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Introduction Immigrants comprise a considerable proportion of those diagnosed with hepatocellular carcinoma (HCC) in the United States. Nativity or birthplace affects incidence and risk factors for HCC, but little is known about its influence on survival after diagnosis. Methods We identified 51 533 adults with HCC with available birthplace in the California Cancer Registry between 1988 and 2017. HCC cases were categorized as foreign born or US born and stratified by mutually exclusive race and ethnicity groups. Primary outcome was all-cause mortality. Race and ethnicity–specific Cox regression propensity score-weighted models evaluated the relationship between nativity and death as well as region of birth among foreign-born patients. Results A total of 40% of all HCC cases were foreign born, and 92.2%, 45.2%, 9.1%, and 5.8% of Asian/Pacific Islander (API), Hispanic, White, and Black patients were foreign born, respectively. Five-year survival rates were higher in foreign-born patients compared with US-born patients: 12.9% vs 9.6% for White patients, 11.7% vs 9.8% for Hispanic patients, 12.8% vs 8.1% for Black patients, and 16.4% vs 12.4% for API patients. Nativity was associated with survival, with better survival in foreign-born patients: White patients: hazard ratio (HR) = 0.86 (95% confidence interval [CI] = 0.81 to 0.90), Hispanic patients: HR = 0.90 (95% CI = 0.86 to 0.93), Black patients: HR = 0.89 (95% CI = 0.76 to 1.05), and API patients: HR = 0.94 (95% CI = 0.88 to 1.00). Among foreign-born patients, lower mortality was observed in those from Central and South America compared with Mexico for Hispanic patients, East Asia compared with Southeast Asia for API patients, and East Europe and Greater Middle East compared with West/South/North Europe for White patients. Conclusion Foreign-born patients with HCC have better survival than US-born patients. Further investigation into the mechanisms of this survival disparity by nativity is needed.

BackgroundPatients with cirrhosis and subcentimeter lesions on liver ultrasound are recommended to undergo short-interval follow-up ultrasound because of the presumed low risk of primary liver cancer (PLC).AimsThe aim of this study is to characterize recall patterns and risk of PLC in patients with subcentimeter liver lesions on ultrasound.MethodsWe conducted a multicenter retrospective cohort study among patients with cirrhosis or chronic hepatitis B infection who had subcentimeter ultrasound lesions between January 2017 and December 2019. We excluded patients with a history of PLC or concomitant lesions ≥1cm in diameter. We used Kaplan Meier and multivariable Cox regression analyses to characterize time-to-PLC and factors associated with PLC, respectively.ResultsOf 746 eligible patients, most (66.0%) had a single observation, and the median diameter was 0.7cm (interquartile range: 0.5-0.8cm). Recall strategies varied, with only 27.8% of patients undergoing guideline-concordant ultrasound within 3-6 months. Over a median follow-up of 26 months, 42 patients developed PLC (39 HCC and 3 cholangiocarcinoma), yielding an incidence of 25.7 cases (95% CI, 6.2-47.0) per 1000 person-years, with 3.9% and 6.7% developing PLC at 2 and 3 years, respectively. Factors associated with time-to-PLC were baseline alpha-fetoprotein >10ng/mL (HR: 4.01, 95% CI, 1.85-8.71), platelet count ≤150 (HR: 4.90, 95% CI, 1.95-12.28), and Child-Pugh B cirrhosis (vs. Child-Pugh A: HR: 2.54, 95% CI, 1.27-5.08).ConclusionsRecall patterns for patients with subcentimeter liver lesions on ultrasound varied widely. The low risk of PLC in these patients supports short-interval ultrasound in 3-6 months, although diagnostic CT/MRI may be warranted for high-risk subgroups such as those with elevated alpha-fetoprotein levels.

