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.

Outcomes of pregnancy in autoimmune hepatitis: A population-based study.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) disproportionately affects young women, which may have implications in pregnancy. However, data on pregnancy outcomes in women with AIH are limited. APPROACH AND RESULTS: Using weighted discharge data from the United States National Inpatient Sample from 2012 to 2016, we evaluated pregnancies after 20 weeks gestation and compared outcomes in AIH to other chronic liver diseases (CLD) or no CLD in pregnancy. The association of AIH with maternal and perinatal outcomes was assessed by logistic regression. Among 18,595,345 pregnancies, 935 (<0.001%) had AIH (60 with cirrhosis) and 120,100 (0.006%) had other CLD (845 with cirrhosis). Temporal trends in pregnancies with AIH remained stable from 2008 to 2016 with 1.4-6.8/100,000 pregnancies per year (p = 0.25). On adjusted analysis, the odds of gestational diabetes (GDM) and hypertensive complications (pre-eclampsia, eclampsia, or hemolysis, elevated liver enzymes, low platelets) were significantly higher in AIH compared to other CLD (GDM: OR 2.2, 95% CI: 1.5-3.9, p < 0.001; hypertensive complications: OR: 1.8, 95% CI: 1.0-3.2, p = 0.05) and also compared to no CLD in pregnancy (GDM: OR: 2.4, 95% CI: 1.6-3.6, p < 0.001; hypertensive complications: OR: 2.4, 95% CI: 1.3-4.1, p = 0.003). AIH was also associated with preterm births when compared with women without CLD (OR: 2.0, 95% CI: 1.2-3.5, p = 0.01). AIH was not associated with postpartum hemorrhage, maternal, or perinatal death. CONCLUSIONS: Rates of pregnancy in women with AIH have remained stable in recent years, although AIH is associated with notable maternal and perinatal risks, such as GDM, hypertensive complications, and preterm birth. Whether these risks are influenced by steroid use and/or AIH disease activity warrants evaluation. These data support a low risk of postpartum hemorrhage and favorable survival of mothers and infants.

Longitudinal Assessment of Bile Duct Loss in Primary Biliary Cholangitis.

INTRODUCTION: Bile duct involvement is a key finding of primary biliary cholangitis (PBC). The aim of this study was to evaluate baseline ductopenia and disease progression. METHODS: Retrospective longitudinal histological follow-up of treatment-naive patients with PBC. RESULTS: Eighty-three patients were included, with ductopenia correlated to fibrosis stage at baseline. The cumulative incidence of severe ductopenia remained stable after 5 years, whereas fibrosis continually increased over time. Baseline AST-to-Platelet Ratio Index and elevated alkaline phosphatase >2 times the normal with abnormal bilirubin were associated with ductopenia progression. DISCUSSION: Bile duct injury does not seem to follow the same course as fibrosis in PBC.

We Are Not Immune: Racial and Ethnic Disparities in Autoimmune Liver Diseases.

Autoimmune liver diseases are attributed to a complex interplay of biologic, acquired, and environmental factors. Increased prevalence, later stage at presentation, worse response to standard therapy, and transplant-related disparities have all been reported in racial and ethnic minorities such as Black and Latinx patients with autoimmune liver diseases. While biology and inherited genetic predispositions may partly explain these disparities, definitive and universal genetic variations underlying these differences in outcomes have not been defined. Nonetheless, socioeconomic status, access to health care, environmental and societal factors, and implicit provider bias can all contribute to poor patient outcomes. There remains an unmet need to understand and mitigate the factors contributing to health inequity in autoimmune liver diseases. In this review, we summarize the data on racial and ethnic disparities in presentation, treatment response, and outcomes pertaining to autoimmune liver diseases in minority populations, on the premise that understanding disparities is the first step toward reaching health equity.

The Spectrum of Hepatic Involvement in Patients With Telomere Disease.

