Global trends in hepatitis C-related hepatocellular carcinoma mortality: A public database analysis (1999-2019).

BACKGROUND: Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma (HCC). However, there are marked variations in the incidence and mortality rates of HCC across different geographical regions. With the advent of new widely available treatment modalities, such as direct-acting antivirals, it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C. Furthermore, gender disparities in HCC mortality related to Hepatitis C are a crucial, yet underexplored aspect that adds to the disease's global impact. While some studies shed light on gender-specific trends, there is a lack of comprehensive data on global and regional mortality rates, particularly those highlighting gender disparities. This gap in knowledge hinders the development of targeted interventions and resource allocation strategies. AIM: To understand the global and regional trends in Hepatitis C-related HCC mortality rates from 1990 to 2019, along with gender disparities. METHODS: We utilized the Global Burden of Disease database, a comprehensive repository for global health metrics to age-standardized mortality rates due to Hepatitis C-related HCC from 1999 to 2019. Rates were evaluated per 100000 population and assessed by World Bank-defined regions. Temporal trends were determined using Joinpoint software and the Average Annual Percent Change (AAPC) method, and results were reported with 95% confidence intervals (CI). RESULTS: From 1990 to 2019, overall, there was a significant decline in HCC-related mortality rates with an AAPC of -0.80% (95%CI: -0.83 to -0.77). Females demonstrated a marked decrease in mortality with an AAPC of -1.06% (95%CI: -1.09 to -1.03), whereas the male cohort had a lower AAPC of -0.52% (95%CI: -0.55 to -0.48). Regionally, East Asia and the Pacific demonstrated a significant decline with an AAPC of -2.05% (95%CI: -2.10 to -2.00), whereas Europe and Central Asia observed an uptrend with an AAPC of 0.72% (95%CI: 0.69 to 0.74). Latin America and the Caribbean also showed an uptrend with an AAPC of 0.06% (95%CI: 0.02 to 0.11). In the Middle East and North Africa, the AAPC was non-significant at 0.02% (95%CI: -0.09 to 0.12). North America, in contrast, displayed a significant upward trend with an AAPC of 2.63% (95%CI: 2.57 to 2.67). South Asia (AAPC -0.22%, 95%CI: -0.26 to -0.16) and Sub-Saharan Africa (AAPC -0.14%, 95%CI: -0.15 to -0.12) trends significantly declined over the study period. CONCLUSION: Our study reports disparities in Hepatitis C-related HCC mortality between 1999 to 2019, both regionally and between genders. While East Asia and the Pacific regions showed a promising decline in mortality, North America has experienced a concerning rise in mortality. These regional variations highlight the need for healthcare policymakers and practitioners to tailor public health strategies and interventions. The data serves as a call to action, particularly for regions where mortality rates are not improving, emphasizing the necessity for a nuanced, region-specific approach to combat the global challenge of HCC secondary to Hepatitis C.

Impact of metabolic dysfunction-associated steatotic liver disease on COVID-19 hospitalizations: A propensity-matched analysis of the United States.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), formally known as nonalcoholic fatty liver disease, is the most common chronic liver disease in the United States. Patients with MASLD have been reported to be at a higher risk of developing severe coronavirus disease 2019 (COVID-19) and death. However, most studies are single-center studies, and nationwide data in the United States is lacking. AIM: To study the influence of MASLD on COVID-19 hospitalizations during the initial phase of the pandemic. METHODS: We retrospectively analyzed the 2020 National Inpatient Sample (NIS) database to identify primary COVID-19 hospitalizations based on an underlying diagnosis of MASLD. A matched comparison cohort of COVID-19 hospitalizations without MASLD was identified from NIS after 1: N propensity score matching based on gender, race, and comorbidities, including hypertension, heart failure, diabetes, and cirrhosis. The primary outcomes included inpatient mortality, length of stay, and hospitalization costs. Secondary outcomes included the prevalence of systemic complications. RESULTS: A total of 2210 hospitalizations with MASLD were matched to 2210 hospitalizations without MASLD, with a good comorbidity balance. Overall, there was a higher prevalence of severe disease with more intensive care unit admissions (9.5% vs 7.2%, P = 0.007), mechanical ventilation (7.2% vs 5.7%, P = 0.03), and septic shock (5.2% vs 2.7%, P <0.001) in the MASLD cohort than in the non-MASLD cohort. However, there was no difference in mortality (8.6% vs 10%, P = 0.49), length of stay (5 d vs 5 d, P = 0.25), and hospitalization costs (42081.5 $ vs 38614$, P = 0.15) between the MASLD and non-MASLD cohorts. CONCLUSION: The presence of MAFLD with or without liver cirrhosis was not associated with increased mortality in COVID-19 hospitalizations; however, there was an increased incidence of severe COVID-19 infection. This data (2020) predates the availability of COVID-19 vaccines, and many MASLD patients have since been vaccinated. It will be interesting to see if these trends are present in the subsequent years of the pandemic.

