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Nonalcoholic fatty liver disease (NAFLD) is a leading etiology for chronic liver disease with an immense public health impact and affects >25% of the US and global population. Up to 1 in 4 NAFLD patients may have nonalcoholic steatohepatitis (NASH). NASH is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Recent data confirm that HCC represents the fifth most common cancer and is the second leading cause of cancer-related death worldwide, and NAFLD has been identified as a rapidly emerging risk factor for this malignancy. NAFLD-associated liver complications are projected to become the leading indication for liver transplantation in the next decade. Despite evidence that NAFLD-associated HCC may arise in the absence of cirrhosis, is often diagnosed at advanced stages, and is associated with lower receipt of curative therapy and with poorer survival, current society guidelines provide limited guidance/recommendations addressing HCC surveillance in patients with NAFLD outside the context of established cirrhosis. Limited data are presently available to guide clinicians with respect to which patients with NAFLD should undergo HCC surveillance, optimal screening tools, frequency of monitoring, and the influence of coexisting host- and disease-related risk factors. Herein we present an evidence-based review addressing HCC risk in patients with NAFLD and provide Best Practice Advice statements to address key issues in clinical management. [ABSTRACT FROM AUTHOR]

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in American children. Noninvasive means to discriminate between NAFLD and nonalcoholic steatohepatitis (NASH) might diminish the requirement for liver biopsy or predict those at increased risk for progression. Methods: Data obtained prospectively from children (age, 6–17 y) enrolled in the NASH Clinical Research Network were analyzed to identify clinical-pathologic correlates of pediatric NAFLD. All participants underwent liver biopsy within 6 months of clinical data that were reviewed by a central pathology committee. Results: A total of 176 children (mean age, 12.4 y; 77% male) were eligible for inclusion. By using ordinal logistic regression analysis, increasing aspartate aminotransferase (AST) level (odds ratio [OR], 1.017 per U/L; 95% confidence interval [CI], 1.004–1.031) and γ-glutamyltransferase level (OR, 1.016 per U/L; 95% CI, 1.000–1.033) were associated independently with increasing severity of NASH. Increasing AST level (OR, 1.015 per U/L; 95% CI, 1.006–1.024), increasing white blood cell count (OR, 1.22 per 1000/mm3; 95% CI, 1.07–1.38), and decreasing hematocrit (OR, 0.87 per %; 95% CI, 0.79–0.96) were associated independently with increasing severity of fibrosis. Area under the receiver operator characteristic curve for a model with AST and alanine aminotransferase was 0.75 (95% CI, 0.66–0.84) and 0.74 (95% CI, 0.63–0.85) for distinguishing steatosis from more advanced forms of NASH and bridging fibrosis from lesser degrees of fibrosis, respectively. Conclusions: Certain components of routine laboratory tests are predictive of NAFLD pattern and fibrosis severity, but do not have adequate discriminate power to replace liver biopsy in evaluating pediatric NAFLD. [Copyright &y& Elsevier]

This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis. This review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors. Global tests of clot formation, such as rotational thromboelastometry, thromboelastography, sonorheometry, and thrombin generation, may eventually have a role in the evaluation of clotting in patients with cirrhosis, but currently lack validated target levels. In general, clinicians should not routinely correct thrombocytopenia and coagulopathy before low-risk therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation in patients with hepatic synthetic dysfunction–induced coagulation abnormalities. Blood products should be used sparingly because they increase portal pressure and carry a risk of transfusion-associated circulatory overload, transfusion-related acute lung injury, infection transmission, alloimmunization, and/or transfusion reactions. The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: hematocrit ≥25%, platelet count >50,000, and fibrinogen >120 mg/dL. Commonly utilized thresholds for international normalized ratio correction are not supported by evidence. Thrombopoietin agonists are a good alternative to platelet transfusion, but require time (about 10 days) to elevate platelet levels. The large volume of fresh frozen plasma required to reach an arbitrary international normalized ratio target, limitations of the usual target, minimal effect on thrombin generation, and adverse effects on portal pressure limit the utility of this agent significantly. The 4-factor prothrombin complex concentrate contains both pro- and anticoagulant factors that offer an attractive low-volume therapeutic to rebalance a disturbed hemostatic system. However, dosage is, in part, based on international normalized ratio, which is problematic in cirrhosis, and published experience in liver disease is limited. Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity. Both ε-aminocaproic acid and tranexamic acid inhibit clot dissolution. Neither is believed to generate a hypercoagulable state, although both may exacerbate pre-existing thrombi. Desmopressin releases von Willebrand factor as its primary hemostatic mechanism. As this factor is usually elevated in cirrhosis, the agent lacks a sound evidence-based foundation, but may be useful in patients with concomitant renal failure. Systemic heparin infusion is recommended for symptomatic deep vein thrombosis and portal and mesenteric vein thrombosis, but there are unresolved issues regarding monitoring with both the anti-Xa assay and the partial thromboplastin time due to cirrhosis-related antithrombin deficiency (heparin cofactor). Treatment of incidental portal and mesenteric vein thrombosis depends on estimated impact on transplantation surgical complexity vs risks of bleeding and falls. Therapy with low-molecular-weight heparin, vitamin K antagonists, and direct-acting anticoagulants improve portal vein repermeation vs observation alone. Direct-acting anticoagulants, such as the factor Xa and thrombin inhibitors, are relatively safe and effective in stable cirrhotic patients, but are in need of further study in patients with more advanced liver disease. [ABSTRACT FROM AUTHOR]

Background & Aims: Participants at a consensus conference proposed defining cirrhosis-associated acute kidney injury (AKI) based on a >50% increase in serum creatinine level from the stable baseline value in <6 months or an increase of ≥0.3 mg/dL in <48 hours. We performed a prospective study to evaluate the ability of these criteria to predict mortality within 30 days of hospitalization among patients with cirrhosis and infection. Methods: We followed up 337 patients with cirrhosis who were admitted to the hospital with an infection or developed an infection during hospitalization (56% men; 56 ± 10 years of age; Model for End-Stage Liver Disease [MELD] score, 20 ± 8) at 12 centers in North America. We compared data on 30-day mortality, length of stay in the hospital, and organ failure between patients with and without AKI. Results: In total, based on the consensus criteria, 166 patients (49%) developed AKI during hospitalization. Patients who developed AKI were admitted with higher Child–Pugh scores than those who did not develop AKI (11.0 ± 2.1 vs 9.6 ± 2.1; P < .0001) as well as higher MELD scores (23 ± 8 vs 17 ± 7; P < .0001) and lower mean arterial pressure (81 ± 16 vs 85 ± 15 mm Hg; P < .01). Higher percentages of patients with AKI died within 30 days of hospitalization (34% vs 7%), were transferred to the intensive care unit (46% vs 20%), required ventilation (27% vs 6%), or went into shock (31% vs 8%); patients with AKI also had longer stays in the hospital (17.8 ± 19.8 vs 13.3 ± 31.8 days) (all P < .001). Of the AKI episodes, 56% were transient, 28% were persistent, and 16% resulted in dialysis. Mortality was higher among those without renal recovery (80%) compared with partial (40%) or complete recovery (15%) or those who did not develop AKI (7%; P < .0001). Conclusions: Among patients with cirrhosis, 30-day mortality is 10-fold higher among those with irreversible AKI than those without AKI. The consensus definition of AKI accurately predicts 30-day mortality, length of hospital stay, and organ failure. [Copyright &y& Elsevier]