Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

Background & Aims: Frailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated liver frailty index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality. Methods: Adults without hepatocellular carcinoma who were on the liver transplant waitlist at 9 centers in the United States (n=1044) were evaluated using the LFI; LFI scores of 4.5 or more indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate subhazard ratios (sHR) of waitlist mortality (death or removal from the waitlist). Results: Of study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio, 1.56; 95% CI, 1.15-2.14) or HE (OR, 2.45; 95% CI, 1.80-3.33) than without these features. Higher proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared to patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR, 1.52; 95% CI, 1.14-2.05), HE (sHR, 1.84; 95% CI, 1.38-2.45), and frailty (sHR, 2.38; 95% CI, 1.77-3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR, 1.82; 95% CI, 1.31-2.52)-ascites and HE were not. Conclusions: Frailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be Lai et al.

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Background and aims: Acute on chronic liver failure (ACLF) yields the highest risk of short-term mortality, along the spectrum of cirrhosis. We evaluated whether the rising prevalence of nonalcoholic steatohepatitis (NASH) in the United States is reflected among waitlist registrants with ACLF. Methods: We analyzed the United Network for Organ Sharing (UNOS) registry, years 2005-2017. Patients with ACLF were identified using the EASL-CLIF criteria and categorized into those with NASH, alcoholic liver disease (ALD), and hepatitis C virus (HCV) infection. Statistical analysis included linear regression and Chow's test to determine significance and divergence in trends, and Fine and Grey's competing risks and Cox proportional hazards regression to assess waitlist outcomes. Results: Between 2005 and 2017, waitlist registrants for NASH-ACLF rose 331.6% (p<0.001). ALD-ACLF increased 206.3% (p<0.001), while HCV-ACLF declined 45.2% (p=0.018). This increase in NASH-ACLF occurred across all UNOS regions, rising by 666.7% in region 11. The NASH-ACLF population is aging, and currently 31.5% of the group is age 65 or older. Although NASH-ACLF candidates did not have greater 90-day waitlist mortality (SHR=0.84, 95% CI 0.77-0.92) relative to other etiologies, since 2014, 90-day waitlist mortality has improved for ALD-ACLF (HR=0.78, 95% CI 0.70-0.88) and HCV-ACLF (HR=0.76, 95% CI 0.67-0.85) but not for NASH (HR=0.93, 95% CI 0.81-1.08). Conclusions: NASH is the fastest rising etiology of cirrhosis among transplant registrants with ACLF in the United States. Since 2014, waitlist outcomes have 4 improved for ALD-ACLF and HCV-ACLF, but not for NASH-ACLF. With the aging NASH population, patients with NASH-ACLF may eventually have the highest risk of death on the waiting list.

Management of hepatic encephalopathy (HE) remains challenging from a medical and psychosocial perspective. Members of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recognized 5 key unresolved questions in HE management focused on (i) driving, (ii) ammonia levels in clinical practice, (iii) testing strategies for covert or minimal HE, (iv) therapeutic options, and (v) nutrition and patient-reported outcomes. The consensus document addresses these topical issues with a succinct review of the literature and statements that critically evaluate the current science and practice, laying the groundwork for future investigations.

Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetyl glutamine, which is excreted in urine. This randomized, double-blind, placebo-controlled phase II trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the previous 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days, and safety. GPB, at 6 mL orally twice-daily, significantly reduced the proportion of patients who experienced an HE event (21% versus 36%; P = 0.02), time to first event (hazard ratio [HR] = 0.56; P < 0.05), as well as total events (35 versus 57; P = 0.04), and was associated with fewer HE hospitalizations (13 versus 25; P = 0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P < 0.01), time to first event (HR = 0.29; P < 0.01), and total events (7 versus 31; P < 0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. Conclusion: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167). (Hepatology 2014;59:1073-1083)

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BACKGROUND & AIMS Patients with cirrhosis have 1-month rates of readmission as high as 35%. Early identification of high-risk patients could permit interventions to reduce readmission. The aim of our study was to construct an automated 30-day readmission risk model for cirrhotic patients using electronic medical record (EMR) data available early during hospitalization. METHODS We identified patients with cirrhosis admitted to a large safety-net hospital from January 2008 through December 2009. A multiple logistic regression model for 30-day rehospitalization was developed using medical and socioeconomic factors available within 48 hours of admission and tested on a validation cohort. Discrimination was assessed using receiver operator characteristic curve analysis. RESULTS We identified 836 cirrhotic patients with 1291 unique admission encounters. Rehospitalization occurred within 30 days for 27% of patients. Significant predictors of 30-day readmission included the number of address changes in the prior year (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.05–1.21), number of admissions in the prior year (OR, 1.14; 95% CI, 1.05–1.24), Medicaid insurance (OR, 1.53; 95% CI, 1.10 –2.13), thrombocytopenia (OR, 0.50; 95% CI, 0.35– 0.72), low level of alanine aminotransferase (OR, 2.56; 95% CI, 1.09 – 6.00), anemia (OR, 1.63; 95% CI, 1.17–2.27), hyponatremia (OR, 1.78; 95% CI, 1.14 –2.80), and Model for End-stage Liver Disease score (OR, 1.04; 95% CI, 1.01–1.06). The risk model predicted 30-day readmission, with c-statistics of 0.68 (95% CI, 0.64 – 0.72) and 0.66 (95% CI, 0.59 – 0.73) in the derivation and validation cohorts, respectively. CONCLUSIONS Clinical and social factors available early during admission and extractable from an EMR predicted 30-day readmission in cirrhotic patients with moderate accuracy. Decision support tools that use EMR-automated data are useful for risk stratification of patients with cirrhosis early during hospitalization.