Hepatic steatosis modeling and MRI signal simulations for comparison of single- and dual-R2* models and estimation of fat fraction at 1.5T and 3T.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) has emerged as a noninvasive clinical tool for assessment of hepatic steatosis. Multi-spectral fat-water MRI models, incorporating single or dual transverse relaxation decay rate(s) (R2*) have been proposed for accurate fat fraction (FF) estimation. However, it is still unclear whether single- or dual-R2* model accurately mimics in vivo signal decay for precise FF estimation and the impact of signal-to-noise ratio (SNR) on each model performance. Hence, this study aims to construct virtual steatosis models and synthesize MRI signals with different SNRs to systematically evaluate the accuracy of single- and dual-R2* models for FF and R2* estimations at 1.5T and 3.0T. METHODS: Realistic hepatic steatosis models encompassing clinical FF range (0-60 %) were created using morphological features of fat droplets (FDs) extracted from human liver biopsy samples. MRI signals were synthesized using Monte Carlo simulations for noise-free (SNRideal) and varying SNR conditions (5-100). Fat-water phantoms were scanned with different SNRs to validate simulation results. Fat water toolbox was used to calculate R2* and FF for both single- and dual-R2* models. The model accuracies in R2* and FF estimates were analyzed using linear regression, bias plot and heatmap analysis. RESULTS: The virtual steatosis model closely mimicked in vivo fat morphology and Monte Carlo simulation produced realistic MRI signals. For SNRideal and moderate-high SNRs, water R2* (R2*W) by dual-R2* and common R2* (R2*com) by single-R2* model showed an excellent agreement with slope close to unity (0.95-1.01) and R2 > 0.98 at both 1.5T and 3.0T. In simulations, the R2*com-FF and R2*W-FF relationships exhibited slopes similar to in vivo calibrations, confirming the accuracy of our virtual models. For SNRideal, fat R2* (R2*F) was similar to R2*W and dual-R2* model showed slightly higher accuracy in FF estimation. However, in the presence of noise, dual-R2* produced higher FF bias with decreasing SNR, while leading to only marginal improvement for high SNRs and in regions dominated by fat and water. In contrast, single-R2* model was robust and produced accurate FF estimations in simulations and phantom scans with clinical SNRs. CONCLUSION: Our study demonstrates the feasibility of creating virtual steatosis models and generating MRI signals that mimic in vivo morphology and signal behavior. The single-R2* model consistently produced lower FF bias for clinical SNRs across entire FF range compared to dual-R2* model, hence signifying that single-R2* model is optimal for assessing hepatic steatosis.

Mechanistically based blood proteomic markers in the TGF-ß pathway stratify risk of hepatocellular cancer in patients with cirrhosis.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers. We address this gap using the TGF-ß pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies. Using machine learning methods with blood levels of 108 proteomic markers in the TGF-ß family, we found a pattern that differentiates HCC from non-HCC in a cohort of 216 patients with cirrhosis, which we refer to as TGF-ß based Protein Markers for Early Detection of HCC (TPEARLE) comprising 31 markers. Notably, 20 of the patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group with as yet undetected HCC or at high risk for developing HCC. In addition, we found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), which were significantly associated with HCC. We tested these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver. They potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.