Huang proposes a method for assessing the impact of a point treatment on mortality either directly or mediated by occurrence of a nonterminal health event, based on data from a prospective cohort study in which the occurrence of the nonterminal health event may be preemptied by death but not vice versa. The author uses a causal mediation framework to formally define causal quantities known as natural (in)direct effects. The novelty consists of adapting these concepts to a continuous-time modeling framework based on counting processes. In an effort to posit "scientifically interpretable estimands," statistical and causal assumptions are introduced for identification. In this commentary, we argue that these assumptions are not only difficult to interpret and justify, but are also likely violated in the hepatitis B motivating example and other survival/time to event settings as well.

Most population-based studies of risk profiles for liver steatosis have relied upon serum markers (e.g., ALT or FIB-4) or ultrasound steatosis index to define cases. We sought to examine racial/ethnic differences in metabolic risk factors associated with liver steatosis and fibrosis at the population level using elastography-based measures. In total, 4509 adults completed vibration-controlled transient elastography (VCTE) with controlled attenuated parameter (CAP) examinations in the 2017–2018 National Health and Nutrition Examinations Survey. Race/ethnicity was self-identified; metabolic parameters included waist circumference, obesity, diabetes, hypertension, and hyperlipidemia. Primary outcome was steatosis defined by CAP score ≥ 280 decibels per meter and secondary outcome significant fibrosis by VCTE median stiffness ≥ 8 kilopascals. Race-specific logistic regression models were performed to assess the relationship between metabolic parameters and hepatic steatosis and fibrosis. Prevalence of elastography-based hepatic steatosis was > 30% for all race/ethnicities. Steatosis was associated with increasing waist circumference for all race/ethnicities (OR ranging 1.7–2.3, p

Under current United Network for Organ Sharing (UNOS) policy, patients with hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) levels ≥1000 ng/mL are required to show a reduction in AFP level to

Hepatocellular carcinoma is a rising indication for liver transplantation in the United States. Downstaging, defined as the reduction of tumor burden using local-regional therapy into Milan criteria, opens an avenue to access cure through transplant for patients who traditionally would not qualify. Approaching the selection of downstaging candidates through an assessment of hepatic function, staying within a modest expansion of tumor burden, and incorporation of serologic/imaging markers for tumor biology provide the best chance for successful downstaging. Following well-defined downstaging protocols with built-in failure criteria ensures excellent post-transplant outcomes.

Background Historically, patients with primary biliary cholangitis (PBC) experience waitlist mortality and low rates of liver transplant (LT). Herein, the impact of MELD-Na based allocation on PBC waitlist mortality was examined. Methods Adult patients with PBC were compared to those with alcohol-related liver disease (ALD) or non-alcoholic steatohepatitis (NASH) listed for LT from 2013-2019 in OPTN. Competing risk regression evaluated waitlist mortality in the MELD and MELD-Na eras using propensity score weights. Results Overall, 1508 patients with PBC, 13581 with ALD, and 10455 with NASH were examined. In the MELD-Na era, 24-month cumulative incidence of waitlist mortality for PBC was 23.0% (95%CI 19.7-26.5%), ALD 13.9% (95%CI 13.1-14.8%), and NASH 20.0% (95%CI 18.9-21.2%). Using propensity score weights, adjusted risk of waitlist mortality was higher for PBC versus ALD (HR = 1.45, 95%CI 1.22-1.71) and NASH (HR = 1.32, 95%CI 1.14-1.55). Furthermore, among PBC, waitlist mortality risk per five-point elevation in MELD-Na (HR = 1.22, 95%CI 1.11-1.35) and Karnofsky score ≤30% (HR = 2.02, 95%CI 1.39-2.92) was significantly higher than among ALD (HR = 1.08, 95%CI 1.04-1.13; HR = 1.28, 95%CI 1.10-1.49) and NASH (HR = 1.05, 95%CI 1.00-1.09; HR = 1.16, 95%CI 0.99-1.37; all p-interactions Conclusions The MELD-Na score continues to underestimate risk of waitlist death for patients with PBC relative to ALD and NASH and highlights need for additional score modifications or exceptions. This article is protected by copyright. All rights reserved.

