African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models. CONCLUSIONS: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.

Low Utilization of External Beam Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma: An Analysis of the United Network for Organ Sharing Database.

PURPOSE: External beam radiation therapy (EBRT) is a safe and emerging bridging liver-directed therapy (LDT) to liver transplant (LT) for patients with hepatocellular carcinoma (HCC). The prevalence and clinical characteristics of patients receiving EBRT as an LDT for LT have not been evaluated. Our aim was to describe the utilization of EBRT in patients with HCC evaluated for LT in the United States. METHODS AND MATERIALS: We analyzed United Network for Organ Sharing data from October 2013 to June 2020 and identified patients with HCC who applied for model for end-stage liver disease (MELD) exceptions for LT wait list prioritization. The primary outcome was the period prevalence of EBRT. We examined associations between clinical variables and EBRT and fit survival models with EBRT as a time-varying predictor. RESULTS: We identified 18,543 patients with HCC with MELD exception applications. EBRT was used in 658 patients (3.5%) either alone (1.2%) or combined with other LDT (2.3%). Transarterial chemoembolization was the most used LDT (59.3%), followed by thermal ablation (27.9%) and radioembolization (15.2%). EBRT prevalence rose by an average of 12.2% per year (P = .001). Use of EBRT differed by geographic region, ranging from 2% to 8% (P < .001). EBRT and no EBRT groups had similar initial MELD score, portal vein thrombosis, tumor diameter, number of tumors, bilirubin, and α-fetoprotein (P > .05). Median time-to-transplant from wait list registration for EBRT versus no EBRT groups was 10 months (95% confidence interval, 9.4-10.9) versus 11.9 months (95% confidence interval, 11.7-12.2; P < .001). Evaluated as a time-varying predictor, EBRT increased the risk of LT by 30% (sub-hazard ratio, 1.30; P < .001), while the effect of EBRT on the risk of wait list removal due to clinical deterioration or death (sub-hazard ratio, 1.07; P = .489) was nonsignificant. CONCLUSIONS: In the United States, EBRT is rarely used compared with other LDTs and exhibits geographic variation. Low EBRT utilization highlights a gap in the treatment armamentarium for HCC.

Muscle Gain after Transjugular Intrahepatic Portosystemic Shunt Creation: Time Course and Prognostic Implications for Survival in Cirrhosis.

PURPOSE: To examine the association of transjugular intrahepatic portosystemic shunt (TIPS) creation with muscle gains and patient mortality, and to identify the timeframe of these changes. MATERIALS AND METHODS: Patients with cirrhosis undergoing TIPS creation with available abdominal computed tomography before and after TIPS from 2004-2015 were included (n = 76). The primary indications for TIPS included refractory ascites (52.6%) or variceal bleeding (47.4%). Axial truncal muscle area and attenuation were measured at the L4 level using free-hand region of interest technique, and pre- and post-TIPS values were compared. The association of TIPS-related muscle changes with mortality was evaluated using Cox multiple regression. Logistic regression analysis was performed to evaluate associations of baseline muscle area and clinical variables with post-TIPS changes. RESULTS: TIPS creation was associated with significant increases in psoas, paraspinal, and total muscle areas (P < .001, 0.004, and 0.002), and psoas muscle attenuation (P = .022) at a median of 13.5 months after TIPS. Maximal muscle gains occurred within 6 months after TIPS creation (P < .001). Muscle gain at 1-year after TIPS was independently associated with lower mortality (psoas hazard ratio [HR] 0.14, P = .016; paraspinal HR 0.15, P = .016; abdominal HR 0.05, P = .005; core HR 0.06, P = .001; and total HR 0.05, P = .003). Baseline demographic or clinical variables were not associated with muscle gain after TIPS. CONCLUSIONS: TIPS creation was strongly associated with truncal muscle gains and attenuation in patients with cirrhosis. Maximal muscle gain occurred within 6 months after TIPS creation. TIPS-related increased muscle mass was independently associated with lower patient mortality.

Influence of spontaneous splenorenal shunts on clinical outcomes in decompensated cirrhosis and after liver transplantation.

