Prevalence of hepatitis B virus (HBV) and latent tuberculosis co-infection and risk of drug-induced liver injury across two large HBV cohorts in the United States.

The epidemiology of latent tuberculosis and hepatitis B virus (HBV-LTBI) co-infection among U.S. populations is not well studied. We aim to evaluate LTBI testing patterns and LTBI prevalence among two large U.S. cohorts of adults with chronic HBV (CHB). Adults with CHB in the Chronic Hepatitis Cohort Study (CHeCS) and Veterans Affairs national cohort were included in the analyses. Prevalence of HBV-LTBI co-infection was defined as the number of HBV patients with LTBI divided by the number of HBV patients in a cohort. Multivariable logistic regression evaluated odds of HBV-LTBI co-infection among CHB patients who underwent TB testing. Among 6019 CHB patients in the CHeCS cohort (44% female, 47% Asian), 9.1% were tested for TB, among whom 7.7% had HBV-LTBI co-infection. Among HBV-LTBI co-infected patient, only 16.7% (n = 7) received LTBI treatment, among whom 28.6% (n = 2) developed DILI. Among 12,928 CHB patients in the VA cohort (94% male, 42% African American, 39% non-Hispanic white), 14.7% were tested for TB, among whom 14.5% had HBV-LTBI. Among HBV-LTBI co-infected patient, 18.6% (n = 51) received LTBI treatment, among whom 3.9% (n = 3) developed DILI. Presence of cirrhosis, race/ethnicity, and country of birth were observed to be associated with odds of HBV-LTBI co-infection among CHB patients who received TB testing. In summary, among two large distinct U.S. cohorts of adults with CHB, testing for LTBI was infrequent despite relatively high prevalence of HBV-LTBI co-infection. Moreover, low rates of LTBI treatment were observed among those with HBV-LTBI co-infection.

Impact of hepatitis C treatment status on risk of Parkinson's disease and secondary parkinsonism in the era of direct-acting antivirals.

Research suggests a possible link between chronic infection with hepatitis C virus (HCV) and the development of Parkinson's Disease (PD) and secondary Parkinsonism (PKM). We investigated the impact of antiviral treatment status (untreated, interferon [IFN] treated, direct-acting antiviral [DAA] treated) and outcome (treatment failure [TF] or sustained virological response [SVR]) on risk of PD/PKM among patients with HCV. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we applied a discrete time-to-event approach with PD/PKM as the outcome. We performed univariate followed by a multivariable modelling that used time-varying covariates, propensity scores to adjust for potential treatment selection bias and death as a competing risk. Among 17,199 confirmed HCV patients, we observed 54 incident cases of PD/PKM during a mean follow-up period of 17 years; 3753 patients died during follow-up. There was no significant association between treatment status/outcome and risk of PD/PKM. Type 2 diabetes tripled risk (hazard ratio [HR] 3.05; 95% CI 1.75-5.32; p < .0001) and presence of cirrhosis doubled risk of PD/PKM (HR 2.13, 95% CI 1.31-3.47). BMI >30 was associated with roughly 50% lower risk of PD/PKM than BMI <25 (HR 0.43; 0.22-0.84; p = .0138). After adjustment for treatment selection bias, we did not observe a significant association between HCV patients' antiviral treatment status/outcome on risk of PD/PKM. Several clinical risk factors-diabetes, cirrhosis and BMI-were associated with PD/PKM.

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

Incidence of Malignancies Among Patients With Chronic Hepatitis B in US Health Care Organizations, 2006-2018.

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006-2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.

Lower Rates of Emergency Department Visits and Hospitalizations Among Patients With Chronic Hepatitis C With Sustained Virological Response to Interferon-Free Direct-Acting Antiviral Therapy (2014-2018).

We compared rates of emergency department visits and hospitalizations between patients with hepatitis C virus who achieved sustained virological response after direct-acting antiviral therapy (case patients) and matched controls. Among 3049 pairs, case patients demonstrated lower rates of liver-related emergency department visits (P = .01) than controls; all-cause and liver-related hospitalization rates and number of hospitalized days were also lower in case patients (P < .001).