BACKGROUND The Affordable Care Act (ACA) and subsequent Medicaid expansion has increased utilization of public health insurance. Living donor liver transplantation (LDLT) increases access to transplant and is associated with improved survival but consistently represents

Background & Aims Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). Methods We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. Results Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29–4.55), decompensated cirrhosis (HR 2.91 [1.70–5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53–7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47–3.70]) and decompensated cirrhosis (OR 2.50 [1.20–5.21]) were independently associated with risk for severe COVID-19. Conclusions The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084

Background Crowdsourcing may be an effective strategy to develop test promotion materials. We conducted an online randomized controlled trial (RCT) to evaluate a crowdsourced intervention to promote hepatitis B virus (HBV) and hepatitis C virus (HCV) testing among men who have sex with men (MSM) in China. Methods MSM never previously tested for hepatitis were recruited through social media. Eligible men were randomized to receive an online crowdsourced intervention or no testing promotion materials. Outcomes including self-reported and confirmed HBV and HCV test uptake were assessed after four weeks. Odds ratios (OR) with 95% confidence intervals (95% CI) of men achieving primary and secondary outcomes between the intervention and control arms were calculated. Findings 556 eligible men were enrolled. Overall, 17•4% (97/556) of men self-reported HBV and HCV testing and 7•9% (44/556) confirmed HBV and HCV test uptake. The intervention was seen by 72•1% and 29•0% of men in the intervention and control arms, respectively. In intention-to-treat analysis, confirmed HBV and HCV test uptake was similar between the two arms, both when using a missing=failure approach (OR 0•98, 95% CI 0•53–1•82) or multiple imputation (OR 1•46, 95% CI 0•72–2•95). Interpretation This RCT extends the literature by developing and evaluating an intervention to spur hepatitis testing in a middle-income country with a high burden of hepatitis. Overall test uptake among MSM in China was similar to previous interventions promoting hepatitis testing in high-income countries. We found frequent intervention sharing, complicating interpretation of the results, and the role of crowdsourcing to promote hepatitis testing remains unclear.

As hepatocellular carcinoma (HCC)-associated mortality continues to rise in the United States, there is a crucial need for strategies to shift diagnoses from late to early stage in order to improve survival.To describe a population-based geospatial approach to identifying areas with high late-stage HCC burden for intervention.Cross-sectional study between 2008 and 2017.Los Angeles County.All incident cases of HCC with residential address at diagnosis in Los Angeles County were identified from a population-based cancer registry. Late stage included AJCC 7th Edition stages III-IV and unstaged cases.Sociodemographic factors.Geographic "hotspots" or areas with a high density of late-stage HCC, identified using kernel density estimation in ArcMap 10.3.1.51.8% of 7,519 incident cases of HCC were late stage. We identified a total of 23 late-stage hotspots, including 30.0% of all late-stage cases. Cases within hotspots were more often racial/ethnic minorities, foreign-born, under or uninsured, and of lower socioeconomic status. The age-adjusted incidence rate of late-stage HCC was twofold higher within hotspots (6.85 per 100,000 in hotspots vs 3.38 per 100,000 outside of hotspots). The calculated population-attributable risk was 43%, suggesting that a substantial proportion of late-stage HCC burden could be averted by introducing interventions in hotspot areas. We mapped the relationship between hotspots and federally qualified health centers primary care clinics and subspecialty clinics in Los Angeles County to demonstrate how clinic partnerships can be selected to maximize impact of interventions and resource use. Hotspots can also be utilized to identify "high-risk" neighborhoods that are easily recognizable by patients and the public and to facilitate community partnerships.Reducing late-stage HCC through geographic late-stage hotspots may be an efficient approach to improving cancer control and equity.

