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Hepatitis C virus (HCV) infection is associated with a myriad of extrahepatic manifestations (EHM), as well as the production of autoantibodies, including rheumatoid factor (RF). This study aims to elucidate whether serum levels of RF change before and after HCV eradication, and whether these changes differ according to the type of therapy used. This is a retrospective cohort study of adults with chronic HCV infection treated with interferon‐free or interferon‐based regimens. All patients had HCV viremia at baseline and documented sustained virological response (SVR) 12 or 24 weeks after completing treatment. We measured the serum levels of RF at baseline and at SVR‐12 or −24 to analyse the changes after eradication. This study enrolled 297 patients (median age, 59 years; female, 48.5%; cirrhosis, 16.8%). Among them, 78 (26.3%) were RF‐positive by qualitative serology at baseline. This number decreased to 49 (16.5%) at SVR‐12 or −24 (p < 0.001). Quantitatively, the median RF also decreased from 1.6 IU/mL (interquartile range [IQR], undetectable—15.8) to undetectable (IQR, undetectable—6.6 IU/mL) (p < 0.001). Significant reductions were observed in both groups. The proportion with RF seropositivity decreased from 24.3% to 15.4% (p = 0.001) in patients treated with interferon‐free agents (n = 214) and from 31.3% to 19.3% (p = 0.006) in patients treated with interferon‐based regimens (n = 83), without significant difference between two groups (p = 0.40). Serum RF decreased after HCV eradication, regardless of treatment regimen. Our findings suggest that HCV eradication may attenuate HCV‐related autoimmunity. [ABSTRACT FROM AUTHOR]

Introduction: We compared clinical characteristics and outcomes in real-world metabolic dysfunction-associated steatotic liver disease (MASLD) patients with or without liver biopsy using a nationwide cohort in United States (USA) to fill in gaps in selection of biopsy patients. Methods: We conducted a retrospective cohort study of adult MASLD patients using Marketscan® Databases (1/2007–12/2021). Patients were categorized into those with or without liver biopsy during follow-up. Results: We analyzed 540,326 MASLD patients: 23,732 with and 516,594 without biopsy. Only 4% of MASLD patients received liver biopsy and biopsy rate decreased in the last 5 years (9.4%–3.6%). After 1:5 propensity score matching on baseline characteristics including age, sex, and comorbidities, a total of 23,731 patients with biopsy and 118,396 matched patients without biopsy were analyzed. The incidence per 1,000 person-years for hepatocellular carcinoma (HCC) was 0.22 versus 2.18, cirrhosis 29.75 versus 90.44, and hepatic decompensation 15.84 versus 28.25 compared patients with and without biopsy. In multivariable analysis, patients with biopsy had more than 9 times higher risk of developing HCC, 3 times higher risk of cirrhosis, and 78% higher risk of hepatic decompensation. In subgroup analysis, the association remained consistent when stratified by age (<50 and ≥50), sex, and diabetes mellitus. Predictors of having biopsy included age, metabolic diseases, and living in North central or Northeast of USA. Conclusion: These data can inform clinical patient management that biopsy patients likely represent a selected group at higher risk for disease progression, especially in clinical trials for MASLD therapies. Introduction: We compared clinical characteristics and outcomes in real-world metabolic dysfunction-associated steatotic liver disease (MASLD) patients with or without liver biopsy using a nationwide cohort in United States (USA) to fill in gaps in selection of biopsy patients. Methods: We conducted a retrospective cohort study of adult MASLD patients using Marketscan® Databases (1/2007–12/2021). Patients were categorized into those with or without liver biopsy during follow-up. Results: We analyzed 540,326 MASLD patients: 23,732 with and 516,594 without biopsy. Only 4% of MASLD patients received liver biopsy and biopsy rate decreased in the last 5 years (9.4%–3.6%). After 1:5 propensity score matching on baseline characteristics including age, sex, and comorbidities, a total of 23,731 patients with biopsy and 118,396 matched patients without biopsy were analyzed. The incidence per 1,000 person-years for hepatocellular carcinoma (HCC) was 0.22 versus 2.18, cirrhosis 29.75 versus 90.44, and hepatic decompensation 15.84 versus 28.25 compared patients with and without biopsy. In multivariable analysis, patients with biopsy had more than 9 times higher risk of developing HCC, 3 times higher risk of cirrhosis, and 78% higher risk of hepatic decompensation. In subgroup analysis, the association remained consistent when stratified by age (<50 and ≥50), sex, and diabetes mellitus. Predictors of having biopsy included age, metabolic diseases, and living in North central or Northeast of USA. Conclusion: These data can inform clinical patient management that biopsy patients likely represent a selected group at higher risk for disease progression, especially in clinical trials for MASLD therapies. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation (LT) is the treatment of choice for end-stage liver disease and certain malignancies such as hepatocellular carcinoma (HCC). Data on the surgical management of de novo or recurrent tumors that develop in the transplanted allograft are limited. This study aimed to investigate the perioperative and long-term outcomes for patients undergoing hepatic resection for de novo or recurrent tumors after liver transplantation. Methods: The study enrolled adult and pediatric patients from 12 centers across North America who underwent hepatic resection for the treatment of a solid tumor after LT. Perioperative outcomes were assessed as well as recurrence free survival (RFS) and overall survival (OS) for those undergoing resection for HCC. Results: Between 2003 and 2023, 54 patients underwent hepatic resection of solid tumors after LT. For 50 patients (92.6 %), resection of malignant lesions was performed. The most common lesion was HCC (n = 35, 64.8 %), followed by cholangiocarcinoma (n = 6, 11.1 %) and colorectal liver metastases (n = 6, 11.1 %). The majority of the 35 patients underwent resection of HCC did not receive any preoperative therapy (82.9 %) or adjuvant therapy (71.4 %), with resection their only treatment method for HCC. During a median follow-up period of 50.7 months, the median RFS was 21.5 months, and the median OS was 49.6 months. Conclusion: Hepatic resection following OLT is safe and associated with morbidity and mortality rates that are comparable to those reported for patients undergoing resection in native livers. Hepatic resection as the primary and often only treatment modality for HCC following LT is associated with acceptable RFS and OS and should be considered in well selected patients. [ABSTRACT FROM AUTHOR]