Akkermansia muciniphila - A Potential Next-generation Probiotic for Non-alcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions, and its growing prevalence is a serious concern worldwide, especially in Western countries. Researchers have pointed out several genetic mutations associated with NAFLD; however, the imbalance of the gut microbial community also plays a critical role in the progression of NAFLD. Due to the lack of approved medicine, probiotics gain special attention in controlling metabolic disorders like NAFLD. Among these probiotics, Akkermansia muciniphila (a member of natural gut microflora) is considered one of the most efficient and important bacterium in maintaining gut health, energy homeostasis, and lipid metabolism. In this perspective, we discussed the probable molecular mechanism of A. muciniphila in controlling the progression of NAFLD and restoring liver health. The therapeutic potential of A. muciniphila in NAFLD has been tested primarily on animal models, and thus, more randomized human trials should be conducted to prove its efficacy.

Defining an approach for therapeutic strategies in metabolic dysfunction-associated steatotic liver disease after liver transplantation.

Occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) is common following liver transplantation (LT). MASLD can be classified as a recurrent disease when it occurs in patients receiving LT for metabolic dysfunction-associated steatohepatitis (MASH) or as de novo when it occurs in patients undergoing transplantation for non-metabolic dysfunction-associated steatohepatitis etiologies of liver disease. Fibrosis progression in patients with MASLD is accelerated, with progression to cirrhosis occurring more rapidly compared with the general (ie, non-LT) population. Moreover, the metabolic burden in LT recipients with MASLD is high and synergizes with liver disease to negatively affect the clinical course. Despite the oversized clinical burden of MASLD among LT recipients, there is currently a lack of regulatory approach and pathway for therapeutics development in this patient population. The present document, thus, provides guidance for therapeutics development that incorporates nuances of transplant care in patients with post-LT MASLD to facilitate drug development.

Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients: A propensity-matched analysis from the United States.

BACKGROUND: Alcohol-associated cirrhosis (AC) contributes to significant liver-related mortality in the United States. It is known to cause immune dysfunction and coagulation abnormalities. Patients with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019 (COVID-19). The specific association between AC and COVID-19 mortality remains inconclusive, given the lack of robust clinical evidence from prior studies. AIM: To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United States. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database 2020. Patients were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC. A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser comorbidities. Primary outcomes included median length of stay, median inpatient charges, and in-hospital mortality. Secondary outcomes included a prevalence of systemic complications. RESULTS: A total of 1325 COVID-19 patients with AC were matched to 1135 patients without AC. There was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC (P > 0.05). There was an increased prevalence of septic shock (5.7% vs 4.1%), ventricular fibrillation/ventricular flutter (0.4% vs 0%), atrial fibrillation (13.2% vs 8.8%), atrial flutter (8.7% vs 4.4%), first-degree atrioventricular nodal block (0.8% vs 0%), upper extremity venous thromboembolism (1.5% vs 0%), and variceal bleeding (3.8% vs 0%) in the AC cohort compared to the non-AC cohort (P < 0.05). There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC, with an odds ratio of 0.97 (95% confidence interval: 0.78-1.22, P = 0.85). Predictors of mortality included advanced age, cardiac arrhythmias, coagulopathy, protein-calorie malnutrition, fluid and electrolyte disorders, septic shock, and upper extremity venous thromboembolism. CONCLUSION: AC does not increase mortality in patients hospitalized with COVID-19. There is an increased association between inpatient complications among COVID-19 patients with AC compared to non-AC.

Nosocomial spontaneous bacterial peritonitis is associated with high mortality - a systematic review and meta-analysis.

INTRODUCTION: It is unclear if Nosocomial Spontaneous Bacteria Peritonitis (NSBP) is associated with higher mortality compared with community acquired spontaneous bacterial peritonitis. METHODS: Database search from inception to May 2022 was conducted. The databases included MEDLINE, EMBASE, Cochrane registry of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Inclusion criteria were as follows: adult patients, age >18 years, with a diagnosis of NSBP. Pooled estimates of mortality were calculated following the restricted maximum likelihood method. The mortality rate between NSBP and CA-SBP was reported as odds ratio (OR) and 95% confidence interval (CI). Data synthesis was obtained using random effects meta-analysis. Heterogeneity was reported as I2. RESULTS: A total of 482 unique titles were screened. Twenty-two articles were included. A total of 2,145 patients with NSBP were included. Patients were followed for a median of 90 days. The pooled mortality rate of NSBP was 52.51% (95% CI 42.77-62.06%; I2 83.72%). Seven studies compared the mortality outcome of patients with NSBP and CA-SBP. NSBP was significantly associated with a higher rate of mortality (OR 2.78, 95% CI 1.87-4.11; I2 36.00%). CONCLUSION: NSBP was associated with higher mortality rate compared to CA-SBP, which could be due to a higher rate of resistance organisms.