Laboratory monitoring and antiviral treatment for chronic hepatitis B among routine care patients in the United States.

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. 'Recommended monitoring' was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the 'definite' category, and 34.1% (208/610 patients) in the 'equivocal' category, of whom 109 moved up to 'definite' status at some point during follow-up. Sex, age and specialist care were independently associated with receipt of treatment in 'definite' patients. Routine monitoring rates were high prior to treatment in 'definite/ treated' patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in 'definite/ untreated' patients (ALT: 48%; DNA: 32%). Among 'equivocal/ treated' patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among 'treatment ineligible' patients was similar to those in the 'equivocal' and untreated 'definite' groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one-third of patients with 'definite' indications for antiviral therapy remained untreated.

Trends in Cirrhosis and Mortality by Age, Sex, Race, and Antiviral Treatment Status Among US Chronic Hepatitis B Patients (2006-2016).

BACKGROUND: Changing US demographics and evolving chronic hepatitis B (CHB) treatments may affect longitudinal trends in CHB-related complications. We studied trends in the prevalence of cirrhosis (past or present) and incidence of all-cause mortality, stratified by patient age, sex, race, and antiviral treatment status, in a sample from US health care systems. METHODS: Joinpoint and Poisson regression (univariate and multivariable) were used to estimate the annual percent change in each outcome from 2006 to 2016. RESULTS: Among 5528 CHB patients, cirrhosis prevalence (including decompensated cirrhosis) rose from 6.7% in 2006 to 13.7% in 2016; overall mortality was unchanged. Overall rates of cirrhosis and mortality were higher among treated patients, but adjusted annual percent changes (aAPC) were significantly lower among treated than untreated patients (cirrhosis: aAPC +2.4% vs. +6.2%, mortality: aAPC -3.9% vs. +4.0%). Likewise, among treated patients, the aAPC for mortality declined -3.9% per year whereas among untreated patients, mortality increased +4.0% per year. CONCLUSIONS: From 2006 to 2016, the prevalence of cirrhosis among CHB patients doubled. Notably, all-cause mortality increased among untreated patients but decreased among treated patients. These results suggest that antiviral treatment attenuates the progression of cirrhosis and the risk of death among patients with CHB.

Dynamic Risk Prediction of Response to Ursodeoxycholic Acid Among Patients with Primary Biliary Cholangitis in the USA.

BACKGROUND: Ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC); however, inadequate treatment response (ITR) is common. The UK-PBC Consortium developed the modified UDCA Response Score (m-URS) to predict ITR (using alkaline phosphatase [ALP] > 1.67 times the upper limit of normal [*ULN]) at 12 months post-UDCA initiation). Using data from the US-based Fibrotic Liver Disease Consortium, we assessed the m-URS in our multi-racial cohort. We then used a dynamic modeling approach to improve prediction accuracy. METHODS: Using data collected at the time of UDCA initiation, we assessed the m-URS using the original formula; then, by calibrating coefficients to our data, we also assessed whether it remained accurate when using Paris II criteria for ITR. Next, we developed and validated a dynamic risk prediction model that included post-UDCA initiation laboratory data. RESULTS: Among 1578 patients (13% men; 8% African American, 9% Asian American/American Indian/Pacific Islander; 25% Hispanic), the rate of ITR was 27% using ALP > 1.67*ULN and 45% using Paris II criteria. M-URS accuracy was "very good" (AUROC = 0.87, sensitivity = 0.62, and specificity = 0.82) for ALP > 1.67*ULN and "moderate" (AUROC = 0.74, sensitivity = 0.57, and specificity = 0.70) for Paris II. Our dynamic model significantly improved accuracy for both definitions of ITR (ALP > 1.67*ULN: AUROC = 0.91; Paris II: AUROC = 0.81); specificity approached 100%. Roughly 9% of patients in our cohort were at the highest risk of ITR. CONCLUSIONS: Early identification of patients who will not respond to UDCA treatment using a dynamic prediction model based on longitudinal, repeated risk factor measurements may facilitate earlier introduction of adjuvant treatment.

