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Summary: Background: Since the inception of the interferon‐free direct‐acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection, guidelines as to who should receive this potentially curative treatment have evolved. Treatment with DAAs is now considered for all patients except for those considered moribund. Aim: To determine the DAA treatment rate for patients with HCV‐related hepatocellular carcinoma (HCC). Methods: This was a retrospective study from January 2015 to March 2021 of a national sample of privately insured patients with HCV‐related HCC using Optum's Clinformatics® Data Mart (CDM) Database – a large, de‐identified, adjudicated claims database. Results: We identified 3922 patients with HCV‐related HCC: 922 (23.5%) received DAA. Compared to untreated patients, DAA‐treated patients were younger (65.2 ± 7.5 vs. 66.4 ± 7.5 years, p < 0.001), more frequently saw a gastroenterology/infectious disease (GI/ID) physician (41.2% vs. 34.2%), and had decompensated cirrhosis (56% vs. 53%, p = 0.001). In multivariable analysis, younger age (HR: 0.98, 95% CI: 0.97–0.99, p < 0.001), GI/ID care (HR: 3.06, 95% CI: 2.13–4.51, p < 0.001), and having cirrhosis (compensated: HR: 1.60, 95% CI: 1.18–2.21, p = 0.003; decompensated: HR: 1.45, 95% CI: 1.07–1.98, p = 0.02) were associated with receiving DAA treatment, but not sex, race, or ethnicity. DAA‐treated patients had significantly higher 5‐year survival than untreated patients (47.2% vs. 35.2%, p < 0.001). Following adjustment for age, sex, race/ethnicity, Charlson Comorbidity Index, and HCC treatment, receiving DAA treatment was associated with lower mortality (aHR: 0.61, 95% CI: 0.53–0.69, p < 0.001). Conclusion: DAA treatment remains underutilised in insured patients with HCV‐related HCC; fewer than one in four patients received treatment. Seeing a specialist and having decompensated cirrhosis were predictors for DAA treatment; additional efforts are needed to increase awareness of HCV treatment. [ABSTRACT FROM AUTHOR]

Regular monitoring/surveillance for liver complications is crucial to reduce morbidity and mortality in patients with cirrhosis. Recommendations from professional societies are available but adherence is not well studied, especially outside of academic centers. We aimed to determine the frequencies and factors associated with laboratory monitoring, and hepatocellular carcinoma (HCC) and esophageal varices (EV) surveillance in patients with cirrhosis. We identified 82,427 patients with cirrhosis (43,280 compensated and 39,147 decompensated) from the Truven Health MarketScan Research Database®, 2007–2016. We calculated the proportion of patients with cirrhosis with various frequencies of procedures/testing: laboratory (complete blood count, comprehensive metabolic panel, and prothrombin time), HCC and EV surveillance. We also used multivariable logistic regression to determine factors associated with having procedures. The proportions of patients undergoing HCC surveillance (8.78%), laboratory testing (29.72%) at least every 6–12 months, or EV surveillance (10.6%) at least every 1–2 years were suboptimal. The majority did not have HCC (45.4%) or EV (80.3%) surveillance during the entire study period. On multivariable regression, age 41–55 (vs. <41) years, preferred provider organization (vs. health maintenance organization) insurance plan, specialist care (vs. primary care and other specialties), diagnosis between 2013–2016 (vs. 2007–2009), decompensated (vs. compensated) cirrhosis, non-alcoholic fatty liver disease (vs. viral hepatitis), and higher Charlson comorbidity index were associated with significantly higher odds of undergoing procedures/testing every 6–12 months and EV surveillance every 1–2 years. Despite modest improvements in more recent years, routine monitoring and surveillance for patients with cirrhosis is suboptimal. Further efforts including provider awareness, patient education, and system/incentive-based quality improvement measures are urgently needed. Patients with cirrhosis should undergo health monitoring for liver complications to achieve early detection and treatment. In a large nationwide cohort of 82,427 patients with cirrhosis in the United States, we found a low rate of adherence (well less than half) to routine blood test monitoring and surveillance for liver cancer and esophageal varices (swollen blood vessels in the abdomen that could lead to fatal bleeding). Adherence has increased in the recent years, but much more improvement is needed. [Display omitted] • Adherence to monitoring/surveillance for liver complications was assessed in patients with cirrhosis. • Adherence rates for HCC surveillance (8.78%), laboratory testing (29.72%) and EV surveillance (10.6%) were disappointing. • Adherence rates did improve in more recent years. • Age, insurance plan, being followed up by specialist, severity of cirrhosis, and comorbidities were linked to adherence. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease is common and is associated with rising morbidity and mortality in the UK. Cardiovascular disease is the main cause of death in people with nonalcoholic fatty liver disease.Aims: To determine the association between baseline cardiovascular risk factors with fatty liver index, and to investigate the association between fatty liver index and the incidence of cardiovascular disease in the UK.Methods: This study is a population-based retrospective cohort study using the UK Biobank database.Results: The mean fatty liver index in the study cohort was 44.9, and 33.7% met the criteria for nonalcoholic fatty liver disease. Fatty liver index was significantly associated with a wide range of cardiovascular risk factors at baseline. During a mean follow-up of 7.86 years, the combined incidence of cardiovascular disease was 6.92 per 1000-person years at risk. We found significant association between fatty liver index and incident cardiovascular disease in the fully adjusted model. We found significant association between fatty liver index and incident cardiovascular disease in subgroups stratified by BMI as well as subgroups with fatty liver index < 30, < 60, and ≥ 60.Conclusions: Fatty liver index not only predicts NAFLD diagnosis, but also indicates baseline and future development of cardiovascular disease on long-term follow-up across weight categories and fatty liver index spectrum. These findings can inform clinicians and other stakeholders on cardiovascular disease management and preventive efforts. Patients with high fatty liver index should be counseled on the increased future risk of developing cardiovascular disease. [ABSTRACT FROM AUTHOR]

