ACG Clinical Guideline: Focal Liver Lesions.

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

Global epidemiology of alcohol-associated liver disease in adolescents and young adults.

BACKGROUND AND AIMS: The objective of the study was to analyse the prevalence, incidence, and death of alcohol-associated liver disease (ALD) among adolescents and young adults globally, continentally, and nationally, focusing on trends over time. METHODS: The study analysed data from the Global Burden of Disease (GBD) study between 2000 and 2019. It examined ALD's prevalence, incidence, and death in adolescents and young adults aged 15-29, segmented by region, nation, and sociodemographic index. The analysis utilised Joinpoint regression modelling to calculate the annual per cent change (APC) in the rate of these parameters over time. RESULTS: In 2019, there were 281,450 ALD prevalences, 18,930 incidences, and 3190 deaths among adolescents and young adults globally. From 2000 to 2019, the age-adjusted prevalence rate per 100,000 increased in the 25-29 age group (APC: +0.6%, p = 0.003), remained stable among ages 20-24 (p = 0.302) and ages 15-19 (p = 0.160). Prevalence increased significantly from age 15-19 to 20-24 (19-fold increase) and from age 20-24 to 25-29 (2.5-fold increase). ALD prevalence rates increased in all age groups in adolescents and young adults in Africa and the Eastern Mediterranean region. Around three-quarters of countries and territories experienced an increase in ALD incidence rates in young adults. CONCLUSION: Over two decades, the burden of ALD among adolescents and young adults has increased globally. The study emphasises the importance of public health policies aimed at reducing alcohol consumption and preventing ALD among younger populations.

Characterization of Individuals With Hepatitis B Virus-Related Cirrhosis in a Large Integrated Health Care Organization, 2008-2019.

CONTEXT: Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a risk factor for cirrhosis. The management of HBV-related cirrhosis is challenging, with guidelines recommending treatment initiation and regular monitoring for those affected. OBJECTIVE: Our study characterized Kaiser Permanente Southern California patients with HBV-related cirrhosis and assessed whether they received recommended laboratory testing and imaging monitoring. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: We identified KPSC members aged ≥18 years with CHB (defined by 2, consecutive positive hepatitis B surface antigens ≥6 months apart) from 2008 to 2019. Of these patients, we further identified patients with potential HBV-related cirrhosis through ICD-10 code diagnosis, adjudicated via chart review. MAIN OUTCOME MEASURES: Age, race/ethnicity, laboratory tests (eg, alanine aminotransferase [ALT]), and hepatocellular carcinoma (HCC) screening (based on standard screening recommendations via imaging) were described in those with HBV-related cirrhosis versus those without. RESULTS: Among patients with CHB, we identified 65 patients with HBV-related cirrhosis over ~8 years. Diabetes was the most common comorbidity and was approximately 3 times more prevalent among patients with cirrhosis compared to patients without cirrhosis (21.5% vs. 7.1%). Of the 65 patients with cirrhosis, 72.3% (N = 47) received treatment. Generally, we observed that liver function tests (eg, ALT) were completed frequently in this population, with patients completing a median of 10 (6, 16) tests/year. All patients with cirrhosis had ≥1 ALT completed over the study period, and almost all cirrhotic patients (N = 64; 98.5%) had ≥1 HBV DNA test. However, the proportion of yearly imaging visits completed varied across the study years, between 64.0% in 2012 and 87.5% in 2009; overall, 35% (N = 23) completed annual imaging. CONCLUSIONS: Our findings suggest that among patients with HBV-related cirrhosis, at the patient-level, completed imaging orders for HCC screening were sub-optimal. However, we observed adequate disease management practices through frequent liver function tests, linkage to specialty care, image ordering, and shared EHR between KPSC providers.

Clinician-Level Knowledge and Barriers to Hepatocellular Carcinoma Surveillance.

