Liver Disease-related Mortality Research Articles

Protein truncating variants in mitochondrial-related nuclear genes and the risk of chronic liver disease

BackgroundMitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of liver diseases have not been extensively explored.MethodsWe extracted 60,928 PTVs across 2466 MT-related nucleus genes using whole-exome sequencing data obtained from 442,603 participants in the UK Biobank. We examined their associations with liver dysfunction that represented by the liver-related biomarkers and the risks of chronic liver diseases and liver-related mortality.Results96.10% of the total participants carried at least one PTV. We identified 866 PTVs that were positively associated with liver dysfunction at the threshold of P value < 8.21e − 07. The coding genes of these PTVs were mainly enriched in pathways related to lipid, fatty acid, amino acid, and carbohydrate metabolisms. The 866 PTVs were presented in 1.07% (4721) of participants. Compared with participants who did not carry any of the PTVs, the carriers had a 5.33-fold (95% CI 4.15–6.85), 2.82-fold (1.69–4.72), and 4.41-fold (3.04–6.41) increased risk for fibrosis and cirrhosis of liver, liver cancer, and liver disease-related mortality, respectively. These adverse effects were consistent across subgroups based on age, sex, body mass index, smoking status, and presence of hypertension, diabetes, dyslipidemia, and metabolic syndrome.ConclusionsOur findings revealed a significant impact of PTVs in MT-related genes on liver disease risk, highlighting the importance of these variants in identifying populations at risk of liver diseases and facilitating early clinical interventions.

Strategic considerations in health economics for the complete treatment of patients with chronic HBV infection

The World Health Organization (WHO) released the Global Health Sector Strategy 2016, which explicitly proposes a 90% reduction in the new hepatitis B virus (HBV) infection rate and a 65% reduction in HBV-related mortality by 2030. However, at present, there are still 296 million chronic hepatitis B virus-infected patients worldwide, and nearly 900,000 patients die every year from cirrhosis and liver cancer caused by HBV infection. Antiviral treatment for chronic hepatitis B virus infection can effectively inhibit HBV replication, reduce liver inflammation and necrosis, effectively block and reverse liver fibrosis, and even early cirrhosis, thereby lowering cirrhosis-related complications, liver cancer, and liver disease-related mortality. Although the domestic and foreign guidelines have gradually eased antiviral treatment indications for chronic hepatitis B, there are still a considerable number of chronic hepatitis B patients with nonconformity who cannot receive antiviral treatment because they do not meet the existing standards, resulting in the progression of more severe diseases. This study analyzed the prevalence of hepatitis B, the therapeutic effect of antiviral drugs, domestic and international guideline treatment standards, the assessment of key indicators changes in the guidelines, comprehensively considered the coverage rate and treatment standards for antiviral treatment, and explored the changes in disease burden and cost-effectiveness following increasing the coverage rate and reducing treatment thresholds in order to achieve the global strategic goal of eliminating hepatitis B as soon as possible as a public health threat.

Association of chronic liver disease with bone diseases and muscle weakness.

The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies.

Association of Diabetic Retinopathy with Midlife Hepatic Steatosis Diagnosed by Elastography and Hepatic Steatosis Index in Type 2 Diabetes in an Indian Population.

Aims: People with type 2 diabetes mellitus are at increased risk of developing hepatic steatosis. We determined the prevalence of hepatic steatosis in middle-aged patients with and without diabetic retinopathy (DR) in an Indian population. We feel this information is critical, with trends of increasing chronic liver disease-related mortality at younger ages. Method: Institution-based analytical cross-sectional study with 114 middle-aged type 2 diabetes patients; 57 in each group with <15 years of duration of DM and without excessive drinking. Hepatic steatosis was determined by the hepatic steatosis index (HSI), hepatic ultrasonography (USG), and elastography. Result: The HSI in DR (37.9 ± 3.9) was more (P = 0.012) than in without diabetic retinopathy (NODR) (36.3 ± 3.3). There was no difference between two groups in liver span (P = 0.829) or in the prevalence of fatty liver (P = 0.562) as determined by conventional USG. Elastography value (kPa) was more (P = 0.001) in DR (6.51 ± 1.85) than in NODR (5.14 ± 1.60). On elastography, 50.9% in DR had a likelihood ratio (Metavir score for a stiffness value) for stage 2 Metavir score. In DR, 11.8% of those missed by USG had a likelihood ratio for ≥ stage 2 Metavir score on elastography. The presence of DR was independently correlated with kPa value (P < 0.001). Conclusion: A significantly higher prevalence of hepatic steatosis was observed in DR in this population. DR can be a useful biomarker for early hepatic screening in midlife, particularly with hepatic elastography, so that timely diagnosis of hepatic steatosis can be made.

