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Background & AimLiver fibrosis is associated with poor patient-reported outcomes (PROs), but the impact of steatosis is unknown. We aimed to evaluate the impact of steatosis on PROs independent of liver fibrosis.MethodsWe evaluated the impact of steatosis, measured by Controlled-Attenuation Parameter (CAP) on transient elastography, and PROs using the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We used univariate and multivariate logistic and ordinal regression to evaluate categorical CAP score with PROs measuring physical disability, general health and depression.ResultsOf 4,509 participants included, 38% had severe steatosis (> 280 dB/m). Those with severe steatosis were older and more likely to be male (56% vs. 43% and 51%). On univariate analysis, severe steatosis was associated with more difficulty walking (P = 0.01), dressing (P = 0.005), lifting objects (P = 0.02), bending (P < 0.001), and moving large objects (P = 0.0006). After multivariate adjustment, severe steatosis remained associated with difficulty lifting objects (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.2–2.4, P = 0.01) and difficulty bending (OR: 1.8, 95% CI: 1.2–2.7, P = 0.006). Severe steatosis increased risk of having any of the disabilities (OR: 1.7, 95% CI: 1.2–2.4, P = 0.008) and had higher ordinal disability index (OR: 1.6, 95% CI: 1.2–2.2, P = 0.007). Lastly, severe steatosis was also associated with worse self-perceived health status (OR: 1.5, 95% CI: 1.2–1.9, P = 0.002), while general health compared to one year ago and depression trended toward significance.ConclusionPatients with severe steatosis are at increased risk of physical disability and have worse self-perceived health status independent of liver fibrosis.

Background and AimsFatigue is the most common complication of primary biliary cholangitis (PBC) and can be debilitating. Numerous interventions have been trialed targeting several proposed mechanisms of PBC-associated fatigue. We sought to summarize and perform a meta-analysis to determine the efficacy of these interventions.MethodsA comprehensive database search was conducted from inception through March 27, 2018. The primary outcome was proportion of fatigued patients or reduction in degree of fatigue. Adverse events were a secondary outcome. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same class.ResultsWe identified 16 studies evaluating ursodeoxycholic acid (UDCA) (7), liver transplantation (2), serotonin reuptake inhibitors (2), colchicine (1), methotrexate (1), cyclosporine (1), modafinil (1), and obeticholic acid (1). On meta-analysis, UDCA was not associated with a reduction in risk of fatigue (RR = 0.86, 95% CI 0.69–1.08, p = 0.19, I2 = 56.2%). While liver transplantation did reduce degree of fatigue (SMD − 0.57, 95% CI − 0.89 to − 0.24, p = 0.001, I2 = 67.3%), fatigue did not return to baseline indicating the underlying cause may not be addressed.ConclusionsWhile there is some improvement in fatigue with liver transplantation, there is a lack of high-quality evidence supporting the efficacy of any other intervention in the treatment of PBC-related fatigue. Further research into the underlying pathophysiology may help guide future trials.

[...]over recent years, efforts have been made to establish an alternative nomenclature that has global consensus. [...]the new MASLD term replaced exclusionary and potentially stigmatizing terms (‘nonalcoholic’ and ‘fatty’) with more etiologically accurate and non-stigmatizing terms (‘metabolic-dysfunction’ and ‘steatotic’, respectively) [6,14]. [...]categorizing MetALD as a continuum, coupled with our limited understanding of the interplay between metabolic dysfunction and alcohol intake on SLD development, may pose challenges in developing disease-specific biomarkers or drugs for this group. [...]while the new term has gained acceptance among experts worldwide, the transition from the long-established NAFLD to MASLD appears to vary with slowness particularly in the broader community.

