Dysregulated meta-organismal metabolism of aromatic amino acids in alcohol-associated liver disease.

BACKGROUND: Chronic alcohol consumption impairs gut barrier function and perturbs the gut microbiome. Although shifts in bacterial communities in patients with alcohol-associated liver disease (ALD) have been characterized, less is known about the interactions between host metabolism and circulating microbe-derived metabolites during the progression of ALD. METHODS: A large panel of gut microbiome-derived metabolites of aromatic amino acids was quantified by stable isotope dilution liquid chromatography with online tandem mass spectrometry in plasma from healthy controls (n = 29), heavy drinkers (n = 10), patients with moderate (n = 16) or severe alcohol-associated hepatitis (n = 40), and alcohol-associated cirrhosis (n = 10). RESULTS: The tryptophan metabolites, serotonin and indole-3-propionic acid, and tyrosine metabolites, p-cresol sulfate, and p-cresol glucuronide, were decreased in patients with ALD. Patients with severe alcohol-associated hepatitis and alcohol-associated cirrhosis had the largest decrease in concentrations of tryptophan and tyrosine-derived metabolites compared to healthy control. Western blot analysis and interrogation of bulk RNA sequencing data from patients with various liver pathologies revealed perturbations in hepatic expression of phase II metabolism enzymes involved in sulfonation and glucuronidation in patients with severe forms of ALD. CONCLUSIONS: We identified several metabolites decreased in ALD and disruptions of hepatic phase II metabolism. These results indicate that patients with more advanced stages of ALD, including severe alcohol-associated hepatitis and alcohol-associated cirrhosis, had complex perturbations in metabolite concentrations that likely reflect both changes in the composition of the gut microbiome community and the ability of the host to enzymatically modify the gut-derived metabolites.

Renal Replacement Therapy for Acute Kidney Injury in Severe Alcohol-Associated Hepatitis as a Bridge to Transplant or Recovery.

BACKGROUND: Acute kidney injury is seen in approximately 30% of patients with severe alcohol-associated hepatitis (AH) and is associated with increased mortality. Controversy exists surrounding initiation of renal replacement therapy (RRT) in these patients, as most are ineligible for early transplantation. AIMS: The primary aim was to identify predictors of survival and identify patients who may benefit from RRT as a bridge to transplant or recovery. METHODS: A retrospective multicenter cohort of adult patients with AH, who received RRT, was developed, including patients from two North American and one European liver transplant centers. RESULTS: Fifty-five patients were included. Survival was 26/55 (47.3%) at 30 days, 17/55 (30.9%) at 3 months, and 15/55 (27.2%) at 6 months. Of those who survived 6 months, 2/15 (13.3%) received simultaneous liver and kidney transplantation, 11/15 (73.3%) had spontaneous recovery of kidney function, and 2/15 (13.3%) remained on RRT. Of patients who survived at least 3 months, 8/17 (47%) completed addiction treatment. Predictors of mortality were pre-RRT MELD (OR 1.10, 1.02-1.19) and pre-RRT MELD-Na (OR 1.14, 1.03-1.27). Pre-RRT MELD-Na < 35 was associated with lower 6-month mortality (OR 0.23, 0.06 - 0.81). Of patients with pre-RRT MELD-Na < 35, 50% survived 6 months compared to 18% of patients with pre-RRT MELD-Na ≥ 35. CONCLUSIONS: Although RRT has a limited role in patients with decompensated cirrhosis, ineligible for transplant, it may be used in select patients with AH. This may allow for spontaneous recovery with alcohol abstinence or completion of addiction treatment prior to transplant.

A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Second-harmonic generation (SHG) microscopy and hepatic venous pressure gradient-based validation of a novel histological staging system for alcoholic hepatitis.