A review: Alcoholic liver disease pathophysiology, current molecular and clinical perspectives

Alcohol-related liver damage (ALD) is a term used for a variety of liver conditions comprising cirrhosis, fibrosis, and steatohepatitis with chronic inflammation that is predominantly brought on by heavy alcohol consumption. ALD is currently regarded as one of the most common causes of liver disease-related mortality on a global scale. The majority of cirrhosis in the liver cases seen in district general hospitals in the UK are caused by alcohol, which is a key factor in the Western world. Alcoholic cirrhosis, acute alcoholic hepatitis, and alcoholic fatty liver (steatosis) are the three most widely recognized types of alcoholic liver disease. According to the National Institute on Alcohol Abuse and Alcoholism's the most recent surveillance report, liver cirrhosis was among the top twelve causes of death in the country, contributing to a total of 14,477 deaths in the year 2014.This page speaks about the various types of alcoholic liver damage (ALD), with a focus on cirrhosis because it is the type of liver diseases that is most frequently linked to alcohol misuse and has the most studies investigating it. Epidemiological studies have assessed the incidence of ALD and the factors who frequently cause the condition. Although excessive alcohol use is the main cause of ALD, gender and cultural variations also have a significant role in the prevalence of liver disease. Since the 1970s, cirrhosis-related mortality rates have decreased in the United States and certain other countries as well. This dip may have been caused by a variety of variables, including increasing enrollment in alcohol rehab facilities and in Alcoholics Anonymous, drops in alcohol consumption, and more

Low geriatric nutritional risk index predicts poor prognosis in patients with cirrhosis: a retrospective study.

Malnutrition, which increases the risk of liver disease-related events and mortality, is a serious complication in cirrhosis. This study aimed to investigate whether the geriatric nutritional risk index (GNRI) could predict the long-term prognosis in patients with cirrhosis. We retrospectively evaluated 266 patients with cirrhosis and classified them into two groups based on baseline GNRI scores: risk (≤98, n = 104) and no-risk groups (>98, n = 162). The cumulative survival rates were compared between the two groups in patients with compensated and decompensated cirrhosis, respectively. Cox proportional hazards regression analysis was used to identify significant and independent factors associated with mortality. The median observation period was 54.9 (33.6-61.7) months and 65 (24.4%) liver disease-related deaths occurred during the follow-up period. The GNRI scores significantly and inversely correlated with Child-Pugh score (r = -0.579), model for end-stage liver disease score (r = -0.286), and Mac-2 binding protein glycosylation isomer (r = -0.494). Multivariate analysis identified low GNRI as a significant and independent factor associated with mortality [overall cohort: hazard ratio (HR), 0.926; p < 0.001; compensated cirrhosis: HR, 0.947; p = 0.003; decompensated cirrhosis: HR, 0.923; p < 0.001]. The risk group demonstrated significantly lower cumulative survival rates than the no-risk group in overall cohort, and patients with compensated and decompensated cirrhosis (p < 0.001, <0.001, and = 0.013, respectively). Low GNRI was associated with poor long-term prognosis in both patients with compensated and decompensated cirrhosis. Therefore, the GNRI is a simple and useful tool for predicting prognosis and modifying the nutritional status in patients with cirrhosis.

Suaeda glauca Attenuates Liver Fibrosis in Mice by Inhibiting TGFβ1-Smad2/3 Signaling in Hepatic Stellate Cells.

Chronic liver injury due to various hepatotoxic stimuli commonly leads to fibrosis, which is a crucial factor contributing to liver disease-related mortality. Despite the potential benefits of Suaeda glauca (S. glauca) as a natural product, its biological and therapeutic effects are barely known. This study investigated the effects of S. glauca extract (SGE), obtained from a smart farming system utilizing LED lamps, on the activation of hepatic stellate cells (HSCs) and the development of liver fibrosis. C57BL/6 mice received oral administration of either vehicle or SGE (30 or 100 mg/kg) during CCl4 treatment for 6 weeks. The supplementation of SGE significantly reduced liver fibrosis induced by CCl4 in mice as evidenced by histological changes and a decrease in collagen accumulation. SGE treatment also led to a reduction in markers of HSC activation and inflammation as well as an improvement in blood biochemical parameters. Furthermore, SGE administration diminished fibrotic responses following acute liver injury. Mechanistically, SGE treatment prevented HSC activation and inhibited the phosphorylation and nuclear translocation of Smad2/3, which are induced by transforming growth factor (TGF)-β1 in HSCs. Our findings indicate that SGE exhibits anti-fibrotic effects by inhibiting TGFβ1-Smad2/3 signaling in HSCs.