Importance: Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is underused. Identifying potentially modifiable factors to address barriers in HCC surveillance is critical to improve patient outcomes. Objective: To evaluate clinician-level factors contributing to underuse of HCC surveillance in patients with cirrhosis. Design, Setting, and Participants: This survey study included primary care clinicians (PCCs) and gastroenterology and hepatology clinicians at 5 safety-net health systems in the US. Clinicians were surveyed from March 15 to September 15, 2023, to assess knowledge, attitudes, beliefs, perceived barriers, and COVID-19-related disruptions in HCC surveillance in patients with cirrhosis. Data were analyzed from October to November 2023. Main Outcome and Measures: HCC surveillance knowledge was assessed with 6 questions querying the respondent's ability to correctly identify appropriate use of HCC surveillance. Attitudes, perceived barriers, and beliefs regarding HCC surveillance and perceived impact of the COVID-19 pandemic-related disruptions with HCC surveillance were assessed with a series of statements using a 4-point Likert scale and compared PCCs and gastroenterology and hepatology clinicians. Results: Overall, 347 of 1362 clinicians responded to the survey (25.5% response rate), among whom 142 of 237 (59.9%) were PCCs, 48 of 237 (20.3%) gastroenterology and hepatology, 190 of 236 (80.5%) were doctors of medicine and doctors of osteopathic medicine, and 46 of 236 (19.5%) were advanced practice clinicians. On HCC knowledge assessment, 144 of 270 (53.3%) scored 5 or more of 6 questions correctly, 37 of 48 (77.1%) among gastroenterology and hepatology vs 65 of 142 (45.8%) among PCCs (P < .001). Those with higher HCC knowledge scores were less likely to report barriers to HCC surveillance. PCCs were more likely to report inadequate time to discuss HCC surveillance (37 of 139 [26.6%] vs 2 of 48 [4.2%]; P = .001), difficulty identifying patients with cirrhosis (82 of 141 [58.2%] vs 5 of 48 [10.4%]; P < .001), and were not up-to-date with HCC surveillance guidelines (87 of 139 [62.6%] vs 5 of 48 [10.4%]; P < .001) compared with gastroenterology and hepatology clinicians. While most acknowledged delays during the COVID-19 pandemic, 62 of 136 PCCs (45.6%) and 27 of 45 gastroenterology and hepatology clinicians (60.0%) reported that patients with cirrhosis could currently complete HCC surveillance without delays. Conclusions and Relevance: In this survey study, important gaps in knowledge and perceived barriers to HCC surveillance were identified. Effective delivery of HCC education to PCCs and health system-level interventions must be pursued in parallel to address the complex barriers affecting suboptimal HCC surveillance in patients with cirrhosis.

Hepatocellular carcinoma among patients with chronic hepatitis B in the indeterminate phase.

Hepatitis B virus (HBV) infection is a dynamic disease where patients progress through several stages defined by HBV e-antigen (HBeAg) status, HBV-DNA levels and transaminase elevations, with antiviral therapy indicated only in specific stages. However, some patients cannot be classified into one of the stages and are said to fall into an 'indeterminate phase' or 'grey zone'. Exact definitions of the indeterminate phase vary from guideline to guideline as a result of different cut-off values for biomarker measurements. Data suggest that as many as 50% of HBV patients may be in an indeterminate phase and may not rapidly transition out of this phase. Clinical data that suggest these patients are at increased risk of hepatocellular carcinoma (HCC) are complemented by molecular evidence of integrations of HBV-DNA into the host genome, chromosomal translocations and immune activation despite liver enzymes that may suggest lack of inflammation. Antiviral therapy reduces these hepatocarcinogenic mechanisms and is reflected in a reduction of fibrosis and HCC risk. We review key data on patients in the indeterminate phase, with emphasis on HCC as an outcome. We take a holistic approach and link new biological data with clinical observations as well as examine the potential role of antiviral therapy in reducing HCC risk among patients in the indeterminate phase. With the availability of safe and effective oral antivirals, consideration must be given as to how much residual risk of HCC should be tolerated among patients in the indeterminate phase.

Estimating the prevalence of hepatitis delta virus infection among adults in the United States: A meta-analysis.