Alcoholic hepatitis (AH) lacks specific histological staging. A novel fibrosis staging that encompasses perisinusoidal fibrosis and cirrhosis sub-stages, substantiated by Hepatic venous pressure gradient (HVPG) and automated fibrosis quantification, is imperative. To correlate novel histological staging system of AH with second-harmonic generation microscopy (SHG)-based q-fibrosis, HVPG, and activated hepatic stellate cells (HSCs). Liver biopsies of AH (n = 175) were staged semi-quantitatively as F0, F1, F2, F3A and F3B and Laennec substages of cirrhosis 4A, 4B and 4C. Stages were correlated with SHG q-fibrosis parameters, HVPG and HSCs. Mean age 41.2 ± 9.4 years, 96.6% males, bilirubin 20.58 ± 8.0 mg/dl and Maddrey's discriminant function 78.9 ± 36.7 displayed advanced fibrosis in 98.6%. With increasing histological stages, an increase in q-fibrosis indices and mean HVPG (p < 0.0001) were recorded; stage 4C showed the most significant difference from other stages (p < 0.000). Stages 3A and 3B were comparable with the stages 4A and 4B, respectively, for q-fibrosis (p = 1) and HVPG (p = 1). HSCs (> 30%) were significantly higher in stage 3 (75%) compared with 4 (49%) and 2 (59%), p = 0.018. Overall agreement for histological staging was excellent for all stages (0.82). SHG quantified fibrosis and HVPG corroborates the novel histological staging of AH. Expansive PCF matches with collagen content and clinical severity to early sub-stages of cirrhosis. This highlights the need for an accurate quantification and inclusion of PCF as a separate stage. SHG-based quantification can be a useful adjunct to histological fibrosis staging systems.

Sex Differences in Alcohol Consumption and Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is becoming increasingly prevalent throughout the United States. Previously alcohol-associated liver disease was known to affect men more often than women; however, this gap between the sexes is narrowing. Studies show that women develop liver disease with lesser alcohol exposure and suffer worse disease as compared with men. This review article explores the increasing prevalence of alcohol-associated liver disease in women, reasons for changing patterns in alcohol consumption and liver disease development including obesity and bariatric surgery, proposed mechanisms of sex-specific differences in alcohol metabolism that may account for this discrepancy between men and women, and sex differences in treatment enrollment and response. Studies were identified by performing a literature search of PubMed and Google Scholar and through review of the references in retrieved articles. Search terms included alcohol-associated liver disease, alcoholic hepatitis, alcoholic cirrhosis, sex, gender, female, epidemiology, bariatric surgery, obesity, treatment. Due to the paucity of literature on some of the relevant subject matter and inclusion of landmark studies, no date range was selected. Studies were included if their methods were sufficiently robust and they made a comparison between the sexes that is clinically relevant. Understanding of the changing epidemiology and mechanisms of liver disease development unique to women are paramount in creating appropriate and effective interventions for women who represent a rapidly growing subset of patients with alcohol-associated liver disease.

Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis.

In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004-1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042-1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943-0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan-Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient's background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.

Endovascular Treatment of Acute Posttransplant Portal Vein Thrombosis Due to Portal Steal From Mesocaval And Coronary Portosystemic Shunts.

The management of portosystemic shunts in liver transplant recipients relies on appropriate perioperative study. There are several strategies for shunt handling, ranging from preoperative interventional procedures to intraoperative surgical interruption or embolization. Appropriate management often results in a successful outcome, although wrong decisions could lead to serious consequences. Here, we report a liver transplant recipient with grade 2 portal vein thrombosis associated with 2 large portosystemic shunts (coronary and mesocaval), which were managed intraoperatively via thrombectomy without shunt ligation. Acute portal vein thrombosis developed early after transplant due to portal steal syndrome. The patient underwent a successful endovascular shunt embolization, with prompt restoration of hepatopetal portal flow and resolution of the portal steal. Use of interventional radiology in perioperative management of transplant patients has recently gained wider importance; our case reported here is particularly suggestive of the good outcomes of a multidisciplinary approach to a threatening complication such as postoperative acute portal vein thrombosis.

Bone microarchitecture and bone turnover in hepatic cirrhosis.

