National prevalence estimates for steatotic liver disease and subclassifications using consensus nomenclature.

BACKGROUND AND AIMS: The multisociety consensus nomenclature has renamed NAFLD to steatotic liver disease (SLD) with various subclassifications. There is a paucity of data regarding how the new nomenclature modifies our understanding of disease prevalence and patient phenotypes. APPROACH AND RESULTS: Using the National Health and Nutrition Examination Survey from January 2017 to March 2020, we included all participants aged 18 years or above with complete vibration-controlled transient elastography measures. SLD and its subclassifications [metabolic dysfunction-associated SLD (MASLD), MASLD + increased alcohol intake (MetALD), alcohol-associated liver disease (ALD), etiology-specific/cryptogenic] were defined according to consensus nomenclature. National SLD prevalence and subclassifications were estimated, and among key subgroups [age, sex, race/ethnicity, advanced liver fibrosis (liver stiffness measurement [LSM] ≥11.7 kPa)]. Among 7367 participants, 2549 had SLD (mean age 51 y, 57.7% male, 63.2% non-Hispanic White). The estimated prevalence of SLD was 34.2% (95% CI 31.9%-36.5%): MASLD 31.3% (29.2%-33.4%), MetALD 2% (1.6%-2.9%), ALD 0.7% (0.5-0.9%), etiology-specific/cryptogenic 0.03% (0.01%-0.08%). In exploratory analyses, participants classified as non-SLD with (vs. without) advanced fibrosis had a higher mean number of metabolic risk factors [2.7 (2.3-3.1) vs. 2.0 (1.9-2.0)] and a higher proportion with average alcohol use ≥20 g/d (women)/≥30 g/d (men) [20.9% (6.2%-51.3%) vs. 7.2% (6.1%-8.4%)]. In another exploratory analysis, increasing quantities of alcohol use remaining below the threshold for MASLD + increased alcohol intake were associated with advanced liver fibrosis in men, but not women. There was 99% overlap in cases of NAFLD and MASLD. CONCLUSIONS: Our findings highlight the utility of the new consensus nomenclature to address deficiencies present with the old nomenclature, and identify areas that require research to further refine classifications of SLD.

Liver transplantation for alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a major cause of morbidity and mortality worldwide, and a leading indication for liver transplantation (LT) in many countries, including the United States. However, LT for ALD is a complex and evolving field with ethical, social, and medical challenges. Thus, it requires a multidisciplinary approach and individualized decision-making. Short-term and long-term patient and graft survival of patients undergoing LT for ALD are comparable to other indications, but there is a continued need to develop better tools to identify patients who may benefit from LT, improve the pretransplant and posttransplant management of ALD, and evaluate the impact of LT for ALD on the organ donation and transplantation systems. In this review, we summarize the current evidence on LT for ALD, from alcohol-associated hepatitis to decompensated alcohol-associated cirrhosis. We discuss the indications, criteria, outcomes, and controversies of LT for these conditions and highlight the knowledge gaps and research priorities in this field.

Liver stiffness progression in biopsy-proven metabolic dysfunction-associated steatotic disease among people with diabetes versus people without diabetes: A prospective multicenter study.

BACKGROUND AND AIMS: There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective, multicenter cohort study. APPROACH AND RESULTS: This study included 1231 adult participants (62% female) with biopsy-proven metabolic dysfunction-associated steatotic liver disease who had VCTEs at least 1 year apart. LSM progression and regression were defined by a ≥20% increase and an upward or downward change, respectively, in the LSM category in the Baveno VII categories for compensated advanced chronic liver disease, compared between participants with T2DM (n = 680) versus no T2DM (n = 551) at baseline. The mean (±SD) age and body mass index were 51.8 (±12.0) years and 34.0 (±6.5) kg/m 2 , respectively. The median (IQR) time between the first and last VCTE measurements was 4.1 (2.5-6.5) years. Participants with T2DM had higher LSM progression at 4 years (12% vs. 10%), 6 years (23% vs. 16%), and 8 years (50% vs. 39%), p = 0.04. Using a multivariable Cox proportional hazards model adjusted for multiple confounders, the presence of T2DM remained an independent predictor of LSM progression (adjusted HR: 1.35, 95% CI: 1.01-1.81, p = 0.04). T2DM was not associated with LSM regression ( p = 0.71). Mean HbA1c was significantly associated with LSM progression ( p = 0.003) and regression ( p = 0.02). CONCLUSIONS: Using serial VCTE data from a multicenter study of participants with biopsy-proven metabolic dysfunction-associated steatotic liver disease, we demonstrate that T2DM and HbA1c are associated with LSM progression.