Loss-of-function mutations in genes that encode for components of the telomere repair complex cause accelerated telomere shortening. Hepatic involvement has been recognized as a cause of morbidity in telomere diseases, but very few studies have characterized the nature and extent of liver involvement in affected patients. We report the prevalence and characteristics of liver involvement in a large cohort of patients with telomere disease evaluated serially at the National Institutes of Health. One hundred twenty-one patients with known or suspected telomere disease were screened; 40 patients with liver involvement were included in the current study. Median follow-up was 2.4 years. Data were collected regarding their demographic information, laboratory analysis, imaging, and histopathology. Forty patients (40% of the cohort) with a median age of 42 years were found to have liver involvement. Liver enzyme elevation was cholestatic in pattern; 8 (21%) had drug-related enzyme elevations. The most common imaging finding was increased hepatic echogenicity on ultrasound in 39% (9) of patients, followed by hepatomegaly in 26% (6). Biopsies were infrequent because of risk associated with thrombocytopenia, but in 6 patients, there were varying findings: nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, and cirrhosis with hepatic steatosis. Almost half the cohort had pulmonary diffusion abnormalities, and 25% died during the follow-up period. Conclusion: In patients with telomere disease, hepatic involvement is common and can present in diverse ways, including elevated liver enzymes as well as histopathologic and imaging abnormalities. Liver disease has important implications for morbidity and mortality in patients with telomere disease.

Race/Ethnicity and Insurance-Specific Disparities in In-Hospital Mortality Among Adults with Primary Biliary Cholangitis: Analysis of 2007-2014 National Inpatient Sample.

BACKGROUND: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease that can result in cirrhosis and end-stage liver disease. AIMS: We aim to evaluate hospitalization burden and in-hospital mortality among PBC patients in the USA. METHODS: Using data from the Nationwide Inpatient Sample from 2007 to 2014, hospitalizations among US adults with PBC were stratified by sex, age, and race/ethnicity. Overall in-hospital mortality was stratified by these variables and adjusted multivariate regression models evaluated for predictors of in-hospital mortality. RESULTS: From 2007 to 2014, there were 18,279 hospitalizations among adults with PBC (15.0% male, mean age 63.8 years, 41.3% cirrhosis). Among non-Hispanic whites, the proportion of total PBC hospitalizations increased from 57.8% in 2007 to 71.2% in 2014, compared to 4.1-6.3% for African-Americans, 8.6-10.9% for Hispanics, and 1.7-2.8% for Asians (p < 0.001 for all). While overall in-hospital mortality was low (4.2%), increasing age was associated with higher odds of in-hospital mortality (OR: 1.02, 95% CI 1.01-1.03, p < 0.001). Compared to non-Hispanic white PBC patients, higher in-hospital mortality was observed in African-American PBC patients (OR: 1.40, 95% CI 1.16-2.03, p < 0.05). Compared to patients with private/commercial insurance, significantly higher odds of in-hospital mortality were observed in patients with Medicaid insurance (OR 1.42, 95% CI 1.00-1.99, p < 0.05). CONCLUSION: In summary, among adults with PBC hospitalized in the USA from 2007 to 2014, the overall number of hospitalizations is increasing. Significant disparities in in-hospital mortality were observed; African-Americans with PBC and Medicaid patients with PBC have disproportionately higher odds of in-hospital mortality.

Hospitalizations for Autoimmune Hepatitis Disproportionately Affect Black and Latino Americans.

