Increasing risk of hepatocellular carcinoma with successive generations in the United States among Mexican American adults: The Multiethnic Cohort.

BACKGROUND: US-born Latinos have a higher incidence of hepatocellular carcinoma (HCC) than foreign-born Latinos. Acculturation to unhealthy lifestyle behaviors and an immigrant self-selection effect may play a role. In this study, the authors examined the influence of generational status on HCC risk among Mexican American adults. METHODS: The analytic cohort included 31,377 self-reported Mexican Americans from the Multiethnic Cohort Study (MEC). Generational status was categorized as: first-generation (Mexico-born; n = 13,382), second-generation (US-born with one or two parents born in Mexico; n = 13,081), or third-generation (US-born with both parents born in the United States; n = 4914). Multivariable Cox proportional hazards regression was performed to examine the association between generational status and HCC incidence. RESULTS: In total, 213 incident HCC cases were identified during an average follow-up of 19.5 years. After adjusting for lifestyle and neighborhood-level risk factors, second-generation and third-generation Mexican Americans had a 37% (hazard ratio [HR], 1.37; 95% confidence interval [CI], 0.98-1.92) and 66% (HR, 1.66; 95% CI, 1.11-2.49) increased risk of HCC, respectively, compared with first-generation Mexican Americans (p for trend = 0.012). The increased risk associated with generational status was mainly observed in males (second-generation vs. first-generation: HR, 1.60 [95% CI, 1.05-2.44]; third-generation vs. first-generation: HR, 2.08 [95% CI, 1.29-3.37]). CONCLUSIONS: Increasing generational status of Mexican Americans is associated with a higher risk of HCC. Further studies are needed to identify factors that contribute to this increased risk.

Development and Validation of a Noninvasive Model for the Detection of High-Risk Varices in Patients with Unresectable HCC.

BACKGROUND & AIMS: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC. METHODS: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019. We included patients who completed an esophagogastroduodonoscopy (EGD) within 12 months of index imaging but before HCC treatment. We divided the cohort into a 70:30 training set and validation set, with the goal of maximizing negative predictive value (NPV) to avoid EGD in low-risk patients. RESULTS: We included 707 patients (median age, 64.6 years; 80.6% male; 74.0% White). Median time from HCC diagnosis to EGD was 47 (interquartile range, 114) days, with 25.0% of patients having high-risk varices. A model using clinical variables alone achieved an NPV of 86.3% in the validation cohort, whereas a model integrating clinical and imaging variables had an NPV 97.4% in validation. The clinical and imaging model would avoid EGDs in more than half of low-risk patients while misclassifying 7.7% of high-risk patients. CONCLUSIONS: A model incorporating clinical and imaging data can accurately predict the absence of high-risk varices in patients with HCC and avoid EGD in many low-risk patients before the initiation of systemic therapy, thus expediting their care and avoiding treatment delays.

Barriers to liver transplant referral in safety net settings: A national provider survey.

Safety net systems care for patients with a high burden of liver disease yet experience many barriers to liver transplant (LT) referral. This study aimed to assess safety net providers' perspectives on barriers to LT referrals in the United States. We conducted a nationwide anonymous online survey of self-identified safety net gastroenterologists and hepatologists from March through November 2022. This 27-item survey was disseminated via e-mail, society platforms, and social media. Survey sections included practice characteristics, transplant referral practices, perceived multilevel barriers to referral, potential solutions, and respondent characteristics. Fifty complete surveys were included in analysis. A total of 60.0% of respondents self-identified as White and 54.0% male. A total of 90.0% practiced in an urban setting, 82.0% in tertiary medical centers, and 16.0% in community settings, with all 4 US regions represented. Perceived patient-level barriers ranked as most significant, followed by practice-level, then provider-level barriers. Patient-level barriers such as lack of insurance (72.0%), finances (66.0%), social support (66.0%), and stable housing/transportation (64.0%) were ranked as significant barriers to referral, while medical mistrust and lack of interest were not. Limited access to financial services (36.0%) and addiction/mental health resources (34.0%) were considered important practice-level barriers. Few reported existing access to patient navigators (12.0%), and patient navigation was ranked as most likely to improve referral practices, followed by an expedited/expanded pathway for insurance coverage for LT. In this national survey, safety net providers reported the highest barriers to LT referral at the patient level and practice level. These data can inform the development of multilevel interventions in safety net settings to enhance equity in LT access for vulnerable patients.

Diverging Incidence Trends for Hepatocellular Carcinoma in Rural and Urban Settings in the United States.

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.

Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States.

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 US 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 < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). CONCLUSIONS: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.

Geographic hotspot detection for late-stage hepatocellular carcinoma: novel approach to cancer control.

IMPORTANCE: 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. OBJECTIVE: To describe a population-based geospatial approach to identifying areas with high late-stage HCC burden for intervention. DESIGN: Cross-sectional study between 2008 and 2017. SETTING: Los Angeles County. PARTICIPANTS: 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. EXPOSURE: Sociodemographic factors. MAIN OUTCOME(S): Geographic "hotspots" or areas with a high density of late-stage HCC, identified using kernel density estimation in ArcMap 10.3.1. RESULTS: 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. CONCLUSION AND RELEVANCE: Reducing late-stage HCC through geographic late-stage hotspots may be an efficient approach to improving cancer control and equity.

Lower Alpha-Fetoprotein Threshold of 500 ng/mL for Liver Transplantation May Improve Posttransplant Outcomes in Patients With Hepatocellular Carcinoma.

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 <500 ng/mL before liver transplantation (LT). However, effects of AFP reduction on post-LT HCC outcomes among patients with HCC with moderately elevated AFP levels between 100 and <1000 ng/mL are unclear. Adults in the UNOS registry who underwent LTs from January 2005 to September 2015 with initial AFP levels of 100 to 999 ng/mL at listing for Model for End-Stage Liver Disease exceptions were included. Primary predictor was AFP level at LT, categorized as <100, 100 to 499, or ≥500 ng/mL, and patients with only 1 recorded pre-LT AFP value (AFP 1-value). Survival was compared using the Kaplan-Meier curve method. Factors associated with post-LT survival and HCC recurrence were assessed in a multivariable Cox regression model. Among 1766 included patients, 50.2% had AFP 1-value, followed by 24.7%, 18.9%, and 6.2% with AFP levels <100, 100 to 499, and ≥500 ng/mL, respectively. The 5-year post-LT survival rate was lowest in the AFP ≥500 category, at 56.1%, compared with 72.7%, 70.4%, and 65.6% in the AFP <100, 100 to 499 ng/mL, and AFP 1-value categories, respectively. In multivariable analysis, AFP ≥500 ng/mL at LT was associated with a greater risk of post-LT death (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.1-2.1) and HCC recurrence (HR, 1.9; 95% CI, 1.1-3.1) when compared with the AFP <100 ng/mL category; other significant variables included donor risk index, age, race/ethnicity, Child-Turcotte-Pugh class, and tumor diameter. Among AFP levels ≥500 ng/mL at LT, 40.4% had AFP levels ≥1000, but no difference in post-LT survival or recurrence was seen between those patients with AFP levels < or ≥1000 ng/mL. Mandating AFP <500 ng/mL at LT for all patients, not only for those with initial AFP levels ≥1000 ng/mL, may improve post-LT outcomes and can be considered in future UNOS policy.

Excess liver transplant waitlist mortality for patients with primary biliary cholangitis under MELD-Na allocation.

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 to 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 .99-1.37; all P-interactions < .05). 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.

Metabolic Risk Profiles for Hepatic Steatosis Differ by Race/Ethnicity: An Elastography-Based Study of US Adults.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study.

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.

Discussion on "Causal mediation of semicompeting risks" by Yen-Tsung Huang.

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.

Potential association between public medical insurance, waitlist mortality, and utilization of living donor liver transplantation: An analysis of the Scientific Registry of Transplant Recipients.

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 < 5% of LT in the United States. STUDY DESIGN: National registry data were analyzed to evaluate the impact of insurance payor on waitlist mortality and LDLT rates at LDLT centers since implementation of the ACA. RESULTS: Public insurance [Medicare RR 1.18 (1.13-1.22) P < .001, Medicaid RR 1.22 (1.18-1.27) P < .001], Latino ethnicity (P < .001), and lower education level (P = .02) were associated with increased waitlist mortality at LDLT centers. LDLT recipients were more likely to have private insurance (70.4% vs. 59.4% DDLT, P < .001), be Caucasian (92.1% vs. 83% DDLT, P < .001), and have post-secondary education (66.8% vs. 54.1% DDLT, P < .001). Despite 78% of LDLT centers being located in states with Medicaid expansion, there was no change in LDLT utilization among recipients with Medicaid (P = .196) or Medicare (P = .273). CONCLUSION: Despite Medicaid expansion, registry data suggests that patients with public medical insurance may experience higher waitlist mortality and underutilize LDLT at centers offering LDLT. It is possible that Medicaid expansion has not increased access to LDLT.

