Heparin-like Effect Associated With Risk of Bleeding, Sepsis, and Death in Patients With Severe Alcohol-Associated Hepatitis.

BACKGROUND & AIMS: Endogenous heparinoids or heparin-like effects (HLEs) can cause coagulation failure in patients with cirrhosis and sepsis. We performed a prospective study of the association between HLE and bleeding events, sepsis, and outcomes of patients with severe alcohol-associated hepatitis. METHODS: Our final analysis comprised 78 patients with severe alcohol-associated hepatitis (44.3 ± 11.7 years; all male; discriminant function >32) who presented without sepsis at a single center in India from August 2015 through August 2016. Blood samples were collected at days 0, 3, and 7 after presentation and assessed by a global coagulation assay; by SONOCLOT (global and heparinase treated); and in assays for factor VIII, von Willebrand factor, protein C, and antithrombin. Patients were followed for sepsis, bleeding and outcome. The primary outcome was association of HLE with survival 28 days after presentation. RESULTS: HLEs were observed in 32 patients (41%) at day 0, 27 patients (34.6%) at day 3, and 28 patients (35.9%) patients at day 7. Factors associated with mortality at day 0 were factor VIII activity >160% (hazard ratio [HR], 3.1; 95% CI, 1.4-9.5; P = .026), level of protein C <34% (HR, 0.7; 95% CI, 0.5-0.8; P = .037), antithrombin activity <28% (HR, 0.7; 95% CI, 0.3-1.1; P = .008) and international normalized ratio >2.6 (HR, 2.3; 95% CI, 1.8-9.7; P = .010). In multivariate analyses, only factor VIII activity (HR, 2.3; 95% CI, 1.6-7.8; P = .046), international normalized ratio (1.9; 95% CI, 1.2-4.3; P = .039), level of protein C (HR, 0.9; 95% CI, 0.7-1.1; P = .052) and model for end-stage liver disease score (HR, 3.2; 95% CI, 1.9-10.2; P = .042) were associated with mortality. Episodes of epistaxis, hemorrhoid bleeding, hemoperitoneum, and pulmonary hemorrhage occurred in 10.2%, 12.3%, 3.4%, and 4.5% of patients respectively. The presence of HLE at day 0 increased the risk of sepsis (HR, 2.5; 95% CI, 2.2-4.3; P = .002), bleeding (HR, 1.4; 95% CI, 1.2-5.3; P = .004) and death (HR, 1.2; 95% CI, 1.4-1.7; P = .044). CONCLUSIONS: In a prospective study of patients with severe alcohol-associated hepatitis, we associated HLE with coagulation abnormalities, risk of sepsis, and mortality. Clinicaltrials.govNCT02307409.

Clinical and Endoscopic Management of Synchronous Amoebic Liver Abscess and Bleeding Colonic Ulcers.

BACKGROUND: Intestinal amebiasis is endemic in India, with myriad clinical presentations. The liver is the most common extra-intestinal organ to be involved in invasive amoebiasis up to 37% of cases. Synchronous presentation of hepatic and intestinal disease is unusual, and presentation as acute gastrointestinal bleed, or amoeboma even more atypical. GOALS: We aimed to assess the frequency of synchronous hepatic and colonic amebiasis and the efficacy of endoscopic management of colonic bleeding. RESULTS: We screened 52 consecutive patients with amebic liver abscess for synchronous intestinal amoebiasis and report the clinical course of 28 patients (mean age 48.3 years, all male) with amoebic liver abscess (ALA), (mean size, 7.2 ± 2.8 cm) who presented to us with lower gastrointestinal bleed requiring endotherapy. Patients with synchronous infection had higher bilirubin, liver enzymes and prothrombin time. Most needed percutaneous drainage of the liver abscess, and had prolonged hospital stay. They had ileocaecal ulcers with active bleeding; ulcer with adherent clot in 10(50%), and visible vessel in 8(37.5%), or active ooze in 4(12.5%). One patient had an ulcerated rectal mass, which appeared malignant on endoscopy, which was later found to be an amoeboma on microscopy. Hemostasis was achieved with dilute epinephrine injection, one patient required argon plasma coagulation, and 4 subjects required haemoclip placement at the site to control ooze from a visible vessel. CONCLUSION: Synchronous hepatic and intestinal amoebiasis is not uncommon, and often requires endoscopic haemostasis in case of gastrointestinal bleeding due to colonic disease. We report the successful endoscopic control of bleeding amoebic ulcers in all 24 patients.