BACKGROUND AND AIMS: Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of U.S. HDV prevalence. We aim to provide an updated assessment of HDV prevalence in the U.S. using a comprehensive literature review and meta-analysis approach. METHODS: A comprehensive literature review of articles reporting HBsAg seroprevalence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of foreign-born (FB) persons in the U.S. in 2022 from U.S. Census Bureau to estimate total numbers of FB with CHB and HDV, respectively. These estimates were further combined with updated estimates of U.S.-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. RESULTS: In 2022, we estimated 1.971 million (M) (95% CI 1.547-2.508) persons with CHB; 1.547 M (95% CI 1.264-1.831) were FB and 0.424 M (95% CI: 0.282-0.678) were U.S.-born. The weighted average HDV prevalence among FB persons in the U.S. was 4.20% (64 938 [95% CI 33055-97 392] persons), among whom 45% emigrated from Asia, 25% from Africa, and 14% from Europe. When combined with updated estimates of U.S.-born persons with HDV, we estimate 75 005 (95% CI: 42187-108 393) persons with HDV in the U.S. CONCLUSIONS: Including both FB and U.S.-born persons, we estimated that 1.971 M and 75 005 persons were living with CHB and HDV, respectively, in the U.S. in 2022.

An updated assessment of hepatitis delta prevalence among adults in Canada: A meta-analysis.

Foreign-born (FB) persons represent a large proportion of adults with chronic hepatitis B (CHB) in Canada due to higher prevalence rates in countries of birth for FB persons. Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of Canada HDV prevalence. We aim to provide an assessment of CHB and HDV prevalence in Canada using a comprehensive literature review and meta-analysis. A comprehensive literature review of articles reporting HBsAg seroprevalence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of FB persons in Canada in 2021 from Statistics Canada to estimate total numbers of FB with CHB and HDV, respectively. These estimates were combined with estimates of Canada-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. In 2021, we estimated 0.550 million (M) (95% CI 0.488-0.615) persons with CHB; 0.344 M (95% CI 0.288-0.401) were FB and 0.206 M (95% CI: 0.200-0.214) were Canada-born. The weighted average HDV prevalence among FB persons in Canada was 5.19% (17,848 [95% CI 9611-26,052] persons), among whom 50% emigrated from Asia and 31% from Africa. When combined with estimates of Canada-born persons with HDV, we estimate 35,059 (95% CI: 18,744-52,083) persons with HDV in Canada. In conclusion, we estimate 0.550 M and 35,059 persons living with CHB and HDV, respectively, in Canada in 2021.

Hepatic Encephalopathy: Clinical Manifestations.

Hepatic encephalopathy (HE) can occur as a complication of chronic liver disease as well as acute liver failure. HE is associated with significantly increased morbidity and worse patient outcomes. The clinical manifestation of HE ranges from early less-severe presentations that may only be accurately detected on dedicated psychomotor diagnostic testing to overt alterations in cognition and mental status to the most severe form of coma. Greater awareness of the clinical manifestations of HE across the spectrum of symptom severity is critical for early identification and timely initiation of appropriate therapy to improve patient outcomes.

Impact of HIV Infection on Liver and Cardiovascular Outcomes in Veterans With Metabolic Dysfunction-Associated Steatotic Liver Disease.

INTRODUCTION: Hepatic steatosis is highly prevalent in people living with HIV. It remains unclear whether HIV in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with greater risks of liver disease progression and cardiovascular disease (CVD). We aim to evaluate the impact of HIV infection on risks of liver and CVD outcomes among US Veterans with MASLD. METHODS: Using national Veterans Administration data from 2010 to 2022, we created a propensity score-matched cohort of MASLD patients with vs without HIV. Primary outcomes were incidence of cirrhosis and hepatocellular carcinoma (HCC) among patients with vs without HIV and patients with MASLD-HIV on antiretroviral therapy (ART) vs not on ART. Secondary outcomes included incidence of major adverse cardiovascular events and overall survival. RESULTS: The propensity-matched cohort included 920 MASLD patients with HIV and 920 MASLD patients without HIV and was similar in demographics and comorbidities. Compared with MASLD patients without HIV, incidences of cirrhosis and HCC were similar among MASLD with HIV. Compared with MASLD patients without HIV, incidence of major adverse cardiovascular event was higher among MASLD patients with HIV (5.18 vs 4.48 per 100 person-years, P = 0.03). Overall 5-year survival was significantly lower among MASLD patients with HIV and even lower among those not on ART. DISCUSSION: Among US Veterans with MASLD, concurrent HIV infection, and particularly not being on ART, is associated with greater risks of CVD and decreased overall survival. No differences in risks of cirrhosis or HCC were observed.