Daytime napping, nighttime sleeping duration, and risk of hepatocellular carcinoma and liver disease-related mortality

Background & AimsSleep duration has been linked to metabolic dysfunction and chronic inflammation, which may contribute to the development of liver cancer and chronic liver disease (CLD). However, little is known about the relationship between sleep or napping duration and hepatocellular carcinoma (HCC) risk and CLD mortality. MethodsWe followed 295,837 individuals in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. We examined the associations of nighttime sleep duration and daytime napping duration with risk of HCC incidence and CLD mortality. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs). ResultsA total of 357 incident HCC cases and 578 CLD deaths were identified after a median follow-up time of 15.5 years. After adjusting for confounder factors, we found U-shaped associations of nighttime sleep duration with the incidence of HCC (HR<5 vs. 7–8 h = 2.00, 95% CI: 1.22–3.26 and HR≥9 vs. 7–8 h = 1.63, 95% CI: 1.04–2.65) and CLD mortality (HR<5 vs. 7–8 h = 1.78, 95% CI: 1.18–2.69 and HR≥9 vs. 7–8 h = 1.91, 95% CI: 1.35–2.70). Daytime napping was associated with higher risk of HCC (HR≥1 vs. non-nappers = 1.46, 95% CI: 1.04–2.06) and higher CLD mortality (HR≥1 h vs. non-nappers = 1.54, 95% CI: 1.18–2.01) compared with no napping. ConclusionsWe observed U-shaped associations for nighttime sleeping and risk of HCC and CLD mortality. Additionally, longer daytime napping duration was associated with higher risk of HCC and CLD death. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep. Impact and implicationsSleep or napping duration may play a role in the development of liver cancer and chronic liver disease, but little is known about the relationship between them. In addition, abnormal sleep patterns in patients with chronic liver disease may further promote the development of liver disease, creating a vicious cycle. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep, as they can be potentially important factors in the development and progression of liver disease.

Noninvasive imaging biomarkers for liver fibrosis in nonalcoholic fatty liver disease: current and future.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide and becoming a major cause of liver disease-related morbidity and mortality. The presence of liver fibrosis in patients with NAFLD is closely related to prognosis, including the development of hepatocellular carcinoma and other complications of cirrhosis. Therefore, assessment of the presence of significant or advanced liver fibrosis is crucial. Although liver biopsy has been considered the "gold standard" method for evaluating the degree of liver fibrosis, it is not suitable for extensive use in all patients with NAFLD owing to its invasiveness and high cost. Therefore, noninvasive biochemical and imaging biomarkers have been developed to overcome the limitations of liver biopsy. Imaging biomarkers for the stratification of liver fibrosis have been evaluated in patients with NAFLD using different imaging techniques, such as transient elastography, shear wave elastography, and magnetic resonance elastography. Furthermore, artificial intelligence and deep learning methods are increasingly being applied to improve the diagnostic accuracy of imaging techniques and overcome the pitfalls of existing imaging biomarkers. In this review, we describe the usefulness and future prospects of noninvasive imaging biomarkers that have been studied and used to evaluate the degree of liver fibrosis in patients with NAFLD.

How to Effectively Monitor Aging Patients with Chronic Hepatitis B: A Review.

Hepatitis B virus (HBV) infection is a major global public health challenge associated with significant morbidity and mortality. Due to worldwide population aging, HBV infection in the elderly will become increasingly prevalent. Effective universal vaccination programs exist but these are largely targeted towards the younger population. Therefore, the elderly population remains at risk of higher disease burden. New diagnoses of HBV infection in the elderly are usually asymptomatic chronic infections which increases their risk of developing cirrhosis, hepatocellular carcinoma, and liver disease-related mortality, especially if left untreated. Physiological changes and the increasing prevalence of multimorbidity associated with aging also potentially worsen outcomes in elderly patients with chronic HBV infection. Therefore, this cohort of patients should be monitored closely and effectively. Current international clinical practice guidelines unfortunately do not provide hard treatment endpoints specific to elderly patients with chronic HBV infection. Management of these patients is complex and requires an individualized approach. Multiple factors such as physiological changes, comorbidities, compliance, treatment tolerability and efficacy, burden of treatment, and realistic treatment goals need to be considered. Shared decision-making between patient and clinician is essential to ensure that the final decision for or against treatment aligns with the patient's values and preferences. This review article aims to summarize the monitoring and management of chronic HBV infection in the aging population.