Left Ventricular Diastolic Dysfunction is Associated with Renal Dysfunction, Poor Survival and Low Health Related Quality of Life in Cirrhosis.

BACKGROUND: The presence of left ventricular diastolic dysfunction (LVDD) in patients with cirrhosis leads to a restriction of activities and a poor health related quality of life (HRQoL), which should be taken into consideration when treating them for liver and cardiac complications. AIMS: The prevalence, complications, predictors of HRQoL and survival in cirrhotic patients with LVDD were studied. METHODS: We report a prospective cohort study of 145 consecutive cirrhotic patients with LVDD who were evaluated for cardiac functional status at enrollment and followed up for hepatic complications, cardiac events, outcome and HRQoL using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) over a period of 2 years. RESULTS: In total, 145 (mean age 61 years, 59% male) patients were included. Seventeen patients died with 10.5%, 22.5% and 40% mortality rates in patients with Grades 1, 2 and 3 LVDD respectively over 24 months. The parameters that were significant for predicting mortality on bivariate analysis were MELD, MELDNa, hepatic venous pressure gradient, MLHFQ, and left ventricular (LV) diastolic function (e' and E/e' ratio), but only MELD, MELDNa and E/e' remained significant on multivariate analysis. The E/e' ratio (8.7 ± 3.3 in survivors vs. 9.1 ± 2.3 in non-survivors) predicted outcome. On univariate analysis, the predictors of poor HRQoL were the Child-Pugh score ≥9.8 (OR 2.6; 95% confidence intervals (CI) 2.3-9.1, P = 0.041), MELD score ≥ 15.7 (OR 2.48; 95% CI 1.4-3.9, P = 0.029), refractory ascites (OR 1.9; 95% CI 1.1-6.1, P = 0.050), and E/e' ratio ≥7.6 (OR 1.9; 95% CI 1.8-7.1, P = 0.036) The presence of Class II/III (P = 0.046) symptoms of heart failure and MLHFQ≥ 45 (P = 0.042) were predictors of mortality at 24 months. CONCLUSION: The grade of LVDD correlates with liver function, clinical events, risk of renal dysfunction and HRQoL. Evaluation of novel therapies which target symptomatic improvement in LVDD, should be done with suitable outcome measures, including HRQoL assessment.

A/H1N1/09 Influenza is Associated With High Mortality in Liver Cirrhosis.

BACKGROUND/AIMS: A/H1N1/09 influenza is associated with a high risk of complications in patients with chronic diseases. In view of patients with cirrhosis being recognized as another high-risk group for influenza morbidity and mortality, we report a cluster of suspected A/H1N1/09 infection in 110 patients admitted to a hepatology intensive care unit. METHODS: The pattern of spread, clinical outcome, and respiratory parameters of A/H1N1/09 of 22 positive cirrhotic patients were compared with those from a control group of 88 patients with chronic liver disease (CLD) with influenza-like pneumonia who tested negative for A/H1N1/09. RESULTS: A/H1N1/09 infection was confirmed in 22 (20%) patients. Eighteen of 22 (81.8%) CLD patients with A/H1N1/09 died of pneumonia and acute respiratory distress syndrome despite timely antiviral treatment. In contrast, only 35 (40%)of the control group of cirrhotic patients without A/H1N1/09 died. On univariate analysis, age > 45 years [OR 1.3; 95% CI 1.1-5.7, (P = 0.054)], encephalopathy > grade 2 [OR 5.4; 95% CI 2.8-12.3, (P = 0.042)], serum bilirubin >8 mg/dl [OR 2.1; 95% CI 1.8-12.3, (P = 0.052)], serum creatinine >1.8 mg/dl [OR 2.8; 95% CI 1.9-9.2, (P = 0.042)], PaO2/FiO2 ratio <200 [OR 4.5; 95% CI 3.1-18.5, (P = 0.026)] and INR > 2.5 [OR 2.2; 95% CI 1.8-6.7, (P = 0.032)] were risk factors for mortality at presentation. However, on multivariate analysis only PaO2/FiO2 ratio <200 and serum creatinine >1.8 mg/dl remained predictors of mortality. Secondary infections, whether fungal or bacterial, were noted to be independent risk factors for disease severity in patients with cirrhosis. CONCLUSION: Early detection and referral, and early antiviral treatment with a strict control of nosocomial spread is essential in patients with cirrhosis during epidemic influenza.