A global action agenda for turning the tide on fatty liver disease.

BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

HBV RNA as a Biomarker for Safe Antiviral Discontinuation: A Prospective Study of Nucleos(t)ide Analogue Withdrawal.

INTRODUCTION: Withdrawal of nucleos(t)ide analog (NA) therapy is associated with hepatitis B surface antigen (HBsAg) loss and sustained, off-therapy partial cure (normal ALT [≤30 U/L males, ≤20 U/L females) with HBV DNA <2000 IU/mL) but should be offered only to those most likely to benefit. HBVRNA may be useful for risk stratification. METHODS: The Hepatitis B Research Network Immune-Active Trial prospectively evaluated treatment with tenofovir (TDF) for 192 weeks ± peginterferon-α (PegIFN) for initial 24 weeks followed by protocolized withdrawal of TDF amongst eligible participants (NCT01369212). HBV RNA was evaluated as predictor of ALT flares and sustained partial cure (HBV DNA<2000 IU/mL) 48 weeks after TDF withdrawal. RESULTS: Of 93 participants discontinuing TDF (52 in TDF+PegIFN and 41 in TDF alone), 52 (55.9%) had unquantifiable HBVRNA at end-of-treatment. ALT flares (>5xULN) at 48 weeks off-therapy occurred in 33.3%, with pre-treatment age (≥35 years) and quantifiable HBV RNA at end-of-treatment, the best predictors (AUROC 0.74 and 0.85, training and test set) of ALT flare. A total of 26 (28.3%) had sustained partial cure; 3 (11.5%) with ALT flare. Non-quantifiable HBVRNA and qHBsAg <100 IU/mL at end-of-treatment were the best predictors of sustained partial cure (AUROC 0.84 and 0.93, training and test set). If HBVRNA was quantifiable at end-of-treatment, the likelihood of sustained partial cure was only 3% whereas if HBV RNA was unquantifiable and qHBsAg <100 IU/mL, this likelihood was 73%. CONCLUSIONS: HBVRNA is a useful biomarker in predicting likelihood of achieving sustained partial cure and safe withdrawal of NAs.

Hepatitis C.

Hepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required.

Antimullerian Hormone, a Marker of Ovarian Reserve, Is Protective Against Presence and Severity of NASH in Premenopausal Women.

BACKGROUND & AIMS: Antimüllerian hormone (AMH) is a marker of ovarian reserve with emerging data linking lower levels to some metabolic and inflammatory diseases in women. Whether AMH levels influence nonalcoholic fatty liver disease (NAFLD) is unknown. METHODS: Leveraging the NASH Clinical Research Network we determined the association of AMH levels within 6 months of liver biopsy with presence and severity of histologic measures of NAFLD in premenopausal women. Outcomes included presence of nonalcoholic steatohepatitis (NASH), presence and severity of fibrosis, and NAFLD Activity Score and its components. Logistic and ordinal logistic regression models were adjusted for age, race/ethnicity, homeostatic model assessment for insulin resistance, body mass index, dyslipidemia, polycystic ovary syndrome, estrogen-progestin use, and menstrual cyclicity. RESULTS: Median cohort age was 35 years; 73% were white and 24% Hispanic. Thirty-three percent had diabetes, 81% had obesity, and 95% had dyslipidemia. On biopsy 71% had NASH, 68% had any fibrosis, and 15% had advanced fibrosis. On adjusted analysis (n = 205), higher AMH quartiles were inversely associated with NAFLD histology including prevalent NASH (adjusted odds ratio [AOR], 0.64; 95% confidence interval [CI], 0.41-1.00), NAFLD Activity Score ≥5 (AOR, 0.52; 95% CI, 0.35-0.77), Mallory hyaline (AOR, 0.54; 95% CI, 0.35-0.82), and higher fibrosis stage (AOR, 0.70; 95% CI, 0.51-0.98). The protective effects of AMH were more pronounced among women without polycystic ovary syndrome (n = 164), including lower odds of NASH (AOR, 0.53; 95% CI, 0.32-0.90) and any NASH fibrosis (AOR, 0.54; 95% CI, 0.32-0.93). CONCLUSIONS: AMH may reflect a unique biomarker of NASH in premenopausal women and findings suggest a novel link between reproductive aging and histologic severity of NAFLD in women.

Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study.

BACKGROUND & AIMS: There are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis progression in people with T2DM compared with people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies. METHODS: This study included 447 adult participants (64% were female) with NAFLD who had paired liver biopsies more than 1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis in participants with T2DM compared with participants without T2DM. RESULTS: The mean (SD) age and body mass index (calculated as weight in kilograms divided by the square of the height in meters) were 50.9 (11.5) years and 34.7 (6.3), respectively. The median time between biopsies was 3.3 years (interquartile range, 1.8-6.1 years). Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4 years (24% vs 20%), 8 years (60% vs 50%), and 12 years (93% vs 76%) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95% CI, 1.17-2.43; P = .005). The cumulative incidence of fibrosis regression by ≥1 stage was similar in participants with T2DM compared with participants without T2DM (P = .24). CONCLUSIONS: In this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we found that fibrosis progressed faster in participants with T2DM compared with participants without T2DM. These data have important implications for clinical practice and trial design.

ACG Clinical Guideline: Alcohol-Associated Liver Disease.

ABSTRACT: Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful alcohol use as the primary risk factor, increasing alcohol use over the past decade has resulted in rapid growth of the ALD-related healthcare burden. The spectrum of ALD ranges from early asymptomatic liver injury to advanced disease with decompensation and portal hypertension. Compared with those with other etiologies of liver disease, patients with ALD progress faster and more often present at an advanced stage. A unique phenotype of advanced disease is alcohol-associated hepatitis (AH) presenting with rapid onset or worsening of jaundice, and acute on chronic liver failure in severe forms conveying a 1-month mortality risk of 20%-50%. The model for end stage disease score is the most accurate score to stratify AH severity (>20 defined as severe disease). Corticosteroids are currently the only available therapeutic with proven efficacy for patients with severe AH, providing survival benefit at 1 month in 50%-60% of patients. Abstinence of alcohol use, a crucial determinant of long-term outcomes, is challenging to achieve in ALD patients with concurrent alcohol use disorder (AUD). As patients with ALD are rarely treated for AUD, strategies are needed to overcome barriers to AUD treatment in patients with ALD and to promote a multidisciplinary integrated care model with hepatology, addiction medicine providers, and social workers to comprehensively manage the dual pathologies of liver disease and of AUD. Liver transplantation, a definitive treatment option in patients with advanced cirrhosis, should be considered in selected patients with AH, who are unresponsive to medical therapy and have a low risk of relapse to posttransplant alcohol use. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the American College of Gastroenterology Practice Parameters Committee.

The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints.

INTRODUCTION: One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis. METHODS: The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee. RESULTS: The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient-reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding because of portal gastropathy, and hepatocellular carcinoma were also codified. DISCUSSION: The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multicenter cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion. REGISTRATION: NCT05740358.

Safety of acamprosate for alcohol use disorder Post-Liver transplant: a pilot randomized controlled trial.