OBJECTIVES: The healthcare burden of autoimmune hepatitis (AIH) in the United States has not been characterized. We previously showed that AIH disproportionately affects people of color in a single hospital system. The current study aimed to determine whether the same disparity occurs nationwide. METHODS: We analyzed hospitalizations with a primary discharge diagnosis corresponding to the ICD-9 code for AIH in the National Inpatient Sample between 2008 and 2012. For each racial/ethnic group, we calculated the AIH hospitalization rate per 100,000 population and per 100,000 all-cause hospitalizations, then calculated a risk ratio compared to the reference rate among whites. We used multivariable logistic regression models to assess for racial disparities and to identify predictors of in-hospital mortality during AIH hospitalizations. RESULTS: The national rate of AIH hospitalization was 0.73 hospitalizations per 100,000 population. Blacks and Latinos were hospitalized for AIH at a rate 69% (P<0.001) and 20% higher (P<0.001) than whites, respectively. After controlling for age, gender, payer, residence, zip code income, region, and cirrhosis, black race was a statistically significant predictor for mortality during AIH hospitalizations (odds ratio (OR) 2.81, 95% confidence interval (CI) 1.43, 5.47). CONCLUSIONS: Hospitalizations for AIH disproportionately affect black and Latino Americans. Black race is independently associated with higher odds of death during hospitalizations for AIH. This racial disparity may be related to biological, genetic, environmental, socioeconomic, and healthcare access and quality factors.

Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis.

BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.

Race/ethnicity-specific disparities in cancer incidence, burden of disease, and overall survival among patients with hepatocellular carcinoma in the United States.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the fastest rising causes of cancer-related deaths in the United States, with disparities observed in cancer incidence and survival between ethnic groups. This report provides updated analyses on race-specific disparities in US HCC trends. METHODS: This large, population-based cohort study was conducted using Surveillance, Epidemiology, and End Results cancer registry data from 2003 to 2011 to investigate race-specific disparities in HCC incidence and survival. Survival was analyzed using Kaplan-Meier methods and multivariate Cox proportional-hazards models. RESULTS: From 2003 to 2011, Asians had the highest HCC incidence, followed by blacks, Hispanics, and non-Hispanic whites. During the same period, Hispanics had the greatest increase in HCC incidence (+35.8%), whereas Asians experienced a 5.5% decrease. Although patients aged ≥65 years had the highest HCC incidence among all racial/ethnic groups, the higher HCC incidence in Asians was observed only for patients ages <50 and ≥65 years, whereas HCC incidence among patients ages 50 to 64 years was similar among Asians, blacks, and Hispanics. The overall 5-year HCC survival rate was highest among Asians (26.1%; 95% confidence interval [CI], 24.5%-27.6%) and lowest among blacks (21.3%; 95% CI, 19.5%-23.1%). On multivariate regression, Asians (hazard ratio, 0.83; 95% CI, 0.79-0.87; P < .001) and blacks (hazard ratio, 0.94; 95% CI, 0.89-0.99; P = .01) had significantly higher survival compared with non-Hispanic whites. CONCLUSIONS: Asians were the only group to demonstrate a declining HCC incidence in the form of a shift from advanced HCC to more localized HCC. These findings most likely reflect improved screening and surveillance efforts for this group. Cancer 2016;122:2512-23. © 2016 American Cancer Society.

Race/Ethnicity-specific Disparities in Hepatocellular Carcinoma Stage at Diagnosis and its Impact on Receipt of Curative Therapies.

