Real-World Safety and Effectiveness of an 8-Week Regimen of Glecaprevir/Pibrentasvir in Patients with Hepatitis C and Cirrhosis.

INTRODUCTION: In 2019, an 8-week regimen of glecaprevir/ pibrentasvir (GLE/PIB) was FDA-approved for treatment of chronic hepatitis C (HCV) in patients with cirrhosis. We used data from the Chronic Hepatitis Cohort Study (CHeCS) to evaluate treatment response and adverse events among patients with HCV and cirrhosis under routine clinical care. METHODS: Using an intention-to-treat (ITT)/modified ITT (mITT) approach, endpoints were (1) sustained virological response (SVR) at 12 weeks (SVR12) post-treatment; and (2) adverse events (AEs)/serious AEs during treatment. Patients with cirrhosis from two CHeCS sites were included if they were prescribed GLE/PIB from August 2017 to June 2020. Detailed treatment and clinical data were collected. Patient baseline characteristics were described with mean/standard deviation (std) for continuous variables, and proportions for categorical variables. Analyses were propensity score adjusted. The final model retained variables that were significant with p value < 0.05. RESULTS: The ITT sample included 166 patients, with 43, 116, and 7 patients in the 8-week, 12-week, and > 12-week planned treatment groups. Among them, 159 had confirmed SVR (95.8%, LCL 93.2%). The mITT analysis included 160 patients after excluding 6 with unknown HCV RNA results; 159 achieved SVR (99.4%, LCL 98.3%). There were no significant differences in rates of SVR between the 8-week and 12-week regimens in either analysis, nor any association with patient characteristics. SAEs were experienced by 1 patient (2%) in the 8-week group, 7 (5%) in the 12-week group (including one death), and 2 (29%) in the > 12-week group; 4 patients (from the 12-week group) experienced serious AEs or hepatic events that were "likely attributable" to GLE/PIB treatment. CONCLUSION: An 8-week regimen of GLE/PIB is well tolerated and highly effective among US patients with HCV and cirrhosis receiving routine clinical care.

Antiviral Treatment and Response are Associated With Lower Risk of Dementia Among Hepatitis C Virus-Infected Patients.

OBJECTIVE: Eradication of hepatitis C virus (HCV) infection has been linked with improvement in neurocognitive function, but few studies have evaluated the effect of antiviral treatment/ response on risk of dementia. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we investigated how antiviral therapy impacts the risk of developing dementia among patients with HCV. METHODS: A total of 17,485 HCV patients were followed until incidence of dementia, death, or last follow-up. We used an extended landmark modeling approach, which included time-varying covariates and propensity score justification for treatment selection bias, as well as generalized estimating equations (GEE) with a link function as multinominal distribution for a discrete time-to-event data. Death was considered a competing risk. RESULTS: After 15 years of follow-up, 342 patients were diagnosed with incident dementia. Patients who achieved sustained virological response (SVR) had significantly decreased risk of dementia compared to untreated patients, with hazard ratios (HRs) of 0.32 (95% CI 0.22-0.46) among patients who received direct-acting antiviral (DAA) treatment and 0.41 (95% CI 0.26-0.60) for interferon-based (IFN) treatment. Risk reduction remained even when patients failed antiviral treatment (HR 0.38, 95% CI 0.38-0.51). Patients with cirrhosis, Black/African American patients, and those without private insurance were at significantly higher risk of dementia. CONCLUSION: Antiviral treatment independently reduced the risk of dementia among HCV patients, regardless of cirrhosis. Our findings support the importance of initiation antiviral therapy in chronic HCV-infected patients.

Persistent pruritus associated with worse quality of life in patients with chronic hepatitis.