The Persistence of Underreporting of Hepatitis C as an Underlying or Contributing Cause of Death, 2011-2017.

Using electronic health records, we found that hepatitis C virus (HCV) reporting on death certificates of 2901 HCV-infected decedents from 4 US healthcare organizations during 2011-2017 was documented in only 50% of decedents with hepatocellular carcinoma and less than half with decompensated cirrhosis. National figures likely underestimate the US HCV mortality burden.

Sex Differences in Extrahepatic Outcomes After Antiviral Treatment for Hepatitis C.

INTRODUCTION: Despite recognized differences in the rates of cardiovascular and renal disease between men and women in the general population, studies of the downstream effects of antiviral treatment for hepatitis C (HCV) have not investigated differences in outcomes based on sex. We analyzed sex differences in risk of acute coronary syndrome (ACS), end-stage renal disease (ESRD), and ischemic stroke by treatment and response in a large US-based multisite cohort of HCV patients. METHODS: Observation started at the HCV diagnosis date (untreated) or last antiviral treatment start (treated). Treatment selection bias was addressed using an inverse probability-weighting approach. We estimated the effect of treatment on the cumulative incidence of outcomes using the Fine-Gray method (subdistribution hazard ratios [sHR] and 95% confidence intervals [95% CI]). Death was a competing risk. RESULTS: Roughly 40% of 15,295 HCV patients were women. After controlling for other risk factors, sustained virological response (SVR) (interferon-based [IFN] or direct-acting antiviral [DAA]) significantly reduced risk of all outcomes, particularly among female patients. Female patients who achieved SVR after IFN-based treatment had significantly lower risk of ACS compared with male patients with SVR from either treatment type (sHR 0.45 [95% CI 0.35-0.59] vs 0.81 [95% CI 0.69-0.96, for DAA SVR] and sHR 0.72 [95% 0.62, 0.85, for IFN SVR]). Successful treatment seemed to be most protective against ESRD; female patients who achieved SVR were at 66%-68% lower risk than untreated patients (sHR 0.32 [95% CI 0.17-0.60 for DAA SVR] and 0.34 [95% CI 0.20-0.58 for IFN SVR]), whereas men were at 38%-42% lower risk (sHR 0.62 [95% CI 0.46-0.85 for DAA SVR] and 0.58 [95% CI 0.43-0.76 for IFN SVR]). IFN treatment failure significantly increased risk of all outcomes by 50%-100% among female patients. Compared with no treatment, female patients who experienced IFN treatment failure were at 63% increased risk of ACS (sHR 1.63 [95% CI 1.35-1.96]), almost twice the risk of ESRD (sHR 1.95 [95% CI 1.43-2.66]) and 51% increased risk of stroke (sHR 1.49 [95%CI 1.11-2.00]). DISCUSSION: SVR reduced the risk of extrahepatic complications, particularly in females. The significantly increased risk associated with IFN TF in women-a subset who represented roughly 10% of that group-underscores the importance of prioritizing these patients for DAA treatment irrespective of the fibrosis stage.

Low Uptake of Direct-acting Antiviral Therapy Among Hepatitis C Patients With Advanced Liver Disease and Access to Care, 2014-2017.

GOALS: To determine the proportion and characteristics of adults with hepatitis C at health care organizations in 4 US states who initiated direct-acting antivirals (DAAs). BACKGROUND: There are almost no data to assess the penetrance of treatment of the hepatitis C population in general US health care settings. STUDY: We conducted a prospective observational study using electronic clinical, pharmacy, and mortality data to determine the fraction of patients who initiated DAAs between January 2014 and December 2017, by start date and regimen. We used stepwise multivariate logistic regression analysis to identify sociodemographic and clinical characteristics associated with receipt of DAAs. RESULTS: Of 8823 patients, 2887 (32.7%) received DAAs. Quarterly (Q) uptake ranged from 1.1% in Q3 2014 to a high of 5.6% in Q2 2015. Characteristics associated with receipt of DAAs included age 51 to 70 years, higher income, pre-2014 treatment failure, and higher noninvasive fibrosis score (FIB4); however, over one half of patients with FIB4 scores >3.25, consistent with severe liver disease, were not treated. A lower likelihood of initiation was associated with Medicaid coverage. Of 5936 patients who did not initiate treatment, 911 (15.3%) had died and 2774 (46.7%) had not had a clinical encounter in ≥12 months by the end of the study. Fewer than 1% of DAA prescriptions originated from nonspecialty providers. CONCLUSIONS: During 4 calendar years of follow-up, one third of patients initiated DAAs. Large fractions of untreated patients had advanced liver disease, died, or were lost to follow-up. Even among patients in integrated health care systems, receipt of DAAs was limited.

