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.

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.

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.

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.

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.

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.

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.

Fatigued Patients with Chronic Liver Disease Have Subtle Aberrations of Sleep, Melatonin and Cortisol Circadian Rhythms.

AIMS: We sought to examine whether disturbances in central and peripheral circadian rhythms were related to the experience of fatigue in patients with chronic liver disease (CLD). METHODS: Fatigued and non-fatigued patients with compensated CLD were enrolled in a prospective pilot study. Patients underwent a one week evaluation of free-living sleep and physical activity patterns, followed by a 24-hour admission, during which they underwent serial blood sampling, polysomnography, a 6-minute walk test and continuous core temperature measurements under standardized conditions. Blood samples were analyzed for liver tests, melatonin levels, lipids, and cortisol. Circadian rhythms were analyzed using single cosinor analyses. RESULTS: Six fatigued and six non-fatigued patients were studied; five participants had cirrhosis. Fatigue severity was positively associated higher peak melatonin levels (rho=0.59, p=0.04) and a delay in night-time melatonin peak and inversely associated with sleep efficiency (rho=-0.63, p=0.04). Polysomnography, 6-minute walk test, and core temperature measurements did not differ significantly between the fatigued and non-fatigued patients. Although liver enzymes, bilirubin and albumin demonstrated a circadian pattern, it was not associated with fatigue. Fatigued patients showed a blunted and delayed cortisol rhythm and fatigue was strongly correlated with cortisol amplitude (rho=-0.77, p=0.004) and phase (r=-0.66, p=0.02). CONCLUSION: Subtle aberrations in melatonin and adrenal circadian rhythms, as well as reduced sleep efficiency, likely contribute to fatigue in patients with CLD. These abnormalities may ultimately be a therapeutic target to improve quality of life for fatigued patients with CLD.

Race/ethnicity is an independent risk factor for autoimmune hepatitis among the San Francisco underserved.

Although autoimmune hepatitis (AIH) is more common in women and affects people of all races/ethnicities, there is currently limited information regarding the relationship between race/ethnicity and AIH, especially in the context of underserved populations. We aim to evaluate the relationship between race/ethnicity and AIH and better characterize its clinical features among different racial groups. We conducted a 15-year retrospective analysis, from January 2002 to June 2017, of patients seen at Zuckerberg San Francisco General Hospital (ZSFG). Sixty-three AIH patients and 2049 non-AIH controls were eligible for the study. The main predictor of interest was race/ethnicity, and the main outcome of interest was AIH diagnosis; other secondary measures recorded include clinical features such as ALT, bilirubin, and biopsy fibrosis at presentation. In a multivariable model adjusting for age and sex, we found that black (OR 9.6, 95% CI 1.8-178), Latino (OR 25.0, 95% CI 5.3-448), and Asian/Pacific Islander (API) (OR 10.8, 95% CI 2.2-196) race/ethnicity were associated with increased odds of an AIH diagnosis compared to the white reference group. Among people of colour with AIH, there were no significant differences in baseline ALT (p = .45), total bilirubin at presentation (p = .06), fibrosis at presentation (p = .74), and hospitalization (p = .27). Race/ethnicity is an independent risk factor for AIH. The clinical features of AIH did not differ significantly among black, Latino, and API patients.

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.

A comparison of methods for evaluation of a case of suspected macro-aspartate aminotransferase.

BACKGROUND: Macro-aspartate aminotransferase (macroAST) is a high molecular weight form of AST that is usually formed through association with immunoglobulin (Ig) in the circulation. As a result of reduced inactivation, clearance or excretion, AST values are persistently increased. This can lead to problems interpreting these values and diagnosing the patient, especially if clinicians are not aware of this phenomenon. METHODS: For a case of suspected macroAST, we compared three simple methods: polyethylene glycol precipitation, ultrafiltration, and Ig depletion using protein A and G. RESULTS: All three methods were consistent with a diagnosis of macroAST. CONCLUSIONS: The protein A and G method was straightforward and provided unambiguous results. However, given the affinity of protein A and protein G, it likely only detects AST-IgG macrocomplexes.

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.

The Significance of Autoantibody Changes Over Time in Primary Biliary Cirrhosis.

OBJECTIVES: In primary biliary cirrhosis (PBC), the antimitochondrial antibody is a cornerstone of diagnosis, but there have been conflicting reports about the correlation of autoantibodies with disease stage and prognosis. We studied whether autoantibody levels changed over time and sought correlations with clinical outcomes in a cohort of patients with PBC. METHODS: We tested serial serum samples from patients with PBC at a research institution for several autoantibodies. Long-term clinical follow-up data were used to calculate the slopes (change over time) for autoantibodies, platelet count, Ishak fibrosis score, biopsy copper, and number of portal areas with bile ducts. An adverse clinical outcome was defined as hepatic decompensation, development of hepatocellular carcinoma, liver transplantation, or liver-related death. We performed linear or logistic regression or Fisher exact test as appropriate, adjusting for multiple comparisons. RESULTS: Twenty-seven patients with PBC with 145 serum samples were studied. Of the cohort, 85% was white, 81% was female, and median follow-up time was 20 years. Of the autoantibodies tested, only sp100 changed significantly over time. The sp100 slope was inversely associated with the Ishak fibrosis slope (parameter estimate, -0.05; P = .0003). CONCLUSIONS: While changes in most autoantibodies over time do not seem to correlate with clinical outcomes in PBC, a change in the sp100 autoantibody level may have prognostic utility with respect to the development of fibrosis on liver biopsy.

Factors associated with the platelet count in patients with chronic hepatitis C.

BACKGROUND: There are many potential causes of thrombocytopenia in patients with chronic hepatitis C (CHC). AIMS: We sought to determine the association between thrombopoietin (TPO) level, immature platelet fraction (IPF), immunoglobulin G (IgG) level, spleen size, and the platelet count in CHC. METHODS: We studied a consecutive sample of patients enrolled in an observational study at a referral-based research center, excluding subjects based on eligibility criteria. TPO, glycocalicin, and von Willebrand Factor (vWF) levels were determined using stored sera. Hepatic fibrosis was assessed via transient elastography (TE) when available, and clinical laboratory values and radiologic data were obtained from the medical record. We performed analyses of the relationships between independent variables and the platelet count. RESULTS: On univariate analysis, the following variables were significantly associated with the platelet count: age, alanine aminotransferase (ALT), direct bilirubin, total bilirubin, IPF, international normalized ratio (INR), spleen size, vWF, glycocalicin, fibrosis stage on liver biopsy, and TE (P-values all <0.05). A multivariable model determined that imputed TE score, TPO, IPF, and spleen size were independently associated with the platelet count (P-values all<0.05). CONCLUSIONS: The platelet count in CHC is significantly associated with fibrosis, TPO level, IPF, and spleen size. Our findings challenge the proposed mechanism of decreased TPO levels or decreased bone marrow production of platelets as a cause of thrombocytopenia in CHC. Future studies focusing on the effects of fibrosis and splenomegaly on platelets may shed more light on the pathophysiology of thrombocytopenia in patients with CHC.