients, 16 HCC had previously been identified in the explants by one or more imaging methods. In the other 19 explanted livers (63.3%), HCC was incidentally found. All HCC identified in 9 patients and some of them in 10 patients were incidentally found, varying from microscopic focuses to 2 cm diameter lesions. They varied from only one (5 cases) to multiple nodules (7 cases). Discussion. Imaging methods may underestimate the number of HCC in cirrhotic livers. Histological study is an essential tool that can early detect tumor nodules not previously detected by imaging methods. In our study, although small, multicentric HCC were identified, illustrating the multifocal nature of the hepatic carcinogenesis. Future studies must correlate these findings with patient outcomes. Conclusion. Characterization of explanted cirrhotic livers for HCC is important for previously known and incidentally found lesions.

Acute intravenous amino acid infusion or a highprotein diet increases renal plasma flow and the glomerular filtration rate in healthy subjects. Conversely, a low-protein diet reduces renal plasma flow and glomerular filtration rate. The aim of this study was to investigate the effect of intravenous amino acid infusion and dietary proteins on kidney function in cirrhosis. Protocol 1: renal plasma flow and glomerular filtration rate were measured before and during intravenous administration of a 10% amino acid solution (0.043 ml/kg/min) to eight compensated cirrhotic patients (group l), nine nonazotemic cirrhotic patients with ascites (group 2) and seven cirrhotic patients with ascites and functional renal failure (group 3). Amino acid administration induced a significant increase in renal plasma flow and glomerular filtration rate in all groups studied. Renal plasma flow and glomerular filtration rate increased by 16% and 14%, respectively, in group 1; 31% and 22% in group 2 and 25% and 21% in group 3. Protocol 2: Renal plasma flow and glomerular filtration rate were measured in nine cirrhotic patients with ascites after 11 days on a low-protein diet (0.5 gm/kg body weight/day) and also after the patients followed for 11 days a moderately high-protein diet (1.5 g m / kg body weight /day). The moderately high-protein diet was associated with a significant increase in renal plasma flow (12%) and glomerular filtration rate (13%) compared with values obtained while the patients followed the low-protein diet. Plasma glucagon levels increased markedly during the intravenous administration of amino acid and the intake of the moderately highprotein diet. However, no correlation existed between changes in renal plasma flow and glomerular filtration rate induced by intravenous amino acid or dietary proteins and changes in plasma glucagon levels. The renal effects of intravenous amino acid or dietary pro-

In order to assess the interaction between alcohol intake, tobacco smoking and coffee consumption in determining the risk of liver cirrhosis we carried out a hospital-based case-control study involving 115 patients at their first diagnosis of cirrhosis and 167 control patients consecutively enrolled in the General Hospitals of the Province of L'Aquila (Central Italy). The mean life-time daily alcohol intake (as g ethanol consumed daily) was measured by direct patient interviews, whose reproducibility was > 0.80 and similar for cases and controls, as checked by interviewing the relatives of a sample of 50 cases and 73 controls. During the same patient's interview we also measured the mean consumption of coffee (daily number of cups of filtered coffee) and tobacco (life-time daily number of cigarettes smoked). A dose-effect relationship on the risk of cirrhosis was present both for alcohol intake -for which the risk was significantly increased above 100 g of daily intake -and for cigarette consumption. The latter did not however improve the goodness-of-fit of a logistic regression model including alcohol intake as covariate. By contrast, coffee consumption had a protective effect on the risk of cirrhosis and significantly improved the goodness-of-fit of such a model. Abstaining from coffee consumption determined both a significantly increased risk of cirrhosis, even for daily alcohol intake below 100 g, and a multiplicative effect with alcohol intake on this risk. In patients drinking /> 101 g ethanol daily the relative risk increased from 5.5 (95% confidence interval: 1.4-22.0) for coffee consumers to 10.8 (95% confidence interval: 1.3-58.1) for coffee abstainers. We conclude that: (t) tobacco smoking is likely to be a faint risk factor for cirrhosis, and studies on wider patients series should be performed for confirmation; (2) coffee drinking is associated with a reduced risk of cirrhosis. Whether coffee contains some hitherto unknown protective substances, or is just a marker of other life-style or dietary protective factors, deserves further clarification.