Background: The Fibrosis-4 (FIB-4) index is widely recommended as a first-tier method for screening advanced hepatic fibrosis; however, its diagnostic performance is known to be suboptimal in patients with Type 2 diabetes mellitus (T2DM). We aim to propose a modified FIB-4, using the parameters of the existing FIB-4, tailored specifically for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A total of 1503 patients who underwent liver biopsy were divided into T2DM (n = 517) and non-T2DM (n = 986) groups. The model was developed using multiple regression analysis in the derivation cohort and validated in the validation cohort. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic (AUC) curves. Results: Among the 1503 individuals, those with T2DM were older, more likely to be male, and had a higher prevalence of advanced hepatic fibrosis (≥F3) compared to non-T2DM individuals. Independent risk factors for advanced fibrosis in T2DM included age, AST, AST/ALT ratio, albumin, triglycerides, and platelet count. The optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index) demonstrated superior diagnostic accuracy (AUC 0.771) compared to the FIB-4 (AUC 0.735, p = 0.012). The model showed a higher negative predictive value than the original FIB-4 across all age groups in the diabetic group. Conclusions: The newly optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index), incorporating a non-linear predictive model, improves diagnostic performance (AUC) and the negative predictive value in MASLD with T2DM. [ABSTRACT FROM AUTHOR]

Summary: Background/Aims: With polarizing income disparities, this study investigated the prevalence and trends of liver disease in a U.S. population‐based sample based on income‐to‐poverty ratio (IPR). Methods: This cross‐sectional study analysed survey data from the 1999–2018 National Health and Nutrition Examination Survey with highest (HIG), middle‐income (MIG), and lowest income (LIG) groups defined as IPR ≤ 1, 1 < IPR <5, and IPR ≥ 5, respectively. Results: We analysed 59,204 adult participants with 48.2% male, 39.7% aged 18–39, 36.2% 40–59, and 24.1% ≥60 years. The weighted prevalence of hepatitis C (HCV), B (HBV) infection, non‐alcoholic fatty liver disease (NAFLD), alcohol‐associated liver disease (ALD), and advanced fibrosis in LIG were 3.9% (n = 276), 7.4% (n = 527), 33.2% (n = 714), 5.2% (n = 401), and 9.0% (n = 694), respectively, compared to lower rates for HIG: 1.0% (n = 82), 3.2% (n = 263), 29.6% (n = 798), 3.9% (n = 354), and 5.0% (n = 638). After adjusting for age, sex, race and ethnicity, education, and birthplace, HIG had the lowest odds of having any liver disease [adjusted odds ratio (aOR) 0.67, p < 0.0001], with similar findings for specific conditions including HCV, HBV, and advanced fibrosis (aOR 0.24, 0.52, and 0.64, all p < 0.0001, respectively). While viraemic HCV prevalence decreased over time for HIG, there were no changes for MIG nor LIG. Similarly, NAFLD prevalence was stable for HIG but increased for MIG and LIG. Conclusion: LIG and MIG in the United States have higher liver disease burdens than HIG, with increasing NAFLD prevalence and lack of decline in current HCV infection prevalence over time as opposed to declining or stable trend in HIG. [ABSTRACT FROM AUTHOR]

