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Introduction and Objectives: Cirrhosis-related mortality is underestimated and is increasing; extrahepatic factors may contribute. We examined trends in cirrhosis mortality from 1999-2017 in the United States attributed to liver-related (varices, peritonitis, hepatorenal syndrome, hepatic encephalopathy, hepatocellular carcinoma, sepsis) or extrahepatic (cardiovascular disease, influenza and pneumonia, diabetes, malignancy) causes, and compared mortality trends with congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) populations., Materials and Methods: A national mortality database was used. Changes in age-standardized mortality over time were determined by joinpoint analysis. Average annual percentage change (AAPC) was estimated., Results: Cirrhosis cohort: From 1999-2017, both liver-related (AAPC 1.3%; 95% confidence interval [CI] 0.7-1.9) and extrahepatic mortality (AAPC 1.0%; 95% CI 0.7-1.2) increased. Cirrhosis vs other chronic disease cohorts: changes in all-cause mortality were higher in cirrhosis (AAPC 1.0%; 95% CI 0.7-1.4) than CHF (AAPC 0.1%; 95% CI -0.5- 0.8) or COPD (AAPC -0.4%; 95% CI -0.6- -0.2). Sepsis mortality was highest in cirrhosis (AAPC 3.6%, 95% 3.2- 4.1) compared to CHF (AAPC 0.6%, 95% CI -0.5- 1.7) or COPD (AAPC 0.8%, 95% CI 0.5- 1.2). Cardiovascular mortality increased in cirrhosis (AAPC 1.3%, 95% CI 1.1- 1.5), declined in CHF (AAPC -2.0%, 95% CI -5.3- 1.3) and remained unchanged in COPD (AAPC 0.1%, 95% CI -0.2- 0.4). Extrahepatic mortality was higher among women, rural populations, and individuals >65 years with cirrhosis., Conclusions: Extrahepatic causes of death are important drivers of mortality and differentially impact cirrhosis compared to other chronic diseases., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Chronic liver disease (CLD) and cirrhosis accounts for approximately 2 million deaths annually worldwide. CLD and cirrhosis-related mortality has increased steadily in the United States. 1,2 With the global pandemic of coronavirus disease 2019 (COVID-19), patients with CLD and cirrhosis represent a vulnerable population at higher risk for complications and mortality. 3,4 Although high mortality from COVID-19 among patients with CLD and cirrhosis have been reported, 5 national trends in mortality related to CLD and cirrhosis before and during the COVID-19 pandemic have not been assessed. This study estimated the temporal quarterly trends in CLD and cirrhosis-related mortality in the United States from 2017 Q1 to 2020 Q3 using provisional data releases from the National Vital Statistics System. 6,7 ., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aims: The number of cases with coronavirus disease 2019 (COVID-19) has exceeded seven million worldwide. However, the data describing the global prevalence of liver injury associated with COVID-19 is lacking secondary to the novelty of this ongoing pandemic. Therefore, we conducted a meta-analysis to determine the association between COVID-19 and liver injury., Methods: A systematic literature search of indexed databases including, PubMed, Medline, and Embase databases from inception to 14 April 2020, was used to identify studies that reported data of liver chemistry in patients diagnosed with COVID 19. The overall prevalence of abnormal liver chemistry and relevant 95% confidence interval was used to estimate the pooled results studies., Results: Sixty-four studies with 11 245 patients with COVID-19 were included. The pattern of abnormal liver enzymes was notable for higher aspartate aminotransferase (AST) than alanine aminotransferase (ALT) levels. The overall global prevalence of elevated AST, ALT, total bilirubin, gamma-glutamyltransferase (GGT), and alkaline phosphatase was 23.2, 21.2, 9.7, 15.0, and 4.0%, respectively. The prevalence of elevated AST was substantially higher among those with severe cases (45.5%) compared to non-severe cases (15.0%). Co-existing chronic liver disease presented up to 37.6% of patients with COVID-19., Conclusion: A fourth of COVID-19 patients had elevated liver enzymes and associated with disease severity. Our study may be used as a guide for clinicians and epidemiologists to proactively identify other sources of injury and illness in patients diagnosed with COVID-19. Intensive monitoring for liver injury may be needed in cases with severe COVID-19., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The age-standardized prevalence of diabetes increased from 9.8% in 1988-1994, to 10.8% in 2001-2002, to 12.4% in 2011-2012 in the United States. 1 According to the National Vital Statistics System data, diabetes-related mortality has remained stable as the seventh-leading cause of death nationally since 2006. 