INTRODUCTION: Transplant eligibility for hepatocellular carcinoma (HCC) is determined by the imaging identification of tumor burden within Milan criteria. Transjugular intrahepatic portosystemic shunts (TIPS) reduce portal hypertension but may impact HCC visualization. It was hypothesized that the presence of pre-transplant TIPS would correlate with occult HCC and reduced survival. METHODS: A single-center retrospective case control study was performed among liver transplant recipients with HCC (2000–2017). The primary endpoint was occult disease on explant pathology. Backward stepwise elimination of candidate variables was modeled with logistic regression (LR). Secondary endpoints included disease-free survival (DFS) and overall survival (OS), evaluated with Kaplan-Meier curves and Cox regression analysis. RESULTS: 40 of 640 patients had TIPS and more frequently exhibited occult disease (80.0% vs. 43.1%, p

Most population-based studies of risk profiles for liver steatosis have relied upon serum markers (e.g., ALT or FIB-4) or ultrasound steatosis index to define cases. We sought to examine racial/ethnic differences in metabolic risk factors associated with liver steatosis and fibrosis at the population level using elastography-based measures.In total, 4509 adults completed vibration-controlled transient elastography (VCTE) with controlled attenuated parameter (CAP) examinations in the 2017-2018 National Health and Nutrition Examinations Survey. Race/ethnicity was self-identified; metabolic parameters included waist circumference, obesity, diabetes, hypertension, and hyperlipidemia. Primary outcome was steatosis defined by CAP score ≥ 280 decibels per meter and secondary outcome significant fibrosis by VCTE median stiffness ≥ 8 kilopascals. Race-specific logistic regression models were performed to assess the relationship between metabolic parameters and hepatic steatosis and fibrosis.Prevalence of elastography-based hepatic steatosis was 30% for all race/ethnicities. Steatosis was associated with increasing waist circumference for all race/ethnicities (OR ranging 1.7-2.3, p 0.01). Steatosis was associated with diabetes for Whites (OR 2.4, 95% CI 1.2-4.7), Asians (OR 3.0, 1.4-6.3), and Hispanics (OR 2.2, 1.3-3.6), but not Blacks (OR 1.3, 0.8-2.2); hypertension for Whites (OR 1.7, 1.3-4.7) and Asians (OR 2.1, 1.1-3.8); and hyperlipidemia for Blacks only (OR 2.2, 1.3-3.7). Of metabolic risk factors, higher odds of fibrosis were demonstrated with higher waist circumference per 10 cm increase (OR 2.1, 1.8-2.4) and diabetes (OR 2.5, 1.6-3.7), but the effect of diabetes was present in all racial/ethnic groups except Blacks (p-interaction 0.05).Blacks have a distinct metabolic phenotype for steatosis, while Asians, Whites, and Hispanics are more similar. Racial/ethnic differences in risk profiles are important to consider in prevention, screening strategies, and interventions for fatty liver disease.

Chronic hepatitis B virus (HBV) infection affects over 240 million individuals worldwide. Detection of the disease is dependent on active surveillance and testing by healthcare providers. The Center for Disease Control (CDC) recommends HBV screening in all individuals with opioid use disorders. Prompt identification of chronic infection and vaccination of susceptible persons at initial point of contact with the healthcare system is a priority. HBV diagnosis and prevention strategies should be coupled with effective harm reduction programs. Safe and well-tolerated oral antiviral therapy is available and is highly efficacious at suppressing viral replication and ameliorating long-term complications; however, there is at present no cure. Successful navigation of chronically infected individuals through the HBV care cascade is critical to reduce HBV-related morbidity and mortality.

In the United States, hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related deaths and was the 5th most common cause in 2020.1 One in 5 Americans lives in a rural area,2 yet little is known about temporal changes in HCC incidence by rural-urban residence. Area-specific data are critical to guide public health strategies and clinical interventions. Our study compared the overall and subgroup incidence trends for HCC across rural and urban communities in the United States over the past 20 years using the North American Association of Central Cancer Registries database, which covers 93% of the United States and well-represents the rural United States (North American Association of Central Cancer Registries 14.6% rural vs United States 14.8% rural).3.