Cirrhosis and portal hypertension can lead to the formation of a spontaneous splenorenal shunt (SSRS) that may divert portal blood flow to the systemic circulation and reduce hepatic perfusion. Our aims were to evaluate SSRSs as an independent prognostic marker for mortality in patients with decompensated cirrhosis and the influence of SSRSs on liver transplantation (LT) outcomes. We retrospectively analyzed adult patients with decompensated cirrhosis undergoing LT evaluation from January 2001 to February 2016 at a large U.S. center. All patients underwent liver cross-sectional imaging within 6 months of evaluation, and images were reviewed by two radiologists. Clinical variables were obtained by electronic health record review. The cohort was followed until death or receipt of LT, and the subset receiving LT was followed for death after LT or graft failure. Survival data were analyzed using multivariable competing risk and Cox proportional-hazards regression models. An SSRS was identified in 173 (23%) of 741 included patients. Patients with an SSRS more often had portal vein thrombosis and less often had ascites (P < 0.01). An SSRS was independently associated with a nonsignificant trend for reduced mortality (adjusted subhazard ratio, 0.81; Gray's test P = 0.08) but had no association with receipt of LT (adjusted subhazard ratio, 1.02; Gray's test P = 0.99). Post-LT outcomes did not differ according to SSRS for either death (hazard ratio, 0.85; log-rank P = 0.71) or graft failure (hazard ratio, 0.71; log-rank P = 0.43). Conclusion: Presence of an SSRS does not predict mortality in patients with decompensated cirrhosis or in LT recipients. (Hepatology Communications 2018;2:437-444).

Close observation versus upfront treatment in hepatocellular carcinoma: are the exception points worth the risk?

INTRODUCTION: To assess the outcomes of immediate LDT versus observation strategies for T1 hepatocellular carcinoma (HCC) with respect to progression beyond Milan and survival. METHOD: T1 HCCs were retrospectively reviewed from a multidisciplinary tumour board database between September 2007 and May 2015. In the observation group, T1 lesions were observed until the tumour grew to meet T2 criteria (=2 cm). The treatment group consisted of T1 lesions treated at diagnosis with liver directed therapy (LDT). Kaplan-Meier plots were constructed for tumour progression beyond Milan and overall survival. RESULTS: 87 patients (observation n=56; LDT n=31) were included in the study. A total of 22% (n=19) of patients progressed beyond Milan with no difference in progression between treatment and observation groups (19% vs 23%, p=0.49). Median time to progression beyond Milan was 16 months. Overall transplantation rate was 22% (observation group n=16; treatment group n=3, p=0.04). Median survival was 55 months with LDT versus 36 months in the observation group (p=0.22). In patients who progressed to T2 (n=60), longer time to T2 progression was a predictor of improved survival (HR=0.94, 95% CI 0.88 to 0.99, p=0.03). CONCLUSIONS: Immediate LDT of T1 lesions was not associated with increased risk of progression beyond Milan criteria when compared with an observation approach. Longer time to T2 progression was associated with increased survival and may be a surrogate for favourable tumour biology.

The Braden Scale, A standard tool for assessing pressure ulcer risk, predicts early outcomes after liver transplantation.

The Braden Scale is a standardized tool to assess pressure ulcer risk that is reported for all hospitalized patients in the United States per requirements of the Center for Medicare and Medicaid Services. Previous data have shown the Braden Scale can predict both frailty and mortality risk in patients with decompensated cirrhosis. Our aim was to evaluate the association of the Braden Scale score with short-term outcomes after liver transplantation (LT). We performed a retrospective cohort study of deceased donor LT recipients at 2 centers and categorized them according to the Braden Scale at hospital admission as low (>18), moderate (16-18), or high risk (<16) for pressure ulcer. We created logistic and Poisson multiple regression models to evaluate the association of Braden Scale category with in-hospital and 90-day mortality, length of stay (LOS), nonambulatory status at discharge, and discharge to a rehabilitation facility. Of 341 patients studied, 213 (62.5%) were low risk, 59 (17.3%) were moderate risk, and 69 (20.2%) were high risk. Moderate- and high-risk patients had a greater likelihood for prolonged LOS, nonambulatory status, and discharge to a rehabilitation facility, as compared with low-risk patients. High-risk patients additionally had increased risk for in-hospital and 90-day mortality after LT. Multiple regression modeling demonstrated that high-risk Braden Scale score was associated with prolonged LOS (IRR, 1.56; 95% confidence interval [CI], 1.47-1.65), nonambulatory status at discharge (odds ratio [OR], 4.15; 95% CI, 1.77-9.71), and discharge to a rehabilitation facility (OR, 5.51; 95% CI, 2.57-11.80). In conclusion, the Braden Scale, which is currently assessed in all hospitalized patients in the United States, independently predicted early disability-related outcomes and greater LOS after LT. Liver Transplantation 23 1153-1160 2017 AASLD.