GOALS: To evaluate race/ethnicity-specific disparities in hepatocellular carcinoma (HCC) stage at diagnosis and how this impacts receiving curative therapies. BACKGROUND: HCC is a leading cause of morbidity and mortality worldwide. The highest incidence of HCC is seen among ethnic minorities in the United States. STUDY: Using the 2003-2011 Surveillance, Epidemiology, and End Results database and United Network of Organ Sharing, population-based registries for cancer and liver transplantation (LT) in the United States, race/ethnicity-specific cancer stage at diagnosis and treatment received among adults with HCC were evaluated. RESULTS: Compared with non-Hispanic whites, blacks had significantly more advanced HCC at diagnosis [odds ratio (OR), 1.20; 95% confidence interval (CI), 1.10-1.30; P<0.001], whereas Asians were less likely to have advanced disease (OR, 0.87; CI, 0.80-0.94; P<0.001). Among patients with HCC meeting Milan criteria, Hispanics (OR, 0.64; 95% CI, 0.57-0.71; P<0.001) and blacks (OR, 0.67; 95% CI, 0.59-0.76; P<0.001) were significantly less likely to receive curative therapy (resection or LT), whereas Asians were more likely to receive curative therapy (OR, 1.22; 95% CI, 1.10-1.35; P<0.001) compared with non-Hispanic whites. However, Asians (OR, 0.49; 95% CI, 0.42-0.58; P<0.001) and Hispanics (OR, 0.51; 95% CI, 0.44-0.60; P<0.001) were less likely to receive LT. CONCLUSIONS: Among US adults with HCC, blacks consistently had more advanced stage at diagnosis and lower rates of receiving treatment. After correcting for cancer stage and evaluating the subset of patients eligible for curative therapies, blacks and Hispanics had significantly lower rates of curative HCC treatment.

Utility and impact of magnetic resonance elastography in the clinical course and management of chronic liver disease.

We aimed to characterize scenarios where magnetic resonance elastography (MRE) of the liver was ordered and its impact on clinical course and management. 96 consecutive MRE examinations and subsequent encounters over 14 months were reviewed. Indication for MRE of the liver and subsequent management were abstracted from the medical record. In all cases, non-invasive assessment of liver fibrosis was the primary indication and at least one additional rationale was noted. There was a significant decrease in recommendations to undergo liver biopsy after MRE. Additionally, a greater percentage of those recommended to undergo biopsy completed the procedure after discussion of the results. Given the significant cost and rare but serious risks of liver biopsy, MRE of the liver provides an attractive, safer alternative that may have a comparable impact on management, or select cases where biopsy is essential to guide management. We demonstrate the versatility of MRE in real-world hepatology practice, including its utility as a non-invasive surrogate for liver biopsy.

Factors Associated With Liver Transplant Referral Among Patients With Cirrhosis at Multiple Safety-Net Hospitals.

Importance: A high proportion of underserved patients with cirrhosis receive care at safety-net hospitals (SNHs). While liver transplant (LT) can be a life-saving treatment for cirrhosis, data on referral patterns from SNHs to LT centers are lacking. Objective: To identify factors associated with LT referral within the SNH context. Design, Setting, and Participants: This retrospective cohort study included 521 adult patients with cirrhosis and model for end-stage liver disease-sodium (MELD-Na) scores of 15 or greater. Participants received outpatient hepatology care at 3 SNHs between January 1, 2016, and December 31, 2017, with end of follow-up on May 1, 2022. Exposures: Patient demographic characteristics, socioeconomic status, and liver disease factors. Main Outcomes and Measures: Primary outcome was referral for LT. Descriptive statistics were used to describe patient characteristics. Multivariable logistic regression was performed to evaluate factors associated with LT referral. Multiple chained imputation was used to address missing values. Results: Of 521 patients, 365 (70.1%) were men, the median age was 60 (IQR, 52-66) years, most (311 [59.7%]) were Hispanic or Latinx, 338 (64.9%) had Medicaid insurance, and 427 (82.0%) had a history of alcohol use (127 [24.4%] current vs 300 [57.6%] prior). The most common liver disease etiology was alcohol associated liver disease (280 [53.7%]), followed by hepatitis C virus infection (141 [27.1%]). Median MELD-Na score was 19 (IQR, 16-22). One hundred forty-five patients (27.8%) were referred for LT. Of these, 51 (35.2%) were wait-listed, and 28 (19.3%) underwent LT. In a multivariable model, male sex (adjusted odds ratio [AOR], 0.50 [95% CI, 0.31-0.81]), Black race vs Hispanic or Latinx ethnicity (AOR, 0.19 [95% CI, 0.04-0.89]), uninsured status (AOR, 0.40 [95% CI, 0.18-0.89]), and hospital site (AOR, 0.40 [95% CI, 0.18-0.87]) were associated with lower odds of being referred. Reasons for not being referred (n = 376) included active alcohol use and/or limited sobriety (123 [32.7%]), insurance issues (80 [21.3%]), lack of social support (15 [4.0%]), undocumented status (7 [1.9%]), and unstable housing (6 [1.6%]). Conclusions: In this cohort study of SNHs, less than one-third of patients with cirrhosis and MELD-Na scores of 15 or greater were referred for LT. The identified sociodemographic factors negatively associated with LT referral highlight potential intervention targets and opportunities to standardize LT referral practices to increase access to life-saving transplant among underserved patients.