BackgroundHepatocellular carcinoma is 1 of few cancers with rising incidence and mortality in the United States. Little is known about disease presentation and outcomes across the rural-urban continuum.MethodsUsing the population-based Surveillance, Epidemiology, and End Results registry, we identified adults with incident hepatocellular carcinoma between 2000 and 2016. Urban, suburban, and rural residence at time of cancer diagnosis were categorized by the Census Bureau’s percent of the population living in nonurban areas. We examined association between place of residence and overall survival. Secondary outcomes were late tumor stage and receipt of therapy.ResultsOf 83 368 incident cases of hepatocellular carcinoma, 75.8%, 20.4%, and 3.8% lived in urban, suburban, and rural communities, respectively. Median survival was 7 months (interquartile range = 2-24). All stage and stage-specific survival differed by place of residence, except for distant stage. In adjusted models, rural and suburban residents had a respective 1.09-fold (95% confidence interval [CI] = 1.04 to 1.14; P ConclusionsResidence in a suburban and rural community at time of diagnosis was independently associated with worse indicators across the cancer continuum for liver cancer. Further research is needed to elucidate the primary drivers of these rural-urban disparities.

Purpose of review Lack of availability of donor organs is a constant challenge that patients and providers face in transplantation. To address this shortage, donors that test positive for hepatitis B, in particular those with resolved infection, have been increasingly utilized in clinical practice. We review here the potential risks for the recipient and the advances in hepatitis B management that have made use of these donors a well tolerated and advisable proposition. Recent findings As routine administration of antiviral prophylaxis in the posttransplant setting among those deemed high risk for transmission, outcomes for recipients of hepatitis B donors, including liver transplant recipients, have been comparable to uninfected donors. Universal hepatitis B nucleic acid testing of donors has also enhanced our ability to accurately inform recipients regarding transmission risk. Appropriate use of prophylaxis and careful monitoring for transmission posttransplant is key to ensuring no adverse outcomes occur. Summary Treatment of hepatitis B has evolved over the past two decades. Expanding the donor pool with hepatitis B donors is now well tolerated, ethical, and advantageous to the transplant community at large. A clear discussion with recipients on the substantial benefit and low harm of using hepatitis B donors will lead to greater acceptance and utilization of these organs.

Hepatocellular carcinoma is a rising indication for liver transplantation in the United States. Downstaging, defined as the reduction of tumor burden using local-regional therapy into Milan criteria, opens an avenue to access cure through transplant for patients who traditionally would not qualify. Approaching the selection of downstaging candidates through an assessment of hepatic function, staying within a modest expansion of tumor burden, and incorporation of serologic/imaging markers for tumor biology provide the best chance for successful downstaging. Following well-defined downstaging protocols with built-in failure criteria ensures excellent post-transplant outcomes.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers’ opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient’s HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 U.S. medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient’s HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; p

Background Chronic hepatitis B infection is an important contributor to mortality in the United States, yet impact of available and effective oral antivirals on mortality among infected individuals is unknown. Aims To compare risks and predictors of mortality in a recent time period between those with chronic, prior and no hepatitis B infection. Methods This is a population-based cohort study of National Health and Nutrition Examination Surveys participants between 1999 and 2014 linked to National Death Index data. Adults aged 20 years or older with hepatitis B serologic testing were included. Outcomes of all-cause and liver-related mortality were evaluated using Cox regression. Results Of 39 206 participants, 192 (0.5%) had chronic and 2694 (6.9%) had prior hepatitis B infection. The all-cause age/sex-standardised mortality rates for chronic, prior and uninfected were 21.4, 15.1 and 11.8 per 1000 person-years respectively. Liver-related mortality occurred at respective rates of 4.1, 0.3 and 0.1 per 1000 person-years. In multivariable analyses, those with chronic infection had 1.9-fold (95% CI 1.1-3.3) increased hazard of all-cause mortality and 13.3-fold (95% CI 3.9-45.5) increased hazard of liver-related mortality compared to uninfected. Predictors of all-cause mortality among chronic infection included heavy alcohol use (HR 18.3, 95% CI 3.3-100.6) and higher alanine aminotransferase (HR 1.02, 95% CI 1.00-1.03). Conclusions Mortality among adults living with chronic hepatitis B infection still exceeds that of uninfected despite availability of improved therapeutics. Identification of chronic infection, initiation of treatment among eligible and modulation of co-factors for disease progression are needed to improve survival.

