BACKGROUND:Portal vein thrombosis (PVT) is a common sequela of cirrhosis. Despite regression of fibrosis/cirrhosis observed among some patients after disease-specific treatment, few studies have considered the role of treatment and response on risk of PVT among patients with cirrhosis across different liver disease states. We considered aetiological treatment and response as well as whether non-selective beta-blockers (NSBBs), statins, and anticoagulants were associated with risk of PVT. METHODS:We used data for patients with cirrhosis (compensated or decompensated) from two large, US-based multisite cohort studies. Patients with hepatitis C (HCV) were drawn from the Chronic Hepatitis Cohort Study. Patients with primary biliary cholangitis (PBC) were drawn from the Fibrotic Liver Disease Consortium. Risk for PVT was assessed using a discrete survival model that includes both fixed covariates and time-dependent variables. RESULTS:Among 6659 HCV patients, 274 developed PVT across ~13 years of follow-up. Significant risk factors included time-varying decompensated cirrhosis (adjusted hazard ratio [aHR] 27.41, 95% confidence interval [CI] 15.89-47.30), male sex (aHR 1.48, 95% CI 1.12-1.94), and use of NSBBs (aHR 2.07, 95% CI 1.61-2.67). Among 786 PBC patients, 67 developed PVT across ~8 years of follow-up. Use of NSBBs was the only significant PVT risk factor in these patients (aHR 2.56, 95% CI 1.52-4.31). Neither sustained virological response [SVR] after antiviral treatment (HCV patients) nor response to ursodeoxycholic acid [UDCA] treatment (PBC patients) was associated with risk of PVT. CONCLUSIONS:In two large well-characterized samples of cirrhotic patients with HCV or PBC, disease-specific treatments were not associated with PVT risk. NSBB treatment was independently associated with > 2 times the risk of PVT in both samples, regardless of compensated or decompensated status.

Introduction: Ursodeoxycholic acid (UDCA) slows disease progression among patients with primary biliary cholangitis (PBC), yet not all patients receive this standard-of-care medication. Our study aims to identify reasons why PBC patients did not receive the recommended UDCA treatment. Methods: Using medical record data collected by the Fibrotic Liver Disease (FOLD) Consortium for 20062016, we identified PBC patients from a single site with no UDCA therapy record. Two independent reviewers used a structured data collection instrument to systematically confirm and record the reasons for the lack of treatment. Results: Among 494 PBC patients (11% men and 13.2% Black patients) with a median follow-up of 5.2 years, 35 (7%) had never received UDCA (16% men and 24% Black patients). Of these, 18 (51%) had laboratory indications of PBC but were not formally diagnosed. Among the remaining 17 patients with recognized PBC, six were never offered UDCA, seven declined treatment, and four remained untreated despite being offered treatment. We did not find a statistically significant association between the lack of PBC diagnosis and treatment and patients' age (p = 0.139), gender (p = 0.222), race (p = 0.081), or insurance coverage (p = 0.456), perhaps due to our small sample size. Conclusions: Multiple factors influencing the lack of evaluation and treatment in PBC patients were identified at the provider and patient levels. The most common reasons included financial barriers, loss to follow-up, severe decompensated disease at diagnosis, and lack of referral to specialists for further evaluation. Future interventions targeting modifiable provider and patient barriers may improve rates and timeliness of PBC diagnosis and treatment.

Introduction: A previous study by the U.S. based Fibrotic Liver Disease Consortium (FOLD) demonstrated that black and male Primary Biliary Cirrhosis (PBC) patients are less likely to receive PBC therapy than white and female PBC patients. We sought to examine the reasons that FOLD PBC patients never received ursodeoxycholic (UDCA) or obeticholic acid therapy. Methods: FOLD-consortium PBC patients were previously identified and their medical record data from 2006-2016 collected and stored in the FOLD database. For the present study, we conducted in-depth manual reviews of the medical records of the PBC patients at one of the 11 participating FOLD sites with no record of PBC therapy. A structured data collection instrument was used to systematically collect reasons that these patients had never initiated treatment. Two reviewers independently reviewed and collected the data for each patient under the supervision of a senior hepatologist. Discrepant results between the two reviewers were discussed and resolved, or failing resolution, were adjudicated by the senior hepatologist. Results: Among 494 patients with PBC (11% male, 71% white/12% black) with a median follow-up of 5.2 years, 38 (7.7%) had never received PBC therapy (16% male, 66% white/24% black). Out of the 38 patients that had never received PBC therapy, 20 (53%) were recognized by providers to have PBC and 18 (47%) were not recognized to have PBC. Of the 20 patients recognized to have PBC, 6/20 were willing to accept treatment. The most common reasons cited for not starting UDCA or obeticholic acid therapy were advanced age, mild symptoms, severe disease/rapid decompensation, liver transplant evaluation, loss of follow-up, and insurance/cost issue. Conclusion: Multiple factors influencing the lack of evaluation and treatment in PBC patients were identified at the provider and patient levels. Predominant provider factors were lack of referral to specialists by primary care providers and specialist knowledge, attitudes and information management leading to inadequate PBC recognition. At the patient level, Important factors included mild asymptomatic disease, severe decompensated disease, competing health concerns, medication cost difficulties, UDCA intolerance due to side effects and lack of appropriate follow up. Future interventions targeting modifiable provider and patient barriers may improve rates and timeliness of PBC diagnosis and treatment.