Impact of Longitudinal Alcohol Use Patterns on Long-Term Risk of Cirrhosis Among US Veterans With Steatotic Liver Disease.

BACKGROUND & AIMS: Conflicting data exist on the impact of alcohol use on risk of liver disease progression in patients with steatotic liver disease. We aimed to evaluate the effect of longitudinal alcohol use on risk of cirrhosis among veterans with steatotic liver disease. METHODS: US veterans with steatotic liver disease were identified from January 2010 through December 2022. Alcohol use was assessed using documented Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scores and categorized as no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1-3 for men), and high-risk alcohol (AUDIT-C ≥ 3 for women and ≥ 4 for men). Incidence of cirrhosis was evaluated with competing risks Nelson-Aalen methods. Adjusted multivariable regression models evaluated risks of cirrhosis associated with baseline alcohol use and changes in alcohol use during follow-up. RESULTS: There were 1,156,189 veterans with steatotic liver disease identified (54.2% no alcohol, 34.6% low-risk alcohol, and 11.2% high-risk alcohol). Veterans with steatotic liver disease and high-risk alcohol have a 43% higher incidence of cirrhosis compared with patients reporting no alcohol use. Compared with patients with baseline high-risk alcohol who reported no change in alcohol use, those who decreased their alcohol use during follow-up experienced a 39% reduction in long-term risk of cirrhosis (hazard ratio, 0.61; 95% CI, 0.45-0.83; P < .01). CONCLUSIONS: One in 9 veterans with steatotic liver disease report concurrent high-risk alcohol use, which is associated with 43% greater risk of cirrhosis compared with no alcohol use. However, reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease.

Epidemiology and Treatment Outcomes of Tuberculosis with Chronic Hepatitis B Infection-California, 2016-2020.

BACKGROUND: Improved epidemiologic and treatment data for active tuberculosis (TB) with chronic hepatitis B virus (cHBV) infection might inform and encourage screening and vaccination programs focused on persons at risk of having both conditions. METHODS: We matched the California Department of Public Health TB registry during 2016-2020 to the cHBV registry using probabilistic matching algorithms. We used chi-square analysis to compare the characteristics of persons with TB and cHBV with those with TB only. We compared TB treatment outcomes between these groups using modified Poisson regression models. We calculated the time between reporting of TB and cHBV diagnoses for those with both conditions. RESULTS: We identified 8,435 persons with TB, including 316 (3.7%) with cHBV.- Among persons with TB and cHBV, 256 (81.0%) were non-U.S.-born Asian vs 4,186 (51.6%) with TB only (P <0.0001). End-stage renal disease (26 [8.2%] vs 322 [4.0%]; P <0.001) and HIV (21 [6.7%] vs 247 [3.0%]; P value = 0.02) were more frequent among those with TB and cHBV compared with those with TB only. Among those with both conditions, 35 (11.1%) had TB diagnosed >60 days before cHBV (median 363 days) and 220 (69.6%) had TB diagnosed >60 days after cHBV (median 3,411 days). CONCLUSION: Persons with TB and cHBV were found more frequently in certain groups compared with TB only, and infrequently had their conditions diagnosed together. This highlights an opportunity to improve screening and treatment of TB and cHBV in those at high risk for coinfection.

Problematic alcohol use and its impact on liver disease quality of life in a multicenter study of patients with cirrhosis.

BACKGROUND: Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL). METHODS: Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity. RESULTS: Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status. CONCLUSIONS: Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population.

