García–Tsao, Guadalupe

Disorders of the mesenteric, portal, and hepatic veins and mesenteric and hepatic arteries have important clinical consequences and may lead to acute liver failure, chronic liver disease, noncirrhotic portal hypertension, cirrhosis, and hepatocellular carcinoma. Although literature in the field of vascular liver disorders is scant, these disorders are common in clinical practice, and general practitioners, gastroenterologists, and hepatologists may benefit from expert guidance and recommendations for management of these conditions. These guidelines represent the official practice recommendations of the American College of Gastroenterology. Key concept statements based on author expert opinion and review of literature and specific recommendations based on PICO/GRADE analysis have been developed to aid in the management of vascular liver disorders. These recommendations and guidelines should be tailored to individual patients and circumstances in routine clinical practice.

OBJECTIVES: Nosocomial infections (NIs) can be a major cause of morbidity and mortality in cirrhosis. This study aims to define the determinants of NI development and its impact on 30-day outcomes among hospitalized patients with cirrhosis. METHODS: North American Consortium for the Study of End-Stage Liver Disease enrolled patients with cirrhosis who were admitted nonelectively. Admission variables and 30-day outcomes were compared between patients with and without NI. These were also compared based on whether there was an isolated admission infection, NI, or both. Models were created for NI development using admission variables and for 30-day mortality. RESULTS: The study included 2,864 patients; of which, 15% (n = 436) developed NI. When comparing NI vs no NI, 1,866 patients were found to be infection free, whereas 562 had admission infections only, 228 had only NI, and 208 had both infections. At admission, patients with NI were more likely to be infected and have advanced cirrhosis. NIs were associated with higher rates of acute-on-chronic liver failure, death, and transplant regardless of admission infections. Patients with NI had higher respiratory infection, urinary tract infection, Clostridium difficile infection, fungal infections, and infection with vancomycin-resistant enterococci compared with patients without NI. Risk factors for NIs were admission infections, model for end-stage liver disease (MELD) > 20, systemic inflammatory response syndrome criteria, proton pump inhibitor, rifaximin, and lactulose use, but the regression model (sensitivity, 0.67; specificity, 0.63) was not robust. Age, alcohol etiology, admission MELD score, lactulose use, acute-on-chronic liver failure, acute kidney injury, intensive care unit, and NI increased the risk of death, whereas rifaximin decreased the risk of death. DISCUSSION: NIs are prevalent in hospitalized patients with cirrhosis and are associated with poor outcomes. Although higher MELD scores and systemic inflammatory response syndrome are associated with NI, all hospitalized patients with cirrhosis require vigilance and preventive strategies.

We hypothesize that the prevalence of chronic kidney disease (CKD) among patients with cirrhosis has increased due to the increased prevalence of CKD‐associated comorbidities, such as diabetes. We aimed to assess the characteristics of hospitalized patients with cirrhosis with CKD and its impact on renal and patient outcomes. The North American Consortium for the Study of End‐Stage Liver Disease (NACSELD) prospectively enrolled nonelectively admitted patients with cirrhosis and collected data on demographics, laboratory results, in‐hospital clinical course, and postdischarge 3‐month outcomes. CKD positive (CKD+) patients, defined as having an estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease–4 variable formula) of ≤60 mL/minute for >3 months, were compared with chronic kidney disease negative (CKD–) patients for development of organ failures, hospital course, and survival. There were 1099 CKD+ patients (46.8% of 2346 enrolled patients) who had significantly higher serum creatinine (2.21 ± 1.33 versus 0.83 ± 0.21 mg/dL in the CKD– group) on admission, higher prevalence of nonalcoholic steatohepatitis cirrhosis etiology, diabetes, refractory ascites, and hospital admissions in the previous 6 months compared with the CKD– group (all P < 0.001). Propensity matching (n = 922 in each group) by Child‐Pugh scores (9.78 ± 2.05 versus 9.74 ± 2.04, P = 0.70) showed that CKD+ patients had significantly higher rates of superimposed acute kidney injury (AKI; 68% versus 21%; P < 0.001) and eventual need for dialysis (11% versus 2%; P < 0.001) than CKD– patients. CKD+ patients also had more cases of acute‐on‐chronic liver failure as defined by the NACSELD group, which was associated with reduced 30‐ and 90‐day overall survival ( P < 0.001 for both). A 10 mL/minute drop in eGFR was associated with a 13.1% increase in the risk of 30‐day mortality. In conclusion, patients with CKD should be treated as a high‐risk group among hospitalized patients with cirrhosis due to their poor survival, and they should be monitored carefully for the development of superimposed AKI.

Acute‐on‐chronic liver failure (ACLF) characterized with ≥2 extrahepatic organ failures in cirrhosis carries a high mortality. Outcomes of patients listed for liver transplantation (LT) after ACLF and after LT are largely unknown. The North American Consortium for the Study of End‐Stage Liver Disease prospectively enrolled 2793 nonelectively hospitalized patients with cirrhosis; 768 were listed for LT. Within 3 months, 265 (35%) received a LT, 395 remained alive without LT, and 108 died/delisted. Compared with nonlisted patients, those listed were younger and more often had ACLF, acute kidney injury, and a higher admission Model for End‐Stage Liver Disease (MELD) score. ACLF was most common in patients who died/delisted, followed by those alive with and without LT respectively, (30%, 22%, and 7%, respectively; P < 0.001). At LT, median MELD was 27.9% and 70% were inpatients; median time from hospitalization to LT was 26 days. Post‐LT survival at 6 months was unchanged between those with and without ACLF (93% each at 6 months). There was no difference in 3‐ and 6‐month mean post‐LT creatinine in those with and without ACLF, despite those with ACLF having a higher mean pre‐LT creatinine and a higher rate of perioperative dialysis (61%). In conclusion, patients with and without ACLF had similar survival after transplant with excellent renal recovery in both groups.