Baseline Albumin-Bilirubin grade as a predictor of response and outcome of regorafenib therapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The use of regorafenib in the treatment of hepatocellular carcinoma (HCC) is widespread. Albumin-Bilirubin (ALBI) has been shown to be a potential prognostic marker for regorafenib treatment, but its prognostic value remains controversial. Therefore, we conducted a meta-analysis to investigate the value of the baseline ALBI grade in predicting the efficacy and survival outcomes of HCC patients after regorafenib treatment. METHODS: PubMed, Embase, Cochrane library, Web of Science, CNKI, Wan Fang Data, and Vip Database were searched from January 2010 to October 2022. Studies treating HCC patients with regorafenib and with ALBI as a categorical variable, overall survival (OS) and progression-free survival (PFS) as outcome indicators were included. After applying Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included studies, Review Manager 5.4 was used to statistically analyze. Chi-square Q test and I2 statistics were used to detect heterogeneity. Funnel plot asymmetry, Egger's and Begg's test were used to evaluate publication bias. RESULTS: A total of 12 studies, comprising 1,918 patients, were included in the meta-analysis. The included studies were all evaluated as high quality. Compared to the high-grade baseline ALBI group, patients in the low-grade group had a longer survival time after receiving regorafenib and also more suitable for regorafenib treatment [odds ratio (OR) = 6.50, 95% confidence interval (CI): 2.22-18.96, P < 0.01]. The low-grade baseline ALBI group before sorafenib treatment was significantly correlated with better OS [hazard ratio (HR) = 2.36, 95% CI: 1.68-3.31, P < 0.00001] and PFS (HR = 1.56, 95% CI: 1.16-2.08, P = 0.003). Likewise, the low-grade baseline ALBI group before regorafenib was also significantly correlated with better OS (HR = 1.56, 95% CI: 1.15-2.13, P = 0.005) and PFS (HR = 2.06, 95% CI: 1.37-3.11, P = 0.0005). In addition, the ALBI grade was significantly correlated with disease control rate (DCR) (OR = 2.90, 95% CI: 1.45-5.79, P = 0.003), but not the objective response rate (OR = 1.98, 95% CI: 0.71-5.46, P = 0.19). CONCLUSIONS: The baseline ALBI grade could be a valuable prognostic indicator for predicting response and outcomes in HCC patients treated with regorafenib.

Real-world use of avatrombopag in patients with chronic liver disease and thrombocytopenia undergoing a procedure.

The phase 4 observational cohort study assessed the effectiveness and safety of the thrombopoietin receptor agonist avatrombopag in patients with chronic liver disease (CLD) and thrombocytopenia undergoing a procedure. Patients with CLD may have thrombocytopenia, increasing the risk of periprocedural bleeding. Prophylactic platelet transfusions used to reduce this risk have limitations including lack of efficacy and transfusion-associated reactions. Prophylactic thrombopoietin receptor agonists have been shown to increase platelet counts and decrease platelet transfusions. Effectiveness was assessed by change from baseline in platelet count and proportion of patients needing a platelet transfusion. Safety was assessed by monitoring adverse events (AEs). Of 50 patients enrolled, 48 were unique patients and 2 patients were enrolled twice for separate procedures. The mean (standard deviation) change in platelet count from baseline to procedure day was 41.1 × 109/L (33.29 × 109/L, n = 38), returning to near baseline at the post-procedure visit (change from baseline -1.9 × 109/L [15.03 × 109/L], n = 11). The proportion of patients not requiring a platelet transfusion after baseline and up to 7 days following the procedure was 98% (n = 49). Serious AEs were infrequent (n = 2 [4%]). No treatment-emergent AEs were considered related to avatrombopag. There were 2 mild bleeding events, no thromboembolic events or deaths, and no patients received rescue procedures (excluding transfusions). This study found that in a real-world setting, treatment with avatrombopag was well tolerated, increased the mean platelet count by procedure day, and reduced the need for intraoperative platelet transfusions in patients with CLD and thrombocytopenia.