Summary: Background: The World Health Organization (WHO) has set an elimination goal for hepatitis B virus (HBV) by 2030, so a comprehensive review of current HBV testing and care gaps are needed to help formulate solutions and opportunities for action. Aims: To summarise current gaps and barriers, and to propose solutions for HBV prevention, testing and linkage to care in the United States Methods: Relevant guidelines and studies were reviewed including a systematic review of HCC surveillance adherence. Results: A total of 64.5 million (95% CI, 61.3‐67.5) high‐risk US adults had no evidence of HBV immunity. Only 18.6% (95% CI, 13.5‐29.9) of privately insured patients with HBV infection have been diagnosed. Among those with known HBV infection, linkage to care rate (33.3%‐57%) was poor and the adherence to guidelines regarding anti‐viral therapy (30.66% [95% CI, 30.28‐31.03]) and HCC surveillance (8%‐87%, from a systematic review) were poor with even more concerning data for care and treatment retention. The causes are complex and include lack of access to medical care, lack of physician knowledge, lack of patient health literacy and awareness, linguistic and cultural barriers and fear of stigma. Conclusions: A 'scale‐up' effort is needed to optimise the care continuum to achieve the WHO 2030 targets. As targeted screening policy has leftover 80% of patients undiagnosed, we advocate for universal screening which can help to remove barriers regarding stigma. More active and system level interventions are also needed to improve linkage to care for patients with HBV infection. [ABSTRACT FROM AUTHOR]

Background and Aims: Liver cirrhosis is a substantial health burden in the USA, but population-based data regarding the trend and medical expenditure are limited and outdated. We investigated the trends of inpatient admissions, costs, and inpatient mortality from 2005 to 2015 among cirrhotic patients.Methods: A retrospective analysis was conducted using the National Inpatient Sample database. We adjusted the costs to 2015 US dollars using a 3% inflation rate. National estimates of admissions were determined using discharge weights.Results: We identified 1,627,348 admissions in cirrhotic patients between 2005 and 2015. From 2005 to 2015, the number of weighted admissions in cirrhotic patients almost doubled (from 505,032 to 961,650) and the total annual hospitalization cost in this population increased three times (from 5.8 to 16.3 billion US dollars). Notably, admission rates varied by liver disease etiology, decreasing from 2005 to 2015 among patients with hepatitis C virus (HCV)-related cirrhosis while increasing (almost tripled) among patients with nonalcoholic fatty liver disease (NAFLD)-related cirrhosis. The annual inpatient mortality rate per 1000 admissions overall decreased from 63.8 to 58.2 between 2005 and 2015 except for NAFLD (27.2 to 35.8) (P < 0.001).Conclusions: Rates and costs of admissions in cirrhotic patients have increased substantially between 2005 and 2015 in the USA, but varied by liver disease etiology, with decreasing rate for HCV-associated cirrhosis and for HBV-associated cirrhosis but increasing for NAFLD-associated cirrhosis. Inpatient mortality also increased by one-third for NAFLD, while it decreased for other diseases. Cost also varied by etiology and lower for HCV-associated cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Athough curative therapy is now available for hepatitis C virus (HCV) infection in the United States, it is not clear whether all affected persons have been diagnosed and/or linked to care.Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (1999-2016) and included 46 465 nonincarcerated and noninstitutionalized participants.Results: Viremic HCV prevalence decreased from 1.32% in 1999-2004 to 0.80% in 2011-2016, although most of the decrease occurred in US-born whites and blacks but not the foreign-born or those born after 1985. In 2011-2016, approximately 1.90 million US adults remained viremic with HCV, and 0.33 million were at higher risk for advanced fibrosis, but only 49.8% were aware of their HCV infection, with higher disease awareness in those with health insurance coverage and US-born persons.Conclusions: The prevalence of viremic HCV has decreased in recent years among US born whites and blacks but not in other race/ethnicities and foreign-born persons and birth cohort born after 1985. Less than half of the viremic population was aware of having HCV infection. Improved HCV screening and linkage to care are needed, especially for the uninsured, foreign-born, birth cohort after 1985 and certain ethnic minorities. [ABSTRACT FROM AUTHOR]