Surveillance of chronic hepatitis C virus (HCV) cases faces limitations that result in delays and under-reporting. With increasing use of electronic health records (EHRs), the authors evaluated the predictive value of using International Classification of Diseases, Ninth Revision (ICD-9) codes to identify chronic HCV cases from EHR data. Longitudinal EHR data from 4 health care systems during 2006-2012 were evaluated. Using chart abstraction and review to confirm chronic HCV cases ("gold standard" definition), the authors calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 2 case definitions: (1) ≥2 ICD-9 codes separated by ≥6 months and (2) ≥1 positive HCV RNA (ribonucleic acid) test. Among 2,718,995 patients, 20,779 (0.8%) with ICD-9 codes indicating a likely diagnosis of chronic HCV infection were identified; 13,595 (65.4%) of these were randomly selected for review. Case definition 1 (≥2 ICD-9 codes separated by ≥6 months) had 70.3% sensitivity, 91.9% PPV, 99.9% specificity, and 99.9% NPV while case definition 2 (≥1 positive HCV RNA test) had 74.1% sensitivity, 97.4% PPV, 99.9% specificity, and 99.9% NPV. The predictive values of these alternate EHR-derived ICD-9 code-based case definitions suggest that these measures may be useful in capturing the burden of diagnosed chronic HCV infections. Their use can augment current chronic HCV case surveillance efforts; however, their accuracy may vary by length of observation and completeness of EHR data.

BACKGROUNDHepatitis A and B vaccines are effective in preventing superinfection and sequelae in patients with chronic hepatitis B or C. We describe immunity and vaccination against hepatitis A and B in chronic hepatitis patients from the US Chronic Hepatitis Cohort Study.METHODSWe identified chronic hepatitis B and C patients with healthcare utilization during 2006-2008 and 12 months of enrollment. We used electronic laboratory records to determine immunity and medical and billing records for vaccination history. Immunity against hepatitis A was defined by positive hepatitis A antibody or documented vaccination. Immunity against hepatitis B was defined as hepatitis B surface antibody level ≥10 mIU/mL or core antibody positive, or by documented vaccination.RESULTSAmong 1635 chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%) had no testing or vaccination record. Among 5328 chronic hepatitis C patients, 2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis B.CONCLUSIONSApproximately 40% of chronic hepatitis B and C patients are susceptible to or have no documented immunity or vaccination against hepatitis A or hepatitis B. Clinicians should consider antibody testing and vaccination for this vulnerable population.

Purpose: A recent economic analysis of the cost of HCV infection utilized a panel of diagnosis (ICD-9) and procedure (CPT) codes to stratify patients into liver disease severity categories (Hepatology 2012;56:1651). We attempted to validate whether a panel of diagnosis and procedure codes can be used to determine stage of liver disease in patients with chronic viral hepatitis. Methods: The 41 ICD-9 and CPT codes associated with cirrhosis and decompensated cirrhosis were compiled from the medical records of a random sample of 283 patients in our institution with chronic hepatitis B and/or C who had undergone liver biopsies. Two physician reviewers independently classified the patients as not cirrhotic (NC), compensated cirrhotic (CC), or end-stage liver disease (ESLD), based upon imaging, laboratory parameters, biopsy results, and clinical events. Any discrepancy between the two reviewers was independently adjudicated by a clinical hepatologist. Inter-rater agreement between the two reviewers' classifications was assessed with weighted kappa coefficient. NC/CC were grouped together to allow for a clear, binary outcome. Logistic regression modeling was used to evaluate for ESLD verses NC/CC based upon the ICD-9/CPT codes found in the patients' medical records and was compared to the final adjudicated classifications from the physician reviewers. Results: The inter-rater kappa coefficient for classification of stage of liver disease was 0.88. Logistic regression based on the presence or absence of any of the ICD-9/CPT codes for ESLD vs. NC/CC had an AUC of 0.81 (p-value < 0.0001). Utilizing the codes to predict ESLD provided a sensitivity of 91% and specificity of 72%, and yielded a positive predictive value of 71% and negative predictive value of 91%. Conclusion: These results demonstrate that the 41 ICD-9/CPT codes reflect stage of liver disease with a reasonable compromise between sensitivity and specificity, as demonstrated by the AUC of 0.81. Additionally, the prediction model's high sensitivity of 91% for determining which patients have ESLD demonstrates the potential future use of this model for both research and clinical purposes. This research was supported by an industry grant from Funded by the CDC Foundation, which received grants from AbbVie; Genentech, a member of the Roche Group; Janssen Pharmaceutical Companies of Johnson & Johnson; and Vertex Pharmaceuticals.