M. Lu

APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS)

We aim to determine the predictive ability of APRI, FIB‐4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2–F4) from none to minimal fibrosis (F0–F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0–4 equivalent fibrosis stage. Mean APRI and FIB‐4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut‐offs, the AUROCs in distinguishing F2–F4 from F0 to F1 were 0.81 (0.76–0.87) for APRI, 0.81 (0.75–0.86) for FIB‐4 and 0.56 (0.49–0.64) for AST/ALT ratio. APRI and FIB‐4 distinguished F2–F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis.

Predictors of Poor Mental and Physical Health Status Among Patients With Chronic Hepatitis C Infection: The Chronic Hepatitis Cohort Study (CHeCS)

Our objective was to assess the extent and risk factors for depression and poor physical health among patients with chronic hepatitis C virus (HCV) infection. We surveyed HCV‐infected patients seen at four large healthcare systems participating in the Chronic Hepatitis Cohort Study (CHeCS). Survey data included demographics, depression and physical health measures, substance use history, current social support, recent stressor exposures, and, from the electronic medical record, treatment history, and Charlson Comorbidity Index scores. There were 4,781 respondents, who were a mean of 56.7 years old, 71% White, and 57% male. Altogether, 51.4% reported past injection drug use, 33.9% were current smokers, and 17.7% had abused alcohol in the previous year. Additionally, 47.4% had been previously treated for HCV and 14.8% had a 12‐week sustained viral response (SVR) following HCV therapy. Overall, 29.7% of patients met criteria for current depression and 24.6% were in poor physical health. In multivariate analyses, significant predictors of depression and poor health included: male gender (versus female, odds ratios [ORs], 0.70 and 0.81), Black race (versus white, ORs, 0.60 and 0.61), having education less than high school (versus college, ORs, 1.81 and 1.54), being employed (versus not, ORs, 0.36 and 0.25), having high life stressors (versus low, ORs, 2.44 and 1.64), having low social support (versus high, ORs = 2.78 and 1.40), and having high Charlson scores (versus none, ORs = 1.58 and 2.12). Achieving a 12‐week SVR was found to be protective for depression. Conclusion: This large survey of U.S. HCV patients indicates the extent of adverse health behaviors and mental and physical comorbidities among these patients. (Hepatology 2015;61:802–811)

Late diagnosis of hepatitis C virus infection in the Chronic Hepatitis Cohort Study (CHeCS): Missed opportunities for intervention.

To determine the stage of liver disease at initial diagnosis of hepatitis C virus (HCV) infection, we analyzed data from the Chronic Hepatitis Cohort Study (CHeCS), a large U.S. observational study. We examined the temporal relationships of initial HCV infection diagnosis with cirrhosis—defined by liver biopsy or mean FIB‐4 score >5.88—and time to onset of cirrhotic decompensation in electronic medical records. We determined time in the health system prior to HCV diagnosis and rates of hospitalization and death following HCV diagnosis. Of 14,717 patients with chronic HCV seen during 2006‐2011, 6,166 (42%) had a definable time of initial HCV diagnosis. Of these, 1,056 (17%) patients met our definition for “late diagnosis” with either cirrhosis concurrent with initial HCV diagnosis (n = 550), a first diagnosis of hepatic decompensation before or within 12 months after initial HCV diagnosis (n = 506), or both (n = 314). Patients with late diagnosis had an average of 6 years in the health system before their HCV diagnosis. In a comparison with patients without late diagnosis, hospitalization (59% versus 35%) and death (33% versus 9%) were more frequent among patients with late diagnosis. Among all who died, mean (median) time from initial HCV diagnosis to death was 4.8 (4.2) years. Conclusion: Many CHeCS patients had advanced liver disease concurrent with their initial HCV diagnosis despite many years of engagement with the healthcare system, and these patients had high rates of hospitalization and mortality. (Hepatology 2015;61:1479–1484)

Hepatitis C treatment failure is associated with increased risk of hepatocellular carcinoma.