Gaps in Viral Hepatitis Awareness in the United States in a Population-based Study.

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.

New and Old Biomarkers for Diagnosis and Management of Chronic Hepatitis B Virus Infection.

Tests to detect the presence and activity of hepatitis B virus (HBV) are the cornerstones of diagnosis and management. Assays that detect or measure serum levels of HB surface antigen, HB surface antibody, and HB core antibody are used to identify patients with exposure to HBV, whereas other tests provide information on the level of virus replication, presence of specific variants, and presence of virus reservoirs. Newer diagnostic tests, used only in research settings so far, aim to quantify levels of intrahepatic HBV replication. Other tests have been developed to detect HBV infection in resource-limited settings. We review point-of-care tests (essential in global screening efforts), standard diagnostic tests used in routine clinical management, and newer tests that might be used in clinical trials of agents designed to cure HBV infection.

Risk of disease transmission in an expanded donor population: the potential of hepatitis B virus donors.

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.

Phase Transition Is Infrequent Among North American Adults With e-Antigen-Negative Chronic Hepatitis B and Low-Level Viremia.

INTRODUCTION: 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. METHODS: 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 DNA > 10,000 IU/mL and alanine aminotransferase (ALT) > 2× upper limit of normal or initiated treatment during follow-up. RESULTS: 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 (P < 0.001). 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 (P < 0.001). 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 antigen > 1,000 IU/mL, and hyperlipidemia. Only higher ALT, higher HBV DNA, and lower platelets were associated with phase transition when patients starting treatment were censored. DISCUSSION: 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.

A crowdsourced intervention to promote hepatitis B and C testing among men who have sex with men in China: study protocol for a nationwide online randomized controlled trial.

BACKGROUND: The World Health Organization recommends all men who have sex with men (MSM) receive Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) testing. MSM in China are a high-risk group for HBV and HCV infection, but test uptake is low. Crowdsourcing invites a large group to solve a problem and then shares the solution with the public. This nationwide online randomized controlled trial will evaluate the effectiveness of a crowdsourced intervention to increase HBV and HCV testing among MSM in China. METHODS: Seven hundred MSM will be recruited through social media operated by MSM organizations in China. Eligible participants will be born biologically male, age 16 years or older, report previous anal sex with another man, and reside in China. After completing a baseline online survey, participants will be randomly assigned to intervention or control arms with a 1:1 allocation ratio. The intervention will include two components: (1) a multimedia component will deliver two videos and two images promoting HBV and HCV testing developed through a crowdsourcing contest in China; (2) a participatory component will invite men to submit suggestions for how to improve crowdsourced videos and images. The control arm will not view any images or videos and will not be invited to submit suggestions. All participants will be offered reimbursement for HBV and HCV testing costs. The primary outcome is HBV and HCV test uptake confirmed through electronic submission of test report photos within four weeks of enrolment. Secondary outcomes include self-reported HBV and HCV test uptake, HBV vaccination uptake, and change in stigma toward people living with HBV after four weeks. Primary and secondary outcomes will be calculated using intention to treat and as-exposed analyses and compared using two-sided 95% confidence intervals. DISCUSSION: Few previous studies have evaluated interventions to increase HBV and HCV testing in middle-income countries with a high burden of hepatitis. Delivering a crowdsourced intervention using social media is a novel approach to increasing hepatitis testing rates. HBV and HCV test uptake will be confirmed through test report photos, avoiding the limitations of self-reported testing outcomes. TRIAL REGISTRATION: NCT03482388 (29 March 2018).

Facilitators of HCV treatment adherence among people who inject drugs: a systematic qualitative review and implications for scale up of direct acting antivirals.

BACKGROUND: While the public health benefits of new HCV treatments depend on treatment adherence, particularly among people who inject drugs (PWID), several social and medical factors can jeopardize treatment adherence. The aim of this study is to examine the qualitative literature on facilitators to HCV treatment adherence among PWID. METHODS: We searched six databases to identify qualitative research studies on HCV treatment adherence facilitators among PWID. Two reviewers independently extracted and analyzed data using PRISMA guidelines and the CASP tool to evaluate study quality. RESULTS: From ten studies representing data from 525 participants, three major themes emerged across studies: logistical facilitators within health systems enhanced HCV treatment adherence, positive social interactions between PWID and staff provided positive feedback during treatment, and HCV treatment may complicate the addiction recovery process. CONCLUSIONS: Although PWID face several barriers to adherence, we identified treatment adherence facilitators that could be incorporated into clinical practice.