INTRODUCTION: Acamprosate is a therapy for alcohol use disorder but data on feasibility and safety in liver transplant (LT) recipients are lacking. METHODS: This was a single-center unblinded prospective pilot randomized controlled trial of adults (≥18 years) with LT for ALD enrolled between 2021-2023 who were randomized 2:1 to the intervention of acamprosate (666mg dose three times daily) or standard of care (SOC) over 14 weeks. Outcomes included safety [prevalence of adverse events (AE)], feasibility (weekly survey response rate >60%), adherence (self-reported acamprosate use>60%), and efficacy (reduction in Penn Alcohol Craving Scale [PACS]) and relapse-blood phosphatidylethanol≥20ng/mL/reported alcohol use) evaluated by standardized weekly surveys. The efficacy analysis was done in both the intention to treat (ITT) (excluding withdrawals before medication administration) and per-protocol (PP) population (excluding withdrawals/<4 weeks participation). RESULTS: Of 78 participants approached, 30 enrolled (19 acamprosate, 11 SOC) with similar baseline characteristics. Eight participants withdrew (6 acamprosate prior to medication administration and 2 SOC). AEs were similar between acamprosate and SOC groups (92.3% vs. 90.0%, p>0.99), including Grade 3 AEs (53.9% vs. 60.0%, p>0.99) with no reported grade 4/5 AEs. Survey response rates were similar in acamprosate vs SOC groups (61.0% vs. 76.0%, p=0.19), and 69.0% were acamprosate adherent. Baseline PACS values were low with no difference by group in median absolute change in PACS for ITT (0, IQR:-4-0 vs. 0, IQR:0-0, p=0.32) and PP analyses (-1, IQR:-6-0 vs. 0, IQR:0-0, p=0.36). There were no reported or biochemical evidence of alcohol relapse. CONCLUSION: In this pilot study, preliminary data suggests that acamprosate may be safe and feasible. These data can inform larger studies and clinician efforts to address alcohol use disorder in post-LT care. (ClinicalTrials.gov, Number: NCT06471686).

Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis.

BACKGROUND: Early liver transplantation for alcohol-associated hepatitis is controversial in part because patients may recover, and obviate the need for liver transplantation. METHODS: In this retrospective study among 5 ACCELERATE-AH sites, we randomly sampled patients evaluated and then declined for liver transplantation for alcohol-associated hepatitis. All had Model of End-Stage Liver Disease (MELD) >20 and <6 months of abstinence. Recompensation was defined as MELD <15 without variceal bleeding, ascites, or overt HE requiring treatment. Multilevel mixed effects linear regression was used to calculate probabilities of recompensation; multivariable Cox regression was used for mortality analyses. RESULTS: Among 145 patients [61% men; median abstinence time and MELD-Na was 33 days (interquartile range: 13-70) and 31 (interquartile range: 26-36), respectively], 56% were declined for psychosocial reasons. Probability of 30-day, 90-day, 6-month, and 1-year survival were 76% (95% CI, 68%-82%), 59% (95% CI, 50%-66%), 49% (95% CI, 40%-57%), and 46% (95% CI, 37%-55%), respectively. Probability of 1-year recompensation was low at 10.0% (95% CI, 4.5%-15.4%). Among patients declined because of clinical improvement, 1-year probability of recompensation was 28.0% (95% CI, 5.7%-50.3%). Among survivors, median MELD-Na at 30 days, 90 days, and 1-year were 29 (interquartile range: 22-38), 19 (interquartile range : 14-29), and 11 (interquartile range : 7-17). Increased MELD-Na (adjusted HR: 1.13, p <0.001) and age (adjusted HR: 1.03, p <0.001) were associated with early (≤90 d) death, and only history of failed alcohol rehabilitation (adjusted HR: 1.76, p =0.02) was associated with late death. CONCLUSIONS: Liver recompensation is infrequent among severe alcohol-associated hepatitis patients declined for liver transplantation. Higher MELD-Na and age were associated with short-term mortality, whereas only history of failed alcohol rehabilitation was associated with long-term mortality. The distinction between survival and liver recompensation merits further attention.

Maternal neighbourhood-level social determinants of health and their association with paediatric hepatitis C screening among children exposed to hepatitis C in pregnancy.