Liver cirrhosis leads to bone loss. To date, information on bone quality (three-dimensional microarchitecture) and, thus, bone strength is scarce. We observed decreased bone quality at both assessed sites, independent of disease severity. Therefore, all patients should undergo early-stage screening for osteoporosis. INTRODUCTION: Recent studies found low bone mineral density in cirrhosis, but data on bone microstructure are scarce. This study assessed weight-bearing and non-weight-bearing bones in patients with cirrhosis and healthy controls. The primary objective was to evaluate trabecular and cortical microarchitecture. METHODS: This was a single-center study in patients with recently diagnosed hepatic cirrhosis. Thirty-two patients and 32 controls participated in this study. After determining the type of cirrhosis, the parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. RESULTS: Both cortical and trabecular microarchitectures showed significant alterations. At the radius, trabecular bone volume fraction was 17% lower (corrected p = 0.028), and, at the tibia, differences were slightly more pronounced. Trabecular bone volume fraction was 19% lower (p = 0.024), cortical bone mineral density 7% (p = 0.007), and cortical thickness 28% (p = 0.001), while cortical porosity was 32% higher (p = 0.023), compared to controls. Areal bone mineral density was lower (lumbar spine - 13%, total hip - 11%, total body - 9%, radius - 17%, and calcaneus - 26%). There was no correlation between disease severity and microarchitecture. Areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) correlated well with parameters of cortical and trabecular microarchitecture. CONCLUSIONS: Hepatic cirrhosis deteriorates both trabecular and cortical microarchitecture, regardless of disease severity. Areal bone mineral density is diminished at all sites as a sign of generalized affection. In patients with hepatic cirrhosis, regardless of its origin or disease severity, aBMD measurements are an appropriate tool for osteologic screening.

Endotension after Abdominal Aortic Aneurysm Endovascular Repair in Cirrhotic Patients.

BACKGROUND: Endotension can present a real challenge for the long-term success of endovascular aortic repair (EVAR). Sometimes, it can be associated with liver dysfunction and consequent plasmatic alterations as in the 2 cases reported here. METHODS: Significant and progressive abdominal aortic aneurysms (AAA) sac enlargement, without radiologic signs of endoleak, was observed in 2 patients during a 3-year follow-up after EVAR. The first was a 70-year-old man affected by viral liver cirrhosis and the second was a 71-year-old man with cirrhosis due to alcoholic liver disease. RESULTS: Both patients underwent successful conversion to open AAA repair; intraoperative findings confirmed the diagnosis of endotension. CONCLUSIONS: Cirrhosis-induced plasmatic alterations may affect long-term efficacy of EVAR and should be considered when weighing endovascular treatment against open AAA repair in these high-risk patients. Surgical conversion is feasible despite the high procedural risk associated with liver disease.

Association between Serum Selenium Concentrations and Levels of Proinflammatory and Profibrotic Cytokines-Interleukin-6 and Growth Differentiation Factor-15, in Patients with Alcoholic Liver Cirrhosis.

According to some authors, serum selenium levels are strongly associated with the severity of liver diseases, including liver cirrhosis. The aim of this study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines-interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in the serum of 99 patients with alcoholic liver cirrhosis divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower, whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.

Pathophysiology and Management of Alcoholic Liver Disease: Update 2016.

Alcoholic liver disease (ALD) is a leading cause of cirrhosis, liver cancer, and acute and chronic liver failure and as such causes significant morbidity and mortality. While alcohol consumption is slightly decreasing in several European countries, it is rising in others and remains high in many countries around the world. The pathophysiology of ALD is still incompletely understood but relates largely to the direct toxic effects of alcohol and its main intermediate, acetaldehyde. Recently, novel putative mechanisms have been identified in systematic scans covering the entire human genome and raise new hypotheses on previously unknown pathways. The latter also identify host genetic risk factors for significant liver injury, which may help design prognostic risk scores. The diagnosis of ALD is relatively easy with a panel of well-evaluated tests and only rarely requires a liver biopsy. Treatment of ALD is difficult and grounded in abstinence as the pivotal therapeutic goal; once cirrhosis is established, treatment largely resembles that of other etiologies of advanced liver damage. Liver transplantation is a sound option for carefully selected patients with cirrhosis and alcoholic hepatitis because relapse rates are low and prognosis is comparable to other etiologies. Still, many countries are restrictive in allocating donor livers for ALD patients. Overall, few therapeutic options exist for severe ALD. However, there is good evidence of benefit for only corticosteroids in severe alcoholic hepatitis, while most other efforts are of limited efficacy. Considering the immense burden of ALD worldwide, efforts of medical professionals and industry partners to develop targeted therapies in ALF has been disappointingly low.