Risk and protective factors associated with mental health among female military veterans: results from the veterans' health study.

BACKGROUND: This study focuses on factors that may disproportionately affect female veterans' mental health, compared to men, and is part of a larger study assessing the prevalence of mental health disorders and treatment seeking among formerly deployed US military service members. METHODS: We surveyed a random sample of 1,730 veterans who were patients in a large non-VA hospital system in the US. Based on previous research, women were hypothesized to be at higher risk for psychological problems. We adjusted our results for confounding factors, including history of trauma, childhood abuse, combat exposure, deployments, stressful life events, alcohol misuse, psychological resources, and social support. RESULTS: Among the veterans studied, 5% were female (n = 85), 96% were White (n = 1,161), 22.9% were Iraq/Afghanistan veterans (n = 398), and the mean age was 59 years old (SD = 12). Compared to males, female veterans were younger, unmarried, college graduates, had less combat exposure, but were more likely to have lifetime PTSD (29% vs. 12%.), depression (46% vs. 21%), suicidal ideation (27% vs. 11%), and lifetime mental health service use (67% vs. 47%). Females were also more likely to have low psychological resilience and to have used psychotropic medications in the past year. Using multivariate logistic regression analyses that controlled for risk and protective factors, female veterans had greater risk for lifetime PTSD, depression, suicidal thoughts, and for lifetime use of psychological services, compared to males. Since 95% of the population in this study were male and these results may have been statistically biased, we reran our analyses using propensity score matching. Results were consistent across these analyses. CONCLUSION: Using a sample of post-deployment veterans receiving healthcare services from a large non-VA health system, we find that female veterans are at greater risk for lifetime psychological problems, compared to male veterans. We discuss these findings and their implications for service providers.

Ursodeoxycholic Acid Treatment Preferentially Improves Overall Survival Among African Americans With Primary Biliary Cholangitis.

BACKGROUND: We used data from the Fibrotic Liver Disease Consortium to evaluate the impact of ursodeoxycholic acid (UDCA) treatment across race/ethnicity, gender, and clinical status among patients with primary biliary cholangitis. METHODS: Data were collected from "index date" (baseline) through December 31, 2016. Inverse Probability of Treatment Weighting was used to adjust for UDCA treatment selection bias. Cox regression, focusing on UDCA-by-risk factor interactions, was used to assess the association between treatment and mortality and liver transplant/death. RESULTS: Among 4,238 patients with primary biliary cholangitis (13% men; 8% African American, 7% Asian American/American Indian/Pacific Island [ASINPI]; 21% Hispanic), 78% had ever received UDCA. The final multivariable model for mortality retained age, household income, comorbidity score, total bilirubin, albumin, alkaline phosphatase, and interactions of UDCA with race, gender, and aspartate aminotransferase/alanine aminotransferase ≥1.1. Among untreated patients, African Americans and ASINPIs had higher mortality than whites (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.08-1.67 and aHR = 1.40, 95% CI 1.11-1.76, respectively). Among treated patients, this relationship was reversed (aHR = 0.67, 95% CI 0.51-0.86 and aHR = 0.88, 95% CI 0.67-1.16). Patterns were similar for liver transplant/death. UDCA reduced the risk of liver transplant/death in all patient groups and mortality across all groups except white women with aspartate aminotransferase/alanine aminotransferase ≥1.1. As compared to patients with low-normal bilirubin at baseline (≤0.4 mg/dL), those with high-normal (1.0 > 0.7) and mid-normal bilirubin (0.7 > 0.4) had significantly higher liver transplant/death and all-cause mortality. DISCUSSION: African American and ASINPI patients who did not receive UDCA had significantly higher mortality than white patients. Among African Americans, treatment was associated with significantly lower mortality. Regardless of UDCA treatment, higher baseline bilirubin, even within the normal range, was associated with increased mortality and liver transplant/death compared with low-normal levels.