BACKGROUND: Current guidelines recommend HCV screening by 18 months of age for those exposed to HCV in utero; yet, screening occurs in the minority of children. OBJECTIVES: To evaluate the association between maternal neighbourhood-level social determinants of health (SDOH) and paediatric HCV screening in the general population in a publicly funded healthcare system in Canada. METHODS: Retrospective cohort study using administrative healthcare data held at ICES. Children born to individuals positive for HCV RNA in pregnancy from 2000 to 2016 were identified and followed for 2 years. Major SDOH were identified, and the primary outcome was HCV screening in exposed children (HCV antibody and/or RNA). Associations between SDOH and HCV screening were determined using multivariate Poisson regression models adjusting for confounding. RESULTS: A total of 1780 children born to persons with +HCV RNA were identified, and 29% (n = 516) were screened for HCV by age two. Most mothers resided in the lowest income quintile (42%), and most vulnerable quintiles for material deprivation (41%), housing instability (38%) and ethnic diversity (26%) with 11% living in rural locations. After adjustment for confounding, maternal rural residence (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.62, 1.07) and living in the highest dependency quintile (RR 0.83, 95% CI 0.65, 1.07) were the SDOH most associated with paediatric HCV screening. Younger maternal age (RR 0.98 per 1-year increase, 95% CI 0.97, 0.99), HIV co-infection (RR 1.69, 95% CI 1.16, 2.48) and GI specialist involvement (RR 1.18, 95% CI 1.00, 1.39) were associated with higher probabilities of screening. CONCLUSIONS: Among children exposed to HCV during pregnancy, rural residences and living in highly dependent neighbourhoods showed a potential association with a lower probability of HCV screening by the age of 2. Future work evaluating barriers to paediatric HCV screening among rural residing and dependent residents is needed to enhance the screening.

Liver transplantation for alcohol-associated liver disease: A call for national standards of best practices to monitor and bridge disparities in access and outcomes.

Early (ie, without a mandated abstinence period) liver transplantation for alcohol-associated liver disease is the fastest-growing indication for liver transplantation in the United States. Despite widespread adoption, there is no standardization of practice or policies across transplant centers, nor are there any quality metrics from regulatory organizations specific to alcohol, all of which have likely contributed to confirmed disparities in transplant access and patient outcomes. In this article, we propose new mandates and best practices that could be put forth by the organ procurement and transplantation network regarding processes related to candidate selection, monitoring of alcohol use, and services to prevent and treat harmful alcohol use among early transplant candidates and recipients. We hope that this article stimulates discussion and leads to policy changes to maximize equity and quality of transplant care.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Pregnancy-Associated Liver Diseases.

The liver disorders unique to pregnancy include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, and preeclampsia-associated hepatic impairment, specifically hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP). Their importance lies in the significant maternal and fetal/neonatal morbidity and mortality. Expeditious diagnosis and clinical evaluation is critical to ensure timely, appropriate care and minimize risks to the pregnant woman and her fetus/baby. A multidisciplinary approach is essential, including midwives, maternal-fetal-medicine specialists, anesthetists, neonatologists, and hepatologists.

Geographic Density of Gastroenterologists Is Associated With Decreased Mortality From Alcohol-Associated Liver Disease.

BACKGROUND & AIMS: Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality and has been increasing. To inform public health efforts to address the growing incidence of ALD, we assessed the association of geographic density of gastroenterologists with ALD-related mortality. METHODS: National data were obtained for adults aged ≥25 years with state-level demographics and 2010-2019 mortality estimates by linking federally maintained registries (WONDER, NSSATS, BRFSS, HRSA, US Census Bureau). Multivariable linear regression was used to assess the association of state-level geographic density of gastroenterologists with ALD-related mortality, adjusting for age, sex, race/ethnicity, and other potential confounders. RESULTS: Among 50 states and the District of Columbia, the national mean geographic density of gastroenterologists was 4.6 per 100,000 population, and annual ALD-related mortality rate was 85.6 per 1,000,000 population. There was greater than 5-fold differences in geographic density of gastroenterologists and ALD-related mortality across states. In multivariable analysis, the geographic density of gastroenterologists was significantly associated with lower ALD-related mortality (9.0 [95% confidence interval, 1.3-16.7] fewer ALD-related deaths per 1,000,000 population for each additional gastroenterologist per 100,000 population). The association appeared to peak at a threshold of ≥7.5 gastroenterologists per 100,000 population. We estimated that differences in geographic density of gastroenterologists across states may potentially represent 40% of national ALD-related mortality. Exploratory analyses to assess for confounding by generalized subspecialty care, transplant access, alcohol taxation, and substance use or mental health services, including negative control analyses, did not affect primary results. CONCLUSIONS: State-level geographic density of gastroenterologists is associated with lower ALD-related mortality. These results may inform medical societies and health policymakers to address anticipated workforce gaps to address the growing epidemic of ALD.

Liver Transplantation 2023: Status Report, Current and Future Challenges.