Bleeding 'downhill' esophageal varices associated with benign superior vena cava obstruction: case report and literature review.

BACKGROUND: Proximal or 'downhill' esophageal varices are a rare cause of upper gastrointestinal hemorrhage. Unlike the much more common distal esophageal varices, which are most commonly a result of portal hypertension, downhill esophageal varices result from vascular obstruction of the superior vena cava (SVC). While SVC obstruction is most commonly secondary to malignant causes, our review of the literature suggests that benign causes of SVC obstruction are the most common cause actual bleeding from downhill varices. Given the alternative pathophysiology of downhill varices, they require a unique approach to management. Variceal band ligation may be used to temporize acute variceal bleeding, and should be applied on the proximal end of the varix. Relief of the underlying SVC obstruction is the cornerstone of definitive treatment of downhill varices. CASE PRESENTATION: A young woman with a benign superior vena cava stenosis due to a tunneled internal jugular vein dialysis catheter presented with hematemesis and melena. Urgent upper endoscopy revealed multiple 'downhill' esophageal varices with stigmata of recent hemorrhage. As there was no active bleeding, no endoscopic intervention was performed. CT angiography demonstrated stenosis of the SVC surrounding the distal tip of her indwelling hemodialysis catheter. The patient underwent balloon angioplasty of the stenotic SVC segment with resolution of her bleeding and clinical stabilization. CONCLUSION: Downhill esophageal varices are a distinct entity from the more common distal esophageal varices. Endoscopic therapies have a role in temporizing active variceal bleeding, but relief of the underlying SVC obstruction is the cornerstone of treatment and should be pursued as rapidly as possible. It is unknown why benign, as opposed to malignant, causes of SVC obstruction result in bleeding from downhill varices at such a high rate, despite being a less common etiology of SVC obstruction.

Higher Mortality and Survival Benefit in Obese Patients Awaiting Liver Transplantation.

BACKGROUND: Over 85% of US centers adhere to practice guidelines that consider morbid obesity to be a contraindication to liver transplantation (LT). The relationship of morbid obesity with LT outcomes and survival benefit in the current era is unknown. METHODS: We investigated the association of body mass index with waitlist and post-LT outcomes, and survival benefit, using the United Network for Organ Sharing registry. We categorized body mass index as follows: 18.5 to 29.9 kg/m, normal/overweight; 30 to 34.9 kg/m, obese; 35 to 39.9 kg/m, severely obese; and ≥40 kg/m, morbidly obese, and evaluated waitlist outcomes using competing risk regression and post-LT outcomes and survival benefit using Cox regression. RESULTS: 3.9% of 80 221 waitlisted and 3.5% of 38 177 transplanted patients were morbidly obese. Waitlist mortality was higher for morbidly obese than normal/overweight patients (subdistribution hazard ratio, 1.16; 95% confidence interval [CI]:1.08-1.26), but post-LT mortality and graft failure were comparable (hazard ratio [HR], 1.01; 95% CI, 0.86-1.19; and HR, 1.15; 95% CI, 0.95-1.40). Morbidly obese patients also benefited more from LT (88% mortality reduction vs 80% for normal/overweight). Morbid obesity predicted higher post-LT mortality before 2007 (HR, 1.18; 95% CI, 1.04-1.34), but not afterward (HR, 0.98; 95% CI, 0.81-1.18). CONCLUSIONS: Morbid obesity is associated with higher mortality on the LT waitlist, but no longer predicts inferior outcomes after LT. Morbidly obese patients should be considered potential candidates for LT.