Tramadol is a synthetic opioid agonist used extensively in human and, to a lesser extent, veterinary medicine throughout the world. The clinical efficacy and pharmacokinetic profile of intravenous (i.v.) and extradural (e.d.) tramadol (2 mg/kg) and its o-desmethyl metabolite were studied in dogs undergoing tibial plateau levelling osteotomy (TPLO). Intra-operative cardiorespiratory variables were monitored and post-operative pain was assessed using the short form of the Glasgow Composite Pain Scale. A rapid (&lt;5 min) and effective production of o-desmethyl tramadol was recorded. The pharmacokinetic profile was similar for tramadol and its metabolite irrespective of the route of administration. E.d. tramadol provided sufficient intra- and post-operative analgesia without significant clinical side-effects, but the post-operative analgesia was comparable to that following i.v. administration and the e.d. route could therefore not be considered a practical alternative to the i.v. route.

The new england journal of medicine 2674 * The most common adverse events are those that occurred in 10 percent or more of the patients in any treatment group. † Fisher's exact test was used for the comparison with the placebo-adefovir group (P<0.05). ‡ Fisher's exact test was used for the comparison with the adefovir-placebo group (P<0.05).

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, longterm 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.

Numerous clinical and epidemiological studies have identified elevated homocysteine levels in plasma as a risk factor for atherosclerotic vascular disease and thromboembolism. Hyperhomocysteinemia may develop as a consequence of defects in homocysteine-metabolizing genes; nutritional conditions leading to vitamin B 6 , B 12 , or folate deficiencies; or chronic alcohol consumption. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver. Impaired liver function leads to altered methionine and homocysteine metabolism; however, the molecular basis for such alterations is not completely understood. In addition, the mechanisms behind homocysteineinduced cellular toxicity are not fully defined. In the present work, we have examined the expression of the main enzymes involved in methionine and homocysteine metabolism, along with the plasma levels of methionine and homocysteine, in the liver of 26 cirrhotic patients and 10 control subjects. To gain more insight into the cellular effects of elevated homocysteine levels, we have searched for changes in gene expression induced by this amino acid in cultured human vascular smooth muscle cells. We have observed a marked reduction in the expression of the main genes involved in homocysteine metabolism in liver cirrhosis. In addition, we have identified the tissue inhibitor of metalloproteinases-1 and ␣1(I)procollagen to be upregulated in vascular smooth muscle cells and liver stellate cells exposed to pathological concentrations of homocysteine. Taken together, our observations suggest (1) impaired liver function could be a novel determinant in the development of hyperhomocysteinemia and a role for elevated homocysteine levels in the development of liver fibrosis. (Hypertension. 2001;38:1217-1221.)

Cirrhotic cardiomyopathy is a clinical syndrome in patients with liver cirrhosis characterized by an abnormal and blunted response to physiologic, pathologic, or pharmacologic stress but normal to increased cardiac output and contractility at rest. As many as 50% of cirrhotic patients undergoing liver transplantation show signs of cardiac dysfunction, and 7% to 21% of deaths after orthotopic liver transplantation result from overt heart failure. In this review, we critically evaluate the existing literature on the pathophysiology and clinical implications of cirrhotic cardiomyopathy. (J Am Coll Cardiol 2010;56:539-49)

The Patient Treatment File of the Department of Veterans Affairs comprises the computerized records of all inpatients treated in all Veterans Affairs hospitals distributed throughout the United States. This database was used to study the association between liver disease and clinically manifest cholelithiasis. The computerized medical records of 38,459 patients with various forms of liver disease and 69,336 controls without the diagnosis were extracted from the annual files between 1990 and 1993. In a multiple logistic regression analysis, the occurrence of cholelithiasis served as the outcome variable, whereas different forms of liver disease and demographic characteristics, such as age, gender, and ethnicity, served as predictor variables. Among the control population, cholelithiasis was reported in 5.2% (3,571 of 69,336) of subjects. Cholelithiasis occurred in 7.5% (2,898 of 38,459) of patients with all liver disease, 9.5% (1,642 of 17,287) of patients with alcoholic liver cirrho...

Background & Aims: In healthy subjects, exercise pro-During exercise, an increase in cardiac output and a motes marked hemodynamic and humoral changes redistribution of blood flow from other territories (especharacterized by an increase in cardiac output, a rediscially the splanchnic area) through an adrenergic-meditribution of blood flow to muscular territories under acated vasoconstriction 6 are the main physiological changes tivity, and an increase in sympathoadrenergic activity.

countries. It is important to accurately determine the stage of fibrosis in these patients. The enhanced liver fibrosis (ELF) test has been validated for staging liver fibrosis in adult patients with chronic liver diseases, including NAFLD. We investigated the performance of this test in assessing liver fibrosis in children and adolescents with NAFLD, identified by biopsy. Methods: The ELF test was performed on a panel of serum samples collected from 112 consecutive subjects that were likely to have NAFLD (64 male, mean age of 13.8 ؎ 3.3). A previously described and validated algorithm was used to analyze the data on hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels. Results: In pediatric patients with NAFLD, the ELF test predicted liver fibrosis stage with a high degree of sensitivity and specificity; results were superior to those reported for adults. The area under receiver operating characteristic curves/best possible ELF test cut-off values for the prediction of "any" (>stage 1), moderateperisinusoidal (>stage 1b), moderate-portal/periportal (>stage 1c), significant (>stage 2), or advanced (>stage 3) fibrosis were 0.92/9.28, 0.92/9.33, 0.90/9.54, 0.98/ 10.18 and 0.99/10.51, respectively. Conclusions: The ELF test can be used to accurately assess the level of liver fibrosis in pediatric patients with NAFLD. This information is important for identifying patients with progressive fibrosis that require further histopathological analysis or therapeutic follow-up.