Synergistic Associations of PNPLA3 I148M Variant, Alcohol Intake, and Obesity With Risk of Cirrhosis, Hepatocellular Carcinoma, and Mortality

Alcohol drinking and obesity are associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC), but the risk is not uniform among people with these risk factors. Genetic variants, such as I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, may play an important role in modulating cirrhosis and HCC risk. To investigate the joint associations of the PNPLA3 I148M variant, alcohol intake, and obesity with the risk of cirrhosis, HCC, and liver disease-related mortality. This prospective cohort study analyzed 414 209 participants enrolled in the UK Biobank study from March 2006 to December 2010. Participants had no previous diagnosis of cirrhosis and HCC and were followed up through March 2021. Self-reported alcohol intake (nonexcessive vs excessive), obesity (body mass index ≥30 [calculated as weight in kilograms divided by height in meters squared]), and PNPLA3 I148M variant status (noncarrier, heterozygous carrier, or homozygous carrier) from initial assessment. The primary outcomes were incident cirrhosis and HCC cases and liver disease-related death ascertained from inpatient hospitalization records and death registry. The risks were calculated by Cox proportional hazards regression models. A total of 414 209 participants (mean [SD] age, 56.3 [8.09] years; 218 567 women [52.8%]; 389 452 White race and ethnicity [94.0%]) were included. Of these participants, 2398 participants (0.6%) developed cirrhosis (5.07 [95% CI, 4.87-5.28] cases per 100 person-years), 323 (0.1%) developed HCC (0.68 [95% CI, 0.61-0.76] cases per 100 person-years), and 878 (0.2%) died from a liver disease-related cause (1.76 [95% CI, 1.64-1.88] cases per 100 person-years) during a median follow-up of 10.9 years. Synergistic interactions between the PNPLA3 I148M variant, obesity, and alcohol intake were associated with the risk of cirrhosis, HCC, and liver disease-related mortality. The risk of cirrhosis increased supramultiplicatively (adjusted hazard ratio [aHR], 17.52; 95% CI, 12.84-23.90) in individuals with obesity, with excessive drinking, and who were homozygous carriers compared with those with no obesity, with nonexcessive drinking, and who were noncarriers. Supramultiplicative associations between the 3 factors and risks of HCC were found in individuals with 3 risk factors (aHR, 30.13; 95% CI, 16.51-54.98) and liver disease-related mortality (aHR, 21.82; 95% CI, 13.78-34.56). The PNPLA3 I148M variant status significantly differentiated the risk of cirrhosis, HCC, and liver disease-related mortality in persons with excessive drinking and obesity. This study found synergistic associations of the PNPLA3 I148M variant, excessive alcohol intake, and obesity with increased risk of cirrhosis, HCC, and liver disease-related death in the general population. The PNPLA3 I148M variant status may help refine the risk stratification for liver disease in persons with excessive drinking and obesity who may need early preventive measures.

Chronic liver disease-related mortality in diabetes before and during the COVID-19 in the United States.

BackgroundGlobal pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease.AimsWe estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic.MethodsUtilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes.ResultsThe quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men.ConclusionsThe sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD.

Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States.

BackgroundThe 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 U.S, focusing on alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD).MethodsUsing data from the National Vital Statistic System from the CDC WONDER platform and ICD-10 codes, we identified deaths associated with liver disease. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010-2019 with joinpoint and prediction modeling analysis.ResultsAmong 626,090 chronic liver disease-related deaths between 2010 and 2021, Age-standardized mortality rates (ASMR) 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%), while 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 while 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%, versus 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).ConclusionsASMR 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.Lay summaryThe impact of the pandemic on people with liver disease in the U.S remains unclear. This study indicated that age-standardized mortality rates for alcohol associated liver disease and non-alcohol fatty liver disease greatly accelerated during the COVID-19 pandemic with the largest disparities among the young, non-Hispanic White, and Alaska Indian/Native American populations. Increasing awareness about the care importance of chronic liver disease in specific populations must be prioritized.