Waiting time predicts survival after liver transplantation for hepatocellular carcinoma: a cohort study using the United Network for Organ Sharing registry.

Recipients of liver transplantation (LT) for hepatocellular carcinoma (HCC) have an 8% to 20% risk of HCC recurrence. Single-center studies suggest that a period of waiting after HCC therapy may facilitate the selection of patients at low risk for post-LT HCC recurrence and mortality. We evaluated whether a longer waiting time after Model for End-Stage Liver Disease (MELD) prioritization for HCC predicts longer post-LT survival. From the United Network for Organ Sharing registry, we selected 2 groups registered for LT between March 2005 and March 2009: (1) HCC patients receiving MELD prioritization and (2) non-HCC patients. Patients were stratified by their MELD status at LT (a marker of time on the wait list after HCC MELD prioritization) and were followed from LT until death or censoring through October 2012. By comparing post-LT survival to intention-to-treat (ITT) survival from registration, we assessed predictors of post-LT survival and estimated the benefit of LT. The median MELD scores at LT were 22 (HCC) and 24 (non-HCC). A higher MELD score at LT was independently associated with lower post-LT mortality in the HCC group [hazard ratio (HR) = 0.84, 95% confidence interval (CI) = 0.73-0.98] and higher post-LT mortality in the non-HCC group (HR = 1.20, 95% CI = 1.15-1.25). Compared with the HCC group, the non-HCC group had lower post-LT mortality [relative risk (RR) = 0.85, log-rank P < 0.01] but higher ITT mortality (RR = 1.25, log-rank P < 0.01) because of a 33 percentage point lower probability of undergoing LT. In conclusion, a longer waiting time before LT for HCC predicted longer post-LT survival in a national transplant registry. Delaying LT for HCC may reduce disparities in ITT survival and access to LT among different indications and thereby improve system utility and organ allocation equity for the overall pool of LT candidates.

Portal Biliopathy Causing Recurrent Biliary Obstruction and Hemobilia.

A 63-year-old man with extrahepatic portal vein thrombosis presented with biliary obstruction and hemobilia after a liver biopsy. Balloon sweep of the common bile duct removed clotted blood, and cholangiogram showed a common bile duct narrowing, treated with biliary stenting. A percutaneous biliary catheter was later required for recurrent biliary obstruction and hemobilia, and repeat cholangiogram confirmed portal biliopathy-a large peri-biliary varix was compressing the common bile duct, causing biliary obstruction and intermittent portal hypertensive hemobilia. A transjugular intrahepatic portosystemic shunt was inserted, followed by embolization of the peri-biliary varix. Delayed diagnosis of portal biliopathy may lead to significant patient morbidity.

Guideline adherence and outcomes in esophageal variceal hemorrhage: comparison of tertiary care and non-tertiary care settings.

BACKGROUND: Implementation of consensus guidelines for esophageal variceal hemorrhage yields improved outcomes. We evaluated guideline adherence and outcomes after variceal hemorrhage at a university hospital (UH) and a staff-model health maintenance organization (HMO). STUDY: Factors associated with short-term bleeding, infection, and death were retrospectively identified in UH (n=160) and HMO (n=123) patients with esophageal variceal hemorrhage from January 2000 to December 2006. A second analysis of factors associated with long-term rebleeding was conducted in patients who survived ≥14 days without rebleeding. RESULTS: UH patients were younger, with more severe liver disease and overall illness (P<0.01). UH patients more often received vasoactive agents and prophylactic antibiotics (P<0.01), however the rate of endoscopic therapy did not differ. Infections at 14-days were similar (18.2% vs. 13.0%, P=0.25), but UH patients had greater in-hospital rebleeding (16.4% vs. 5.7%, P<0.01) and mortality (15.2% vs. 4.1%, P<0.01). Poor liver function and overall illness predicted infection, rebleeding, and death (adjusted odds ratio 2.75 to 13.39). Long-term rebleeding occurred in 36.1% of UH patients and 25.9% of HMO patients. Secondary prophylaxis reduced late rebleeding (hazard ratio 0.37 to 0.41). Poor liver function did not predict late rebleeding. Adherence to secondary prophylaxis was greater at the HMO (P<0.05), but late rebleeding did not differ (36% vs. 26%, P=0.13). CONCLUSIONS: Irrespective of practice setting, poor liver function and critical illness predicted short-term bleeding, infection, and death after esophageal variceal hemorrhage, and secondary prophylaxis prevented long-term rebleeding. Differing guideline adherence did not influence outcomes between tertiary care and non-tertiary care centers.