Background: Detailed subgroup incidence rates for steatotic liver disease (SLD)-related hepatocellular carcinoma (HCC) are critical to inform practice and public health interventions but remain sparse. We aimed to fill in this gap. Methods and findings: In a retrospective cohort study of adults with SLD from the United States (US) Merative Marketscan Research Databases (1/2007 to 12/2021), we estimated HCC incidence stratified by sex, age, cirrhosis, diabetes mellitus (DM), and a combination of all these 4 factors. We excluded patients with significant alcohol use and chronic viral hepatitis. We analyzed data from 741,816 patients with SLD (mean age 51.5 ± 12.8 years, 46% male, 14.7% cirrhosis). During a 2,410,166 person-years (PY) follow-up, 1,740 patients developed HCC. The overall HCC incidence yielded 0.72 per 1,000 PY (95% confidence interval [CI, 0.68, 0.75]). The incidence was higher in males (0.95, 95% CI [0.89, 1.01]) compared to females (0.52, 95% CI [0.48, 0.56]) (p < 0.001). For those with cirrhosis, the incidence was significantly higher at 4.29 (95% CI [4.06, 4.51]) compared to those without cirrhosis (0.14, 95% CI [0.13, 0.16]) (p < 0.001). Additionally, the incidence was higher in patients with DM (1.19, 95% CI [1.12, 1.26]) compared to those without DM (0.41, 95% CI [0.38, 0.44]) (p < 0.001). Chronic kidney disease (CKD) was also associated with a higher HCC incidence of 2.20 (95% CI [2.00, 2.41]) compared to those without CKD (0.58, 95% CI [0.55, 0.62]) (p < 0.001). Similarly, individuals with cardiovascular disease (CVD) had a higher HCC incidence of 1.89 (95% CI [1.75, 2.03]) compared to those without CVD (0.51, 95% CI [0.48, 0.54]) (p < 0.001). Finally, the incidence of HCC was significantly higher in patients with non-liver cancer (3.90, 95% CI [3.67, 4.12]) compared to those without other cancers (0.29, 95% CI [0.26, 0.31]) (p < 0.001). On further stratification, HCC incidence incrementally rose by 10-year age intervals, male sex, cirrhosis, and DM, reaching 19.06 (95% CI [16.10, 22.01]) and 8.44 (95% CI [6.78, 10.10]) in males and females, respectively, but only 0.04 for non-diabetic, noncirrhotic aged <40 years patients in both sexes. The main limitation of this methodology is the potential misclassification of the International Classification of Diseases (ICD) codes inherent in claims database studies. Conclusions: This nationwide study provided robust granular estimates for SLD-related HCC incidence stratified by several key risk factors. In addition to cirrhosis, future surveillance strategies, prevention, public health initiatives, and future research models should also take into account the impact of sex, age, and DM. Rongtao Lai and team estimate hepatocellular carcinoma incidence stratified by a combination of age, sex, cirrhosis, diabetes, and other comorbidities as derived from data of ~750,000 real-world patients with steatotic liver disease. Author summary: Why was this study done?: Hepatocellular carcinoma (HCC) risk among people with steatotic liver disease (SLD) varies greatly by factors such as age, sex, and comorbidities such as diabetes, cardiovascular disease (CVD), chronic kidney disease (CKD), and liver disease severity. There is a lack of precise and detailed subgroup data regarding HCC incidence in people with SLD. This study aims to address this knowledge gap. What did the researchers do and find?: Using real-world population data from US patients with commercial insurance, the current study provides precise HCC incidence rate estimates by such factors to inform precision medicine. The overall incidence rate of HCC in individuals with SLD was 0.72 per 1,000 people-years. Patients aged >70 years with cirrhosis and diabetes had the highest HCC incidence. Those aged <40 years without cirrhosis or diabetes aged <40 years had the lowest HCC incidence. What do these findings mean?: These findings indicate that precise subgroup estimates help facilitate surveillance and prevention strategies, enrich the decision-making process for cost-effective healthcare, and provide robust evidence to inform future practice guidelines as well as public health policy. The main limitation of the study is that it did not evaluate HCC incidence in uninsured/underinsured populations. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the liver manifestation of a metabolic syndrome and is highly prevalent in the general population. There has been significant progress in non-invasive tests for MAFLD, from the diagnosis of fatty liver and monitoring of liver fat content in response to intervention, to evaluation of liver fibrosis and its change over time, and from risk stratification of patients within the context of clinical care pathways, to prognostication. Various non-invasive tests have also been developed to assess for fibrotic metabolic dysfunction-associated steatohepatitis, which has emerged as an important diagnostic goal, particularly in the context of clinical trials. Non-invasive tests can be used to diagnose clinically significant portal hypertension so that intervention can be administered to reduce the risk of decompensation. Furthermore, the use of risk stratification algorithms can identify at-risk patients for hepatocellular carcinoma surveillance. Beyond the liver, various tests that evaluate cardiovascular disease risk, assess sarcopenia and measure patient reported outcomes, can be utilized to improve the care of patients with MAFLD. This review provides an up-to-date overview of these non-invasive tests and the limitations of liver biopsy in the management of patients with MAFLD. [ABSTRACT FROM AUTHOR]