Novel autoantibody targets identified in patients with autoimmune hepatitis (AIH) by PhIP-Seq reveals pathogenic insights.

Autoimmune hepatitis (AIH) is a severe autoimmune disease, characterized by the presence of autoantibodies. However, the role of autoantibodies in the pathophysiology of AIH remains uncertain. Here, we employed Phage Immunoprecipitation-Sequencing (PhIP-Seq) to identify novel autoantibodies in AIH. Using these results, a logistic regression classifier was able to predict which patients had AIH, indicating the presence of a distinct humoral immune signature. To further investigate the autoantibodies most specific to AIH, significant peptides were identified relative to a broad array of controls (298 patients with non-alcoholic fatty liver disease (NAFLD), primary biliary cholangitis (PBC), or healthy controls). Top ranked autoreactive targets included SLA, the target of a well-recognized autoantibody in AIH, and disco interacting protein 2 homolog A (DIP2A). The autoreactive fragment of DIP2A shares a 9-amino acid stretch nearly identical to the U27 protein of HHV-6B, a virus found in the liver. In addition, antibodies against peptides derived from the leucine rich repeat N-terminal (LRRNT) domain of the relaxin family peptide receptor 1 (RXFP1) were highly enriched and specific to AIH. The enriched peptides map to a motif adjacent to the receptor binding domain, which is required for RXFP1 signaling. RXFP1 is a G protein-coupled receptor that binds relaxin-2, an anti-fibrogenic molecule shown to reduce the myofibroblastic phenotype of hepatic stellate cells. Eight of nine patients with antibodies to RXFP1 had evidence of advanced fibrosis (F3 or greater). Furthermore, serum from AIH patients positive for anti-RFXP1 antibody was able to significantly inhibit relaxin-2 signaling in the human monocytic cell line, THP1. Depletion of IgG from anti-RXFP1 positive serum abrogated this effect. These data provide supporting evidence that HHV6 plays a role in the development of AIH and point to a potential pathogenic role for anti-RXFP1 IgG in some patients. Identification of anti-RXFP1 in patient serum may enable risk stratification of AIH patients for fibrosis progression and lead to the development of novel strategies for disease intervention.

Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.

Autoimmune hepatitis (AIH) is a poorly understood, chronic disease, for which corticosteroids are still the mainstay of therapy and most patients undergo liver biopsy to obtain a diagnosis. We aimed to determine if there was a transcriptomic signature of AIH in the peripheral blood and investigate underlying biologic pathways revealed by gene expression analysis. Whole blood RNA from 75 AIH patients and 25 healthy volunteers was extracted and sequenced. Differential gene expression analysis revealed 249 genes that were significantly differentially expressed in AIH patients compared to controls. Using a random forest algorithm, we determined that less than 10 genes were sufficient to differentiate the two groups in our cohort. Interferon signaling was more active in AIH samples compared to controls, regardless of treatment status. Pegivirus sequences were detected in five AIH samples and 1 healthy sample. The gene expression data and clinical metadata were used to determine 12 genes that were significantly associated with advanced fibrosis in AIH. AIH patients with a partial response to therapy demonstrated decreased evidence of a CD8+ T cell gene expression signal. These findings represent progress in understanding a disease in need of better tests, therapies, and biomarkers.