Hepatitis A (HAV) has emerged in outbreaks across the United States particularly in at-risk populations such as men who have sex with men, as well as patients with a history of drug use, homelessness, and incarceration. Immunization among these high-risk populations remains underused. In this study, we describe a case of acute HAV and hepatitis B (HBV) coinfection in an MSM patient occurring in the period of these outbreaks. Clinical resolution of acute HAV and HBV coinfection was attained by 5 months from the time of initial hospitalization without viral hepatitis treatment. This case highlights the need for increased awareness of at-risk populations for HAV and HBV infection in promoting guideline-based vaccination efforts.

Summary Background Advances in therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) have ushered in a new era in chronic hepatitis treatment. To maximise the effectiveness of these medicines, individuals must be engaged and retained in care. We analysed operational interventions to enhance chronic viral hepatitis testing, linkage to care, treatment uptake, adherence, and viral suppression or cure. Methods We did a systematic review of operational interventions, and did meta-analyses for sufficiently comparable data. We searched PubMed, Embase, WHO library, International Clinical Trials Registry Platform, PsycINFO, and CINAHL for randomised controlled trials and controlled non-randomised studies that examined operational interventions along the chronic viral hepatitis care continuum, published in English up to Dec 31, 2014. We included non-pharmaceutical intervention studies with primary or secondary outcomes of testing, linkage to care, treatment uptake, treatment adherence, treatment completion, treatment outcome, or viral endpoints. We excluded dissertations and studies of children only. Data were extracted by two independent reviewers, with disagreements resolved by a third reviewer. Studies were assessed for bias. Data from similar interventions were pooled and quality of evidence was assessed using GRADE. This study was registered in PROSPERO (42014015094). Findings We identified 7583 unduplicated studies, and included 56 studies that reported outcomes along the care continuum (41 for HCV and 18 for HBV). All studies except one were from high-income countries. Lay health worker HBV test promotion interventions increased HBV testing rates (relative risk [RR] 2·68, 95% CI 1·82–3·93). Clinician reminders to prompt HCV testing during clinical visits increased HCV testing rates (3·70, 1·81–7·57). Nurse-led educational interventions improved HCV treatment completion (1·14, 1·05–1·23) and cure (odds ratio [OR] 1·93, 95% CI 1·44–2·59). Coordinated mental health, substance misuse, and hepatitis treatment services increased HCV treatment uptake (OR 3·03, 1·24–7·37), adherence (RR 1·22, 1·05–1·41), and cure (RR 1·21, 1·07–1·38) compared with usual care. Interpretation Several simple, inexpensive operational interventions can substantially improve engagement and retention along the chronic viral hepatitis care continuum. Further operational research to inform scale-up of hepatitis services is needed in low-income and middle-income countries. Funding World Health Organization and US Fulbright Program.

Patients with hepatitis B early antigen (HBeAg)-negative chronic hepatitis B (CHB) and low-level viremia are a heterogeneous group. Identifying those at risk of developing active CHB requiring antiviral therapy is important. In this study, we prospectively characterize incidence rates and predictors of transitioning from inactive to active CHB in a North American adult cohort.Participants in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis B Research Network cohort who were HBeAg negative with baseline hepatitis B virus (HBV) DNA ≤ 10,000 IU/mL were included in the study. Cox regression models were used to estimate the proportion of individuals in 3 baseline HBV DNA categories (≤100, 101 to ≤2,000, and 2,001 to ≤10,000 IU/mL) who developed phase transition defined by HBV DNA10,000 IU/mL and alanine aminotransferase (ALT)2× upper limit of normal or initiated treatment during follow-up.Of 970 participants meeting inclusion criteria, 15% experienced phase transition or initiated treatment over a median follow-up of 4 years: 9% of those with baseline HBV DNA ≤ 100 IU/mL, 14% with HBV DNA 101 to ≤2,000 IU/mL, and 24% with HBV DNA 2,001 to ≤10,000 IU/mL (P0.001). The overall rate of phase transition or treatment initiation was 7.6 per 100 person-years: 4.6 in those with HBV DNA ≤ 100 IU/mL, 6.8 in those with HBV DNA 101 to ≤2,000 IU/mL, and 12.2 in those with HBV DNA 2,001 to ≤10,000 IU/mL (P0.001). Factors independently associated with higher rate of phase transition or treatment initiation included HBV genotype B or C, higher baseline ALT and HBV DNA levels, lower platelet count, quantitative hepatitis B surface antigen1,000 IU/mL, and hyperlipidemia. Only higher ALT, higher HBV DNA, and lower platelets were associated with phase transition when patients starting treatment were censored.Most adults in this North American cohort with HBeAg-negative CHB and low-level viremia remained inactive and off treatment over 4 years. Transition from inactive to active CHB is infrequent and predominantly associated with viral rather than host factors.