Association of nonalcoholic fatty liver disease with acute cholangitis: a nationwide propensity-matched analysis from the United States.

Background: Nonalcoholic fatty liver disease (NAFLD) has previously been linked to several disease states with an impact on patient outcomes. However, clinical evidence on the association between NAFLD and acute cholangitis (AC) remains scarce. We aimed to evaluate the potential association between NAFLD and AC. Methods: We conducted a retrospective cohort study using the US National Inpatient Sample database from 2016 to 2019 to analyze primary AC hospitalizations with NAFLD compared to non-NAFLD in a 1:1 propensity-matched population. Results: A total of 1550 AC patients with NAFLD were matched to 1550 AC patients without NAFLD. NAFLD had a higher association with AC when compared to patients without NAFLD, with an odds ratio of 2.33 (95% CI [1.81-3.0], P < 0.001). The length of stay was higher in NAFLD than in non-NAFLD (4 vs 3 days, P < 0.001). The median inpatient charges in NAFLD were also higher than in the non-NAFLD cohort ($36,182 vs $35,244, P < 0.001). Inpatient mortality was higher in NAFLD compared to non-NAFLD (1.6% vs 0%, P < 0.001). There was an increased prevalence of portal vein thrombosis (3.2% vs 0%), acute kidney injury (24.2% vs 17.7%), sepsis (3.2% vs 1.6%), mechanical ventilation (3.2% vs 0%), and percutaneous cholecystostomy tube insertion (3.2% vs 1.6%) in NAFLD compared to non-NAFLD (P < 0.05). NAFLD also had a higher association with acute cholecystitis, with an odds ratio of 3.70 (95% CI [3.19-4.29], P < 0.001). Conclusions: This study showed an association between NALFD and AC, resulting in increased length of stay, hospital charges, and inpatient mortality. Underlying NAFLD also increases acute complications of AC.

Use of albumin infusion for cirrhosis-related complications: An international position statement.

Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.

Rising alcohol-associated liver disease-related mortality rates in the United States from 1999 to 2022.

We examined trends in alcohol-associated liver disease (ALD)-related mortality in the United States from 1999 to 2022, focusing on sex, racial differences, and specific age groups. We analyzed age-adjusted mortality rates for ALD-related deaths using the CDC WONDER database and assessed differences between sex and racial groups. ALD-related mortality rates increased significantly between 1999 and 2022, with a more pronounced increase in females. White, Asian, Pacific Islander (AAPI), and American Indian or Alaska Native (AI/AN) groups showed significant uptrends in ALD-related mortality, while African Americans (AA) experienced a nonsignificant decline. Age-specific trends revealed substantial increases in crude mortality rates across various age groups, with the largest increase observed in the younger age groups of 25-34 years, with an average percent change of 11.12% from 2006 to 2022 (average annual percent change of 7.1% for the study period), and 35-44 years, which showed an average percent change of 17.2% from 2018 to 2022 (average annual percent change of 3.8% for the study period). This study reveals increased ALD-related mortality rates in the United States from 1999 to 2022, with disparities among sex, racial groups, and younger age groups. Continued monitoring and evidence-based interventions are needed to address the growing burden of ALD-related mortality, particularly in the younger population.

INASL-SAASL Consensus Statements on NAFLD Name Change to MAFLD.

There is an ongoing debate on the change of terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). Experts from the Indian National Association for Study of the Liver (INASL) and the South Asian Association for Study of the Liver (SAASL) involved in diagnosing, managing, and preventing NAFLD met in March 2022 to deliberate if the name change from NAFLD to MAFLD is appropriate, as proposed by a group of experts who published a "consensus" statement in 2020. Proponents of name change to MAFLD opined that NAFLD does not reflect current knowledge, and the term MAFLD was suggested as a more appropriate overarching term. However, this "consensus" group which proposed the name change to MAFLD did not represent the views and opinions of gastroenterologists and hepatologists, as well as perceptions of patients across the globe, given the fact that change of nomenclature for any disease entity is bound to have multidimensional impact on all aspects of patient care. This statement is the culmination of the participants' combined efforts who presented recommendations on specific issues concerning the proposed name change. The recommendations were then circulated to all the core group members and updated based on a systematic literature search. Finally, all the members voted on them using the nominal voting technique as per the standard guidelines. The quality of evidence was adapted from the Grades of Recommendation, Assessment, Development and Evaluation system.

