All-Cause Mortality and Progression Risks to Hepatic Decompensation and Hepatocellular Carcinoma in Patients Infected With Hepatitis C Virus

Background. A key question in care of patients with chronic hepatitis C virus (HCV) infection is beginning treatment immediately vs delaying treatment. Risks of mortality and disease progression in "real world" settings are important to assess the implications of delaying HCV treatment. Methods. This was a cohort study of HCV patients identified from 4 integrated health systems in the United States who had liver biopsies during 2001-2012. The probabilities of death and progression to hepatocellular carcinoma, hepatic decompensation (hepatic encephalopathy, esophageal varices, ascites, or portal hypertension) or liver transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4) determined by biopsy at beginning of observation. Results. Among 2799 HCV-monoinfected patients who had a qualifying liver biopsy, the mean age at the time of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white (66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34 (1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy stage F3 or F4 and platelet count below normal were the strongest predictors of progression to hepatic decompensation or hepatocellular carcinoma. Conclusions. The risks of death and progression to liver failure varied greatly by fibrosis stage. Clinicians and policy makers could use these progression risk data in prioritization and in determining the timing of treatment for patients in early stages of liver disease

Long-term fibrosis and viral level progression among treated and untreated patients with chronic hepatitis B

Background and Aims: The temporal relationship between HBV DNA viral load and liver fibrosis progression remains controversial. Using data from in the Chronic Hepatitis Cohort Study (CHeCS), a longitudinal study of patients from four large US health systems,we investigated long-term trajectories of viral load and FIB4 among HBV patients with and without antiviral therapy. Methods: Observation for each patient commenced at the“indexdate,” either the date of first treatment initiation (treated) or the earliest date of viral load measurement (untreated). Median FIB4scores and viral load levels derived from routine testing were summarized in 30-day intervals for up to 5 years after index.Propensity scores for inverse probability of treatment weighting (IPTW) were used to control for bias in treatment selection. The propensity scores were derived using multiple logistic regression with a large selection of baseline covariates. Changes in FIB4 and viral load over time were modeled using a bivariate piecewise linear spline mixed effects model. Results:1,126 untreated and 928 treated patients were included. The five-year dynamics of viral load and FIB4 exhibited a bi-phasic pattern. Viral load declined 31% (p \u3c 0.001) per month for the first 5months after treatment initiation, then slowed to a 2.3% (p \u3c 0.001)decline per month thereafter. A non-significant viral load decline was observed for untreated patients. FIB4 began to decline 0.4%per month (p \u3c 0.001) at 5 months post-treatment initiation and stabilized at 28 months. Starting at approximately 28 months after index, FIB4 significantly increased by 0.6% per month (p \u3c 0.001)among untreated patients. FIB4 trajectories were consistent across baseline FIB4 levels. Conclusions: Antiviral therapy results in a rapid HBV DNA viral load decline followed by a delayed decline in FIB4. In untreated patients,viral load remains stable and significantly higher than in treated patients, and FIB4 gradually increases over time, suggesting fibrosis progression

The predictive value of international classification of disease codes for chronic hepatitis c virus infection surveillance: The utility and limitations of electronic health records

Surveillance of chronic hepatitis C virus (HCV) cases faces limitations that result in delays and underreporting. 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) \u3e/=2 ICD-9 codes separated by \u3e/= 6 months and (2) \u3e/=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 (\u3e/= 2 ICD-9 codes separated by \u3e/= 6 months) had 70.3% sensitivity, 91.9% PPV, 99.9% specificity, and 99.9% NPV while case definition 2 (\u3e/= 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

HBV-related cirrhosis in the Chronic Hepatitis Cohort Study (CHeCS)

PURPOSE: The overall spectrum of liver disease among Americans with chronic hepatitis B (CHB) infection remains unknown, and staging liver biopsy has become increasingly uncommon. We used four different methods, including liver biopsy, to identify potential cirrhosis among CHB patients enrolled in the Chronic Hepatitis Cohort Study (CHeCS), an ongoing observational study at four large, integrated health systems in the United States. METHODS: We included patients who met predefined inclusion criteria for CHB whose case status had been confirmed through chart abstraction. We excluded patients coinfected with hepatitis C and liver transplant recipients. Data were collected through 2012 from liver biopsy reports, lab results, and diagnosis/procedure codes contained in the electronic health record. We calculated FIB-4 scores based on most recently available aminotransferase and platelet count values collected when a patient was not on antiviral therapy. Cirrhosis was identified via four methods: (1) liver biopsy reports, (2) presence of a diagnosis code for cirrhosis (ICD-9 diagnosis codes 571.2 and 571.5), (3) presence of a diagnosis or procedure code for end stage liver disease (ESLD), and (4) FIB-4 score \u3e5.17, a cut-off value previously validated as predictive of cirrhosis in this cohort. We compared the extent to which cirrhosis was indicated by each method individually and by multiple methods. RESULTS: Among the 2,731 CHB patients, 24% were \u3c40 and 26% \u3e60 years old, 54% were male, and 53% were Asian. Median follow-up time was 6.0 years. Of the total, 564 (21%) patients had at least one biopsy report during follow-up, and of those, 85 (15% of those who had a biopsy) had a recent biopsy less than two years old. Overall, cirrhosis was indicated for 520 (19%) patients by at least one of the four methods: by liver biopsy for 66 patients (2% of patients overall, and 12% among those with any liver biopsy report); by FIB-4 score for 281 (10%); by diagnosis code for cirrhosis for 318 (12%); and by diagnosis or procedure code for ESLD for 216 (8%), 145 of whom had a diagnosis code for both cirrhosis and ESLD. Of the 281 patients with FIB-4 score \u3e5.17, only 26 (9%) had been diagnosed with cirrhosis via biopsy, 135 (48%) via ICD-9 code for cirrhosis, and 113 (40%) via diagnosis or procedure code indicating ESLD. CONCLUSION: An estimated 19% of CHB patients among our cohort had indication of cirrhosis at some point in their follow-up through 2012. The use of additional parameters, including a previously validated biomarker as a surrogate for more advanced liver disease, potentially identifies additional unrecognized cirrhosis in untreated CHB 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