Introduction: Chronic liver disease (CLD) is associated with increased morbidity and mortality. Understanding health disparities can inform appropriate interventions. We aimed to study mortality outcomes of those with CLD by the income level (income-to-poverty ratio <5 as lower income and ≥5 as higher income). Methods: In this retrospective cohort study, we analyzed data of adults from the National Health and Nutrition Examination Survey, 1999–2018. CLD included viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD). Results: We analyzed 59,204 adults: 47,224 without CLD and 11,980 with CLD. The CLD group was older, more likely male, racial/ethnic minority groups or foreign-born, and had lower educational and income levels (p < 0.001). Most (80.02%) CLD participants did not have college degrees and had lower income (79.18%). Among CLD participants, similar differences were observed between lower and higher income groups. Lower income participants with CLD had significantly higher 10-year cumulative mortality compared to higher income CLD participants (15.26 vs. 8.00%, p < 0.001), with consistent findings in viral hepatitis and NAFLD subgroups (p < 0.001) but not ALD (p = 0.71). Adjusting for age, sex, race, birthplace, lower income CLD participants were 2.01 (hazard ratio [HR]: 2.01; 95% CI: 1.79–2.26) times more likely to die overall and in viral hepatitis (HR: 2.05; 95% CI: 1.31–3.24) and NAFLD subgroups (HR: 2.32; 95% CI: 1.69–3.18) but not ALD (HR: 1.17; 95% CI: 0.55–2.51). Conclusion: Lower income, foreign-born, and racial/ethnic minority groups were disproportionately represented among those with CLD, with lower income and CLD individuals having double the mortality risk compared to their higher income counterparts. Interventions should be culturally appropriate and address socioeconomic barriers. [ABSTRACT FROM AUTHOR]

Summary: Background: Adverse outcomes of cirrhosis remain a top priority. Aims: We examined the distribution of cirrhosis causes, HCC incidence and mortality and related changes over time in a nationwide U.S. cohort. Methods: A retrospective study of a national sample of commercially insured patients with cirrhosis from Optum's de‐identified Clinformatics® Data Mart Database (CDM). Results: A total of 628,743 cirrhosis cases were identified with 45% having NAFLD, 19.5% HCV, and 16.3% ALD. African Americans had the highest rate of decompensation (60.6%), while Asians had the highest rate of HCC (2.4%), both p < 0.001. African Americans more frequently had HCV (28.4%) while Hispanic/Latinos more frequently had NAFLD (49.2%, p < 0.001). Patients in the 2014–2021 cohort were significantly older (63.0 ± 12.8 vs. 57.0 ± 14.3), less frequently decompensated (54.5% vs. 58.3%) but more frequently had HCC (1.7% vs. 0.6%) and NAFLD (46.5% vs. 44.2%), all p < 0.001. The overall annual incidence of HCC was 0.76% (95% CI: 0.75–0.77) with a 5‐year cumulative incidence of 4.03% (95% CI: 3.98–4.09), with significant variation by sex, race/ethnicity, and cirrhosis aetiology. The overall median years of survival were 11.4 (95% CI: 11.3–11.5) with a 5‐year cumulative survival of 73.4% (95% CI: 73.3%–73.6%), also with significant disparities in similar subgroups (lowest in cryptogenic cirrhosis and worse in 2014–2021 vs. 2003–2013). The 2014–2021 period was independently associated with worse survival (aHR: 1.14, 95% CI: 1.08–1.20). Conclusions: HCC incidence and survival vary by aetiology among patients with cirrhosis, with cryptogenic cirrhosis having the lowest survival and lower survival in the more recent time period. [ABSTRACT FROM AUTHOR]

The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB‐FL) and without FL (non‐FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB‐FL patients as compared with non‐FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p =.04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p =.05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p =.89). However, at week 48, there were no statistically significant differences between CHB‐FL and non‐FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p =.67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p =.27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p =.58) with similar findings for week 96. BR rate was lower in CHB‐FL patients after 12 weeks of antiviral treatment. However, after a longer follow‐up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review summarizes the feasibility, benefits, and concerns of utilizing hepatitis B virus (HBV)-positive allografts for liver transplant. Recent Findings: Analyses of registry-based and multi-center cohorts, in this current era of high-barrier nucleos(t)ide analogue therapies, have shown that recipients of HBV-positive allografts have long-term graft and recipient rates comparable to recipients of HBV-negative allografts. The utilization of HBV-positive allografts can also be cost-effective. However, early evidence indicates that for recipients with hepatocellular carcinoma (HCC), the utilization of HBV-positive allografts may increase the risk of recurrent HCC and mortality. Summary: Although HBV-positive allografts have the potential to expand the organ pool and shorten candidate waitlist times and mortality, certain recipient subgroups including those with HCC require closer attention and additional data. There are also important economic and ethical issues surrounding informed consent, equity, society stigma, and transparency to consider. [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: A substantial proportion of patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) do not have cirrhosis. Data regarding the incidence and predictors of HCC development in NAFLD without cirrhosis are limited. We conducted a large, national study of NAFLD patients without documented cirrhosis to examine the incidence and predictors for HCC development. Methods: This retrospective study included 751,603 NAFLD patients (54% female) without documented cirrhosis derived from the deidentified Optum Clinformatics® Data Mart Database. Patients with cirrhosis, platelets < 120,000/µL or FIB-4 values > 2.67 were excluded. Results: The mean age was 53.7 ± 15.0 years, 45.9% were male, 39.5% had diabetes, 57.6% were White, 18.4% Hispanic, 8.2% Black and 4.9% were Asian. The mean platelet count was 264,000 ± 72,000/µL, and 96.3% of patients had a FIB-4 < 1.30. Over 1,686,607 person-years of follow-up, there were 76 incident cases of HCC, resulting in an HCC incidence rate of 0.05 per 1000 person-years. There was a higher HCC incidence rate among patients with platelets ≤ 150,000/µL, versus those with platelets > 150,000/µL (0.23 per 1000 person-years, vs. 0.04 per 1000 person-years, p = 0.02) but not in subgroup analyses for age, sex, race/ethnicity or diabetes. Using multivariable Cox proportional hazards model adjusted multiple confounders, platelet count ≤ 150,000/µL remained an independent predictor of HCC development (adjusted HR 5.80, 95% CI 1.67–20.1, p = 0.006). Conclusion: HCC incidence in NAFLD without documented cirrhosis was below the threshold for cost-effective HCC surveillance in overall and multiple subgroup analyses. Platelet count < 150,000/µL may be a useful predictor of HCC development in this population. [ABSTRACT FROM AUTHOR]

