Renal dysfunction increases risk of death for patients with cirrhosis. We investigated whether mortality differs significantly among patients with acute kidney injury (AKI), chronic kidney disease ...(CKD), and both.
We performed a retrospective analysis of all non-status 1 adults on the waitlist for liver transplantation for at least 90 days, collected from the Organ Procurement and Transplantation Network registry from July 1, 2007 through July 1, 2014. We assigned patients to groups of AKI (an increase of ≥0.3 mg/dL or ≥50% in serum creatinine in the last 7 days or fewer than 72 days of hemodialysis), CKD (an estimated glomerular filtration rate <60 ml/min/1.73 m
for 90 days with a final rate ≥30 ml/min/1.73 m
or ≥72 days of hemodialysis), AKI and CKD (meet both definitions), or normal (meet neither definition). We performed competing risk analyses to associate patterns of renal dysfunction with waitlist mortality, accounting for liver transplantation, with renal pattern as a time-dependent covariate. Logistic regression for 6-month mortality determined the added benefit of including renal function pattern in the assessment.
There were 22,680 patients in the cohort; they spent a median 1.6 years (range, 0.7-3.1 years) on the waitlist and a median 5 years (range, 2-9 years) undergoing assessments of renal function. In competing risk analysis, even after adjusting for confounders including final model for end-stage liver disease sodium (MELD-Na) scores, the pattern of renal function was significantly associated with waitlist mortality: AKI and CKD (subhazard ratio SHR, 2.86; 95% CI, 2.65-3.10), AKI (SHR, 2.42; 95% CI 2.22-2.64), CKD (SHR, 1.56; 95% CI, 1.45-1.67) compared with normal. The area under the curve values, based on MELD-Na score at time of placement on the waitlist, were 0.80 with renal function pattern and 0.71 without (P < .001).
In competing risk analysis, even after adjusting for confounders including final MELD-Na score, we found the pattern of renal dysfunction to associate with mortality in patients with cirrhosis. Including information on type of renal dysfunction could improve risk analysis.
The burden of chronic kidney disease (CKD) is rising among patients with cirrhosis, though it is not known what impact this has had on outcomes after liver transplantation (LT). All patients listed ...for LT in the United States between 2002 and 2017 were analyzed, excluding those listed with Model for End‐Stage Liver Disease (MELD) exceptions. The primary outcome was post‐LT mortality. We defined pre‐LT CKD as an estimated glomerular filtration rate <60 mL/minute for 90 days or ≥42 days of hemodialysis. Cox regression determined the association between pre‐LT CKD and post‐LT mortality. Of 78,640 LT candidates, the proportion with CKD among LT recipients increased from 7.8% in 2002 to 14.6% in 2017 (test for trend, P < 0.001). Among the 39,719 LT recipients, pre‐LT CKD was significantly associated with post‐LT mortality (hazard ratio HR, 1.16; P < 0.001) even after adjusting for donor risk index (DRI), age, MELD, etiology, hepatic encephalopathy, simultaneous liver‐kidney transplantation (SLKT), and diabetes. There was no mediating influence of SLKT on the effect of pre‐LT CKD on post‐LT survival (P > 0.05). Therefore, pre‐LT CKD has a deleterious impact on post‐LT outcomes, which is an impact that is not mediated through SLKT. These findings highlight the need for the identification of CKD when preventative measures are possible.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Acute‐on‐chronic liver failure (ACLF) is a feared complication that can develop at any stage of chronic liver disease. The incidence of ACLF is increasing, leading to a significant burden to both the ...affected individual and health care systems. To date, our understanding of ACLF suggests that it may be initiated by precipitants such as systemic infection, alcohol use, or viral hepatitis. The prevalence of these vary significantly by geography and underlying liver disease, and these precipitants have a varying impact on patient prognosis. Herein, we present a review of our current understanding of the precipitants of ACLF, including gaps in current data and opportunities for meaningful intervention and areas of future research.
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•Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis.•Total and conjugated bile acids correlated positively with FGF19 and with disease ...severity (MELD score).•Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis.
The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis.
Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis.
We found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis.
Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans.
Understanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The aim of this document is to provide a concise scientific review of the currently available COVID‐19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein ...approaches. The anticipated use of COVID‐19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID‐19 vaccines are associated with a 94%‐95% vaccine efficacy compared to placebo against COVID‐19. Local site reactions of pain and tenderness were reported in 70%‐90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%‐70% of participants, but these reactions were generally mild and self‐limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID‐19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID‐19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID‐19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about‐aasld/covid‐19‐resources will be updated as additional data become available regarding the safety and efficacy of other COVID‐19 vaccines in development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite ...few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.
Perturbation of bacterial microflora of the gastrointestinal (GI) tract may play an important role in the pathophysiology of some GI disorders. Probiotics have been used as a treatment modality for ...over a century. They may restore normal bacterial microflora and effect the functioning of the GI tract by a variety of mechanisms. Probiotics are not currently regulated and only few randomized controlled trials exist investigating their efficacy in different GI disorders. They are available in a variety of formulations and delivery systems making interpretation and comparison of studies even more difficult. The efficacy of probiotics, either as a single strain or a combination of probiotics, has been tested in antibiotic-associated diarrhea, Clostridium difficile colitis, infectious diarrhea, ulcerative colitis, Crohn’s disease, pouchitis, and irritable bowel syndrome, among other disorders. Results of the studies are reviewed in this article and recommendations for probiotic use in these disorders are made. Although probiotics appear to be generally safe in an outpatient setting, the situation may be different in immunocompromised, hospitalized patients who may be at a greater risk of developing probiotic sepsis. No studies exist addressing the issue of safety specifically. Many questions regarding use of probiotics in GI disorders remain to be answered in future studies, such as most optimal doses, duration of treatment, physiological and immunological effects, efficacy of specific probiotics in specific disease states, and safety in debilitated patients.
Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with ...SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.
In this multicenter study of 90 solid organ transplant recipients diagnosed with COVID‐19 during the first three weeks of the outbreak in New York City, the authors report on the clinical presentation, laboratory abnormalities, risk factors, disease severity, and outcomes.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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