Liver transplantation offers live-saving therapy for patients with complications of cirrhosis and stage T2 hepatocellular carcinoma. The demand for organs far outstrips the supply, and innovations aimed at increasing the number of usable deceased donors as well as alternative donor sources are a major focus. The etiologies of cirrhosis are shifting over time, with more need for transplantation among patients with alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease and less for viral hepatitis, although hepatitis B remains an important indication for transplant in countries with high endemicity. The rise in transplantation for alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease has brought attention to how patients are selected for transplantation and the strategies needed to prevent recurrent disease. In this review, we present a status report on the most pressing topics in liver transplantation and future challenges.

Randomized Trial of Tenofovir With or Without Peginterferon Alfa Followed by Protocolized Treatment Withdrawal in Adults With Chronic Hepatitis B.

INTRODUCTION: Hepatitis B surface antigen (HBsAg) loss is associated with improved long-term outcomes of patients with chronic hepatitis B but is infrequently achieved with current monotherapies. We assessed whether combination strategies that included treatment withdrawal enhanced HBsAg loss. METHODS: A randomized (1:1) trial of tenofovir disoproxil fumarate (TDF) for 192 weeks with or without peginterferon (PegIFN) alfa-2a for the first 24 weeks, followed by withdrawal of TDF at week 192 with 48 weeks of off-treatment follow-up to week 240. The primary end point was HBsAg loss at week 240. RESULTS: Of 201 participants (52% HBeAg positive, 12%/6% genotype A/A2, 7% cirrhosis) randomized to TDF + PegIFN (n = 102) or TDF alone (n = 99), 6 participants had lost HBsAg at the end of the treatment phase (week 192), 5 (5.3%) in the combination group, and 1 (1.0%) in the TDF alone group ( P = 0.09). By week 240, 9 participants had cleared HBsAg, 5.3% in combination, and 4.1% in monotherapy arms ( P = 0.73). HBsAg decline and loss occurred earlier with TDF + PegIFN than TDF, with a ≥1-logIU/mL qHBsAg decline by week 24 in 28% in TDF + PegIFN compared with 6% in TDF ( P = 0.04). HBsAg loss occurred in 7 of 12 (58%) with hepatitis B virus subgenotype A2 (all HBeAg positive) compared with only 2 of 189 (1%) with other hepatitis B virus genotypes and in 8 of 93 (8.6%) HBeAg positive vs 1 of 87 (1.1%) HBeAg negative. DISCUSSION: PegIFN combined TDF followed by protocolized TDF withdrawal led to earlier but not higher percentages of HBsAg clearance. Pretreatment HBeAg positivity and subgenotype A2 were strongly associated with HBsAg clearance.

Strategies to increase primary care provider capacity for hepatitis C care: The California ECHO-PLUS study.

Expanding capacity to screen and treat those infected with the hepatitis C virus (HCV) is an essential element of the global elimination strategy. We evaluated the hub-and-spoke Project ECHO training versus telementoring models to educate, train and support HCV care by primary care providers in 13 targeted counties in northern California. A novel provider engagement strategy was used. Provider engagement and retention, time to readiness to treat HCV, and knowledge and confidence were the outcomes of interest. 94 participants from 60 unique clinics in the target counties participated in the ECHO-PLUS programme; 39.4% were physicians, 48.9% were advanced practice providers, and 11.7% were nurses. The median (range) participation time was 5 (1-49) hours. Confidence scores (minimum score = 13 and maximum score = 65) increased by a mean of 14.0 (SD:8.2) and 11.4 (SD:12.0) points for the hub-and-spoke and telementoring programmes, respectively (p = .53), with the largest changes in confidence seen in treating patients per guidelines, managing side effects and in serving as a consultant for HCV in their clinic. Among 24 participants with data on time to treatment, median time from beginner to experienced was 8 h (IQR:6-12) for hub-and-spoke and 2 h (IQR:1-2.4) for the telementoring programme (p = .01). A 'boots on the ground' approach to recruiting HCV champions was effective within rural communities. Both tele-ECHO hub-and-spoke and telementoring approaches to training primary care providers yielded increase in knowledge and confidence in HCV care and amplified the number of patients who were screened and treated. Telementoring accelerated the timeline of novice providers being 'ready to treat'.