Telehepatology Satisfaction Is Associated with Ethnicity: The Real-World Experience of a Vulnerable Population with Fatty Liver Disease.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) pandemic began, telemedicine use has transformed healthcare delivery. Yet there is concern that telemedicine may widen care disparities for vulnerable populations, and patient experience data are limited. AIMS: We aimed to assess patient satisfaction with hepatology-related telemedicine (telehepatology) for delivery of fatty liver disease (FLD) care in a safety-net healthcare system. METHODS: Adult patients with FLD were surveyed regarding satisfaction with telehepatology. Clinical, demographic, resources, and social determinants of health (SDoH) data were collected to identify factors associated with satisfaction through multivariable modeling. RESULTS: From June 2020 to March 2022, 220 participants were enrolled: the median age was 52 years, 37% were men, and 68% were Hispanic. One hundred nineteen (54%) had prior telehepatology experience. Overall, satisfaction was high; 70% reported being somewhat or very satisfied. On univariate analysis, Hispanic ethnicity (versus non-Hispanic, OR 0.34, 95% CI 0.1-0.9, p = 0.03) and limited access to personal cellphone/internet (OR 0.16, 95% CI 0.04-0.6, p = 0.01) were associated with lower satisfaction. On multivariable logistic regression modeling adjusted for pandemic duration, age, sex, severity of liver disease, and coexisting liver disease, Hispanic ethnicity and lack of personal cellphone/internet remained independently associated with lower telehepatology satisfaction (OR 0.24, 95% CI 0.07-0.9, p = 0.03 and OR 0.2, 95% CI 0.04-0.9, p = 0.04, respectively). The association remained statistically significant after inclusion of various SDoH in the multivariable model. CONCLUSIONS: Satisfaction with telehepatology among FLD patients in a safety-net clinical setting was high overall. However, Hispanic ethnicity and lack of personal cellphone/internet were independently associated with lower telehepatology satisfaction. A better understanding of patients' experience with telehepatology is needed to identify reasons for dissatisfaction, and in-person visits should remain an option for patients to ensure equitable care.

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.

Understanding the Natural History of Chronic Hepatitis D: Proposal of a Model for Cost-Effectiveness Studies.

BACKGROUND: As new therapeutic options become available, better understanding the potential impact of emerging therapies on clinical outcomes of hepatits D virus (HDV) is critical. OBJECTIVE: The aim of this study was to develop a natural history model for patients with hepatitis D virus. METHODS: We developed a model (decision tree followed by a Markov cohort model) in adults with chronic HDV infection to assess the natural history and impact of novel treatments on disease progression versus best supportive care (BSC). The model time horizon was over a lifetime (up to 100 years of age); state transitions and health states were defined by responder status. Patients in fibrosis stages 0 through 4 received treatment; decompensated patients were not treated. Response was defined as the combined response endpoint of achievement of HDV-RNA undetectability/≥2-log10 decline and alanine aminotransferase normalization; response rates of 50% and 75% were explored. Health events associated with advanced liver disease were modeled as the number of events per 10,000 patients. Scenario analyses of early treatment, alternate treatment response, and no fibrosis regression for treatment responders were also explored. RESULTS: The model was able to reflect disease progression similarly to published natural history studies for patients with HBV/HDV infection. In a hypothetical cohort of patients reflecting a population enrolled in a recent clinical trial, fewer advanced liver disease events were observed with a novel HDV treatment versus BSC. Fewer liver-related deaths were observed under 50% and 75% response (900 and 1,358 fewer deaths, respectively, per 10,000 patients). Scenario analyses showed consistently fewer advanced liver disease events with HDV treatment compared with BSC, with greater reductions observed with earlier treatment. CONCLUSION: This HDV disease progression model replicated findings from natural history studies. Furthermore, it found that a hypothetical HDV treatment results in better clinical outcomes for patients versus BSC, with greater benefit observed when starting treatment early. This validated natural history model for HBV/HDV infection can serve as a foundation for future clinical and economic analyses of novel HDV treatments that can support healthcare stakeholders in the management of patients with chronic HDV.

Alcohol Use Patterns During and After the COVID-19 Pandemic Among Veterans in the United States.