Pulmonary complications of portal hypertension: The overlooked decompensation.

The systemic nature of cirrhosis and portal hypertension has long been recognized, and the amount of data characterizing the interplay between each system is becoming ever so complex. Lung involvement was among the first described associated entities in cirrhosis, with reports dating back to the late nineteenth century. However, it appears that throughout the years, interest in the pulmonary complications of portal hypertension has generally faded, especially in contrast to other decompensating events, as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers. Despite affecting up to 10%-15% of patients with advanced liver disease and having a proven prognostic impact, hepato-pulmonary syndrome, porto-pulmonary hypertension, and hepatic hydrothorax are frequently misdiagnosed, mistreated, or misinterpreted. This lack of precision might adversely impact patient care, referral to expert centers, and, ultimately, liver disease-related mortality and successful transplantation odds. The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities. The paper focuses on the essential theoretical aspects, addressing the most critical knowledge gaps on the one hand and, on the other hand, critically discussing one key issue for each complication.

Non-alcoholic Fatty Liver Disease and Liver Fibrosis during Aging.

Non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease-related mortality. The prevalence of NAFLD/NASH is expected to increase given the epidemics of obesity and type 2 diabetes mellitus. Older patients are disproportionally affected by NASH and related complications such as progressive fibrosis, cirrhosis and hepatocellular carcinoma; however, they are often ineligible for liver transplantation due to their frailty and comorbidities, and effective medical treatments are still lacking. In this review we focused on pathways that are key to the aging process in the liver and perpetuate NAFLD/NASH, leading to fibrosis. In addition, we highlighted recent findings and cross-talks of normal and/or senescent liver cells, dysregulated nutrient sensing, proteostasis and mitochondrial dysfunction in the framework of changing metabolic milieu. Better understanding these pathways during preclinical and clinical studies will be essential to design novel and specific therapeutic strategies to treat NASH in the elderly.

Changes in County-Level Economic Prosperity Are Associated With Liver Disease–Related Mortality Among Working-Age Adults

There is significant variability in county-level rates of liver disease-related mortality. Although this variability is explained partly by demographics, risk factors for liver disease, and access to specialty liver care, little is known about temporal changes in mortality, and its association with economic prosperity. Therefore, we sought to explore the association between changes in county-level economic prosperity and liver disease-related mortality. We performed a retrospective cohort study using county-level mortality data from the Centers for Disease Control and Prevention, economic prosperity measures from the Distressed Communities Index, and county-level markers of demographics, risk factors for liver disease, and access to health care. Primary analyses focused on adults aged 20 to 64 years of age. We used generalized linear mixed models (outcome= annual percentage change in age-adjusted liver disease-related mortality), with the primary exposure being an interaction between year and change in economic prosperity. There was an inverse relationship between county-level changes in economic prosperity and changes in county-level age-adjusted liver disease-related mortality rates (eg, counties with the smallest increase in economic prosperity had the biggest annual increase in liver disease-related mortality). In generalized linear mixed models accounting for county-level covariates, there was a significant association between economic prosperity and liver disease-related mortality, that is, for every 10-point higher mean rank for change in economic prosperity, there was an additional 0.65% decrease (95% CI, 0.19%-1.10%; P= .006) in mortality per year. County-level changes in economic prosperity, independent of other county-level clinical, demographic, and access-to-care variables, may play a role in population-level trends in liver disease-related deaths among the working age population.

Mechanism of T lymphocyte subsets in the malignant transformation of non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease is becoming the main cause of global liver disease-related morbidity and mortality. Notably, its pathological mechanism is complicated and not yet fully understood. Therefore, immune regulation is undoubtedly an important link in its pathogenesis, especially the change of T lymphocyte subsets. This article introduces the research progress of T lymphocytes involved in steatosis, inflammation, fibrosis, malignant transformation and immunotherapy.

Joint associations of adiposity and alcohol consumption with liver disease-related morbidity and mortality risk: findings from the UK Biobank.