Mental and physical health status among chronic hepatitis B patients.

PURPOSE: Little is known about health-related quality of life (HRQoL) in patients with chronic hepatitis B virus (CHB) infection in the United States. Our goal is to understand factors associated with HRQoL in this population. METHODS: We conducted a survey to assess HRQoL and behavioral risks among patients with CHB infection from four large U.S. health care systems. Primary outcomes were generated from the SF-8 scale to assess HRQoL, as measured by the mental component scores (MCS) and physical component scores (PCS). The survey also measured socio-demographic information, hepatitis-related behavioral risk factors, treatment exposure/history, stress, and social support. We supplemented survey data with electronic health records data on patient income, insurance, disease severity, and comorbidities. Multivariate analysis was used to estimate and compare adjusted least square means of MCS and PCS, and examine which risk factors were associated with lower MCS and PCS. RESULTS: Nine hundred sixty-nine patients (44.6%) responded to the survey. Current life stressors and unemployment were associated with both lower MCS and PCS results in multivariate analyses. Lower MCS was also associated with White race and low social support, while lower PCS was also associated with Medicaid insurance. CONCLUSIONS: Stressful life events and unemployment were related to mental and physical health status of CHB patients. Those who have social support have better mental health; White and Medicaid patients are more likely to have poorer mental and physical health, respectively. Management of CHB patients should include stress management, social support, and financial or employment assistance.

Mortality Among Patients With Chronic Hepatitis B Infection: The Chronic Hepatitis Cohort Study (CHeCS).

BACKGROUND: According to death certificates, approximately 1800 persons die from hepatitis B annually in the United States; however, this figure may underestimate true mortality from chronic hepatitis B (CHB). METHODS: We analyzed data from CHB patients seen in the Chronic Hepatitis Cohort Study (CHeCS) between 1 January 2006 and 31 December 2013. We compared overall and cause-specific death rates and mean ages at death between CHeCS CHB decedents and U.S. decedents from the Multiple Cause of Death (MCOD) file. RESULTS: Of 4389 CHB patients followed for a mean of 5.38 years, 492 (11%) CHB patients died after a mean follow-up of 3.00 years. Compared to survivors, decedents were older, more likely to be White (40.6%), African-American (27.1%), or male (74.2%); and more likely to have had cirrhosis (59.8%), diabetes (27.2%), alcohol abuse (17.7%), hepatocellular carcinoma (17.5%), or a liver transplant (5.7%); whereas survivors were more likely to be Asian (48.8%; all P < .001). CHB patients died at an average age of 59.8 years-14 years younger than the general U.S. population-and at higher rates for all causes (relative risk [RR] = 1.85, 95% confidence interval [CI], 1.851-1.857) and liver-related causes (RR = 15.91, 95% CI, 15.81-16.01). Only 19% of CHB decedents and 40% of those dying of liver disease had hepatitis B reported on their death certificates. CONCLUSIONS: Compared to the general population, CHB patients die at younger ages and higher rates from all causes and liver-related causes. Death certificates underrepresent the true mortality from CHB.

Adjuvant ribavirin and longer direct-acting antiviral treatment duration improve sustained virological response among hepatitis C patients at risk of treatment failure.