• The present study summarizes the SVR rate in patients with/without liver cancer treated with all oral DAAs. • The cure rate was lower in patients with liver cancer, especially those with active cancer. • Additional controlled studies are needed to study the impact of liver cancer on HCV cure rate in DAA-treated patients. The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8–92.1%, I 2 = 79.1% vs. 93.3%, 95% CI 91.9–94.7%, I 2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2–7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p < 0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p < 0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background and Aim: The eradication rate of Helicobacter pylori (H. pylori) has been declining over the past decades. A rescue plan is needed for increasing populations with treatment failure. However, the optimum second‐line eradication regimen remains inconclusive. We conducted a network meta‐analysis to assess the comparative effectiveness of second‐line H. pylori eradication therapies and determine the optimum regimen. Methods: We searched electronic databases from January 2005 to February 2018 for randomized controlled trials assessing the effectiveness of second‐line regimens in patients with persistent H. pylori infection after first‐line treatment. Bayesian network meta‐analysis was performed to combine the direct and indirect evidence and to investigate the rank order of second‐line therapies. We also appraised the quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation guidance. Results: Twenty‐six trials with 3628 participants who received second‐line eradication therapy were identified. All regimens showed pooled eradication rates < 90%. Compared with 7‐day triple therapy, quinolone‐based (odds ratio [OR] 4.29, 95% credible interval [CrI] 1.67–12.12, surface under the cumulative ranking [SUCRA] 0.95), non‐quinolone‐based bismuth‐containing quadruple therapies for 10 days or more (OR 2.25, 95% CrI 1.10–4.62, SUCRA 0.78), and sequential therapy (OR 2.91, 95% CrI 1.16–7.65, SUCRA 0.66) showed significantly higher effectiveness. Overall, regimens with longer duration demonstrated higher eradication rates but higher rates of adverse events. More adverse events were reported in those patients treated with concomitant therapy. Conclusions: Quinolone‐based bismuth‐containing quadruple therapies for 10 days or more are the optimum second‐line regimens for H. pylori eradication. [ABSTRACT FROM AUTHOR]

Most recent studies on the coronavirus disease 2019 (COVID‐19) pandemic and cutaneous melanoma (CM) focused more on delayed diagnosis or advanced presentation. We aimed to ascertain mortality trends of CM between 2012 and 2022, focusing on the effects of the COVID‐19 pandemic. In this serial population‐based study, the National Vital Statistics System dataset was queried for mortality data. Excess CM‐related mortality rates were estimated by calculating the difference between observed and projected mortality rates during the pandemic. Totally there were 108,853 CM‐associated deaths in 2012–2022. CM‐associated mortality saw a declining trend from 2012 to 2019 overall. However, it increased sharply in 2020 (ASMR 3.73 per 100,000 persons, 5.95% excess mortality), and remained high in 2021 and 2022, with the ASMRs of 3.82 and 3.81, corresponding to 11.17% and 13.20% excess mortality, respectively. The nonmetro areas had the most pronounced rise in mortality with 12.20% excess death in 2020, 15.33% in 2021 and 20.52% in 2022, corresponding to a 4–6 times excess mortality risk compared to large metro areas during the pandemic. The elderly had the most pronounced rise in mortality, but the mortality in the younger population was reduced. [ABSTRACT FROM AUTHOR]

There are currently no studies examining differences in perceptions and expected impact of the Step 1 score change to pass/fail between surgical and non-surgical program directors (PDs). We conducted a systematic review in May 2023 of PubMed, Scopus, Web of Science, and PSYCInfo to evaluate studies examining PDs' perspectives regarding the Step 1 score change. We performed random-effects meta-analyses to determine differences in perspectives among surgical and non-surgical PDs. Surgical PDs (76.8% [95% CI, 72.1%-82.0%], I 2 = 52%) reported significantly greater rates of disagreement with the score change compared to non-surgical (65.1% [95% CI, 57.9%-73.1%], I 2 = 69.7%) (P =.01). Surgical PDs also reported significantly greater rates of agreement that the score change will increase the difficulty in objectively comparing applicants (88.1% [95% CI, 84.6%-91.7%], I 2 = 16.4%), compared to non-surgical (81.0% [95% CI, 75.6%-86.8%], I 2 = 72.6%) (P =.04). There was less heterogeneity among non-surgical PDs (88.7% [95% CI, 86.2%-91.2%], I 2 = 0%), compared to surgical (84.7% [95% CI, 79.0%-90.8%], I 2 = 67.3%), regarding expected increases in emphasis on Step 2, although the difference in rates of agreement was not statistically significant. Overall, there is significant heterogeneity in the literature regarding expected changes in the residency application review process. Most PDs reported significant disagreement with the score change, greater expected difficulty in objectively evaluating applicants, and greater emphasis on Step 2, with surgical PDs reporting greater rates of disagreement, greater expected difficulty, and heterogeneity regarding expected increases in emphasis on Step 2, compared to non-surgical. Additionally, there is significant heterogeneity in the overall literature regarding expected changes in the residency application review process. Further research is needed to establish evidence-based guidelines that improve the overall residency application process for all stakeholders. [ABSTRACT FROM AUTHOR]