Disease spectrum of alcoholic liver disease in Beijing 302 Hospital from 2002 to 2013: A large tertiary referral hospital experience from 7422 patients.

Alcohol consumption in China has substantially increased over the last 3 decades and the number of patients with alcoholic liver disease (ALD) is rising at an alarming rate. However, accurate and representative data on time trends in its hospitalization rates are not available. The aim of this study is to assess the current status and burden of ALD in China by analyzing the data from a large tertiary referral hospital, Beijing 302 Hospital.Data were retrospectively recorded from patients diagnosed as ALD in Beijing 302 Hospital from 2002 to 2013. The disease spectrum and biochemical parameters of each patient were collected.The patients with ALD accounted for 3.93% (7422) of all patients (188,902) with liver diseases between 2002 and 2013. The number of patients hospitalized with ALD increased from 110 in 2002 to 1672 in 2013. The ratio of patients hospitalized with ALD to all patients hospitalized with liver diseases was rising almost continuously and increased from 1.68% in 2002 to 4.59% in 2013. Most patients with ALD were male. Age distribution of ALD hospitalization showed that the highest rate was in 40- to 49-year-old group in subjects. Notably, the annual proportion of severe alcoholic hepatitis (SAH) increased 2.43 times from 2002 to 2013. We found the highest levels of mean corpuscular volume, the aspartate aminotransferase/alanine aminotransferase ratio, total bilirubin, international normalized ratio, and alkaline phosphatase in SAH patients, while serum levels of hemoglobin, albumin, and cholinesterase were significantly decreased in SAH group. Among these ALD, the SAH patient population has the worst prognosis. Alcoholic cirrhosis (ALC) is the most common ALD, and annual admissions for ALC increased significantly during the analyzed period.The number of hospitalized patients with ALD and the annual hospitalization rate of ALD were increasing continuously in Beijing 302 Hospital from 2002 to 2013. More attention should be paid to develop population-based effective strategy to control ALD.

Risk for alcoholic liver cirrhosis after an initial hospital contact with alcohol problems: A nationwide prospective cohort study.

Alcoholic liver cirrhosis is usually preceded by many years of heavy drinking, in which cessation in drinking could prevent the disease. Alcohol problems are not consistently managed in hospital patients. We followed all Danish patients with an initial hospital contact with alcohol problems (intoxication, harmful use, or dependence) during 1998-2002 for alcoholic liver cirrhosis development (n = 36,044). In this registry-based cohort, we identified predictors of the absolute risk for alcoholic liver cirrhosis. Incidence rate ratios (IRRs) were estimated as the incidence rate of alcoholic liver cirrhosis in these patients relative to the general population. Age and alcohol diagnosis were significant predictors of alcoholic liver cirrhosis risk in men and women, whereas civil status, education, and type of hospital care were not. In men, the 15-year absolute risk was 0.7% (95% confidence interval [CI], 0.4, 0.8) for 20-29 years, 5.5% (95% CI, 4.9, 6.2) for 30-39 years, 9.8% (95% CI, 9.0, 11) for 40-49 years, 8.9% (95% CI, 8.1, 9.8) for 50-59 years, 6.2% (95% CI, 5.1, 7.2) for 60-69 years, and 2.5% (95% CI, 1.7, 3.3) for 70-84 years. According to alcohol diagnosis in men, the 15-year absolute risk was 2.6% (95% CI, 2.3, 2.9) for intoxication, 7.7% (95% CI, 6.4, 7.9) for harmful use, and 8.8% (95% CI, 8.2, 9.4) for dependence. The IRR for alcoholic liver cirrhosis in the cohort relative to the general population was 11 (95% CI, 10, 12) in men and 18 (95% CI, 15, 21) in women. CONCLUSION: Hospital patients with alcohol problems had a much greater risk for alcoholic liver cirrhosis compared to the general population. The risk was particularly increased for patients 40-59 years and for patients diagnosed with harmful use or dependence. (Hepatology 2017;65:929-937).