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]

Background: Noninvasive tests (NITs) are necessary for knowing the true prevalence of fatty liver (FL) and advanced fibrosis. NITs for diagnosis of FL and fibrosis were compared. Methods: Data were obtained from the National Health and Examination Survey (2017–2018). Participants were excluded with other liver diseases, missing data for NIT calculation, and/or excessive alcohol use. Area under the receiver operating characteristic (AUROC) compared the accuracy of 4 FL NITs (CAP, HSI, FLI, USFLI) among themselves and to CAP value of 285 dB/m and 5 fibrosis NITs (transient elastography, APRI, NFS, FIB-4, HEPAmet) among themselves and to LSM ≥8.7 kPa. Results: Among 2,051 participants (average age 47 (±17.7), 48% males, 62% white, 73% overweight/obese, 39% metabolic syndrome), demographics were similar among NIT groups (CAP = 812; HSI = 1,234; FLI = 935; USFLI-824). FL prevalence by NIT: 39% CAP, 58% HSI, 47% FLI, 37% USFLI. Advanced fibrosis prevalence by test: LSM (≥8.7 kPa) 10–14%; FIB-4 (≥2.67) and APRI (≥0.7) 1.3–2.7%; HEPAmet (>0.47) 14–21%. Compared to CAP ≥285, FLI (AUROC = 0.823) and USFLI (AUROC = 0.833) performed better than HSI (AUROC: 0.798). Compared to LSM ≥8.7 kPa, only NFS (AUROC = 0.722) performed well (FIB-4 AUROC = 0.606; APRI = 0.647; HEPAmet = 0.629). Among the CAP cohort, the strongest FL predictor was obesity (OR: 15.2, 95% CI: 7.97–28.9, p < 0.001); the only fibrosis predictor was elevated AST (OR: 1.06, 95% CI: 1.00–1.12, p = 0.04). The addition of CAP or LSM as a second NIT reduced the number of indeterminate patients especially for FL. Conclusions: Regardless of diagnostic method in 2017–2018, the prevalence of NAFLD was >35%. NITs for FL performed well but not for advanced fibrosis. CAP and LSM as a second NIT reduced those considered indeterminate. [ABSTRACT FROM AUTHOR]

Summary: Background: Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB). Aim: To quantify the incidence of severe hepatitis flares following NUC cessation in everyday clinical practice. Methods: This population‐based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first‐line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors. Results: During a median follow‐up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4‐year cumulative incidence of 1.8% (95% confidence interval [CI], 1.5%–2.2%). Significant risk factors were cirrhosis (adjusted sub‐distributional hazard ratio [aSHR], 2.74; 95% CI, 1.82–4.12), manifestations of portal hypertension (aSHR, 2.46; 95% CI, 1.45–4.18), age (aSHR, 1.21 per 10 years; 95% CI, 1.03–1.42) and male sex (aSHR, 1.58; 95% CI, 1.04–2.38). In patients without cirrhosis or portal hypertension (n = 8863), the 4‐year cumulative incidence of severe withdrawal flares stood at 1.3% (95% CI, 1.0%–1.7%). For those patients with available data confirming adherence to the standard stopping rules (n = 1274), the incidence was 1.1% (95% CI, 0.6%–2.0%). Conclusions: Severe flares with hepatic decompensation were observed in 1%–2% of patients with CHB after stopping NUC therapy in daily practice. Risk factors included older age, cirrhosis, portal hypertension and male sex. Our findings argue against NUC cessation as part of routine clinical care. [ABSTRACT FROM AUTHOR]

The article discusses the essential role of social workers in addressing socioeconomic disparities in chronic liver disease. It emphasizes the impact of income, education level, and location on liver health status in the United States. The authors highlight the need for further research and interventions to improve liver health outcomes, acknowledging the importance of considering various socio-determinants of health. The study suggests that income-to-poverty ratio is a key indicator of health disparities over time, while also noting limitations in available data for measuring liver health trends. [Extracted from the article]

The editorial discusses the impact of socioeconomic and ethnic factors on chronic liver disease (CLD), emphasizing the importance of addressing income disparities in improving liver health within communities. The authors highlight the need for country and region-specific studies on socio-determinants of health to develop effective interventions and policies that provide equitable resources. Community health workers are encouraged to consider interventions that address both CLDs and the values of the community, especially when resources are limited. [Extracted from the article]