Background: The readability of online bariatric surgery patient education materials (PEMs) often surpasses the recommended 6th grade level. Large language models (LLMs), like ChatGPT and Bard, have the potential to revolutionize PEM delivery. We aimed to evaluate the readability of PEMs produced by U.S. medical institutions compared to LLMs, as well as the ability of LLMs to simplify their responses. Methods: Responses to frequently asked questions (FAQs) related to bariatric surgery were gathered from top-ranked health institutions. FAQ responses were also generated from GPT-3.5, GPT-4, and Bard. LLMs were then prompted to improve the readability of their initial responses. The readability of institutional responses, initial LLM responses, and simplified LLM responses were graded using validated readability formulas. Accuracy and comprehensiveness of initial and simplified LLM responses were also compared. Results: Responses to 66 FAQs were included. All institutional and initial LLM responses had poor readability, with average reading levels ranging from 9th grade to college graduate. Simplified responses from LLMs had significantly improved readability, with reading levels ranging from 6th grade to college freshman. When comparing simplified LLM responses, GPT-4 responses demonstrated the highest readability, with reading levels ranging from 6th to 9th grade. Accuracy was similar between initial and simplified responses from all LLMs. Comprehensiveness was similar between initial and simplified responses from GPT-3.5 and GPT-4. However, 34.8% of Bard's simplified responses were graded as less comprehensive compared to initial. Conclusion: Our study highlights the efficacy of LLMs in enhancing the readability of bariatric surgery PEMs. GPT-4 outperformed other models, generating simplified PEMs from 6th to 9th grade reading levels. Unlike GPT-3.5 and GPT-4, Bard's simplified responses were graded as less comprehensive. We advocate for future studies examining the potential role of LLMs as dynamic and personalized sources of PEMs for diverse patient populations of all literacy levels. [ABSTRACT FROM AUTHOR]

The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized. [Display omitted] • The overall prevalence of sarcopenia among patients with cirrhosis is 37.5%, with higher prevalence in males, patients with alcohol-related liver disease, and greater severity of cirrhosis. • The 1-, 3-, and 5-year cumulative probabilities of survival in patients with sarcopenia were 76.6%, 64.3%, and 45.3%, respectively. By comparison, they were 93.4%, 82.0%, and 74.2%, respectively in patients without sarcopenia • Sarcopenia is associated with an approximately 2-fold higher risk of death in patients with cirrhosis • Every 1 cm2/m2 increase in L3-SMI and 1 mm/m increase in umbilicus-TPMT were associated with a 3% and 12% decrease in mortality risk, respectively. [ABSTRACT FROM AUTHOR]