Sustained virological response (SVR) to antiviral therapy for hepatitis C (HCV) reduces risk of hepatocellular carcinoma (HCC), but there is little information regarding how treatment failure (TF) compares to lack of treatment. We evaluated the impact of treatment status on risk of HCC using data from the Chronic Hepatitis Cohort Study (CHeCS–an observational study based in four large US health systems, with up to 7 years of follow‐up on patients). Multivariable analyses were used to adjust for bias in treatment selection, as well as other covariates, followed by sensitivity analyses. Among 10 091 HCV patients, 3681 (36%) received treatment, 2099 (57%) experienced treatment failure (TF), and 1582 (43%) of these achieved sustained virological response (SVR). TF patients demonstrated almost twice the risk of HCC than untreated patients [adjusted hazard ratio (aHR) = 1.95, 95% confidence interval (CI) 1.50–2.53]; this risk persisted across all stages of fibrosis. Several sensitivity analyses validated these results. Although African Americans were at increased risk of treatment failure, they were at lower risk for HCC and all‐cause mortality compared to White patients. SVR patients had lower risk of HCC than TF patients (aHR = 0.48, CI 0.31–0.73), whereas treatment – regardless of outcome – reduced all‐cause mortality (aHR = 0.45, CI 0.34–0.60 for SVR patients; aHR = 0.78, CI 0.65–0.93 for TF patients).

Distribution of disease phase, treatment prescription and severe liver disease among 1598 patients with chronic hepatitis B in the Chronic Hepatitis Cohort Study, 2006-2013.

Limited information exists regarding the distribution of disease phases, treatment prescription and severe liver disease among patients with chronic hepatitis B (CHB) in US general healthcare settings.

Impact of sustained virologic response on risk of type 2 diabetes among hepatitis C patients in the United States

Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used the data from the longitudinal Chronic Hepatitis Cohort Study—drawn from four large US health systems—to investigate how response to HCV treatment impacts the risk of subsequent diabetes. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated the incidence of type 2 diabetes from 12 weeks post‐HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virologic response [SVR] or treatment failure) and baseline risk factors on the development of diabetes, considering any possible risk factor‐by‐SVR interactions, and death as a competing risk. Among 5127 patients with an average follow‐up of 3.7 years, diabetes incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR] = 0.79; 95% CI: 0.65‐0.96). Risk of diabetes was higher among African American and Asian American patients than White patients (aHR = 1.82 and 1.75, respectively; P < .05), and among Hispanic patients than non‐Hispanics (aHR = 1.86). Patients with BMI ≥ 30 and 25‐30 (demonstrated higher risk of diabetes aHR = 3.62 and 1.72, respectively; P < .05) than those with BMI < 25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR = 1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for the development of type 2 diabetes mellitus than patients with treatment failure.

P0778 : The effect of HCV antiviral therapy on fibrosis progression

P0777 SOFOSBUVIR-BASED TREATMENT UNDER REAL LIFE CONDITIONS IN GERMANY (THE SOFGER TRIAL) P. Buggisch, C. Sarrazin, S. Mauss, H. Hinrichsen, K.-G. Simon, J. Vermehren, D. Hueppe, J. Petersen. Leberzentrum Hamburg, IFI, Hamburg, Johann Wolfgang Goethe University Hospital, Frankfurt, Center for HIV and Gastroenterology, Duesseldorf, Center for Gastroenterology, Kiel, Center for Gastroenterology, Leverkusen, Center for Gastroenterology, Herne, Germany E-mail: Buggisch@ifi-medizin.de

P1034 ESTIMATED PREVALENCE OF HCV CIRRHOSIS IN THE CHRONIC HEPATITIS COHORT STUDY (CHECS)

Aim: To investigate the accuracy of non-invasive tests for assessing residual cirrhosis in HCV patients after an SVR. Methods: All HCV patients with a pre-treatment histological diagnosis of cirrhosis and available post-SVR liver biopsies had residual liver fibrosis assessed through the following non-invasive methods: APRI, CDS, Fib4, FibroQ, Forns score, Guci Index, King score, Lok Index, PLF. Liver fibrosis staged according to the METAVIR score was the reference standard. The performances of non-invasive tests to diagnose residual cirrhosis were calculated using receiver operating characteristic (ROC) curves analysis. Results: 20 out of 33 patients (61%) included in the study had cirrhosis regression after 61 (48–104) months from an SVR. The overall diagnostic accuracy of all the non invasive serum panels analyzed was suboptimal as indicated by the AUROC values and the operative characteristics of the tests. None of these tests is useful in identifying patients with residual cirrhosis when using both the cut-off indicated by the literature (bold) and the cut off with the best sensitivity and specificity derived from the ROC curves (Table 1).