Background/Aims: Prediction of short-term mortality in patients with acute-on-chronic liver failure (ACLF) admitted to the intensive care unit (ICU) may enhance effective management.Methods: To develop, explain, and validate a predictive machine learning (ML) model for short-term mortality in patients with ACLF with two or more organ failures (OFs). Utilizing a large ICU cohort with detailed clinical information, we identified ACLF patients with two or more OFs according to the EASL-CLIF and NACSELD definitions. ML model was developed for each definition to predict 30-day mortality. The Shapley value was estimated to explain the models. Validation and calibration of these models were performed.Results: Of 5,994 patients with cirrhosis admitted to ICU, 1,511 met NACSELD criteria, and 1,692 met EASL-CLIF grade II or higher criteria. The CatBoost ACLF (CBA) model had the greatest accuracy in the NACSELD cohort (area under curve [AUC] of 0.87), while the Random Forest ACLF (RFA) model performed best in the EASL-CLIF cohort (AUC of 0.83). Both models showed robust calibration. The models were explained by SHAP score analysis, yielding a rank list, and the top twelve predictors were selected. Both simplified models demonstrated similar performance (CBA model: AUC 0.89, RFA model: AUC 0.81) and significantly outperformed contemporary scoring systems, including CLIF-C ACLF and MELD 3.0. The models were validated in both internal and external cohorts. A simple-to-use online tool was created to predict mortality rates.Conclusions: We presented explainable, well-validated, and calibrated predictive models for ACLF patients with two or more OFs, which outperformed existing predictive scores.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease. It has known multifactorial pathophysiology, but the impact of social determinants of health (SDOH) on the rising prevalence of MASLD is poorly understood. We conducted a retrospective cross-sectional study to examine the influence of SDOH on MASLD using nationwide data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) study. Methods: We identified participants with MASLD based on liver ultrasound-based controlled attenuation parameter measurements consistent with diagnostic guidelines. We then used logistic regression models to examine associations between SDOH variables and MASLD, with a pre-specified focus on education and income, sequentially adjusting for sociodemographic factors, medical comorbidities, and other SDOH. Results: Our study found that higher education (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62–0.97, p = 0.024) but not higher income (OR 1.12, 95% CI 0.91–1.37, p = 0.3) was associated with lower odds of MASLD in multivariable adjusted models. We also identified a significant interaction between education level and food security, as well as interactions between food security and other significant SDOH. In the stratified analyses, higher education was significantly associated with lower odds of MASLD among participants with food security (OR 0.71, 95% CI 0.55–0.91, p = 0.007) but not among those with food insecurity (OR 1.26, 95% CI 0.76–2.11, p = 0.4). Conclusions: Our findings identify the potential impact of SDOH on odds of MASLD and suggest increased importance of food security relative to other SDOH.

Primary biliary cholangitis (PBC) is a chronic, cholestatic condition associated with symptoms that directly impact the quality of life in those afflicted with the disease. In addition to pruritus and fatigue, patients with PBC may develop metabolic bone disease from reduced bone density, such as osteopenia and osteoporosis. Osteoporosis increases the risk of fractures, as well as morbidity and mortality. The prevalence of osteoporosis in PBC is expected to increase in conjunction with the rising prevalence of PBC as a whole. Timely diagnosis, prevention and management of osteoporosis are crucial in order to optimize the quality of life. There is a paucity of data evaluating the management of osteoporosis in PBC. The optimal timing for diagnosis and monitoring is not yet established and is guided by expert opinion. National guidelines recommend screening for osteoporosis at the time of diagnosis of PBC. Monitoring strategies are based on results of initial screening and individual risk factors for bone disease. Identifying reduced bone density is imperative to institute timely preventive and treatment strategies. However, treatment remains challenging as efficacious therapies are currently lacking. The data on treatment of osteoporosis in PBC are mostly extrapolated from postmenopausal osteoporosis literature. However, this data has not directly translated to useful treatment strategies for PBC-related osteoporosis, partly because of the different pathophysiological mechanisms of the two diseases. The lack of useful preventive measures and efficacious treatment strategies remains the largest pitfall that challenges the management of patients with PBC. In this review, we comprehensively outline the epidemiology, clinical implications and challenges, as well as management strategies of PBC-related osteoporosis.