The occurrence of HBV-associated liver complications is reduced by antiviral therapy. However, prior studies using local institutional cohorts have suggested that evaluation and treatment are suboptimal. We aimed to determine the proportion of patients with chronic HBV infection who received adequate evaluation, were treatment eligible, and received antiviral treatment using a large, nationwide cohort. This retrospective analysis utilized claims data of approximately 73 million enrollees across the US from Optum's de-identified Clinformatics® Data Mart Database, 2003-2019. Adults observed for ≥6 months before and after an index diagnosis of chronic HBV infection were identified via ICD-9/ICD-10 codes, with the diagnosis confirmed by positive HBsAg, HBeAg or HBV DNA PCR. We included 12,608 eligible patients in the study analysis (mean age 45.7 years, 52.1% male, 54.6% Asian, 18.1% Caucasian, 10.5% African American). About half of the cohort (n = 6,559, 52.3%) did not have a complete laboratory evaluation (defined as having HBeAg, HBV DNA, and ALT tests) and only 72.4% (n = 9,129) had an "adequate" evaluation (at least HBV DNA and ALT) during the entire study period. Of those with an adequate evaluation, 11.2% were treatment eligible by AASLD criteria and 13.9% by EASL criteria; 60.4% of AASLD eligible patients and 54.3% of EASL eligible patients received treatment within 12 months from becoming eligible. Half of patients with chronic HBV infection in the US with private insurance did not have a complete laboratory assessment. Over one-third of treatment-eligible patients did not receive antiviral therapy. Patients who visited a specialist had a higher chance of receiving adequate evaluation and treatment. Urgent intervention is needed to identify and address the barriers to optimal care. In this study, we used a national database that includes laboratory data in addition to medical and pharmacy claims data to assess the current real-world management of chronic HBV infection in the US. Among the 12,608 patients with chronic HBV infection included in our study, 52.3% never had a complete laboratory evaluation and only 73% had an adequate evaluation. Among those who were treatment eligible according to major society guidelines, only 60.4% and 54.3% received treatment within 12 months, respectively. [Display omitted] • We determined the proportion of patients with chronic HBV infection who received adequate evaluation and treatment (if eligible). • Among 12,608 patients with chronic HBV infection, 52.3% did not have a complete evaluation and only 73% had an adequate evaluation. • In the 9,129 patients who had an adequate evaluation, 11.2% and 13.9% were treatment eligible by AASLD or EASL criteria, respectively. • Among those who were treatment eligible by AASLD or EASL criteria, only 60.4% and 54.3% received treatment within 12 months, respectively. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Given the global rise in obesity‐related metabolic diseases, the upper limit of normal (ULN) alanine aminotransferase (ALT) in individuals with and without metabolic diseases may have changed. We performed a meta‐analysis combined with bootstrap modelling to estimate the ALT ULN levels for individuals with and without metabolic diseases. Methods and Results: Two separate searches of the PubMed, Embase and Cochrane databases were performed, one to identify healthy individuals which yielded 12 articles (349,367 individuals); another to include those with potential metabolic diseases but without known liver disease which yielded 35 articles (232,388 individuals). We estimated the mean ALT using a random‐effects mixed model and the ULN level (95th‐percentile value) via a bootstrap model with 10,000 resamples. In individuals without metabolic diseases and known liver disease, the ALT ULN levels were 32 U/L overall; 36 U/L in males and 28 U/L in females. In analyses that included individuals with metabolic diseases, the ALT ULN levels were 40 U/L among the overweight/obese (29 U/L if normal weight) and 36 U/L among those with type 2 diabetes mellitus (T2DM) (33 U/L if no T2DM). On meta‐regression of study‐level factors, body mass index (coefficient 1.49, 95% CI 0.11–2.86, p = 0.03), high‐density lipoprotein (coefficient −0.47, 95% CI −0.85‐(−0.08), p = 0.02) and triglycerides (coefficient 0.19, 95% CI 0.12–0.25, p < 0.0001) correlated with ALT. Conclusion: We provide expected ranges of ALT ULN levels for individuals without known liver disease without metabolic diseases and those with or without T2DM and/or are normal weight or overweight/obese. These data may have implications for clinical care and screening. [ABSTRACT FROM AUTHOR]

Background and Aims: The relationship between moderate alcohol intake and health outcomes among individuals with metabolic dysfunction‐associated fatty liver disease (MAFLD) is complex. Our aim was to investigate the association of minimal alcohol consumption with all‐cause and cause‐specific mortality among MAFLD individuals of different genders. Methods: Our study included 2630 MAFLD individuals from the Third National Health and Nutrition Examination Survey. Cox regression analysis was performed to assess the association between alcohol use measures and all‐cause and cause‐specific mortality. Restricted cubic spline curves were used to evaluate the relationship between alcohol consumption per week and all‐cause mortality. Results: In the entire MAFLD cohort, we observed significant disparities in clinical characteristics between male and female individuals with MAFLD. Higher weekly alcohol consumption was significantly associated with all‐cause and cause‐specific mortality (male, hazard ratios [HRs]: 1.009, 95% CIs: 1.004–1.014; female, HRs: 1.032, 95% CIs: 1.022–1.042). In males with MAFLD, a linear association with all‐cause mortality was observed for weekly alcohol consumption (p for non‐linearity =.21). Conversely, in females with MAFLD, the risk of all‐cause mortality remained relatively stable until 2 drinks per week, after which it rapidly increased with each additional drink consumed, and the increase in mortality risk was higher than that observed in males (p for non‐linearity <.05). Conclusions: Our findings indicate that any increase in weekly alcohol consumption was associated with increased all‐cause mortality in men with MAFLD. Conversely, consuming less than 2 drinks per week had minimal impact on the risk of mortality among female. [ABSTRACT FROM AUTHOR]