Background & Aims The benefits of highly effective therapies for chronic hepatitis B virus (HBV) or HCV infection can only be realized if infected individuals are identified and linked to care. We sought to identify gaps in awareness of diagnosis of HBV or HCV infection in a population-based sample of adults living in the United States (US). Methods Using National Health and Nutrition Examinations Surveys data, we examined factors associated with HBV and HCV awareness. Participants surveyed from 2013 through 2016, age ≥20 years, with complete serologic analyses were included. HBV and HCV infections were defined by detection of serum HBsAg and anti-HCV, respectively. The primary outcome was awareness of infection—if participants replied “yes” to the question: “Has a doctor or other health professional ever told you that you have hepatitis B or C?” Results Of 14,745 participants, 68 had HBV and 211 had HCV infection, corresponding to prevalence values of 0.7% and 1.8%, respectively. Among HBV-infected persons, 32% reported awareness, and 28% of aware persons reported treatment. Among HCV-infected persons, 49% reported awareness, 45% of aware persons were treated, and 59% of treated patients achieved a sustained virologic response. Factors associated with greater awareness in multivariable models included US citizenship, higher education, and abnormal level of alanine aminotransferase for HBV-infected participants and non-Hispanic race, income above the poverty line, not married, and history of injection drug use for HCV-infected participants. Conclusions Fewer than half of US adults with HBV or HCV infection are aware of their infection. Opportunities to increase awareness include provider education on cut-off values for abnormal level of alanine aminotransferase that should prompt screening, and expansion of existing screening interventions to under-recognized at-risk groups.

Background: Survival for hepatocellular carcinoma (HCC) is highly contingent on stage at diagnosis. Identifying high-risk population groups is crucial for efficient delivery of limited resources. We present a population-based geospatial approach to identifying priority targets for early detection interventions in a defined area with high rates of late stage HCC. Methods: We utilized a high-quality population-based cancer registry for cohort identification. Inclusion criteria were: 1) incident HCC (C22.0, 8170-8175), 2) diagnosis between 2008-2017, and 3) residence within boundaries of a single large metropolitan county (Los Angeles). Late stage included AJCC 7th Edition stages III-VI and unstaged cases. We mapped “hotspots” or areas with high density of late stage disease using address coordinates and kernel density estimation in ArcMap 10.3.1. We selected a hotspot density threshold that best optimized number of hotspots, number of cases, and proportion of late stage cases within hotspots. Individual-level factors associated with residence in a hotspot were identified with univariate logistic regression. Age-adjusted incidence rate (AAIR) and population attributable risk (PAR) of late stage disease if residence in a hotspot were calculated. Results: In Los Angeles County, 3894 (51.8%) of 7519 incident cases of HCC were late stage. We identified 23 discrete hotspots that encompassed 26.7% of all cases and 30.0% of late stage cases. Hotspots had 10% more late stage disease (59.1% within vs 49.1% outside hotspots, p25% with unknown birthplace). 45.4% of residents within hotspots were in the lowest socioeconomic status (SES) quintile compared to only 19.1% outside hotspots. Factors associated with residence in a hotspot included non-White race/ethnicity (OR 2.6, 2.7, and 3.1 for Black, Hispanic, and Asian, respectively, compared to White), foreign-born (OR 1.3 vs US-born), and Medicaid insurance (OR 1.7 vs non-Medicaid) (all p Citation Format: Kali Zhou, Laura Thompson, Norah A. Terrault, Myles G. Cockburn. Low-income minorities and immigrants are priority targets in late stage hepatocellular carcinoma hotspots [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PR04.