BACKGROUND: Veterans may be especially susceptible to increased alcohol consumption following the COVID-19 pandemic. We aim to evaluate trends in alcohol use among US Veterans prior to, during, and following the onset of the COVID-19 pandemic. METHODS: All US Veterans utilizing Veterans Affairs health care facilities in the United States from March 1, 2018 to February 28, 2023 with ≥1 AUDIT-C score were categorized into 1) No alcohol use (AUDIT-C = 0), 2) Low-risk alcohol use (AUDIT-C 1-2 for women, 1-3 for men), and 3) High-risk alcohol use (AUDIT-C ≥ 3 for women, ≥ 4 for men). Trends in the proportion of Veterans reporting high-risk alcohol use, stratified by sex, age, race/ethnicity, and urbanicity were evaluated. RESULTS: Among a cohort of 2.15 to 2.60 million Veterans, 15.5% reported high-risk alcohol use during March 2018-February 2019, which decreased to 14.6% during the first year of the pandemic, increased to 15.2% in the second year, and then decreased to 14.9% from March 2022-February 2023. Among non-Hispanic whites, African Americans, Asians, and Hispanics, the proportion of women reporting high-risk alcohol use surpassed that of men during the onset of the pandemic and beyond. The greatest proportion of high-risk alcohol use was observed among young Veterans ages 18-39 years (17%-27%), which was consistent across all race/ethnic groups. CONCLUSIONS: High-risk alcohol use among US Veterans has increased since the COVID-19 pandemic onset, and in the third year following pandemic onset, 15% of Veterans overall and over 20% of young Veterans ages 18-39 years reported high-risk alcohol use.

Prevalence and characteristics of hepatitis delta virus infection in patients with hepatitis B in the United States: An analysis of the All-Payer Claims Database.

BACKGROUND AND AIMS: HDV leads to the most severe form of viral hepatitis; however, the prevalence of HDV is not well understood. Using real-world data from the All-Payer Claims Database, this study estimates the prevalence of HBV/HDV infection among the chronic HBV population and describes patient/clinical characteristics for adults with HBV/HDV infection in the United States. APPROACH AND RESULTS: Adults (≥18 years) with ≥1 inpatient claim or ≥2 outpatient claims for HDV infection or HBV in the All-Payer Claims Database from January 1, 2014, to December 31, 2020, were identified. HDV prevalence was calculated as the proportion of patients with HBV/HDV infection among total patients with HBV infection. Patient characteristics, socioeconomic status, advanced liver complications (eg, cirrhosis, HCC), and comorbidities were assessed. A total of 6719 patients were diagnosed with HBV/HDV among 144,975 with HBV and 12 months of continuous data, for a prevalence of 4.6%. At diagnosis, 31.7% of patients with HBV/HDV had advanced liver complications, including compensated cirrhosis (16.3%) and decompensated cirrhosis (10.4%). Diabetes (50.5%), hypertension (49.8%), and HIV infection (30.9%) were the top 3 comorbidities. CONCLUSIONS: In a large database capturing approximately 80% of the US-insured population, HBV/HDV infection prevalence was 4.6% among adults infected with HBV. Patients infected with HDV had high rates of baseline liver complications and other comorbidities at the time of diagnosis, suggesting potentially delayed diagnosis and/or treatment. Earlier identification of HBV/HDV infection among the population with HBV may provide opportunities to improve linkage to care and treatment, thereby reducing the risk of liver-related morbidity and mortality.

Association of hepatitis delta virus with liver morbidity and mortality: A systematic literature review and meta-analysis.

BACKGROUND AND AIMS: Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events in patients who are HBsAg and HDV antibody positive. APPROACH AND RESULTS: A total of 12 publications were included. Relative rates of progression to advanced liver disease event for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported OR and HRs with 95% CI were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The presence of HDV RNA+ was associated with an increased risk of any advanced liver disease event [random effect (95% CI): risk ratio: 1.48 (0.93, 2.33); HR: 2.62 (1.55, 4.44)]. When compared to the patients with HDV RNA- status, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis [risk ratio: 1.74 (1.24, 2.45)] decompensated cirrhosis [HR: 3.82 (1.60, 9.10)], HCC [HR: 2.97 (1.87, 4.70)], liver transplantation [HR: 7.07 (1.61, 30.99)], and liver-related mortality [HR: 3.78 (2.18, 6.56)]. CONCLUSIONS: The patients with HDV RNA+ status have a significantly greater risk of liver disease progression than the patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.