Background: US progress toward ending the HIV epidemic was disrupted during the COVID‐19 pandemic. Objectives: To determine the impact of the pandemic on HIV‐related mortality and potential disparities. Methods: Using data from the Centers for Disease Control and Prevention and the United States (US) Census Bureau, HIV‐related mortality data of decedents aged ≥25 years between 2012 and 2021 were analyzed. Excess HIV‐related mortality rates were estimated by determining the difference between observed and projected mortality rates during the pandemic. The trends of mortality were quantified with joinpoint regression analysis. Results: Of the 79,725 deaths documented in adults aged 25 years and older between 2012 and 2021, a significant downward trend was noted in HIV‐related mortality rates before the pandemic, followed by a surge during the pandemic. The observed mortality rates were 18.8% (95% confidence interval [CI]: 13.1%–25.5%) and 25.4% (95%CI: 19.9%–30.4%) higher than the projected values in 2020 and 2021, respectively. Both of these percentages were higher than that in the general population in 2020 (16.4%, 95%CI: 14.9%–17.9%) and 2021 (19.8%, 95%CI: 18.0%–21.6%), respectively. Increased HIV‐related mortality was observed across all age subgroups, but those aged 25–44 years demonstrated the greatest relative increase and the lowest COVID‐19‐related deaths when compared to middle‐ and old‐aged decedents. Disparities were observed across racial/ethnic subgroups and geographic regions. Conclusions: The pandemic led to a reversal in the attainments made to reduce the prevalence of HIV. Individuals living with HIV were disproportionately affected during the pandemic. Thoughtful policies are needed to address the disparity in excess HIV‐related mortality. [ABSTRACT FROM AUTHOR]

Background: Little is known about mortality trends among patients with psoriasis (PsO) and psoriatic arthritis (PsA) in the United States. Objectives: To ascertain mortality trends of PsO and PsA between 2010 and 2021, focusing on the effects of the COVID‐19 pandemic. Methods: We collected data from the National Vital Statistic System and calculated age‐standardized mortality rates (ASMR) and cause‐specific mortality for PsO/PsA. We evaluated observed versus predicted mortality for 2020–2021 based on trends from 2010 to 2019 with joinpoint and prediction modelling analysis. Results: Among 5810 and 2150 PsO‐ and PsA‐related deaths between 2010 and 2021, ASMR for PsO dramatically increased between 2010–2019 and 2020–2021 (annual percentage change [APC] 2.07% vs. 15.26%; p < 0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (0.27 vs. 0.22) and 2021 (0.31 vs. 0.23). The excess mortality of PsO was 22.7% and 34.8% higher than that in the general population in 2020 (16.4%, 95% CI: 14.9%–17.9%) and 2021 (19.8%, 95% CI: 18.0%–21.6%) respectively. Notably, the ASMR rise for PsO was most pronounced in the female (APC: 26.86% vs. 12.19% in males) and the middle‐aged group (APC: 17.67% vs. 12.47% in the old‐age group). ASMR, APC and excess mortality for PsA were similar to PsO. SARS‐CoV‐2 infection contributed to more than 60% of the excess mortality for PsO and PsA. Conclusions: Individuals living with PsO and PsA were disproportionately affected during the COVID‐19 pandemic. Both ASMRs increased at an alarming rate, with the most pronounced disparities among the female and middle‐aged groups. [ABSTRACT FROM AUTHOR]

Background: Hepatobiliary cystadenocarcinoma is a rare epithelial malignant neoplasm of the liver or extrahepatic bile ducts. Early diagnosis of hepatobiliary cystadenocarcinoma is difficult because of its asymptomatic features and rarity. Moreover, the molecular pathogenesis of hepatobiliary cystadenocarcinoma remains unclear. Herein, we described a case of hepatobiliary cystadenocarcinoma in female with chronic hepatitis B and repeated hepatolithiasis.Case Presentation: A 65-year-old woman with medical history of latent hepatitis B virus infection, repeated choledocholisthiasis, and cholecystitis was admitted due to a heterogeneous cystic mass (5.6 cm × 4 cm) shown on abdominal ultrasonography during regular physical checkup. The patient complained about irregular bowel movements with intermittent diarrhea for two months before presentation. Computed tomography (CT) disclosed a multiloculated cystic lesion in the left hepatic lobe with the presence of intraductal stones and dilatation of intrahepatic ducts. Histological results obtained from left lobectomy specimens showed hepatobiliary cystadenocarcinoma without accompanied mesenchymal stroma.Conclusion: Notably, hepatobiliary cystadenocarcinoma without mesenchymal stroma seldom occurs in women and is usually associated with poor prognosis. We present the rare findings in this patient and suggest that chronic inflammatory insults in the intrahepatic bile ducts might shed light on the cystadenocarcinogenesis. [ABSTRACT FROM AUTHOR]