The role of ribavirin (RBV) in the era of direct-acting antivirals (DAA) is not clear, and DAA studies have been largely genotype- and regimen-specific. Using data from the Chronic Hepatitis Cohort Study, we evaluated the role of RBV and increased DAA treatment duration among patients with chronic hepatitis C (HCV) in routine clinical care. We performed multivariable analysis of data from 4133 patients receiving any of the following: sofosbuvir (SOF); daclatasvir + SOF; grazoprevir + elbasvir; paritaprevir/ritonavir + ombitasvir; simeprevir + SOF; and SOF + ledipasvir; SOF + velpatasvir ± voxilaprevir; and glecaprevir + pibrentasvir-all with/ without RBV. Inverse probability treatment weighting was used to adjust for treatment selection bias. Sustained virological response (SVR) was defined by undetectable HCV RNA 12 weeks after end of therapy. The overall SVR rate was 95%. Mean treatment duration was 12 ± 4.5 weeks. The final model included treatment duration and diabetes, as well as the interaction of RBV with previous treatment status (treatment naïve, interferon treatment failure [TF] or previous DAA TF), cirrhosis status, and HCV genotype (GT). Each one-month increment of treatment duration increased odds of SVR by 99% (aOR = 1.99). Diabetes, previous DAA TF, and decompensated cirrhosis significantly reduced odds of SVR. RBV significantly increased the likelihood of SVR among patients with decompensated cirrhosis (aOR = 5.05), previous DAA treatment failure (aOR = 5.43), and GT3 (aOR = 13.28). Among RBV-free regimens, patients with GT3 were less likely to achieve SVR than those with GT1 or 2 (aOR 0.07). Diabetes, decompensated cirrhosis, and prior DAA TF independently reduced the likelihood of SVR. Longer treatment duration increased likelihood of SVR. Conclusion: RBV increased likelihood of SVR among patients with GT3, previous DAA TF, or decompensated cirrhosis.

Sustained virological response does not improve long-term glycaemic control in patients with type 2 diabetes and chronic hepatitis C.

BACKGROUND: Sustained virological response to treatment for chronic hepatitis C virus may improve short-term glucose control among patients with type 2 diabetes, but the long-term impact remains largely unknown. We used data from the Chronic Hepatitis Cohort Study to investigate the impact of sustained virological response on long-term trends in haemoglobin A1c in patients with type 2 diabetes. METHODS: "Index date" was defined as the date of treatment initiation (treated patients) or hepatitis C virus diagnosis (untreated patients). To address treatment selection bias, we used a propensity score approach. We used a piecewise, linear spline, mixed-effects model to evaluate changes in haemoglobin A1c over a 5-year period. RESULTS: Our sample included 384 hepatitis C virus patients with type 2 diabetes (192 untreated, 192 treated, with sustained virological response or treatment failure). After adjusting for body mass index, haemoglobin A1c was stable among untreated and treatment failure patients. In sustained virological response patients, Hb1Ac trajectories evolved in three phases: (a) index through 6 months post-index, average haemoglobin A1c decreased significantly from 7.7% to 5.4% per 90 days (P < 0.001); (b) 6-30 months post-index, haemoglobin A1c rebounded at a rate of 1.5% every 90 days (P = 0.003); and (c) from 30 months onward, haemoglobin A1c stabilized at an average level of 7.9 (P-value = 0.34). Results from an analysis restricted to patients receiving direct-acting antivirals were consistent with the main findings. CONCLUSION: Successful hepatitis C virus treatment among patients with type 2 diabetes significantly reduces HbA1c shortly after treatment, but these decreases are not sustained long-term. Less than three years after sustained virological response, haemoglobin A1c rebounds to levels similar to untreated/treatment failure patients, and higher than recommended for type 2 diabetic maintenance.

Race, Age, and Geography Impact Hepatitis C Genotype Distribution in the United States.

GOALS: To determine the impact of geography and patient characteristics on hepatitis C virus (HCV) genotype and subtype distribution in a large sample of patients under routine clinical care BACKGROUND:: HCV genotype impacts disease course and response to treatment. Although several studies have reported genotype distribution within specific US populations, there are no comprehensive descriptions in large, geographically diverse cohorts. STUDY: Using data from the Chronic Hepatitis Cohort Study, we present the distribution of HCV genotypes (GT) and subtypes (ST) among a racially diverse cohort of over 8000 HCV-infected patients from four large US health systems. RESULTS: Genotype distribution varied significantly by geographic and demographic factors. In age-adjusted analyses, African American patients had significantly higher prevalence of GT1 (85%) than other racial categories, largely driven by a markedly higher proportion of GT1 subtype b (∼34%) than in Asian/other (24%) and white (21%) patients. GT3 represented an increasing proportion of infections as birth decade progressed, from 4% in patients born before 1946 to 18% of those born after 1976. Within the cohort of "living/uncured" patients, highly elevated alanine aminotransferase (>2 times the upper limit of normal) was significantly more common in GT3 patients, whereas Fibrosis-4 Index scores indicative of cirrhosis were most common in the combined group of GT4&6 patients. CONCLUSION: Distribution of HCV genotypes and subtypes in the United States is more variable than suggested by previous national-level estimates and single-center studies. "Real-world" prevalence data may improve targeting of prevention, screening, and treatment efforts for hepatitis C.