LINKED CONTENT: This article is linked to Tran et al papers. To view these articles, visit https://doi.org/10.1111/apt.18024 and https://doi.org/10.1111/apt.18245. [ABSTRACT FROM AUTHOR]

Background: Global data on the treatment rate with direct‐acting antivirals (DAAs) for chronic hepatitis C (CHC) are sparse. We aimed to evaluate the CHC treatment rate and barriers to treatment in the DAA era. Methods: We searched PubMed, EMBASE and Cochrane from inception to 5 August 2021, for relevant articles. Patients treated with DAAs without interferon (IFN) therapy were categorized as IFN‐free DAAs. Patients receiving DAA with IFN or unclear IFN status were categorized as DAA/IFN. Results: We identified and analysed data from 146 studies (1 760 352 CHC patients). DAA/IFN treatment rate was 16.0% (95% CI: 9.9–23.3, 49 studies, 886 535 patients). IFN‐free DAA treatment rate was 52.3% (95% CI: 46.2–58.4, 123 studies, 1 276 754 patients): 45.4% in North America, 64.2% in South America (1 study), 90.4% in Africa (most data from Egypt), 54.4% in Europe, 60.7% in Australia and 60.5% in Asia, (p <.0001); 49% with hepatitis B co‐infection and 32.3% with hepatocellular carcinoma (HCC). Treatment was not a priority in 22.8% of patients in Europe and 16.7% in Australia, compared to only 4.8% in North America and 2.1% in Asia (p <.0001). Poor adherence to clinical follow‐up was the cause of no treatment in 74.7% of patients in Australia, 37.0% in North America, 7.9% in Europe and 14.3% in Asia (p <.0001). Conclusion: Though a marked improvement from IFN/DAA, the treatment rate with IFN‐free DAA remains suboptimal (52.3% overall, 32.3% in HCC patients). Non‐adherence to clinical follow‐up and lack of disease awareness were treatment barriers. [ABSTRACT FROM AUTHOR]

Summary: Background: Emerging data suggest that statins, aspirin and metformin may protect against hepatocellular carcinoma (HCC) development. However, prior meta‐analyses were limited by heterogeneity and inclusion of studies without adequate adjustment for baseline risks. Aim: To examine by an updated meta‐analysis the association between these medications and HCC risk. Methods: Medline and Embase databases were searched from inception to March 2022 for studies that balanced baseline risks between study groups via propensity score matching or inverse probability of treatment weighting, that reported the impact of statins, aspirin or metformin on HCC risk. Multivariable‐adjusted hazard ratios (HRs) for HCC were pooled using a random effects model. Results: Statin use was associated with reduced HCC risk overall (HR: 0.52; 95% CI: 0.37–0.72) (10 studies, 1,774,476), and in subgroup analyses for cirrhosis, hepatitis B/C, non‐alcoholic fatty liver disease, studies accounting for concurrent aspirin and metformin consumption and lipophilic statins. Aspirin use was associated with reduced HCC risk overall (HR: 0.48; 95% CI: 0.27–0.87) (11 studies, 2,190,285 patients) but not in studies accounting for concurrent statin and metformin use. Metformin use was not associated with reduced HCC risk overall (HR: 0.57; 95% CI: 0.31–1.06) (3 studies, 125,458 patients). Most analyses had moderate/substantial heterogeneity, except in follow‐up <60 months for aspirin (I2 = 0%). Conclusion: Although statin and aspirin use were associated with reduced HCC risk, only statin use was significant in subgroup analyses accounting for concurrent medications. Metformin use was not associated with reduced HCC risk. These data have implications for future clinical trial design. [ABSTRACT FROM AUTHOR]

Background and aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) establishes new criteria for diagnosis of fatty liver disease independent of alcohol intake. We aimed to describe the prevalence and compare characteristics and mortality outcomes of persons with nonobese and obese MAFLD. Methods: Using data from 13,640 participants from the third National Health and Nutrition Examination Survey (NHANES III) 1988–1994, we identified participants with fatty liver on ultrasound who had MAFLD and analyzed them by the presence of obesity. Results: Overall prevalence of MAFLD was 19%; amongst those, 54% were obese and 46% were nonobese. Nonobese MAFLD was more common in participants older than 65 than in younger participants (56.8% vs. 43.2%, p < 0.0001). Nonobese MAFLD was more common in males (63.2% vs. 48.3%, p < 0.0001). Obese MAFLD was more common in females (51.7% vs. 48.3%, p < 0.0001). After adjusting for several demographic factors and alcohol use, older age [adjusted odds ratio (aOR) 1.02, 95% CI 1.00–1.02, p = 0.003] and being male (aOR: 1.65, 95% CI 1.25–2.17, p = 0.001) were independent risk factors for nonobese MAFLD. Nonobese MAFLD participants had a higher 20-year cumulative incidence for all-cause mortality compared to obese MAFLD participants (33.2% vs. 28.8%, p = 0.0137). However, nonobese MAFLD was not independently associated with mortality after adjusting for relevant confounders, while FIB-4 > 1.3 and cardiovascular disease were the strongest risk factors associated with increased mortality [adjusted hazard ratio (aHR) > 2.7 for both, p < 0.0001 for both]. Conclusions: Nonobese MAFLD constitutes about half of the MAFLD in the United States, especially among males and the elderly. Notably, nonobese MAFLD carries higher mortality than obese MAFLD. Screening and diagnosis of MAFLD should be considered in nonobese populations. [ABSTRACT FROM AUTHOR]

