Faculty Bibliography

Decompensated cirrhosis, defined by the overt manifestations of liver failure and portal hypertension (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased morbidity and mortality in chronic liver disease. Acute kidney injury in the setting of cirrhosis (hepatorenal syndrome-acute kidney injury [HRS-AKI]) is a severe and often fatal complication. The goals of treatment of HRS-AKI are to reverse renal failure and prolong survival in these critically ill patients or perhaps to allow the transplant team to complete the pretransplant evaluation and bridge the patient to transplant. Historically, in the United States, standard-of-care treatments for HRS-AKI were chosen by default despite lack of data, off-label use, and suboptimal results. Terlipressin represents the first drug in the United States indicated for the treatment of HRS-AKI. This review provides an up-to-date overview of HRS-AKI, discusses terlipressin and how to incorporate this new treatment into patient care and streamline society guidelines on HRS diagnosis and treatment in a practical way for clinical use, and concludes with a sample order set that highlights the recommendations discussed throughout the supplement.

Although ammonia is involved in the pathophysiology of hepatic encephalopathy (HE), the use of ammonia levels in clinical practice is problematic.^1-3 For example, in a study of 551 patients with overt HE (OHE) receiving lactulose who had ammonia levels tested, only 60% had an increased ammonia level (defined as >72 μmol/L).² Overall, there was no correlation observed between lactulose dose and whether ammonia levels were obtained (ie, presence/absence of increased ammonia level did not guide therapy), or between time to OHE resolution and ammonia levels.² Additionally, there is substantial interlaboratory variability in sample handling and processing, which may affect ammonia measurements.⁴.

BACKGROUND AND AIMS/UNASSIGNED:While the incidence rates of hepatocellular carcinoma (HCC) are increasing, there are limited comprehensive data on demographic-specific incidence and mortality trends in the USA. We aimed to evaluate recent trends in HCC incidence and mortality among different demographic groups in the USA. METHODS/UNASSIGNED:Age-adjusted HCC incidence rates were calculated from the Centers for Disease Control's United States Cancer Statistics database, which combines incidence data on newly diagnosed cancer cases and covers approximately 98% of the population in the USA. Additionally, age-adjusted HCC mortality rates were obtained from the Centers for Disease Control's National Center for Health Statistics database, which offers comprehensive coverage spanning nearly 100% of deaths attributed to HCC in the USA. Rates were stratified by sex, age (older [≥55 years] and younger [<55 years] adults), race and ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian/Pacific Islander, and Non-Hispanic American Indian/Alaska Native), and tumor stage at diagnosis (early and late). Annual and average annual percentage change (AAPC) were calculated using joinpoint regression. A sex-specific pairwise comparison was conducted. RESULTS/UNASSIGNED:=0.01). CONCLUSIONS/UNASSIGNED:Nationwide USA data, covering nearly all HCC cases, show an increasing incidence and mortality over the last two decades. In younger adults, there was a decreasing incidence in men but not in women, due to early-stage tumors. Mortality improved in younger men at a greater rate than in women, especially in Non-Hispanic American Indian/Alaska Natives. Future studies are warranted to identify the risk factors associated with the occurrence and outcomes of HCC in demographic-specific populations, especially younger women.

BACKGROUND:Severe alcohol-associated hepatitis (sAH) is a life-threatening condition with limited treatment options. Although corticosteroids offer some benefit in short-term survival, their use remains controversial due to concerns about increased infection risk. Infections are a major cause of mortality in sAH; however, the reasons for this remain unclear. METHODS:A post hoc analysis of the prospective VTL-308 multicentre trial on 151 patients with sAH was performed. Competing-risk models evaluated predictors of infections, the influence of corticosteroids on infection risk, and the impact of infections on the clinical outcomes up to 1 year of follow-up. RESULTS:Among 151 patients, 90 (59.6%) developed infections. The most frequent were urinary tract (34.4%) and bloodstream (30%) infections. The causative pathogen was isolated in 40 patients, with Enterococcus spp. being the most common (35%). Fungal infections were detected in 19 (12.6%) patients. Corticosteroid use was not associated with increased bacterial (subdistribution-hazard ratio [sHR] =0.74; 95% Confidence Interval (CI): 0.42-1.33; p = 0.32) or fungal infection risk (sHR = 1.74; 95% CI: 0.59-5.15; p = 0.31). Infections significantly increased multi-organ failure (MOF) in the univariate (sHR = 2.31; 95% CI: 1.03-5.17; p = 0.04) and multivariate models (sHR = 2.46; 95% CI: 1.12-5.39; p = 0.03). 37.8% of infected patients died versus 13.1% of non-infected patients. Bacterial infections strongly predicted mortality, with sHRs ranging from 5.22 to 7.78, indicating a five- to eight-fold increased risk of death (p < 0.001). CONCLUSIONS:Infections in sAH are central drivers of MOF and mortality. Our findings highlight infections as an independent risk factor unaffected by corticosteroid use, addressing previous concerns about the safety of this treatment.

BACKGROUND:The aim was to examine rifaximin plus lactulose efficacy in patients with cirrhosis at a risk of developing overt HE who were stratified by important baseline characteristics such as comorbid ascites or diabetes. METHODS:Pooled post hoc subgroup analysis of adults receiving rifaximin 550 mg twice daily plus lactulose or lactulose alone for 6 months in a phase 3 randomized, double-blind trial and a phase 4 open-label trial was conducted. RESULTS AND CONCLUSION/CONCLUSIONS:Rifaximin plus lactulose was more efficacious than lactulose alone for reducing the risk of overt HE recurrence and HE-related hospitalization in adults grouped by select baseline disease characteristics.

Hepatic encephalopathy is a common cause of morbidity and mortality among patients with decompensated liver cirrhosis. In this article, we review the history, mechanism, and evidence for first-line pharmacologic therapies for hepatic encephalopathy including nonabsorbable disaccharides, antibiotics, and electrolyte management. We also review newer, second-line therapies including polyethylene glycol, albumin, branched-chain amino acids, probiotics and fecal microbiota transplant, zinc, and l-ornithine-l-aspartate.