Introduction: Direct-acting antivirals (DAAs) have resulted in improvement in the virologic cure rate of HCV infection. However, tools to measure regression of hepatic fibrosis after HCV eradication are not perfect. Liver biopsy is not always appropriate and transient elastography has limited availability. Alternative ways to monitor for regression of fibrosis are required in clinical practice. The AST-to-Platelet-Ratio-Index (APRI) and Fibrosis-4 (Fib-4) are validated tools that predict presence of hepatic fibrosis. We examined if treatment of HCV infection resulted in sustained improvement in the APRI and Fib-4 scores. Methods: Clinic records of adult patients with chronic HCV infection who received treatment in a single center were reviewed over a 5-year period. Sustained virologic response (SVR) was achieved if the HCV RNA titer was undetected 12 weeks or more after treatment completion. APRI and Fib-4 scores were calculated before and 12-24 weeks after treatment completion. Cirrhosis was ascertained based on laboratory and imaging data or biopsy. Continuous variables are reported as mean (± SD). Multivariable linear and stepwise linear regression analyses were performed to examine the association between SVR12 and the APRI/FIB-4 scores 12-24 weeks after treatment completion. The analyses were adjusted for baseline APRI/FIB-4 scores, BMI, cirrhosis, use of peg-interferon, and genotype 3. Results: 153 patients were identified. Mean age was 51.2 ± 14.0 years. Mean treatment duration was 14.7 ± 8.2 weeks. 68% were men, 3.3% were HIV co-infected. Genotype 1 was predominant (1a 46%, 1b 17%), followed by genotype 2 (18%), genotype 3 (16%), and genotypes 4-6 (3%). 22% of patients had cirrhosis, 14% received an interferon containing regimen. In the unadjusted analysis, patients who achieved SVR12 had a significant decline in the mean APRI and Fib-4 scores compared to those who did not achieve SVR12. These results remained robust in the multivariable linear regression analyses where all the covariates of interest were forced into the models, as well as in the stepwise analyses where non-significant covariates were eliminated from the models. Conclusion: We herein demonstrate that treatment of chronic HCV infection results in improvement in the APRI and Fib-4 scores among patients who achieved SVR12 suggesting regression of hepatic fibrosis. In the absence of transient elastography, physicians should consider relying on these surrogate markers for risk stratification.

Bouveret's syndrome is a rare complication of cholelithiasis. It is characterized by a gallstone entering the intestine through a cholecystoenteric fistula, impacting the duodenum and causing gastric outlet obstruction. Rarely, it presents with hematemesis and melena. The diagnosis involves computed tomography (CT) and the treatment depends on the patient's stability, the location of the obstruction, stone size, and the fistula. Endoscopy or minimally invasive lithotripsy can be considered initially. If this fails, surgical intervention is recommended. We present a case of upper gastrointestinal bleeding (UGIB) preceding the development of Bouveret's syndrome.

[...]donor liver steatosis is a potential risk factor for post-LT steatosis. [...]close follow-up with initiation or maintenance of guideline-based drugs for management of type 2 diabetes, hypertension, and dyslipidemia is essential. More prospective studies with longer-term follow-up are required to delineate the natural history of this condition, its true effect on patient and graft survival, and whether newly emerging weight loss medications would be effective in mitigating metabolic risks. Saeed, N.; Glass, L.; Sharma, P.; Shannon, C.; Sonnenday, C.J.; Tincopa, M.A. Incidence and Risks for Nonalcoholic Fatty Liver Disease and Steatohepatitis Post-liver Transplant: Systematic Review and Meta-analysis.

Abstract Cirrhosis is associated with debilitating complications that significantly impact on a patient’s physical function and reduce quality of life. Owing to highly prevalent sarcopenia, malnutrition and hepatic encephalopathy, functional impairment or frailty is a common complication of cirrhosis. Frailty in turn increases the patient’s risk of hospitalization, accidental falls and fractures, and death. The management of frailty and its associated adverse effects is imperative in improving the overall prognosis of patients with advanced liver disease. The cornerstone of therapy revolves around optimizing physical function with appropriate nutrition and exercise. Nutritional therapy with protein supplementation has shown significant benefit, while studies on exercise have been controversial. However, newly emerging studies trend towards a beneficial effect of physical exercise with improvement in quality of life. The implementation of technology in liver disease management shows future promise. Fitbits and other wearable devices can be used to help monitor a patient’s personal progress in physical exercise and nutritional optimization. Additionally, the progressive development of new smartphone applications to help aid in the diagnosis and monitoring of complications of cirrhosis provides a sophisticated avenue for improving care of patients with cirrhosis.