Citations

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) is characterized by multiple organ failure (OF) with high short‐term mortality. There is lack of population‐based data on trends on etiology specific ACLF related burden. National Inpatient Sample (2006‐2014) was queried using ICD‐09 codes for admissions with cirrhosis and ACLF (≥2 extrahepatic OF). Of 1,928,764 admissions for cirrhosis between 2006 and 2014, 112,174 (5.9%) had ACLF (4.5%, 1.2%, and 0.2% with ACLF 1, 2, and 3, respectively). The brain was the most common OF in 11.9%, followed by respiratory failure in 7.7%, cardiac failure in 6.3%, and renal failure in 5.6%. ACLF increased by 24% between 2006 and 2014 with a 63% increase in 179,104 patients with nonalcoholic steatohepatitis (NASH) cirrhosis (3.5% to 5.7%); a 28% increase in patients with 429,306 alcoholic cirrhosis (5.6% to 7.2%); a 25% increase in patients with 1,091,053 with other etiologies (5.2% to 6.5%); and no significant change in 229,301 patients with viral hepatitis (VH) (4.0% to 4.1%). In‐hospital mortality was higher among ACLF patients compared with patients without ACLF (44% versus 4.7%; P < 0.0001). Each NASH‐related ACLF patient compared with other etiologies had a longer mean length of stay (14 versus 12 days), was associated with higher median total charges (US $151,196 versus US $134,597), and had more frequent use of dialysis (45% versus 36%) and longterm care (32% versus 26%; P < 0.0001 for all). Results remained similar in a subgroup analysis after including half of admissions with cryptogenic cirrhosis as NASH. In conclusion, NASH cirrhosis is the most rapidly growing indication for ACLF‐related hospitalization and use of hospital resources. In the setting of improved treatment options for chronic hepatitis, the health care burden of chronic viral‐related liver disease remains stable. Population‐based strategies are needed to reduce the health care burden of cirrhosis, particularly related to NASH.

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.

Sepsis in patients with cirrhosis is associated with high mortality. An impaired immune response accounts for the increased infection risk observed in these patients. Hemodynamic and systemic changes suggestive of sepsis may be observed in patients with cirrhosis in the absence of infection; therefore, diagnosis and treatment of sepsis may be delayed. The optimal management of the critically ill patient with sepsis and cirrhosis has not been well established and is generally extrapolated from consensus guidelines and expert recommendations made for management of patients without cirrhosis with sepsis. Despite the lack of strong evidence, we propose a contemporary pragmatic approach to sepsis management in patients with cirrhosis, including the choice of fluids, vasopressors, and antibiotics.

Background. Liver arteriovenous malformations (AVM) in hereditary hemorrhagic telangiectasia (HHT) can necessitate liver transplantation. There is limited data on HHT patients undergoing liver transplantation (LT) in the United States. Methods. Two sources of data were used: (1) Scientific Registry of Transplant Recipients (SRTR) database (1998-2016) (2) Single center liver transplant database (Mayo Clinic Rochester, MN). The aims of this study were (1) to determine trends in LT for HHT-related liver involvement in the United States using the SRTR database; (2) to identify clinical characteristics, indications, and outcomes for LT in HHT. Results. Thirty-nine HHT patients were listed for LT in the SRTR database from 1998-2016 to 1998-2001 (n = 1); 2002-2005 (n = 4); 2006-2010 (n = 10), and 2011-2016 (n = 24). Twenty-four underwent LT at a median age of 47.5 years (interquartile range, 37.0-58.5 years). Median calculated MELD score at time of LT was 8.0 (interquartile range, 7.0-9.5), and 75% received an exception MELD score. Two status-1 patients died during transplant surgery. Nineteen (86%) patients were alive after a median post-LT follow-up of 48 months, whereas 2 patients were lost to follow-up. Five of the aforementioned HHT patients underwent LT at Mayo Clinic, 4 with high output cardiac failure, and 1 with biliary ischemia. All 5 were alive at the time of last follow-up with good graft function and resolution of heart failure. Conclusions. Outcomes after LT for HHT patients are excellent with 86% survival after a median follow-up of 48 months and resolution of heart failure. LT listing for HHT has increased in substantially in more recent eras.

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long‐term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event‐free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver‐related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, P= not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, P= 0.002), but 5‐year event‐free survival was similar (74% versus 77%, P= NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5‐year event‐free survival was better (91% versus 67%, P< 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5‐year event‐free survival 88% versus 61%, P= 0.005). Conclusion:A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5‐year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.