Predictors of Mortality in Long-Term Follow-Up of Patients with Terminal Alcoholic Cirrhosis: Is It Time to Accept Remodeled Scores?

OBJECTIVE: To identify the prognostic score that is the best predictor of outcome in patients hospitalized with decompensated liver cirrhosis. MATERIAL AND METHODS: In this prospective study, 126 patients were enrolled and followed up for 29 months. For each patient, prognostic scores were calculated; these included the Child-Turcotte-Pugh score (CTP score), CTP creatinine-modified I score, CTP creatinine-modified II score, Model for End-Stage Liver Disease (MELD score), MELD model for end-stage liver disease sodium-modified score, Integrated MELD score, updated MELD score, United Kingdom MELD, and the MELD score remodeled by serum sodium index (MESO index). Cox regression analysis was used to assess the ability of each of the scores for predicting mortality in patients with alcoholic cirrhosis. Their discriminatory ability was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The updated MELD score had the highest predictive value (3.29) among the tested scores (95% CI: 2.26-4.78). ROC curve analysis demonstrated that the MELD score of 22.50 (AUC = 0.914, 95% CI: 0.849-0.978; p < 0.001) had the best discriminative ability for identifying patients with a high risk of mortality; the next best was the MESO index of 16.00 (AUC = 0.912, 95% CI: 0.847-0.978; p < 0.001). CONCLUSION: The risk of mortality was highest in patients with the highest updated MELD score, and those with MELD scores >22.50 and a MESO index >16.00.

Ectopic variceal bleeding due to portosystemic shunt via dilated mesenteric veins and a varicous left ovarian vein : case report and literature review of ectopic varices.

Ectopic varices are dilated portosystemic venous collaterals located outside of the gastro-esophageal region. Whereas they are common endoscopic findings in patients with portal hypertension, ectopic variceal bleeding is rather rare and accounts for only 1 to 5 % of all variceal bleedings. The rectum and the duodenum are the most common sites for ectopic varices, but they can be present along the whole intestinal tract and neighborhood. At present, there is no consensus well established on diagnostic workup for ectopic variceal bleeding and their therapeutic strategies. Further investigation of large series or randomized-controlled trials is needed because nowadays most of the data available are based on case reports. We report here an unusual case of an ectopic variceal bleeding, presented as an acute small intestine bleeding, due to a portosystemic shunt via dilated mesenteric veins and a varicous left ovarian vein in a patient with alcoholic cirrhosis. The involvement of an ovarian vein in ectopic variceal bleeding is rarely described.

Collateral Development in Thrombosis of the Hepatic Artery After Transplantation.

OBJECTIVES: The authors sought to identify strictures or hepatic artery obstruction with posterior collateral transformation in our series of liver transplantation, treatment, and evolution. The thrombosis or severe hepatic artery stenosis sometimes presents a compensation mechanism, the collateral transformation of the artery. MATERIAL AND METHODS: From April 2002 to December 2011 we collected 18 cases of collateral transformation. We analyzed data regarding the transplantation, diagnosis, treatment, clinical evolution, liver function, and Doppler-ultrasound. RESULTS: The main indication was alcoholic cirrhosis, followed by hepatocellular carcinoma - hepatitis C virus. The mean cold ischemia time was 292.2 minutes mean hot ischemia was 48.8. The anastomosis was performed on the gastroduodenal-splenic patch donor in 14 cases, the celiac trunk in 2 cases, and on grafts to the aorta in another 2. Doppler ultrasound showed 8 cases without complications, 8 with low flows, and 2 cases with alterations of the right hepatic artery. Computed tomographic (CT) angiography was performed in patients with impaired eco-Doppler and found 4 obstructions, 2 cases with kinking, 1 stenosis, and 3 normal cases. Three patients with low flows were re-operated and another re-transplanted. After diagnosis of collateral transformation, all were treated with antiplatelet agents. Two cases of angioplasty were associated. The collaterals were diagnosed 1 month to 44.8 months after transplantation. Five patients died. In the latest data, 10 patients do not have analytical alteration. The Doppler ultrasound shows 7 cases being normal and 6 with flow but low resistances. CONCLUSIONS: In our series, all patients with collateral transformation, except one who was transplanted, maintain good liver function with permeable vessels.

