Background Patients with acute‐on‐chronic liver failure (ACLF) have coagulation failure in the setting of systemic inflammatory syndrome (SIRS), sepsis and extra‐hepatic organ failures. Methods Consecutive ACLF patients without sepsis at baseline were assessed at days 0, 3 and 7 with thromboelastography (TEG) and specific assays (Factor VIII, von Willebrand factor [vWF], protein C and antithrombin III [ATIII]) and followed for development of sepsis, bleeding and outcome. Results Of 243 patients, 114 (63% ethanol related; mean age 44.3 ± 11.7 years; 90% male) were recruited. SIRS was noted in 39 (34.2%), 45 (39.5%) and 46 (40%) patients at days 0, 3 and 7 and sepsis in 28 (24%) and 52 (56.1%) patients at days 3 and 7 respectively. The 28‐ and 90‐day survivals were 62% and 51% respectively. A hypocoagulable TEG at baseline was a predictor of bleeding (hazard ratio [HR] 2.1; CI 1.6‐4.9; P = 0.050) and mortality (HR 1.9; CI 1.3‐7.9; P = 0.043). ACLF patients had increased Factor VIII, vWF, tissue factor levels and tissue plasminogen activator (tPA) activity with reduced protein C and ATIII. Coagulation parameters like Coagulation Index (HR 2.1; CI 1.1‐4.5; P = 0.044),clot lysis (HR 3.2; CI 1.9‐3.4; P = 0.033), low protein C < 30% (HR 2.1; CI 1.5‐2.8; P = 0.017), ATIII (HR 1.4; CI 1.7‐3.1; P = 0.052) and tPA (HR 1.5; CI 1.1‐2.4; P = 0.052) were predictors of mortality at day 28. Protein C activity <30% (HR 1.3; CI 1.0‐2.9; P = 0.042) and tPA >20 ng/mL (HR 1.2; CI 1.1‐2.1; P = 0.040) predicted mortality when adjusted for age, gender and baseline MELD. Conclusions Dynamic coagulation derangements, measured by TEG, determine the likelihood of bleeding and mortality in ACLF.

Background and Aim Echocardiographic assessment of the inferior vena cava diameter (IVCD) and collapsibility index (IVCCI) is a noninvasive estimate of intravascular volume status (IVS) but requires validation for cirrhosis. We evaluated IVC dynamics in cirrhosis and correlated it with conventional tools such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and right atrial pressure (RAP). Methods A total of 673 consecutive cirrhotic patients were screened by echocardiography, and 125 patients underwent right heart catheterization with recording of hepatic venous pressure gradient (HVPG), RAP, pulmonary artery (PA) pressure, and PCWP. CVP data were available for 80 (64%) patients, and finally, 76 patients (84% male, 50% ethanol related, mean age 52.1 years, 57.8% with ascites) with complete data were enrolled. Results The mean CVP measured was 12.8 ± 4.8 mmHg, and IVCCI was 29.5 ± 10.9%. The IVCD ranged from 0.97 to 2.26 cm and from 0.76 to 1.84 cm during expiration and inspiration, respectively, with a mean of 1.8 ± 0.9 cm. The mean IVCD correlated with RAP ( r = 0.633, P = 0.043) but not with HVPG ( r = 0.344, P = 0.755), PCWP ( r = 0.562, P = 0.072), or PA pressure ( r = 0.563, P = 0.588). A negative linear correlation was observed between the CVP and the IVCCI ( r = −0.827, P = 0.023) in all patients and substratified for those with ( r = −0.748, P = 0.039) and without ascites ( r = −0.761, P = 0.047). A positive correlation was observed between CVP and IVCD max ( r = 0.671, P = 0.037) and IVCD min ( r = 0.612, P = 0.040). Conclusions IVCD and collapsibility index provides noninvasive IVS assessment, independent of HVPG or ascites, with the potential for calculating fluid requirements in cirrhosis.

Background: Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis. Patients and Methods: THR was defined as heart rate reduction to 55 to 65 beats per minute. Of 260 patients with cirrhosis, 189 (72%) with LVDD were randomized to THR [group (Gr.)A; n=94; carvedilol±ivabradine)] or standard care (Gr.B; n=95; no β-blockers) and followed for 12 months. Results: In Gr.A, THR was achieved at 4 weeks in 88 (93%) patients (responders, R): 48 (61.5%) with carvedilol alone and 40 (86.9%) of 46 patients with additional ivabradine. In Gr.A, LVDD reversed in 16 (20.5%) and improved from grade 2 to 1 in 34 (35.4%)], whereas in Gr.B, it progressed from grade 1 to 2 in 10 (10.5%) patients. At 12 months, 21 (11.1%) patients died, 6 (14%) in Gr.A and 15 (18%) in Gr.B (P=0.240), but no mortality was seen in those who had persistent THR at 1 year (n=78; P=0.000). In multivariate analysis, model for end-stage liver disease [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.22-2.75; P=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28; 95% CI, 1.23-2.42; P=0.048) predicted 1-year mortality. Nonresponders had an increased mortality risk (HR, 1.3; 95% CI, 1.2-1.8; P=0.046) independent of age, gender, and baseline model for end-stage liver disease. Levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone were reduced (P<0.01) in responders. More patients in Gr.B developed acute kidney injury (odds ratio, 4.2; 95% CI, 2.8-10.5; P=0.027) and encephalopathy (odds ratio, 6.6; 95% CI, 1.9-9.7; P=0.040). Conclusions: Ivabradine combined with carvedilol improves LVDD, achieves THR more often and reduces risk of encephalopathy, acute kidney injury with improved survival in patients with cirrhosis.

Systemic amyloidosis of amyloid light chain associated protein (AL), also called primary amyloidosis, frequently involves the liver, but rarely causes clinically apparent liver disease. The more common presentation is with acute renal failure. Hepatomegaly and mild elevation of alkaline phosphatase are the most common clinical and biochemical findings, respectively. We report a case of systemic amyloidosis of AL that clinically presented as acute-on-chronic liver failure and resulted in a fatal clinical course in a 56-year-old man.

Sister Mary Joseph nodules represent metastatic cancer of the umbilicus. More than half of these cases are attributable to gastrointestinal malignancies including gastric, colonic, and pancreatic cancer. In addition, gynecologic (ovarian, uterine cancer), unknown primary tumors, and, rarely, bladder or respiratory malignancies may cause umbilical metastasis. We report the case of a Sister Mary Joseph nodule originating from a hilar cholangiocarcinoma. Umbilical nodules should prompt clinical evaluation, as these tumors are usually associated with poor prognosis.