Introduction/Objective The most striking racial/ethnic disparity among those with hepatocellular carcinoma (HCC) in the United States (US) is worse survival among black Americans. However, existing literature does not consider birthplace among blacks. Differences in risk factors for HCC between US-born (USB) and foreign-born (FB) blacks may influence the natural history of the disease. Our objective was to examine impact of nativity on survival among blacks with HCC utilizing a population-based cohort from California. Methods We identified cases of HCC (ICD-O-3: C220 and 8170) diagnosed between 1988 and 2016 in the statewide California Cancer Registry (CCR). Non-Hispanic black HCC cases with available birthplace information were included in this study (9.7% unknown excluded). Cases were identified as foreign-born if reported or estimated birthplace was outside of the US or its territories. Primary outcome was overall survival after HCC diagnosis. We examined distributions of sociodemographic and tumor characteristics by nativity including disease stage at diagnosis (localized, regional, or distant) and type of therapy received (none, surgical, or non-surgical). The association between nativity and survival was examined using Kaplan-Meier survival curves and multivariable Cox regression. Other factors associated with survival were also evaluated. Results A total of 4019 non-Hispanic black HCC cases were identified in CCR, of which 254 (12.6%) were FB. FB were more likely than USB to be female (30 vs 24%, p=0.02) and more likely to be diagnosed under the age of 40 (10 vs 1%) or between ages 40-50 (15 vs 7%, p Citation Format: Kali Zhou, Ziwei Song, Norah A Terrault, Lihua Liu. Impact of nativity on survival among blacks with hepatocellular carcinoma in California (1988-2016) [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B114.

Summary Background Spontaneous loss of HBsAg (known as functional cure) in patients with chronic hepatitis B virus (HBV) infection significantly reduces liver-related complications. HBsAg loss has been suggested to be higher in non-endemic regions than in endemic regions in individual studies. We systematically determined a pooled annual rate of HBsAg loss in adults with untreated chronic HBV infection and examined the effect of regional endemicity. Methods In this systematic review and meta-analysis, we searched PubMed and Embase for observational cohort studies and non-treatment arms of randomised controlled trials reporting proportions of patients with chronic HBV infection that achieved spontaneous HBsAg loss, published up to Oct 1, 2018. We excluded randomised controlled trials from meta-analyses because of substantial cohort differences. Two reviewers (KZ and CC) independently extracted data from accepted full-text studies, with discrepancies discussed with a third reviewer (NT). We assessed rate of HBsAg loss, and stratified results by whether the underlying cohort arose primarily from an endemic region (defined as having prevalence of chronic HBV greater than 2%) or non-endemic region. This study is registered with PROSPERO, number CRD42018074086. Findings Of 5186 studies screened, 67 (11 randomised controlled trials, 39 prospective and 17 retrospective cohort studies) met the inclusion criteria and 56 were included in meta-analyses after exclusion of randomised controlled trials. Spontaneous HBsAg loss occurred in 3837 (7·8%) of 48 972 patients, with cumulative 352 381 person-years of follow-up. The pooled annual incidence of HBsAg loss was 1·17% (95% CI 0·94–1·41, I2=97%). Rates did not differ by endemicity: 1·19% (0·88–1·54) in endemic versus 1·29% (0·99–1·62) in non-endemic cohorts. Interpretation Globally, spontaneous HBsAg loss occurs infrequently (about 1% per year) in treatment-naive adults with chronic HBV infection. The low and homogeneous rate of HBsAg loss highlights the need for new therapeutics aimed at achieving functional cure across different patient groups and geographical regions. Funding NIH National Institute of Diabetes and Digestive and Kidney Diseases.