Background: A substantial number of patients who do not meet treatment criteria for chronic hepatitis B (CHB) later develop adverse outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Our aim was to determine whether current practice guidelines adequately identify CHB patients who will benefit from antiviral therapy. Methods: We performed a retrospective cohort study comparing the incidence of adverse liver outcomes (cirrhosis and/or HCC) in untreated treatment-ineligible (at baseline and throughout follow-up) versus treated treatment-eligible patients according to standard American Association for the Study of Liver Diseases (AASLD) 2018 guidance (alanine aminotransferase [ALT] >70/50 U/L for men/women plus hepatitis B virus [HBV] DNA >20,000/2,000 IU/mL for HBeAg+/−) and with a sensitivity analyses using a lower threshold (ALT >40 U/L and HBV DNA >2,000 IU/mL). Results: We reviewed records of 5,840 patients from 5 clinics in California and identified 2,987 treatment-naive non-HCC CHB patients. Of those, 271 patients remained untreated treatment-ineligible, 514 patients were treatment-eligible and initiated treatment, with 5-year cumulative adverse liver incidences of 12.5% versus 7.2%, p = 0.074. On multivariable analysis adjusting for age, sex, diabetes, albumin, platelet count, and HBV DNA, compared to treated treatment-eligible patients, untreated treatment-ineligible patients had a significantly higher risk of adverse liver outcomes (adjusted hazard ratio: 2.38, 95% confidence interval 1.03–5.48, p = 0.04) in main analysis by AASLD 2018 criteria but not in sensitivity analysis using the lower treatment threshold (p = 0.09). Conclusion: Patients never meeting standard AASLD 2018 criteria for antiviral therapy and never treated had twice the risk of developing cirrhosis and/or HCC when compared to eligible and treated patients. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Eunice et al papers. To view these articles, visit https://doi.org/10.1111/apt.17914 and https://doi.org/10.1111/apt.17951 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tran et al papers. To view these articles, visit https://doi.org/10.1111/apt.18024 and https://doi.org/10.1111/apt.18046. [ABSTRACT FROM AUTHOR]

Surveillance for hepatocellular carcinoma (HCC) is known to be underutilized; however, neither the variation of surveillance adherence by cirrhosis etiology nor the patient-side economic burden of surveillance are well understood. To identify potential barriers to HCC surveillance, we assessed utilization patterns and costs among US patients with cirrhosis monitored in routine clinical practice. We conducted a retrospective study of insured adult patients with cirrhosis using national administrative claims data from January 2013 through June 2019. Time up-to-date with recommended surveillance, correlates of surveillance receipt, and surveillance-associated costs were assessed during a ≥ 6-month follow-up. Among 15,543 patients with cirrhosis (mean [SD] age 64.0 [11.1] years, 50.7% male), 45.8% and 58.7% had received any abdominal imaging at 6 and 12 months, respectively. Patients were up-to-date with recommended surveillance for only 31% of a median 1.3-year follow-up. Those with viral hepatitis were more likely to receive surveillance than those with other etiologies (hazard ratio [HR] 1.55, 95% CI 1.11–2.17, p =.010 for patients without a baseline gastroenterologist [GI] visit and 2.69, 95% CI 1.77–4.09, p <.001 for patients with a GI visit, relative to those with nonalcoholic fatty liver disease and no GI visit). For all etiologies except NAFLD, the HR (95% CI) for surveillance receipt was higher among patients with vs without a baseline GI visit (alcohol-related, 1.164 [1.002–1.351] vs 0.880 [0.796–0.972]; viral hepatitis, 2.688 [1.765–4.093] vs 1.553 [1.111–2.171]; Other, 0.612 [0.519–0.722] vs 0.549 [0.470–0.641]). Mean total and patient-paid daily surveillance-related costs ranged from $540 and $113, respectively (ultrasound) to $1580 and $300, respectively (magnetic resonance imaging), and mean estimated patient productivity costs were $730–$2514 annually. HCC surveillance was underutilized and was lowest among patients with nonviral etiologies and those who had not seen a gastroenterologist. Surveillance-related out-of-pocket expenses and lost productivity were substantial. The development of surveillance strategies that reduce patient burden, such as those using blood-based biomarkers, may help improve surveillance adherence and effectiveness. [ABSTRACT FROM AUTHOR]