Grapheme-Color Synesthesia is Associated with PTSD Among Deployed Veterans: Confirmation of Previous Findings and Need for Additional Research.

Post-traumatic stress disorder (PTSD) is related to alteration in neuropsychological functioning, including visual and other cognitive processes. Grapheme-color synesthesia is a phenomenon in which a letter or number elicits response of a concurrent image or color perception. Since we earlier reported an association between grapheme-color synesthesia and PTSD, our objective in the current study was to validate this association among a new study group and assess risk factors. For this, we surveyed 1,730 military veterans who have been outpatients in the Geisinger Clinic, a multi-hospital system in Pennsylvania, USA. All the study veterans served in a warzone deployment. The association between PTSD and Grapheme-color synesthesia was evaluated. The average age of veterans was 59.6 years among whom 95.1% were male. Current PTSD prevalence rate was observed to be 7.6% (95% C.I. = 6.5-9.0) and in 3.4% of veterans (95% C.I. = 2.7-4.4) grapheme-color synesthesia was found to be positive. Initial bivariate analyses suggested that synesthesia was associated with current PTSD [odds ratio (OR) = 3.3, p<0.001]. Multivariable stepwise logistic regression evaluating the age, sex, education, trauma exposure, current psychological stress, psychotropic medication use, combat exposure, history of concussion, and current depression, confirmed this association (OR = 2.33, p = 0.019). The present study corroborated that Grapheme-color synesthesia was linked to PTSD among a second cohort of deployed military veterans. Further research is recommended in order to validate this observation and to determine whether synesthesia is a risk factor for PTSD.

Factors Associated With Prevalence and Treatment of Primary Biliary Cholangitis in United States Health Systems.

BACKGROUND & AIMS: Reported prevalence of primary biliary cholangitis (PBC) varies widely. Demographic features and treatment patterns are not well characterized in the United States (US). We analyzed data from the Fibrotic Liver Disease (FOLD) Consortium, drawn from 11 geographically diverse health systems, to investigate epidemiologic factors and treatment of PBC in the US. METHODS: We developed a validated electronic health record-based classification model to identify patients with PBC in the FOLD database from 2003 through 2014. We used multivariable modeling to assess the effects of factors associated with PBC prevalence and treatment with ursodeoxycholic acid (UDCA). RESULTS: We identified 4241 PBC cases among over 14.5 million patients in FOLD health systems; median follow-up was 5 years. Accuracy of the classification model was excellent, with an area under the receiver operating characteristic curve value of 93%, 94% sensitivity, and 87% specificity. The average patient age at diagnosis was 60 years; 21% were Hispanic, 8% were African American, and 7% were Asian American/American Indian/Pacific Islander. Half of the cohort (49%) had elevated levels of alkaline phosphatase, and overall, 70% were treated with UDCA. The estimated 12-year prevalence of PBC was 29.3 per 100,000 persons. Adjusted prevalence values were highest among women (42.8 per 100,000), White patients (29.6 per 100,000), and patients 60-70 years old (44.7 per 100,000). Prevalence was significantly lower among men and African Americans (10.7 and 19.7 per 100,000, respectively) than women and whites; men and African Americans were also less likely to receive UDCA treatment (odds ratios, 0.6 and 0.5, respectively; P < .05). CONCLUSIONS: In an analysis of a large cohort of patients with PBC receiving routine clinical care, we observed significant differences in PBC prevalence and treatment by gender, race, and age.