The alterations of sexual function known as the erectile dysfunction are quite frequent among patients affected by liver diseases and they tend to increase in advanced liver failure. This process is directly linked to cirrhosis or its treatments, such as liver transplantation, or to certain drugs (e.g. beta-blockers). Independent of cirrhosis, other factors may cause sexual problems in these patients. Alcohol itself seems to worsen sexual function in the absence of cirrhosis. Viral hepatitis has an uncertain influence on male gonadic function and even antiviral therapy itself can worsen some seminal and hormonal parameters, although it is reversible. Quality of life may be greatly decreased in cases of cirrhosis where these alterations are present, so it is important to value and care for them, if possible. This review investigates the major male sexual disturbances in liver diseases of various origins.

Hemorrhagic ascites in patients with cirrhosis is described as a RBC (Red Blood cell) &gt;50,000/mm³ and leads to increased morbidity and mortality. Positive red blood cells at a level of less than 50,000/mm³ (10,000-50,000) may be encountered in the ascites but it is not known whether this is clinically significant or not. This study aimed to examine the outcome of hemorrhagic ascites in patients with advanced cirrhosis. Data from 329 cirrhotic patients with ascites who received paracentesis at least once due to ascites was retrospectively analyzed from the period of 2007-2013 from the Türkiye Yüksek İhtisas Hospital, Department of Gastroenterology. Patients were divided according to the number of RBC, with greater than 10,000/mm³ being described as hemorrhagic ascites, and less than 10,000 / mm³ described as the normal or control group. Patient data included: number of accepted intensive unit service stays, acute kidney injury (AKI), hepatic encephalopathy (HES), model for end-liv...

Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis, so it could be an effective therapy for portal hypertension. This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG) and its safety in patients with cirrhosis and portal hypertension. Methods: Fifty-nine patients with cirrhosis and portal hypertension (HVPG >12 mm Hg) were randomized to groups that were given simvastatin 20 mg/day for 1 month (increased to 40 mg/day at day 15) or placebo in a double-blind clinical trial. Randomization was stratified according to whether the patient was being treated with ␤-adrenergic blockers. We studied splanchnic and systemic hemodynamics and variables of liver function and safety before and after 1 month of treatment. Results: Simvastatin significantly decreased HVPG (؊8.3%) without deleterious effects in systemic hemodynamics. HVPG decreases were observed in patients who were receiving ␤-adrenergic blockers (؊11.0%; P ‫؍‬ .033) and in those who were not (؊5.9%; P ‫؍‬ .013). Simvastatin improved hepatic, fractional, and intrinsic clearance of indocyanine green, showing an improvement in effective liver perfusion and function. No significant changes in HVPG and liver function were observed in patients receiving placebo. The number of patients with adverse events did not differ significantly between groups. No patient was withdrawn from the study based on adverse events. Conclusions: Simvastatin decreased HVPG and improved liver perfusion in patients with cirrhosis. These effects were additive with those of ␤-adrenergic blockers. The beneficial effects of simvastatin should be confirmed in longterm clinical trials for portal hypertension.

Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70؉/GPC3؉ (59%) when a 2-marker panel was used. Conclusion: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis. (HEPATOLOGY 2007;45:725-734.) Abbreviations: eHCC-G1, early and grade 1 HCC; GPC3, glypican 3; GS, glutamine synthetase; HGDN, high grade dysplastic nodule; HSP70, heat shock protein 70; LGDN, low grade dysplastic nodule; LRN, large regenerative nodule. From the departments of 1 Pathology and

OBJECTIVES: To determine the serum hyaluronic acid (HA) levels as biochemical marker of hepatic fibrosis and cirrhosis and correlate it with the degree of hepatic fibrosis and cirrhosis. DESIGN: Comparative cross-sectional study. PLACE AND DURATION OF STUDY: The ...