2 However, the age-standardized diabetes-related mortality decreased from 112.2 per 100,000 individuals in 2007 to 104.3 per 100,000 individuals in 2017. 3 In terms of cause-specific mortality, the age-standardized mortality for cardiovascular disease, complications of diabetes, and cancer among individuals with diabetes declined annually by approximately 1%. 3 In contrast, chronic liver disease-related mortality has been reported to be increasing in individuals with diabetes. 4,5 However, the trends in mortality due to chronic liver disease in the setting of diabetes remain unknown. In this study, we estimated the trends in chronic liver disease-related mortality among individuals with diabetes from 2007 to 2017 in the United States., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The Asian American population is characterized by remarkable diversity. Studying Asians as an aggregate group may obscure clinically meaningful heterogeneity. We performed a population-based study using data from the US National Vital Statistics System. We determined the trends in age-standardized mortality rates for chronic liver disease stratified by aetiology among the most populous US-based Asian subgroups (Asian Indians, Chinese, Filipino, Japanese, Korean and Vietnamese) and compared it to non-Hispanic whites. Annual percentage change was calculated to determine temporal mortality patterns using joinpoint analysis. Hepatitis C virus-related mortality rates were higher in non-Hispanic whites compared to individual Asian subgroups, but a sharp decline in mortality rates was noted in 2014 among non-Hispanic whites and all Asian subgroups. Age-standardized hepatitis B virus-related mortality rates were higher in all Asian subgroups as compared to non-Hispanic whites in 2016, with the highest mortality among Vietnamese followed by Chinese. Mortality rates for alcoholic liver disease have been steadily trending upwards in all Asian subgroups, with the highest mortality in Japanese. Overall, age-standardized cirrhosis-related mortality rates were highest in non-Hispanic whites, followed by Japanese, and more distantly by Vietnamese and other subgroups. However, hepatocellular carcinoma-related mortality rates were higher in most Asian subgroups led by Vietnamese, Japanese and Koreans compared to non-Hispanic whites. In this population-based study utilizing a nationally representative database, we demonstrated a marked heterogeneity in the mortality rates of aetiology-specific chronic liver disease among Asian subgroups in the United States., (© 2018 John Wiley & Sons Ltd.)

Disease burden is an important indicator of the state of health of a population. It can be measured as the frequency (eg, incidence and prevalence) of a condition or its effects including fatal and non-fatal health loss from disease (eg, disability-adjusted life years) as well as the financial costs (eg, direct healthcare costs and indirect healthcare expenditures related to lost income because of premature death). Accurate disease burden information is essential for policy-making such as prioritization of health interventions and allocation of resources. Chronic liver disease (CLD) causes substantial health and economic burden in the United States, where nearly 2 million deaths annually are attributable to CLD. In the recent past, overall mortality rate of CLD has been increasing. Viral hepatitis and alcoholic liver disease are thought to be the most common etiologies of chronic liver diseases. More recently, the prevalence of nonalcoholic fatty liver disease is rapidly increasing, and nonalcoholic steatohepatitis has become a leading indication for liver transplantation. In this article, we assemble available data on the burden of CLD in the United States, focusing on nonmalignant complications, whereas the impact on mortality and healthcare expenses of hepatocellular carcinoma, an important consequence of CLD, is discussed elsewhere., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world's adult population. While it is associated with obesity and metabolic syndrome, emerging evidence has shown that a substantial number of MASLD patients have a normal body mass index ("lean individuals with MASLD"). In this article, we provide an overview of the definition, epidemiology, pathogenesis, and clinical outcomes associated with lean individuals with MASLD and updates on current management. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: A potent and safe antiviral agent may impact chronic hepatitis C (HCV)‐related end‐stage liver disease (ESLD). We assess aetiology‐based hospitalizations for ESLD in the United States, 2016–2019. Methods: We utilized the National Inpatient Sample (NIS) from 2016 to 2019. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma, criteria obtained from the International Classification of Diseases, Tenth Revision. Results: National hospitalization rates for non‐alcoholic fatty liver disease (NAFLD) increased significantly from 67.1/100 000 persons in 2016 to 93.6 in 2019 with an average annual percentage change (AAPC) of 12.1%, while chronic hepatitis C (HCV) decreased significantly from 71.2/100 000 persons in 2016 to 58.5 in 2019 (−6.5% AAPC). Hospitalizations for ESLD in alcohol‐related liver disease (ALD) increased as well. Conclusions: Hospitalization rates for NAFLD‐ and ALD‐related ESLD increased steadily, while those for HCV‐related ESLD decreased during the direct‐acting antivirals era. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Gawrieh et al papers. To view these articles, visit https://doi.org/10.1111/apt.17849 and https://doi.org/10.1111/apt.17886 [ABSTRACT FROM AUTHOR]

Background: Data on the current estimates of the disease burden of Clostridioides difficile (C. difficile) infection in the setting of end-stage liver disease (ESLD) are emerging. Aims: We examined the recent trends and predictors of hospitalizations and in-hospital mortality from C. difficile infection among hospitalizations with ESLD in the USA. Methods: We performed a retrospective analysis using the National Inpatient Sample, 2005–2014. We defined ESLD and C. difficile infection using the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable logistic regression was used to determine the risk factors that impacted hospitalization and mortality. Results: The prevalence of coding for C. difficile infection in decompensated cirrhosis increased from 1.3% in 2005 to 2.7% in 2014, with an annual rate of 7.8%. In hospitalizations with hepatocellular carcinoma, C. difficile infection increased steadily from 1.0 to 1.7% with an annual incremental rate of 6.4%. Among hospitalizations with ESLD, each passing 2-year period, increasing age, female, higher Charlson index, accompanying infection, hepatorenal syndrome, and ascites were associated with C. difficile infection. Although C. difficile infection was an independent predictor of in-hospital mortality during hospitalization with decompensated cirrhosis (odds ratio 1.53, 95% confidence interval 1.44–1.63), the proportion of in-hospital mortality during hospitalization with C. difficile infection and decompensated cirrhosis decreased from 15.4% in 2005 to 11.1% in 2014, with an annual rate of − 3.1% (95% CI − 5.7% to − 0.3%). Conclusions: While the prevalence of C. difficile infection in hospitalized patients with ESLD increased approximately twofold, the in-hospital mortality decreased significantly during the past decade. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and encompasses a spectrum of pathology from simple steatosis to inflammation and significant fibrosis that leads to cirrhosis. NAFLD and its comorbid conditions extend well beyond the liver. It is a multisystemic clinical disease entity with extrahepatic manifestations such as cardiovascular disease, type 2 diabetes, chronic kidney disease, hypothyroidism, polycystic ovarian syndrome, and psoriasis. Indeed, the most common causes of mortality in subjects with NAFLD are cardiovascular disease, followed by malignancies and then liver-related complications as a distant third. This review focuses on several of the key extrahepatic manifestations of NAFLD and areas for future investigation. Clinicians should learn to screen and initiate treatment for these extrahepatic manifestations in a prompt and timely fashion before they progress to end-organ damage. [ABSTRACT FROM AUTHOR]

We investigated the relationship of H. pylori stratified by cytotoxin-associated gene A (cagA) status with nonalcoholic fatty liver disease (NAFLD) in the general population of the United States (US). We utilized the Third National Health and Nutrition Examination Survey from 1988 to 1994 in this study. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known causes of liver diseases and significant alcohol consumption. Hepatic steatosis was assessed by parenchymal brightness, liver to kidney contrast, deep beam attenuation, bright vessel walls and gallbladder wall definition. Antibodies to H. pylori and cagA of participants were measured using H. pylori IgG and anti-cagA IgG enzyme-linked immunosorbent assays. Among 5,404 participants, the prevalence of NAFLD was higher in H. pylori positive subjects (33.5±1.8%) compared to H. pylori negative subjects (26.1±1.7%, p <0.001). In terms of cagA protein status stratification, while cagA positive H. pylori group did not demonstrate an association with NAFLD (OR: 1.05; 95% CI: 0.81–1.37), cagA negative H. pylori group was noted to have a significant association with NAFLD in a multivariable analysis (OR: 1.30; 95% CI: 1.01–1.67). In conclusion, our study demonstrated that cagA negative H. pylori infection was an independent predictor of NAFLD in the US general population. [ABSTRACT FROM AUTHOR]