OBJECTIVES: Antibiotic prophylaxis is recommended for prevention of the first episode of spontaneous bacterial peritonitis (SBP; primary prophylaxis 1°) and subsequent episodes (secondary prophylaxis 2°). We aimed to compare outcomes in cirrhotic inpatients on 1° vs 2° SBP prophylaxis. METHODS: Data from North American Consortium for the Study of End-Stage Liver Disease were evaluated for cirrhosis details, reasons for admission/medications, inpatient course recorded, and outcomes over 90 days. Outcomes (intensive care units, acute kidney injury, inpatient/90-day mortality) were compared between the 2 groups after propensity-matching on admission model for end-stage liver disease (MELD) score and serum albumin. RESULTS: Among the 2,731 patients enrolled, 305 were on 1° and 187 on 2° SBP prophylaxis. After propensity-matching, 154 patients remained in each group. Patients on 1° prophylaxis were more likely to have admission systemic inflammatory response syndrome ( P = 0.02), with higher intensive care unit admissions (31% vs 21%; P = 0.05) and inpatient mortality (19% vs 9%; P = 0.01) than the 2° prophylaxis group. Patients on 2° prophylaxis had higher total (22% vs 10%; P = 0004), readmission (16% vs 9%; P = 0.03), and nosocomial (6% vs 0.5%; P = 0.01) SBP rates with predominant Gram-negative organisms compared to 1° prophylaxis patients. At 90 days, 1° prophylaxis patients had a higher mortality (35% vs 22%; P = 0.02) and acute kidney injury incidence (48% vs 30%; P = 0.04) compared to 2° prophylaxis patients. DISCUSSION: In this inpatient cirrhosis study, despite prophylaxis, a high proportion of patients developed SBP, which was associated with mortality. Cirrhotic inpatients on 1° prophylaxis had worse outcomes than those on 2° prophylaxis when propensity-matched for the MELD score and serum albumin during the index admission and 90-day follow-up.

Portal hypertension (PH) is the main driver of cirrhosis decompensation, the main determinant of death in patients with cirrhosis. PH results initially from increased intrahepatic vascular resistance. Subsequently, increased inflow from splanchnic vasodilation and increased cardiac output lead to a further increase in portal pressure (PP). Reducing PP in cirrhosis results in better outcomes. Removing the cause of cirrhosis might improve PP. However, this is a slow process and patients may continue to be at risk of decompensation. Additionally, for some chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD), etiological treatments are not yet available. Therefore, there is a need to develop better therapies specifically aimed at reducing PP. For over 35 years, the mainstay of such therapy has been the use of nonselective beta‐blockers (NSBBs) that act by reducing portal venous inflow. Recently, many drugs (mainly targeting intrahepatic mechanisms) have shown promise in preclinical and early clinical studies and may act alone or synergistically with NSBBs in reducing PP in cirrhosis. The objective of this position paper is to propose a novel framework for the design of clinical trials (phase 1, 2, and 3) in patients with cirrhosis and PH and to prioritize targets and pharmacological therapies in this setting. We have focused the discussion on patients with compensated cirrhosis. The paper summarizes discussions held at The American Association for the Study of Liver Diseases (AASLD) Industry Colloquium in January 2018, with the participation of clinical and translational investigators, regulatory professionals, and industry partners.

The North American Consortium for the Study of End‐Stage Liver Disease's definition of acute‐on‐chronic liver failure (NACSELD‐ACLF) as two or more extrahepatic organ failures has been proposed as a simple bedside tool to assess the risk of mortality in hospitalized patients with cirrhosis. We validated the NACSELD‐ACLF's ability to predict 30‐day survival (defined as in‐hospital death or hospice discharge) in a separate multicenter prospectively enrolled cohort of both infected and uninfected hospitalized patients with cirrhosis. We used the NACSELD database of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 2,675). The cohort was randomly split 60%/40% into training (n = 1,605) and testing (n = 1,070) groups. Organ failures assessed were (1) shock, (2) hepatic encephalopathy (grade III/IV), (3) renal (need for dialysis), and (4) respiratory (mechanical ventilation). Patients were most commonly Caucasian (79%) men (62%) with a mean age of 57 years and a diagnosis of alcohol‐induced cirrhosis (45%), and 1,079 patients had an infection during hospitalization. The mean Model for End‐Stage Liver Disease score was 19, and the median Child score was 10. No demographic differences were present between the two split groups. Multivariable modeling revealed that the NACSELD‐ACLF score, as determined by number of organ failures, was the strongest predictor of decreased survival after controlling for admission age, white blood cell count, serum albumin, Model for End‐Stage Liver Disease score, and presence of infection. The c‐statistics were 0.8073 for the training set and 0.8532 for the validation set. Conclusion: Although infection status remains an important predictor of death, NACSELD‐ACLF was independently validated in a separate large multinational prospective cohort as a simple, reliable bedside tool to predict 30‐day survival in both infected and uninfected patients hospitalized with a diagnosis of cirrhosis. (H epatology 2018;67:2367‐2374).