INTRODUCTION: Prevalence and severity of pruritus among US patients with chronic hepatitis B and C (HBV, HCV) are not well-documented. Chronic Hepatitis Cohort Study (CHeCS) patients were surveyed to examine pruritus prevalence and impact on quality of life (QoL). METHODS: Patients who reported experiencing pruritus ≥3 on a Numeric Rating Scale (NRS) within the past 30 days were invited to participate in a 6-month study using the SF-36 questionnaire. General regression (univariate followed by multivariable modelling) was used to analyse pruritus intensity and eight QoL dimensions. RESULTS: Among 1654 patients (HBV = 358, HCV = 1296, HBV/HCV = 6), pruritus prevalence was significantly higher among patients with HCV than those with HBV (44% vs. 35%; p < .05). One hundred and twenty-three patients (21 HBV and 102 HCV) participated in the QoL study (72% ≥60 years; 50% men; 25% Black; 37% with cirrhosis; 66% had BMI > 25). Mean NRS was 4.9-5.3. QoL responses for social functioning and emotional well-being were higher (70-72 points) than responses for energy/fatigue (50-51). Antiviral treatment rates were higher in HCV (92%, SVR 99%) than HBV (71% ever, 43% ongoing). Multivariable analyses showed no significant effect of hepatitis type or antiviral treatments on itch. Antihistamines were associated with severe itch. Higher NRS was associated with significantly reduced QoL. Each unit increase in NRS was associated with a 2-3 unit decline in emotional well-being, general health, physical function, energy/fatigue, social functioning and emotional health. CONCLUSION: Pruritus negatively affects many viral hepatitis patients, regardless of antiviral treatment status. Improved treatment options are needed to address its impact on QoL.

Alcohol-related hepatitis admissions decline in 2021 after a 2020 surge attributed to the COVID-19 pandemic.

OBJECTIVE: We previously investigated the impact of the COVID-19 pandemic on alcohol-related liver disease (ARLD), finding that admissions for alcoholic hepatitis (AH) increased by 50% in the summer of 2020 compared to the same period in 2016-2019. We have now expanded our analysis to consider full years' data and evaluate how rates changed in 2021. We also sought to identify factors associated with ICU admissions, need for dialysis, liver transplant evaluations, and death. METHODS: Using retrospective data, we identified patients admitted to our four Detroit, Michigan area hospitals for acute ARLD for three periods pre-COVID (2016-February 2020), early COVID (June-December 2020), and late COVID (2021). Clustered logistic regression was performed to study rates of AH admissions across the three eras, where the patient was defined as the cluster and the analysis accounted for multiple encounters per cluster. A similar regression approach, univariate followed by multivariable analysis, was also used to study associations between patient characteristics and outcomes during hospitalization for AH. RESULTS: AH-related admissions declined significantly from the early COVID to late COVID eras (OR 0.68, 95% CL 0.52, 0.88), returning to levels similar to that of the pre- COVID period (OR 1.18, 95% CL 0.96, 1.47). In multivariable analysis, baseline MELD score was associated with ICU admission, initiation of dialysis, transplant evaluation, and death while hospitalized for AH. Female patients were at almost twice the risk of death during admission compared to male patients (aOR 1.81, 95% CL 1.1, 2.98). Increasing age was associated with slightly lower odds of transplant (aOR 0.97, 95% CL 0.94, 1) and higher odds of death (aOR 1.03, 95% CL 1.01. 1.06). CONCLUSION: After a spike in AH-related admissions during the first summer of the COVID-19 pandemic, rates declined significantly in 2021, returning to pre-pandemic levels.

Dynamic risk assessment for hepatocellular carcinoma in patients with chronic hepatitis C.

Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon-based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow-up. We used extended landmark modelling, with time-varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time-to-event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval-years of follow-up. SVR from DAA or IFN-based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08-0.20; and aHR 0.45, 95% CI 0.31-0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17-0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17-4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six-variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval-based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring.

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.

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).

Alcohol-related hepatitis admissions increased 50% in the first months of the COVID-19 pandemic in the USA.