Subtle hepatocellular carcinoma: a persisting role for alpha-fetoprotein monitoring in high-risk patients with cirrhosis.

Hepatocellular carcinoma (HCC) is a common, aggressive malignancy that usually develops in a background of liver cirrhosis. Practice guidelines recommend screening of cirrhotic patients with ultrasound and more detailed imaging (computed tomography or magnetic resonance imaging) if abnormalities are detected. The utility of alpha-fetoprotein levels in HCC surveillance is controversial. Although HCC risk differs by etiology of cirrhosis, screening and surveillance guidelines are uniform after cirrhosis is established. We report a case of rapidly progressive HCC occurring in a cirrhotic patient with multiple unique risk factors for neoplasia, detected by a rising alpha-fetoprotein level without imaging features of liver cancer.

Epidemiology of noncardia gastric adenocarcinoma in the United States.

OBJECTIVES: Adenocarcinomas of the cardia (International Classification of Diseases (ICD)-9 code 151.0) and stomach (ICD-9 codes 151.1-151.9) are frequently grouped together in epidemiologic statistics, but are clearly distinct diseases. The objective of this study was to describe the current epidemiology of noncardia gastric cancer (noncardia gastric adenocarcinoma (NCGA)) in the United States. METHODS: Rates of NCGA in the United States from 1997 to 2008 were analyzed in three national databases: the Surveillance, Epidemiology, and End Results registry was used for incidence, the Healthcare Costs and Utilization Project for hospitalizations, and the Compressed Mortality File for mortality. Population-based rates were calculated and age-adjusted to the US 2000 population using direct standardization. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated and adjusted for confounders with the Mantel-Haenszel method. RESULTS: Annually, NCGA was associated with 18,873 incident cases, 17,284 hospitalizations for principal discharge diagnoses, 31,354 hospitalizations for all-listed diagnoses, and 11,562 deaths. Incidence was greater in men (OR=1.56, CI=1.53-1.59) and non-White races (OR=2.38, 2.33-2.43). Hospitalization was more common in men (1.82, 1.81-1.83) and non-White races (2.13, 2.10-2.15). Mortality was more common in men (1.83, 1.81-1.86) and non-White races (2.23, 2.20-2.26). NCGA rates showed a marked age-dependent rise (P<0.001). Hospitalization and mortality were greatest in the Northeast region of the United States (P<0.001). CONCLUSIONS: Epidemiologic patterns of NCGA were congruent in three national databases. Older age, male gender, non-White race, and residence in the Northeast region were associated with increased risk. These patterns may reflect the underlying variations in Helicobacter pylori, lifestyle, and environmental exposures.

Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, antipyretic, and antiinflammatory properties, and aspirin is increasingly employed in the primary and secondary prevention of cardiovascular disease and ischemic stroke. Despite undisputed therapeutic efficacy for these indications, all NSAIDs impart a considerable risk of peptic ulcer disease and upper gastrointestinal hemorrhage. A growing body of evidence supports an association between non-aspirin NSAIDs and acute coronary syndromes, and an expanding understanding of the gastroduodenal effects of aspirin, COX-2 selective agents, clopidogrel, and Helicobacter pylori synergism fuel controversies in NSAID use. In this review, we discuss risk stratification of patients taking NSAIDs and the appropriate application of proven gastro-protective strategies to decrease the incidence of gastrointestinal hemorrhage based upon an individualized assessment of risk for potential toxicities. Prevention of NSAID-related gastropathy is an important clinical issue, and therapeutic strategies for both the primary and secondary prevention of adverse events are continually evolving.