Asian American/Pacific Islander and Hispanic Ethnic Enclaves, Neighborhood Socioeconomic Status, and Hepatocellular Carcinoma Incidence in California: An Update.

BACKGROUND: Using more recent cancer registry data, we analyzed disparities in hepatocellular carcinoma (HCC) incidence by ethnic enclave and neighborhood socioeconomic status (nSES) among Asian American/Pacific Islander (AAPI) and Hispanic populations in California. METHODS: Primary, invasive HCC cases were identified from the California Cancer Registry during 1988-1992, 1998-2002, and 2008-2012. Age-adjusted incidence rates (per 100,000 population), incidence rate ratios, and corresponding 95% confidence intervals were calculated for AAPI or Hispanic enclave, nSES, and the joint effects of ethnic enclave and nSES by time period (and the combination of the three periods), sex, and race/ethnicity. RESULTS: In the combined time period, HCC risk increased 25% for highest versus lowest quintile of AAPI enclave among AAPI males. HCC risk increased 22% and 56% for lowest versus highest quintile of nSES among AAPI females and males, respectively. In joint analysis, AAPI males living in low nSES areas irrespective of enclave status were at 17% to 43% increased HCC risk compared with AAPI males living in areas of nonenclave/high nSES. HCC risk increased by 22% for Hispanic females living in areas of low nSES irrespective of enclave status and by 19% for Hispanic males living in areas of nonenclave/low nSES compared with their counterparts living in areas of nonenclave/high nSES. CONCLUSIONS: We found significant variation in HCC incidence by ethnic enclave and nSES among AAPI and Hispanic populations in California by sex and time period. IMPACT: Future studies should explore how specific attributes of enclaves and nSES impact HCC risk for AAPI and Hispanic populations.

Prospective Study of Withdrawal of Antiviral Therapy in Patients with Chronic Hepatitis B after Prolonged Virological Response.

Nucleoside analogue (NA) therapy for chronic hepatitis B (CHB) is associated with improved clinical outcomes, but usually requires long-term use. Whether treatment can be safely withdrawn and the factors associated with post-withdrawal outcome are not well defined. To assess long-term outcomes after stopping antiviral therapy, patients with hepatitis B e antigen (HBeAg)-negative CHB who had received antiviral therapy for 4 or more years with hepatitis B virus (HBV) DNA (≤100 IU/mL) were prospectively withdrawn from antiviral therapy and monitored monthly for the initial 6 months and every 3 months thereafter. Those with clinical relapse were retreated according to severity of relapse. Fifteen patients were withdrawn from lamivudine (4), adefovir (5), or a combination of the two (6) after a mean treatment duration of 8.4 years. The mean age was 45 years, 13 were male, and 8 were initially HBeAg-positive before treatment. After a mean follow-up of 6.6 years, outcomes differed by pretreatment HBeAg status. All patients who were HBeAg+ before treatment experienced virological relapse (8 of 8); 6 of 8 experienced clinical relapse; 4 of 8 had ALT flares; 5 of 8 required re-initiation of treatment, one of whom cleared hepatitis B surface antigen (HBsAg); and 3 of 8 remained off treatment, one of whom cleared HBsAg. In contrast, 4 of 7 patients who were HBeAg-negative before treatment experienced virological relapse, 3 of 7 experienced clinical relapse, and 1 of 7 had an alanine aminotransferase (ALT) flare. None restarted treatment, and 4 of 7 cleared HBsAg. Low pre-withdrawal HBsAg level was predictive of HBsAg loss. Conclusion: NA therapy can be safely withdrawn with long-term remission and high rates of HBsAg loss in most HBeAg-negative patients without cirrhosis. Patients who were initially HBeAg+ should not be withdrawn from treatment, because clinical relapse was frequent and often severe.

Obesity and metabolic outcomes in a safety-net health system.