The pandemic has resulted in an increase of deaths not directly related to COVID-19 infection. We aimed to use a national death dataset to determine the impact of the pandemic on people with liver disease in the USA, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Using data from the National Vital Statistic System from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed vs. predicted mortality for 2020–2021 based on trends from 2010–2019 with joinpoint and prediction modelling analysis. Among 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardised mortality rates (ASMRs) for ALD dramatically increased between 2010–2019 and 2020–2021 (annual percentage change [APC] 3.5% to 17.6%, p <0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (15.67 vs. 13.04) and 2021 (17.42 vs. 13.41). ASMR for NAFLD also increased during the pandemic (APC: 14.5%), whereas the rates for hepatitis B and C decreased. Notably, the ASMR rise for ALD was most pronounced in non-Hispanic Whites, Blacks, and Alaska Indians/Native Americans (APC: 11.7%, 10.8%, 18.0%, all p <0.05), with similar but less critical findings for NAFLD, whereas rates were steady for non-Hispanic Asians throughout 2010–2021 (APC: 4.9%). The ASMR rise for ALD was particularly severe for the 25–44 age group (APC: 34.6%, vs. 13.7% and 12.6% for 45–64 and ≥65, all p <0.01), which were also all higher than pre-COVID-19 rates (all p <0.01). ASMRs for ALD and NAFLD increased at an alarming rate during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. The pandemic has led to an increase of deaths directly and indirectly related to SARS-CoV-2 infection. As shown in this study, age-standardised mortality rates for alcohol-associated liver disease and non-alcoholic fatty liver disease substantially increased during the COVID-19 pandemic in the USA and far exceeded expected levels predicted from past trends, especially among the young, non-Hispanic White, and Alaska Indian/Native American populations. However, much of this increase was not directly related to COVID-19. Therefore, for the ongoing pandemic as well as its recovery phase, adherence to regular monitoring and care for people with chronic liver disease should be prioritised and awareness should be raised among patients, care providers, healthcare systems, and public health policy makers. [Display omitted] • All-cause ASMR for ALD increased several fold between 2010–2019 and 2020-2021 (APC 3.5% to 17.6%, p <0.01). • For NAFLD, all-cause ASMRs also rose steadily across the entire study period but with a sharper rise after 2019. • ASMR rise for ALD and NAFLD was particularly severe for the 25–44 years age group. • ASMR rise for ALD was also most pronounced in non-Hispanic Alaska Indians/Native American and White people. [ABSTRACT FROM AUTHOR]

The article discusses the potential use of large language models (LLMs), such as ChatGPT, in supporting bariatric surgery patients. LLMs are advanced artificial intelligence models that can generate human-like and easy-to-understand text. They have the potential to provide reliable information, answer patient questions, and offer empathetic responses. However, there are limitations to consider, such as the accuracy of information, potential biases, and the possibility of generating inaccurate information. Further research and validation are needed to ensure the safety and efficacy of LLMs in improving patient care and outcomes. [Extracted from the article]

Background: Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood.Methods: This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.Results: The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%-2.88%) and an annual rate of 0.22% (.17%-.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80-5.49]), elevated serum alanine aminotransferase >200 U/L (3.68 [2.07-6.53]), serum bilirubin (1.11 per mg/dL; [1.06-1.17 mg/dL]), and fatty liver (1.84 [1.03-3.29]).Conclusion: HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance incidence in CHB patients.Methods: In a retrospective cohort study of 6786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups.Results: Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in the antiviral-treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (hazard ratio [HR], 0.19 [95% confidence interval {CI}, .12-.33], P < .001 and HR, 0.21 [95% CI, .09-.51], P = .001, respectively) in antiviral-treated patients but not in untreated patients.Conclusions: FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB. [ABSTRACT FROM AUTHOR]

Matriptase is ectopically expressed in neoplastic B-cells, in which matriptase activity is enhanced by negligible expression of its endogenous inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. HAI-1, however, is also involved in matriptase synthesis and intracellular trafficking. The lack of HAI-1 indicates that other related inhibitor, such as HAI-2, might be expressed. Here, we show that HAI-2 is commonly co-expressed in matriptase-expressing neoplastic B-cells. The level of active matriptase shed after induction of matriptase zymogen activation in 7 different neoplastic B-cells was next determined and characterised. Our data reveal that active matriptase can only be generated and shed by those cells able to activate matriptase and in a rough correlation with the levels of matriptase protein. While HAI-2 can potently inhibit matriptase, the levels of active matriptase are not proportionally suppressed in those cells with high HAI-2. Our survey suggests that matriptase proteolysis might aberrantly remain high in neoplastic B-cells regardless of the levels of HAI-2. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Hemorrhage is responsible for most deaths that occur during the first few hours after trauma. Animal models of trauma have shown that restricting fluid administration can reduce the risk of death; however, studies in patients are difficult to conduct due to logistical and ethical problems. To maximize the value of the existing evidence, we performed a meta-analysis to compare liberal versus restricted fluid resuscitation strategies in trauma patients. DATA SOURCES: Medline and Embase were systemically searched from inception to February 2013. STUDY SELECTION: We selected randomized controlled trials and observational studies that compared different fluid administration strategies in trauma patients. There were no restrictions for language, population, or publication year. DATA EXTRACTION: Four randomized controlled trials and seven observational studies were identified from 1,106 references. One of the randomized controlled trials suffered from a high protocol violation rate and was excluded from the final analysis. DATA SYNTHESIS: The quantitative synthesis indicated that liberal fluid resuscitation strategies might be associated with higher mortality than restricted fluid strategies, both in randomized controlled trials (risk ratio, 1.25; 95% CI, 1.01-1.55; three trials; I, 0) and observational studies (odds ratio, 1.14; 95% CI, 1.01-1.28; seven studies; I, 21.4%). When only adjusted odds ratios were pooled for observational studies, odds for mortality with liberal fluid resuscitation strategies increased (odds ratio, 1.19; 95% CI, 1.02-1.38; six studies; I, 26.3%). CONCLUSIONS: Current evidence indicates that initial liberal fluid resuscitation strategies may be associated with higher mortality in injured patients. However, available studies are subject to a high risk of selection bias and clinical heterogeneity. This result should be interpreted with great caution. [ABSTRACT FROM AUTHOR]