Racial and gender-based disparities and trends in common psychiatric conditions in liver cirrhosis hospitalizations: A ten-year United States study.

BACKGROUND: Chronic liver disease is associated with various neuropsychiatric conditions. There are currently no large studies assessing and comparing the prevalence of psychiatric illnesses based on patient profiles and the etiology of cirrhosis. AIM: To examine the trends of hospitalizations among psychiatric conditions in cirrhosis. METHODS: We used the National Inpatient Sample database 2016-2019 for the primary diagnosis of liver cirrhosis. The outcomes included the prevalence, trends, and associations of psychiatric diagnoses in these hospitalizations. Chi-square for categorical variables and the Wilcoxon rank test for continuous variables were utilized. RESULTS: The prevalence of generalized anxiety disorder (GAD) in liver cirrhosis hospitalizations increased from 0.17% in 2009 to 0.92% in 2019 (P < 0.001). The prevalence of depression increased from 7% in 2009 to 12% in 2019 (P < 0.001). Attention deficit hyperactivity disorder (ADHD) prevalence increased from 0.06% to 0.24%. The prevalence of schizophrenia increased from 0.59% to 0.87% (P < 0.001). Schizoaffective disorder prevalence increased from 0.10% to 0.35% (P < 0.001). Post-traumatic stress disorder (PTSD) prevalence displayed increasing trends from 0.36% in 2009 to 0.93% in 2019 (P < 0.001). The prevalence of suicidal ideation increased from 0.23% to 0.56% in 2019. Cirrhosis related to alcoholic liver disease [adjusted odds ratios (aOR) 1.18, 95%CI 1.08-1.29, P < 0.001] and non-alcoholic fatty liver disease (NAFLD) (aOR 1.14, 95%CI 1.01-1.28, P = 0.025) was associated with depression more than other causes. Alcohol- and NAFLD-associated cirrhosis had a stronger link to psychiatric disorders. Females had a higher association with GAD (aOR 2.56, 95%CI 2.14-3.06, P < 0.001), depression (aOR 1.78, 95%CI 1.71-1.84, P < 0.001), bipolar disorder (aOR 1.64, 95%CI 1.52-1.77, P < 0.001] and chronic fatigue (aOR 2.31, 95%CI 1.31-4.07, P < 0.001) when compared to males. Blacks, Hispanics, and Asian/Native Americans had a significantly lower association with GAD, depression, bipolar disorder, PTSD, and ADHD when compared to the white race. CONCLUSION: The prevalence of psychiatric comorbidities in liver cirrhosis hospitalizations has increased over the last decade. Females had a higher association with psychiatric disorders compared to males. Blacks, Hispanics, and Asian/Native Americans had lower associations with psychiatric comorbidities compared to the white race.

Sarcopenia in the Cirrhotic Patient: Current Knowledge and Future Directions.

Cirrhosis predisposes to abnormalities in energy, hormonal, and immunological homeostasis. Disturbances in these metabolic processes create susceptibility to sarcopenia or pathological muscle wasting. Sarcopenia is prevalent in cirrhosis and its presence portends significant adverse outcomes including the length of hospital stay, infectious complications, and mortality. This highlights the importance of identification of at-risk individuals with early nutritional, therapeutic and physical therapy intervention. This manuscript summarizes literature relevant to sarcopenia in cirrhosis, describes current knowledge, and elucidates possible future directions.

Quantitative MRI of diffuse liver diseases: techniques and tissue-mimicking phantoms.

Quantitative magnetic resonance imaging (MRI) techniques are emerging as non-invasive alternatives to biopsy for assessment of diffuse liver diseases of iron overload, steatosis and fibrosis. For testing and validating the accuracy of these techniques, phantoms are often used as stand-ins to human tissue to mimic diffuse liver pathologies. However, currently, there is no standardization in the preparation of MRI-based liver phantoms for mimicking iron overload, steatosis, fibrosis or a combination of these pathologies as various sizes and types of materials are used to mimic the same liver disease. Liver phantoms that mimic specific MR features of diffuse liver diseases observed in vivo are important for testing and calibrating new MRI techniques and for evaluating signal models to accurately quantify these features. In this study, we review the liver morphology associated with these diffuse diseases, discuss the quantitative MR techniques for assessing these liver pathologies, and comprehensively examine published liver phantom studies and discuss their benefits and limitations.