The incidence of both non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD) are expected to grow as a consequence of the ongoing obesity and alcohol consumption trends. We examined the joint associations of adiposity (body mass index (BMI) and waist circumference (WC)) and alcohol consumption on ALD, NAFLD and liver disease incidence and mortality (n = 465,437). Alcohol consumption was categorised based on current UK guidelines (14 units/week). Data were analysed using Cox proportional hazard models. A total of 1090 liver disease deaths, 230 ALD deaths and 192 NAFLD deaths occurred over an average follow-up length of 10.5 ± 1.7 years. In multivariate models, we observed greater point estimates for risk of ALD, NAFLD and liver disease incidence and mortality among overweight/obese participants who consumed alcohol at the same level as normal weight participants. We found that overweight/obese participants who reported alcohol consumption above the guidelines had a greater HR for liver disease incidence and mortality (HR 1.52, 95% CI 1.32, 1.75 and HR 2.20, 95% CI 1.41, 3.44, respectively) than normal weight individuals (HR 0.95, 95% CI 0.83, 1.09 and HR 1.24, 95% CI 0.8, 1.93, respectively). The results for the associations of alcohol consumption and WC with ALD, NAFLD and liver disease mortality were similar. Participants with high WC who reported alcohol consumption above the guidelines had a greater HR for liver disease incidence (HR 1.59, 95% CI 1.35, 1.87) than normal WC individuals (HR 0.85, 95% CI 0.72, 1.01). We found evidence that being overweight/obese amplified the harmful effect of alcohol on the liver incidence and mortality.

Correlation among age, sex, and liver diseases-related mortality risk in patients with hepatitis B virus-related liver cirrhosis

Objective: To understand and compare the differences between age, sex and liver diseases-related mortality risk in patients with hepatitis B virus-related liver cirrhosis. Methods: Based on the front-page inpatient medical record database and the death registration system of Beijing patients with hepatitis B-related liver cirrhosis from 2008 to 2015 were included. The survival information of all patients were traced up to the occurrence of liver disease-related mortality event or until December 31, 2019. Kaplan-Meier method was used to calculate the cumulative incidence of liver disease-related mortality in patients with liver cirrhosis. Cox regression model was used to analyze the effect of age-gender interaction on liver disease-related mortality risk. Results: A total of 16 738 patients with hepatitis B-related liver cirrhosis were included, of which 13 969 cases (83.46%) were in compensated stage and 2 769 cases (16.54%) were in decompensated stage. Liver cirrhosis complications mortality risk in patients with compensated stage cirrhosis at 3, 5, and 8 years were 10.84%, 12.70%, and 14.37%, respectively; while in decompensated stage patients, the mortality risk was 16.70%, 19.02%, and 20.73%, respectively. The 3, 5, and 8-year liver cancer mortality rates of patients with compensated stage liver cirrhosis were 5.24%, 7.49%, and 10.25%, respectively; while those with decompensated stage liver cancer mortality rates were 9.01%, 11.16%, and 13.50%, respectively. Liver disease-related mortality risk was increased with age in patients with liver cirrhosis. Liver cirrhosis complications mortality risk in female patients with liver cirrhosis at age < 60 years was lower than that of male patients. Liver cirrhosis complications mortality risk in male and female patients aged 60-69 years were similar. Liver cirrhosis complications mortality risk in female patients aged ≥70 years was higher than that of male patients. However, female patients had a lower risk of liver cancer mortality than male patients in utmost age groups. Conclusion: Age is positively correlated with liver diseases-related mortality risk in patients with hepatitis B-related liver cirrhosis. Female sex is a protective factor for liver cancer mortality in patients with liver cirrhosis, and the protective effect on liver cirrhosis complications mortality risk gradually disappears with age.

Acute-on-Chronic Liver Failure Mortality Prediction using an Artificial Neural Network

Acute-on-chronic liver failure (ACLF) is a clinical syndrome affecting patients with chronic liver disease characterized by abrupt hepatic decompensation and associated with high short-term mortality. It is characterized by intense systemic inflammation, organ failure, and a poor prognosis. Using certain liver-specific prognostic scores, and organ failures, it is possible to triage and prognosticate the outcome of patients with ACLF. This work investigates the role of the artificial neural network (ANN), which functionally mimics biological neural systems, in predicting 90-day liver disease-related mortality. This study evaluated ANN among patients with ACLF. An accuracy of 94.12% was noticed at predicting 30-day mortality and 88.2% at predicting 90-day mortality, with an area under the curve of 0.915 and 0.921, respectively. ANN plays a very important role in predicting short term mortality patients with a high accuracy. Its application in patients of ACLF is promising as it automates and eases the method of identifying those patients at a higher risk of mortality. The application of ANN in this field has a vast potential for assisting clinicians in decision making, triaging of patients requiring emergent liver transplantation, and predicting mortality and complications.