The ability of cells to rapidly detect and react to alterations in their chemical environment, such as pH, ionic strength and redox potential, is essential for cell function and survival. We present here evidence that cells can respond to such environmental alterations by rapid induction of matriptase autoactivation. Specifically, we show that matriptase autoactivation can occur spontaneously at physiological pH, and is significantly enhanced by acidic pH, both in a cell-free system and in living cells. The acid-accelerated autoactivation can be attenuated by chloride, a property that may be part of a safety mechanism to prevent unregulated matriptase autoactivation. Additionally, the thio-redox balance of the environment also modulates matriptase autoactivation. Using the cell-free system, we show that matriptase autoactivation is suppressed by cytosolic reductive factors, with this cytosolic suppression being reverted by the addition of oxidizing agents. In living cells, we observed rapid induction of matriptase autoactivation upon exposure to toxic metal ions known to induce oxidative stress, including CoCl2 and CdCl2. The metal-induced matriptase autoactivation is suppressed by N-acetylcysteine, supporting the putative role of altered cellular redox state in metal induced matriptase autoactivation. Furthermore, matriptase knockdown rendered cells more susceptible to CdCl2-induced cell death compared to control cells. This observation implies that the metal-induced matriptase autoactivation confers cells with the ability to survive exposure to toxic metals and/or oxidative stress. Our results suggest that matriptase can act as a cellular sensor of the chemical environment of the cell that allows the cell to respond to and protect itself from changes in the chemical milieu. [ABSTRACT FROM AUTHOR]

Background: Blood culture is viewed as the golden standard for the diagnosis of sepsis but suffers from low sensitivity and long turnaround time. LightCycler SeptiFast (LC-SF) is a real-time multiplex polymerase chain reaction test able to detect 25 common pathogens responsible for bloodstream infections within hours. We aim to assess the accuracy of LC-SF by systematically reviewing the published studies. Method: Related literature on Medline, Embase, and Cochrane databases was searched up to October 2012 for studies utilizing LC-SF to diagnose suspected sepsis and that provided sufficient data to construct two-by-two tables. Results: A total of 34 studies enrolling 6012 patients of suspected sepsis were included. The overall sensitivity and specificity for LC-SF to detect bacteremia or fungemia was 0·75 (95% CI: 0·65–0·83) and 0·92 (95%CI:0·90–0·95), respectively. LC-SF had a high positive likelihood ratio (10·10) and a moderate negative likelihood ratio (0·27). Specifically, LC-SF had a sensitivity of 0·80 (95%CI: 0·70–0·88) and a specificity of 0·95(95%CI: 0·93–0·97) for the bacteremia outcome, and a sensitivity of 0·61 (95%CI: 0·48–0·72) and a specificity of 0·99 (95%CI: 0·99–0·99) for the fungemia outcome. High heterogeneity was found in the bacteremia outcome subgroup but not in the fungemia outcome subgroup. Conclusion: LC-SF is of high rule-in value for early detection of septic patients. In a population with low pretest probability, LC-SF test can still provide valuable information for ruling out bacteremia or fungemia. [ABSTRACT FROM AUTHOR]

Background and aim: Recent practice guidelines suggest healthy normal alanine aminotransferase (ALT) levels should be less than 30 U/L for males and 19 U/L for females. We tried to validate the prediction power of the "low cut off" for liver related outcomes in the general population. Methods: A total of 426,013 subjects were followed up for 10 years using the National Health Screening Cohort database. Prediction ability of long term mortality and liver related outcomes between conventional (<40 U/L in men and women) and low (<30 U/L in men and <19 U/L in women) ALT cut-off values were compared. Results: Both conventional and low ALT cut-offs predicted liver related unfavorable outcomes in Kaplan-Meier analysis. Following adjustment for age, body mass index, smoking, exercise, alcohol consumption, fasting blood glucose, and cholesterol via multivariate Cox regression, abnormal ALT using new 'low ALT cut off' was a significant independent predictor for liver-related mortality, HCC, and decompensated liver events. When the low cut-off criteria were added to the prediction model, the ability to predetect liver-related hard outcomes significantly increased in both men and women (p-values < 0.0001). The C-index values for predicting liver-related adverse events were the same in both ALT cut-offs, after adjusting confounding factors (C index value: 0.73~0.88). Conclusions: New low ALT cut-off showed good prediction power for liver related unfavorable outcomes. [ABSTRACT FROM AUTHOR]