Pharmacotherapeutic efficacy on noninvasive fibrosis progression in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.

BACKGROUND: Fibrosis impacts long-term outcomes among patients with nonalcoholic fatty liver disease (NAFLD). Due to well-documented flaws associated with liver biopsy, there has been a recent emphasis on prioritizing noninvasive testing over liver biopsy for the assessment of fibrosis. METHODS: A comprehensive systematic review and frequentist random effects network meta-analysis was performed among randomized controlled trials reporting pharmacologic intervention in NAFLD. The primary endpoint was the absolute change in liver stiffness measurement (LSM) via elastography. Secondary endpoints included changes in noninvasive serologic tests including APRI, fibrosis-4 index, NAFLD fibrosis score, enhanced liver fibrosis (ELF) and FibroTest (FibroSure in the USA). RESULTS: Forty-five randomized controlled trials enrolling 6932 patients were identified for this network meta-analysis. Across the primary endpoint, firsocostat, semaglutide, montelukast, cilofexor plus firsocostat, obeticholic acid and diacerein (change in LSM via vibration controlled transient elastography), in addition to lubiprostone and pemafibrate (change in LSM via magnetic resonance elastography) were found to be the most effective and statistically significant treatment interventions. Similarly, the following interventions were determined to be most effective as compared to placebo among secondary endpoints: saroglitazar, lubiprostone, and obeticholic acid (change in APRI); saroglitazar, semaglutide, firsocostat and cilofexor plus firsocostat (change in ELF); obeticholic acid and belapectin [change in FibroTest/FibroSure]. CONCLUSION: This is the first systematic review and network meta-analysis reporting pharmacologic efficacy in the progression of fibrosis based on noninvasive testing among patients with NAFLD. Semaglutide, obeticholic acid, firsocostat, cilofexor plus firsocostat and lubiprostone were found to be the most effective treatments based on their consistent efficacy reproduced across multiple endpoints, both via elastography and noninvasive blood tests.

Factors Impacting Survival in Those Transplanted for NASH Cirrhosis: Data From the NailNASH Consortium.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is the leading indication for liver transplant (LT) in women and the elderly. Granular details into factors impacting survival in this population are needed to optimize management and improve outcomes. METHODS: Patients receiving LT for NASH cirrhosis from 1997 to 2017 across 7 transplant centers (NailNASH consortium) were analyzed. The primary outcome was all-cause mortality, and causes of death were enumerated. All outcomes were cross referenced with United Network for Organ Sharing and adjudicated at each individual center. Cox regression models were constructed to elucidate clinical factors impacting mortality. RESULTS: Nine hundred thirty-eight patients with a median follow-up of 3.8 years (interquartile range, 1.60-7.05 years) were included. The 1-, 3-, 5-, 10-, and 15-year survival of the cohort was 93%, 88%, 83%, 69%, and 46%, respectively. Of 195 deaths in the cohort, the most common causes were infection (19%), cardiovascular disease (18%), cancer (17%), and liver-related (11%). Inferior survival was noted in patients >65 years. On multivariable analysis, age >65 (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .04), end-stage renal disease (HR, 1.55; 95% CI, 1.04-2.31; P = .03), black race (HR, 5.25; 95% CI, 2.12-12.96; P = .0003), and non-calcineurin inhibitors-based regimens (HR, 2.05; 95% CI, 1.19-3.51; P = .009) were associated with increased mortality. Statin use after LT favorably impacted survival (HR, 0.38; 95% CI, 0.19-0.75; P = .005). CONCLUSIONS: Despite excellent long-term survival, patients transplanted for NASH at >65 years or with type 2 diabetes mellitus at transplant had higher mortality. Statin use after transplant attenuated risk and was associated with improved survival across all subgroups, suggesting that careful patient selection and implementation of protocol-based management of metabolic comorbidities may further improve clinical outcomes.