A1-4: Pragmatic and Adaptive Methods of Electronic Medical Record (EMR) Cohort Identification for Comparative Effectiveness Research

Background/Aims Accurate EMR-based cohort identification is crucial in the conduct of comparative effectiveness research. CheCS is a longitudinal study of chronic hepatitis B (CHB) and C (CHC) infection being conducted at 4 HMORN sites. Subjects are identified using automated EMR-based ICD-9 diagnosis and laboratory inclusion criteria, and about 12,000 patients were identified in the initial cohort selection. After confirmation of CHB/ CHC status through chart abstraction, we found false discovery rates (FDR) were 13.6% for CHB and 11.3% for CHC. An adaptive approach was proposed to optimize the EMR-based cohort selection. Methods Classification and Regression Tree (CART) was performed to identify a set of electronic variables (or variable combinations) for CHB and CHC. The variables/classifiers that were considered included not only all the initial cohort identificaton criteria, but also HIV status, any outpatient order or pharmacy claim for CHB/CHC antiviral medication, and 41 other liver disease-related procedures/diagnoses. The analysis began with CART model building using one set of data (learning), followed by model validation using the other set of data (testing). Results Of the 12,144 patients identified for the initial CHeCS cohort, 2518 met initial CHB criteria and 9844 met initial CHC criteria, including 218 who met criteria for both. Of these, 10,825 (2176 CHB and 8724 CHC, including 75 co-infected) patients’ diagnoses were confirmed through chart abstraction and the remaining were excluded. CART model FDRs were 8.5% on learning data and 7.1% on testing data for CHB, and 4.9% and 5.7% for CHC, yielding sensitivities and specificities >91% for CHB and >84% for CHC. Overall, FDRs were significantly lower (7.8% for CHB, 5.3% for CHC) than those yielded from the initial inclusion criteria alone (P <0.001). Conclusions Our adaptive approach to using electronic data for prediction of CHB/CHC status is feasible, can be used for sequential CHeCS cohort identification, and may be useful in other studies to identify patients diagnosed with CHB/CHC.

CB3-02: Demographic Differences Between US-born and Foreign-born Asia Pacific Islanders Among the Hepatitis B Patients of Kaiser Permanente, Hawai’i

Background/Aims Approximately two billion people worldwide have been infected with hepatitis B virus (HBV) and about 350 million live with chronic infection. Over half of all liver cancer cases in the world are attributable to chronic, or persistent, HBV infection. Of US residents chronically infected with HBV, 40% to 70% are foreign-born immigrants, mainly Asian/Pacific Islanders (APIs). Disparity by race exists for APIs which makeup approximately 4% of the U.S. population and more than 2% of these races are affected with chronic HBV. The purpose of this study is to investigate the demographic differences between the foreign-born and US-born HBV infected APIs of Kaiser Permanente, Hawai’i (KPHI). Methods This substudy is a part of a prospective, dynamic, longitudinal and observational study, the Chronic Hepatitis Cohort Study (CHeCS). Patients included in this analysis were APIs identified from electronic medical records who met the CHeCS definition for chronic HBV infection at KPHI. Date of birth, race, gender, and country of origin (COO), household income and education were obtained from the Virtual Data Warehouse (VDW) demographic and census tables. Information about the country of origin was also supplemented by surveys and chart abstractions. Results Of the 513 HBV infected APIs, 76% were foreign-born and 24 % were US-born. HBV infected foreign-born APIs were significantly younger than the US-born APIs; approximately 50% of HBV infected foreign-born APIs were in 40–59 years old age group compared to 32% of the US-born. Foreign-born APIs also had significantly higher proportion of females (55%) than US-born (50%). Most of the HBV infected APIs had a median household income between 50,000 and 75,000 with no significant differences between the groups. Approximate prevalence was also calculated using the KPHI utilization data. APIs had an overall HBV prevalence of 0.7%; foreign-born APIs had 2.6% and US-born APIs had 0.3% prevalence. Discussion In summary, foreign-born APIs have higher prevalence of chronic HBV infections compared to US-born APIs in Kaiser Permanente Hawai’i. Foreign-born APIs infected with HBV are younger and more likely to be females than US-born APIs.