Early reports suggest that alcohol misuse increased in 2020 as a result of the COVID-19 pandemic. Using retrospective data from Henry Ford Health System in Detroit MI-an area that experienced an early and severe COVID-19 outbreak-we investigated the impact of the pandemic on alcohol-related liver disease (ARLD) in the summer of 2020 compared with the same period in 2016-2019. Both the number of ARLD admissions and the proportion of total admissions represented by ARLD patients increased significantly in 2020 compared with previous years. The number of ARLD admissions as a proportion of all hospitalizations was 50% higher in 2020 than in 2016-2019 (0.31% vs 0.21%; P = .0013); by September 2020, the number of admissions was 66% higher than previous years. Despite racial and geographical disparities in direct and indirect COVID-related stressors across the Detroit metropolitan area, the demographic profile of ARLD patients did not change compared with previous years.

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.

Availability of PEth testing is associated with reduced eligibility for liver transplant among patients with alcohol-related liver disease.

BACKGROUND: Serum phosphatidylethanol (PEth) is a highly sensitive test to detect alcohol use. We evaluated whether the availability of PEth testing impacted rates of liver transplant evaluation terminations and delistings. METHODS: Medical record data were collected for patients who initiated transplant evaluation due to alcohol-related liver disease in the pre-PEth (2017) or PEth (2019) eras. Inverse probability weighting (IPW) was used to balance baseline patient characteristics. Outcomes included termination of evaluation or delisting due to alcohol use; patients were censored at receipt of transplant; death was considered a competing risk. The Fine-Gray method was performed to determine whether PEth testing affected risk of evaluation termination/ delisting due to alcohol use. RESULTS: Three hundred and seventy-five patients with alcohol-related indications for transplant (157 in 2017; 210 in 2019) were included. The final IPW-adjusted model for the composite outcome of terminations/delisting due to alcohol use retained two significant variables (P < .05): PEth era and BMI category. Patients evaluated during the PEth era were almost three times more likely to experience an alcohol-related termination/delisting than those in the pre-PEth era (sHR = 2.86; 95%CI 1.67-4.97) CONCLUSION: We found that availability of PEth testing at our institution was associated with a higher rate of exclusion of patients from eligibility for liver transplant. Use of PEth testing has significant potential to inform decisions regarding transplant candidacy for patients with alcohol-related liver disease.

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.

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.

Psychosocial Obstacles to Hepatitis C Treatment Initiation Among Patients in Care: A Hitch in the Cascade of Cure.

There are limited data examining the relationship between psychosocial factors and receipt of direct-acting antiviral (DAA) treatment among patients with hepatitis C in large health care organizations in the United States. We therefore sought to determine whether such factors were associated with DAA initiation. We analyzed data from an extensive psychological, behavioral, and social survey (that incorporated several health-related quality of life assessments) coupled with clinical data from electronic health records of patients with hepatitis C enrolled at four health care organizations during 2017-2018. Of 2,681 patients invited, 1,051 (39.2%) responded to the survey; of 894 respondents eligible for analysis, 690 (77.2%) initiated DAAs. Mean follow-up among respondents was 9.2 years. Compared with DAA recipients, nonrecipients had significantly poorer standardized scores for depression, anxiety, and life-related stressors as well as poorer scores related to physical and mental function. Lower odds of DAA initiation in multivariable analysis (adjusted by age, race, sex, study site, payment provider, cirrhosis status, comorbidity status, and duration of follow-up) included Black race (adjusted odds ratio [aOR], 0.59 vs. White race), perceived difficulty getting medical care in the preceding year (aOR, 0.48 vs. no difficulty), recent injection drug use (aOR, 0.11 vs. none), alcohol use disorder (aOR, 0.58 vs. no alcohol use disorder), severe depression (aOR, 0.42 vs. no depression), recent homelessness (aOR, 0.36 vs. no homelessness), and recent incarceration (aOR, 0.34 vs. no incarceration). Conclusion: In addition to racial differences, compared with respondents who initiated DAAs, those who did not were more likely to have several psychological, behavioral, and social impairments. Psychosocial barriers to DAA initiation among patients in care should also be addressed to reduce hepatitis C-related morbidity and mortality.

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.

Validity of an Automated Algorithm to Identify Cirrhosis Using Electronic Health Records in Patients with Primary Biliary Cholangitis.

BACKGROUND: Biopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients. METHODS: Histological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and >100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis. RESULTS: Among 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively). CONCLUSION: An algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients' cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.