Background & aims: The impact of marijuana on nonalcoholic fatty liver disease (NAFLD) is largely unknown. We studied the association between marijuana and NAFLD utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005–2014 and NHANES III (1988–1994). Methods: Suspected NAFLD was diagnosed if serum alanine aminotransferase (ALT) was > 30 IU/L for men and > 19 IU/L for women in the absence of other liver diseases (NHANES 2005–2014). In NHANES III cohort, NAFLD was defined based on ultrasonography. Results: Of the 14,080 (NHANES 2005–2014) and 8,286 (NHANES III) participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed NAFLD were inversely associated with marijuana use (p < 0.001). Compared to marijuana-naïve participants, marijuana users were less likely to have suspected NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82–0.99 for past user; OR: 0.68, 95% CI: 0.58–0.80 for current user) and ultrasonographically-diagnosed NAFLD (OR: 0.75, 95% CI: 0.57–0.98 for current user) in the age, gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58–0.98) and 0.70 (95% CI 0.56–0.89), respectively (P for trend = 0.001) with similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59–1.00 for current user; OR: 0.71, 95% CI: 0.51–0.97 for current light user). In insulin resistance-adjusted model, marijuana use remained an independent predictor of lower risk of suspected NAFLD. Conclusions: In this nationally representative sample, active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. The pathophysiology is unclear and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background and Aims Alcoholic liver diseases often evolve to acute-on-chronic liver failure (ACLF), which increases the risk of (multi-)organ failure and death. We investigated the development and characteristics of alcohol-related ACLF and evaluated prognostic scores for prediction of mortality in Asian patients with active alcoholism. Methods A total of 205 patients who were hospitalized with severe alcoholic liver disease were included in this retrospective cohort study, after excluding those with serious cardiovascular diseases, malignancy, or co-existing viral hepatitis. The Chronic Liver Failure (CLIF) Consortium Organ Failure score was used in the diagnosis and grading of ACLF, and the CLIF Consortium ACLF score (CLIF-C ACLFs) was used to predict mortality. Results Patients with ACLF had higher Maddrey discriminant function, model for end-stage liver disease (MELD), and MELD-sodium scores than those without ACLF. Infections were more frequently documented in patients with ACLF (33.3% vs 53.0%; P = 0.004). Predictive factors for ACLF development were systemic inflammatory response syndrome (odds ratio [OR], 2.239; P < 0.001), serum sodium level (OR, 0.939; P = 0.029), and neutrophil count (OR, 1.000; P = 0.021). For prediction of mortality at predefined time points (28-day and 90-day) in patients with ACLF, areas under the receiver-operating characteristic were significantly greater for the CLIF-C ACLFs than for Child-Pugh, MELD, and MELD-sodium scores. Conclusions Infection and systemic inflammatory response syndrome play an important role in the development of alcohol-related ACLF in Asian patients with active alcoholism. The CLIF-C ACLFs may be more useful for predicting mortality in ACLF cases than liver-specific scoring systems. [ABSTRACT FROM AUTHOR]

The accurate prognostic stratification of alcoholic hepatitis (AH) is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort) and 106 patients with AH between 2005 and 2012 (a validation cohort). The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL) were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC). For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001). In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment. [ABSTRACT FROM AUTHOR]

As a chronic disease encompassing a wide spectrum of liver-related histologic damage, nonalcoholic fatty liver disease (NAFLD) is becoming a global epidemic with significant impacts on all-cause morbidity and mortality. Insulin resistance and type 2 diabetes mellitus predispose individuals to NAFLD and related complications. Therefore, timely intervention with anti-diabetic medications may prevent and delay the development of NAFLD or have a therapeutic implication. The focus of this review is to evaluate the evidence supporting the efficacy of anti-diabetic medications in the treatment of NAFLD. While many of these anti-diabetic agents have shown to improve biochemical parameters, their effect on hepatic histology is limited. Among anti-diabetic medications, only thiazolidinediones and glucagon-like peptide-1 receptor agonists demonstrate significant improvement in hepatic histology. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is characterized by histological evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and hepatic fibrosis in the absence of significant alcohol use and other known causes of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is generally benign but can progress to NASH, which carries a higher risk of adverse outcomes including cirrhosis, end-stage liver disease, hepatocellular carcinoma and death if liver transplantation is not pursued in a timely fashion. Currently, lifestyle modifications including healthy diet and increased physical activity/exercise culminating in weight loss of 5% to >10% is the cornerstone of treatment intervention for patients with NAFLD. Patients with NAFLD who fail to obtain this goal despite the help of dietitians and regimented exercise programs are left in a purgatory state and remain at risk of developing NASH-related advance fibrosis. For such patients with NAFLD who are overweight and obese, healthcare providers should consider a trial of FDA-approved anti-obesity medications as adjunct therapy to provide further preventative and therapeutic options as an effort to reduce the risk of NAFLD-related disease progression. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world. NAFLD encompasses a spectrum of histological features, including steatosis, steatohepatitis with balloon degeneration, and hepatic fibrosis leading to cirrhosis. In patients with advanced liver damage, NAFLD is associated with an increased risk of hepatocellular carcinoma. Diabetes mellitus, hypertension, and dyslipidemia are components of metabolic syndrome and are commonly associated with NAFLD. Cardiovascular disease is the leading cause of mortality in patients with NAFLD. Therefore, it is important to pre-emptively identify and proactively treat conditions like hyperlipidemia in an effort to favorably modify the risk factors associated with cardiovascular events in patients with NAFLD. The management of hyperlipidemia has been shown to reduce cardiovascular mortality and improve histological damage/biochemical abnormalities associated with non-alcoholic steatohepatitis (NASH), a subset of NAFLD with advance liver damage. There are no formal guidelines available regarding the use of anti-hyperlipidemic drugs, as prospective data are lacking. The focus of this article is to discuss the utility of lipid-lowering drugs in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Background & Aims Cirrhosis from hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma worldwide. We determine the prevalence of cirrhosis among HCV-infected American adults including those unaware of their infection. Methods Using the National Health and Nutrition Examination Survey (NHANES) data, we identified participants aged ⩾20 years with detectable serum HCV RNA. The prevalence of advanced fibrosis and cirrhosis was determined for eras 1 (1988–94), 2 (1999–2006) and 3 (2007–2012) by using FIB-4 >3.25 and APRI >2.0, respectively. Results Out of 52,644 NHANES examinees, 49,429 were tested for HCV, of whom 725 met the inclusion criteria (positive HCV RNA with available data for FIB-4 and APRI). Based on APRI, 6.6% (95% confidence interval [CI]: 2.2–11.0) of HCV-infected adults in era 1, 7.6% (95% CI: 3.4–11.8) in era 2 and 17.0% (95% CI: 8.0–26.0) in era 3 had cirrhosis. In the multivariable regression analysis, this era effect was attributable to increasing age (odds ratio [OR]:1.04, 95% CI: 1.02–1.07), diabetes (OR: 2.33, 95% CI: 1.01–5.40) and obesity (OR: 2.96, 95% CI: 1.15–7.57). Cirrhosis was as common among respondents who were unaware of their infection as those who were aware (both 11%). Results were identical when FIB-4 was used. Conclusions Among HCV-infected American adults, the proportion with cirrhosis has increased rapidly. Cirrhosis prevalence remains high in individuals unaware of their HCV infection. These data highlight the urgency for HCV screening regardless of symptoms, systematic assessment for liver fibrosis in those with HCV infection and institution of antivirals to prevent advanced liver disease. Lay summary Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis, creating a large public health burden. Based on the U.S. National Health and Nutrition Examination Survey sample, we found the proportion of patients with cirrhosis among Americans with HCV infection increased from 6.6% to 17.0% over the past two decades. Patients who were unaware of their infection were just as likely to have cirrhosis as those who knew about their infection, which highlights the need for screening and treatment for HCV at the population level. [ABSTRACT FROM AUTHOR]