BACKGROUND: 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. AIM: To determine the distribution of disease phases, treatment prescription and severe liver disease among patients with CHB in general US healthcare settings. METHODS: We analysed demographic and clinical data collected during 2006-2013 from patients with confirmed CHB in the Chronic Hepatitis Cohort Study, an observational cohort study involving patients from healthcare organisations in Michigan, Pennsylvania, Oregon and Hawaii. CHB phases were classified according to American Association for the Study of Liver Disease guidelines. RESULTS: Of 1598 CHB patients with ≥12 months of follow-up (median 6.3 years), 457 (29%) were immune active during follow-up [11% hepatitis B e antigen (HBeAg)-positive, 16% HBeAg-negative, and 2% HBeAg status unknown], 10 (0.6%) were immune tolerant, 112 (7%) were inactive through the duration of follow-up and 886 (55%) were phase indeterminate. Patients with cirrhosis were identified within each group (among 21% of immune active, 3% of inactive and 9% of indeterminate phase patients) except among those with immune-tolerant CHB. Prescription of treatment was 59% among immune active patients and 84% among patients with cirrhosis and hepatitis B virus (HBV) DNA \u3e2000 IU/mL. CONCLUSIONS: Approximately, one-third of the cohort had active disease during follow-up; 60% of eligible patients were prescribed treatment. Our findings underscore the importance of ascertainment of fibrosis status in addition to regular assessment of ALT and HBV DNA levels

The predictive value of international classification of disease codes for chronic hepatitis c virus infection surveillance: The utility and limitations of electronic health records

Surveillance of chronic hepatitis C virus (HCV) cases faces limitations that result in delays and underreporting. 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

Prevalence of Renal Impairment and Associated Conditions Among HCV-Infected Persons in the Chronic Hepatitis Cohort Study (CHeCS)

BACKGROUND: Guidelines for the treatment of HCV-infected persons were updated in August 2015 with new recommendations for patients with renal impairment. Treatment is imperative for patients with severe, renal-associated extrahepatic manifestations of HCV infection. AIMS: We sought to describe the prevalence of these conditions among current HCV-infected patients in a population-based prospective, observational cohort study at four large US health systems. METHODS: Data from cohort patients with chronic HCV infection during 2012 were analyzed for the period from 2006 to 2013. We determined the prevalence of mild to moderately impaired renal function defined as having the most recent estimated glomerular filtration rate [eGFR] ≤ 80 ml/min/1.73 m(2), with severe impairment defined as eGFR \u3c 30 ml/min/1.73 m(2), based on the treatment guidelines. Prevalence of extrahepatic conditions was ascertained using ICD9-codes. RESULTS: Among 5772 persons, the prevalence of eGFR ≤ 80 was 33 % and eGFR \u3c 30 was 2 %, including among patients with hepatic fibrosis. Diagnosed extrahepatic renal manifestations were rare: vasculitis- 0.2 %, nephrotic syndrome- 0.3 %, and cryoglobulinemia- 0.9 %. CONCLUSIONS: While the prevalence of severe renal impairment and diagnosed extrahepatic manifestations was low, mild-to-moderate renal impairment was common in HCV patients, including those with advanced liver fibrosis for whom the need for treatment is urgent

A Point System to Forecast Hepatocellular Carcinoma Risk Before and After Treatment Among Persons with Chronic Hepatitis C

BACKGROUND: Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting. AIM: Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C. METHODS: Using data from the Chronic Hepatitis Cohort Study collected during 2005-2014, we derived HCC risk scores for males and females using an extended Cox model with aspartate aminotransferase-to-platelet ratio index (APRI) as a time-dependent variables and mean Kaplan-Meier survival functions from patient data at two study sites, and used data collected at two separate sites for external validation. For model calibration, we used the Greenwood-Nam-D\u27Agostino goodness-of-fit statistic to examine differences between predicted and observed risk. RESULTS: Of 12,469 patients (1628 with a history of sustained viral response [SVR]), 504 developed HCC; median follow-up was 6 years. Final predictors in the model included age, alcohol abuse, interferon-based treatment response, and APRI. Point values, ranging from -3 to 14 (males) and -3 to 12 (females), were established using hazard ratios of the predictors aligned with 1-, 3-, and 5-year Kaplan-Meier survival probabilities of HCC. Discriminatory capacity was high (c-index 0.82 males and 0.84 females) and external calibration demonstrated no differences between predicted and observed HCC risk for 1-, 3-, and 5-year forecasts among males (all p values \u3e0.97) and for 3- and 5-year risk among females (all p values \u3e0.87). CONCLUSION: This scoring system, based on age, alcohol abuse history, treatment response, and APRI, can be used to forecast up to a 5-year risk of HCC among hepatitis C patients before and after SVR