Background and Aim: Refractory ascites in liver-cirrhosis is associated with a poor prognosis. We performed a prospective study to investigate whether aggressive nutritionalsupport could improve outcomes in cirrhotic patients. Methods: Cirrhotic patients undergoing serial large-volume paracentesis for refractoryascites were enrolled and randomized into three groups. Group A received postparacentesis intravenous nutritional-support in addition to a balanced oral diet and a late-evening protein snack, group B received the same oral nutritional-protocol as the first group but without parenteral support, and group C (the control group) received a lowsodium or sodium-free diet. Clinical, anthropometric and laboratory nutritional parameters and biochemical tests of liver and renal function were reported for 12 months of follow-up. Results: We enrolled 120 patients, who were randomized into three groups of equal size. Patients on the nutritional-protocol showed better preservation of clinical, anthropometric and laboratory nutritional parameters that were associated with decreased deterioration of liver function compared with patients on the low-sodium or sodium-free diet (group C). Groups A and B had lower morbidity and mortality rates than the control group (C). Mortality rates were significantly better in patients who were treated with parenteralnutritional-support than for the other two groups. In patients who were on the nutritionalprotocol, there was a reduction in the requirement of taps for the treatment of refractory ascites. Conclusions: Post-paracentesis parenteral-nutritional-support with a balanced oral diet and an evening protein snack appears to be the best care protocol for patients with liver-cirrhosis that has been complicated by refractory-ascites.

Balloon-occluded retrograde transvenous obliteration (BRTO) of bleeding gastric varices (GV) is well described in the literature. Using Ethanolamine oleate as the sclerosing agent in BRTO, but it is not readily available in the United States in the desired concentrations. The authors' aim is to describe their initial experience with BRTO using sodium tetradecyl sulfate (STS) foam as an alternative sclerosing agent. Materials and Methods: The authors performed a retrospective review of their initial series in which STS foam was used to treat bleeding GV using BRTO. All study subjects had endoscopic evidence of gastric variceal bleeding. STS foam was made using a combination of agents with a 3:2:1 ratio of gas: 3% STS: Lipiodol (Ethiodol; Savage Laboratories, Melville, New York). Mean values and ranges were calculated for each variable, and clinical and imaging outcomes were assessed. Results: The authors performed BRTO in 22 cirrhotic patients (11 men and 11 women) with a mean age of 52 years (range, 23-83 years). Technical success was achieved in 20 of 22 (91%) patients. Complications occurred in three of 22 (14%) patients. The overall mean dose of STS used was 300 mg (range, 30-600 mg) with mean total volume of sclerosant mixture of 34.1 mL (range, 10-65 mL). Follow-up imaging was available for 18 of 20 (90%) technically successful procedures with a mean period of 89 days (range, 1-359 days). Complete obliteration of GV was achieved in 16 of 18 (89%) patients. There were no cases of recurrent variceal bleeding with a mean clinical follow-up period of 130 days (range, 1-510). Conclusions: BRTO utilizing STS foam appears effective in obliterating bleeding GVs with good short-term outcomes. ABBREVIATIONS BRTO ϭ balloon-occluded retrograde transvenous obliteration, EBC ϭ endoscopic N-butyl-2-cyanoacrylate, EO ϭ ethanolamine oleate, EUS ϭ endoscopic ultrasound, GRS ϭ gastrorenal shunt, GV ϭ gastric varices, STS ϭ sodium tetradecyl sulfate, TIPS ϭ transjugular intrahepatic portosystemic shunts

The journal is pleased to debut a new feature, a debate. This one is on the use of albumin colloid replacement after large-volume paracentesis. Whether or not such a practice is warranted is argued vigorously and informatively by three experts in the field, Drs Cárdenas and Ginès for the 'pro' side and Runyon for the 'con' side. Topics for future debates will be controversial issues in research or clinical hepatology. Debates are generally commissioned, but if you have an interesting suggestion for a debate, please contact the editor.

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 Ill 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 (12st17 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

Objective: A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)-enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus-positive liver cirrhosis. Methods: In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study. Results: Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group. Conclusion: Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.

In the last year, different diseases possibly linked to Helicobacter pylori infection but localized outside of the stomach have been investigated. There are, in fact, several studies concerning cardiovascular diseases, hematologic disorders, neurologic diseases, metabolic, hepatobiliary diseases, and other conditions. Some of those studies, such as those on sideropenic anemia and idiopathic thrombocytopenic purpura, are quite large and well conducted, while in other cases there are just small or isolated studies or even case reports. Nonetheless, there is much interest among researchers all over the world for such a topic as demonstrated by the large number of studies published in the last year.

The gold standard method for HBV genotyping is whole genome sequencing followed by phylogenetic analysis. 4,23 Although this technique is highly sensitive and allows the detection of new and recombinant genotypes, it is expensive, time-consuming, and