Functional Capacity, Respiratory Muscle Strength, and Oxygen Consumption Predict Mortality in Patients with Cirrhosis.

Introduction. Liver diseases influence musculoskeletal functions and may negatively affect the exercise capacity of patients with cirrhosis. Aim. To test the relationship between the six-minute walk test (6MWT), maximal inspiratory pressure (MIP), and exercise capacity (VO2peak) measures and the survival rate of patients with cirrhosis. Methods. This prospective cohort study consisted of 86 patients diagnosed with cirrhosis with the following aetiology: hepatitis C virus (HCV), hepatitis B virus (HBV), and/or alcoholic cirrhosis (AC). All patients were followed up for three years and submitted to the 6MWT, pressure measurements with a compound gauge, and an exercise test (VO2peak). Results. The survival analysis showed that the individuals who covered a distance shorter than 410 m during the 6MWT had a survival rate of 55% compared with a rate of 97% for the individuals who walked more than 410 m (p = 0.0001). Individuals with MIPs below -70 cmH2O had a survival rate of 62% compared with a rate of 93% for those with MIPs above -70 cmH2O (p = 0.0001). The patients with values below 17 mL/kg had a survival rate of 55% compared with a rate of 94% for those with values above 17 mL/kg (p = 0.0001). Conclusion. The 6MWT distance, MIP, and oxygen consumption are predictors of mortality in patients with cirrhosis.

Alcoholic hepatitis: How far are we and where are we going?

 The burden of alcoholic liver disease continues to be a major public health problem worldwide. The spectrum of disease ranges from fatty liver to cirrhosis and hepatocellular carcinoma. Alcoholic hepatitis (AH) is a type of acute-on-chronic liver failure and the most severe form of alcoholic liver disease. Severe AH carries a poor short-term prognosis and its management is still challenging, with scarce advances in the last decades. Corticosteroids are still the first line of therapy in severe cases. Unfortunately, many patients do not respond and novel targeted therapies are urgently needed. Liver transplantation has shown extraordinary results in non-responders to corticosteroids however; its applicability is very low. This review summarizes the epidemiology, natural history, risk factors and pathogenesis of alcoholic liver disease with special focus on the latest advances in prognostic stratification and therapy of patients with alcoholic hepatitis.

Cardiac manifestations in alcoholic liver disease.

Alcoholic liver disease is the most prevalent cause of progressive liver disease in Europe. Alcoholic cirrhosis occurs in 8%-20% of cases of alcoholic liver disease. It has significant influence on cardiovascular system and haemodynamics through increased heart rate, cardiac output, decreased systemic vascular resistance, arterial pressure and plasma volume expansion. Cirrhotic cardiomyopathy is characterised by systolic and diastolic dysfunction and electrophysiological abnormalities, if no other underlying cardiac disease is present. It is often unmasked only during pharmacological or physiological stress, when compensatory mechanisms of the heart become insufficient to maintain adequate cardiac output. Low-to-moderate intake of alcohol can be cardioprotective. However, heavy drinking is associated with an increased risk of cardiovascular diseases, such as alcoholic cardiomyopathy, arterial hypertension, atrial arrhythmias as well as haemorrhagic and ischaemic stroke. Alcoholic cardiomyopathy is characterised by dilated left ventricle (LV), increased LV mass, normal or reduced LV wall thickness and systolic dysfunction.