In the United States, obesity has increased in prevalence over time and is strongly associated with subsequent outcomes such as diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). It is unclear, however, as to how the magnitude of NAFLD risk from obesity and DM is increased in safety-net health system settings. Among the San Francisco Health Network (SFHN) patients (N = 47,211), we examined the association between Body Mass Index (BMI) and elevated liver enzyme levels, including interaction by DM status. Our findings revealed that 32.2 percent of SFHN patients were obese, and Pacific Islanders in the safety-net had the highest rates of obesity compared to other racial groups, even after using higher race-specific BMI cutoffs. In SFHN, obesity was associated with elevated liver enzymes, with the relationship stronger among those without DM. Our findings highlight how obesity is a stronger factor of NAFLD in the absence of DM, suggesting that practitioners consider screening for NAFLD among safety-net patients with obesity even if DM has not developed. These results highlight the importance of directing efforts to reduce obesity in safety-net health systems and encourage researchers to further examine effect modification between health outcomes in such populations.

Texture features from computed tomography correlate with markers of severity in acute alcohol-associated hepatitis.

The aim of this study was to use texture analysis to establish quantitative CT-based imaging features to predict clinical severity in patients with acute alcohol-associated hepatitis (AAH). A secondary aim was to compare the performance of texture analysis to deep learning. In this study, mathematical texture features were extracted from CT slices of the liver for 34 patients with a diagnosis of AAH and 35 control patients. Recursive feature elimination using random forest (RFE-RF) was used to identify the best combination of features to distinguish AAH from controls. These features were subsequently used as predictors to determine associated clinical values. To compare machine learning with deep learning approaches, a 2D dense convolutional neural network (CNN) was implemented and trained for the classification task of AAH. RFE-RF identified 23 top features used to classify AAH images, and the subsequent model demonstrated an accuracy of 82.4% in the test set. The deep learning CNN demonstrated an accuracy of 70% in the test set. We show that texture features of the liver are unique in AAH and are candidate quantitative biomarkers that can be used in prospective studies to predict the severity and outcomes of patients with AAH.

Disparities in Hepatocellular Carcinoma Incidence in California: An Update.

BACKGROUND: Given changes in hepatocellular carcinoma (HCC) incidence and the ethnodemographic landscape, we analyzed recent HCC incidence patterns and trends in California. METHODS: Using 47,992 primary, invasive HCC cases diagnosed from 1988 to 2014 from the California Cancer Registry, we calculated age-adjusted incidence rates (IR), annual percent change (APC), and 95% confidence intervals (CI) by sex, race/ethnicity, and nativity among Hispanics and Asian ethnic groups. RESULTS: Compared with non-Hispanic Whites (NHW), all other racial/ethnic groups had higher HCC incidence. Vietnamese had the highest IRs (males: 47.4, 95% CI, 45.3-49.5; females: 14.1, 95% CI, 13.0-15.3). Foreign-born Chinese, Japanese, Korean, and Vietnamese had higher incidence than U.S.-born. The reverse was observed for Hispanic males, whereas no differences by nativity were seen for Hispanic females. IRs increased most for NHWs. Among Asians, male and female Filipinos and Japanese males experienced rate increases, whereas male and female Koreans and Chinese males experienced rate decreases. U.S.-born male and female Hispanics and Japanese had higher APCs than foreign-born, as did Filipino males, whereas Chinese males had a reverse pattern. Annual increases in HCC incidence slowed down in recent years for U.S.-born Hispanic males and females and stabilized among male NHWs and non-Hispanic Blacks. For some Asian groups, early time periods exhibited increasing/stable APCs, whereas later time periods showed decreasing APCs. CONCLUSIONS: We found significant racial/ethnic and nativity differences in HCC IRs and trends. IMPACT: With changing trends, closer surveillance of HCC incidence by disaggregated race/ethnicity and nativity is warranted among Hispanics and Asians.