Suboptimal adherence to guidelines for hepatocellular carcinoma (HCC) surveillance among high‐risk patients is a persistent problem with substantial detriment to patient outcomes. While patients cite cost as a barrier to surveillance receipt, the financial burden they experience due to surveillance has not been examined. We conducted a retrospective administrative claims study to assess HCC surveillance use and associated costs in a US cohort of insured patients without cirrhosis but with hepatitis B virus (HBV) infection, monitored in routine clinical practice. Of 6831 patients (1122 on antiviral treatment, 5709 untreated), only 39.3% and 51.3% had received any abdominal imaging after 6 and 12 months, respectively, and patients were up to date with HCC surveillance guidelines for only 28% of the follow‐up time. Completion of surveillance was substantially higher at 6 and 12 months among treated patients (51.7% and 69.6%, respectively) compared with untreated patients (36.9% and 47.6%, respectively) (p < 0.001). In adjusted models, treated patients were more likely than untreated patients to receive surveillance (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.53–2.01, p < 0.001), and the proportion of those up to date with surveillance was 9.7% higher (95% CI 6.26–13.07, p < 0.001). Mean total and patient‐paid daily surveillance‐related costs ranged from $99 (ultrasound) to $334 (magnetic resonance imaging), and mean annual patient costs due to lost productivity for surveillance‐related outpatient visits ranged from $93 (using the federal minimum wage) to $321 (using the Bureau of Labor Statistics wage). Conclusion: Use of current HCC surveillance strategies was low across patients with HBV infection, and surveillance was associated with substantial patient financial burden. These data highlight an urgent need for accessible and easy‐to‐implement surveillance strategies with sufficient sensitivity and specificity for early HCC detection. [ABSTRACT FROM AUTHOR]

Background: The skin is a major target organ for extrahepatic manifestations of liver diseases, and dermatologic abnormalities are common in patients with hepatic disorders. Clinical examination of the skin, nails and hair can allow for appropriate recognition, early diagnosis and treatment of liver diseases, and improvement in the quality of life and life expectancy of affected patients. Methods: We searched 3 databases (Pubmed,Medline and Embase) and selected studies about cirrhosis related skin manifestations and their pathophysiology. Results: A total of 73 articles were included in the review. Studies displayed the spectrum of cutaneous manifestations related to hormonal and vascular changes as well as nail and hair changes in patients with cirrhosis and/or portal hypertension. Conclusion: Cutaneous alterations are important clues or potential indications in the diagnosis of liver cirrhosis. Familiarity with skin conditions can be promptly diagnosed and appropriate management initiated. Manifestations of the liver and skin disorders are interrelated in various ways. Cutaneous changes may be the first clue that a patient has liver disease. The skin is a major target organ for extrahepatic manifestations of liver diseases. A broad range of cutaneous alterations can be present in patients with cirrhosis, such as vascular, nail, hair, hormonal changes, etc. Recognizing these signs is crucial so that potential underlying diseases including liver disease can be promptly diagnosed and appropriate management timely initiated. [ABSTRACT FROM AUTHOR]

Summary: Background: Advanced practice providers (APP) may be able to play a role in improving the linkage to care in patients with chronic hepatitis B (CHB), but data are limited. Aim: To compare management of patients with CHB under APP‐assisted versus physician‐only care Methods: This retrospective analysis identified patients with CHB infection from Optum's de‐identified Clinformatics® Data Mart Database (2003–2021) using ICD‐9/ICD‐10 codes. We compared the proportion of patients with CHB who had adequate evaluation for treatment (defined as ALT, HBV DNA, ± HBeAg), and the proportion of treatment‐eligible patients with CHB who received treatment between APP versus physician‐only care. Results: We included 42,140 eligible patients (mean age: 51.9 ± 15.1; 56.1% male). Overall, 34.3% received APP care with increasing utilisation over time. Compared to physician‐only care, patients who also received APP care were more likely to have viral co‐infection, and more likely to have been seen by a specialist (72.1%). Overall, 62.8% and 56.2% of treatment‐eligible patients based on AASLD and EASL guidelines, respectively, received treatment. APP care patients were more likely to be treated (AASLD adjusted HR: 1.18, 95%CI: 1.03–1.34; EASL adjusted HR:1.24, 95%CI: 1.09–1.41) after adjustment for age, sex, race/ethnicity, viral dual infection, baseline cirrhosis/liver cancer, number of HBV DNA and alanine aminotransferase measurements, and physician provider type. Conclusion: Treatment‐eligible patients with CHB receiving APP care were more likely to receive antiviral therapy. APP care may help to expand the pool of providers for patients with CHB, and to improve current suboptimal treatment rates. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hepatitis B (CHB) patients with metabolic syndrome (MetS) may present increased risk of liver-related outcomes (LROs), but prior studies were limited by small sample size and/or conflicting results. Using a systematic review and meta-analytic approach, we aimed to determine the association between MetS and LROs in CHB. Methods: Two researchers independently screened studies from the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to January 21, 2020, and extracted the data. Estimates were pooled using a random-effects model. Results: We screened 2,228 articles and included 10 eligible studies (18,360 CHB patients, 2,557 with MetS). MetS was significantly associated with LROs overall (odds ratio = 2.45, 95% confidence interval = 1.39–4.32) but not the individual LRO components but subgroup analyses were limited by small study numbers. Discussion/Conclusion: MetS is associated with almost 3-folds higher risk of LROs in CHB and should be considered in management decisions. However, additional studies are needed. [ABSTRACT FROM AUTHOR]