Sue Currie

Management and Treatment of Hepatitis C Viral Infection: Recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office

Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the general U.S. population and 5–10% of veterans who use Department of Veterans Affairs medical services. Chronic HCV is clearly linked to the development of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation. The consequences of HCV infection constitute a significant disease burden and demonstrate the need for effective medical care. Treatment of chronic HCV is aimed at slowing disease progression, preventing complications of cirrhosis, reducing the risk of HCC, and treating extrahepatic complications of the virus. As part of a comprehensive approach to HCV management, antiviral therapy with peginterferon alfa combined with ribavirin is the current standard of care. Antiviral therapy should be provided to those individuals who meet criteria for treatment and who are at greatest risk for progressive liver disease. Many of these patients may have comorbid medical and psychiatric conditions, which may worsen while on antiviral therapy. Current antiviral regimens are associated with significant adverse effects that can lead to noncompliance, dose reduction, and treatment discontinuation. To overcome these barriers and to address these issues, it has become crucial to facilitate a multidisciplinary team who can respond to and provide HCV-specific care and treatment. Screening for HCV, preventing transmission, delaying disease progression, ensuring appropriate antiviral therapy, and managing treatment-related adverse effects can improve patient quality of life, treatment adherence, and ultimately, improve patient outcomes.

Prospective multicenter study of eligibility for antiviral therapy among 4,084 U.S. veterans with chronic hepatitis C virus infection

BACKGROUND:Many veterans may not be candidates for hepatitis C virus (HCV) treatment due to contraindications to therapy. The aims of this study were to determine the proportion of HCV-infected veterans who were eligible for interferon alfa and ribavirin therapy and to evaluate barriers to HCV treatment.METHODS:We prospectively enrolled 4,084 veterans who were referred for HCV treatment over a 1-yr period at 24 Veterans Affairs (VA) Medical Centers. Treatment candidacy was assessed using standardized criteria and the opinion of the treating clinician.RESULTS:Overall, 32.2% (95% CI, 30.8–33.7%) were candidates for HCV treatment according to standardized criteria, whereas 40.7% (95% CI, 39.2–42.3%) were candidates in the opinion of the treating clinician. Multivariable analysis identified ongoing substance abuse (OR = 17.68; 95% CI, 12.24–25.53), comorbid medical disease (OR = 9.62; 95% CI, 6.85–13.50), psychiatric disease (OR = 9.45; 95% CI, 6.70–13.32), and advanced liver disease (OR = 8.43; 95% CI, 4.42–16.06) as the strongest predictors of not being a treatment candidate. Among patients who were considered treatment candidates, 76.2% (95% CI, 74.0–78.3%) agreed to be treated and multivariable analysis showed that persons ≥50 yr of age (OR = 1.37; 95% CI, 1.07–1.76) and those with >50 lifetime sexual partners (OR = 1.44; 95% CI, 1.08–1.93) were more likely to decline treatment.CONCLUSIONS:The majority of veteran patients are not suitable candidates for HCV treatment because of substance abuse, psychiatric disease, and comorbid medical disease, and many who are candidates decline therapy. Multidisciplinary collaboration is needed to overcome barriers to HCV therapy in this population.

Hepatitis C Virus Infection among Prisoners in the California State Correctional System

BACKGROUND Incarcerated populations are at high risk for hepatitis C virus (HCV) infection, yet prisoners are not routinely screened or treated for HCV infection. Understanding the risk factors of HCV infection among prisoners could help improve HCV interventions. METHODS Prevalence and risk of HCV infection among 469 prisoners entering California State correctional facilities were assessed using HCV antibody screening, HCV RNA measurement, and structured interviews. Multivariate logistic regression analysis was used to identify independent correlates of HCV infection. RESULTS The prevalence of HCV infection was 34.3% overall (95% confidence interval [CI], 30%-38%) and was 65.7% among those with a history of injection drug use (IDU), compared with 10.2% among those with no history of IDU (odds ratio [OR], 17.24; 95% CI, 10.52-28.25). Significant differences in HCV antibody positivity were found in association with age at first detention but not with the nature of the crime. Independent correlates of HCV infection included age, history of IDU, cumulative time of incarceration, biological sex (OR for females subjects compared with males subjects, 0.35; 95% CI, 0.13-0.96), and a history of having sex with a male IDU (OR, 4.42; 95% CI, 1.46-13.37). We identified significant differences in risk factors between male and female subjects--notably, that the risk of HCV infection was significantly elevated among female non-IDUs who reported having sexual partners with a history of IDU. Among non-IDUs, correlates of HCV infection included history of receipt of blood products and cumulative years of incarceration. CONCLUSIONS HCV infection is pervasive among the California prison population, including prisoners who are non-IDUs and women with high-risk sexual behavior. These results should promote consideration of routine HCV antibody screening and behavioral interventions among incarcerated men and women.

Chronic hepatitis C in Latinos: natural history, treatment eligibility, acceptance, and outcomes.

OBJECTIVES:The natural history of chronic hepatitis C and treatment response are different between blacks and Caucasians, but little comparable data is available about Latinos.METHODS:A cross-sectional secondary analysis to investigate differences between 421 anti-HCV-positive, treatment-naïve, HCV-viremic Latinos and 2,510 Caucasians in 24 VA medical centers enrolled in a prospective study.RESULTS:Latinos were infected at a younger age and were less likely to have blood contact during combat, surgery, and needle stick injury, but were more frequently HIV coinfected (20.4% vs 3.9%, p < 0.0001) and prior HAV infection (39.9% vs 26.4%, p = 0.0001). Latinos were more likely to be treatment candidates, but less likely to actually initiate treatment. Liver histology (123 Latinos, 743 Caucasians) showed no difference in fibrosis or fibrosis rate, but steatosis (54.7% vs 43.2%, p = 0.038) was more common in Latinos. Eighty-eight Latinos and 481 Caucasians were subsequently treated with interferon-ribavirin: body mass index (BMI), duration of infection, baseline tests, liver histology and genotype distribution were similar. Compared with Caucasians, Latinos discontinued treatment prematurely more often (39.8% vs 28.9%, p = 0.043) and tended to have lower sustained virological response (SVR) rates (14.8% vs 22.5%, p = 0.10). Multivariate analysis found Latino race and history of recent alcohol use to be associated with early treatment discontinuation, whereas genotype and viral load but not ethnicity to be associated with SVR.CONCLUSIONS:Latinos were infected younger, more frequently HIV coinfected, more likely to meet criteria for antiviral therapy yet less likely to initiate treatment and had a trend toward lower SVR rates than Caucasians, but not in severity of liver disease. Latino ethnicity was associated with early discontinuation but not as an independent predictor of SVR.

CAN WE PREDICT THE DEGREE OF FIBROSIS IN CHRONIC HEPATITIS C PATIENTS USING ROUTINE BLOOD TESTS IN OUR DAILY PRACTICE

Goals To determine the validity of fibrosis indexes based on simple laboratory tests in daily practice. Background Fibrosis indexes were developed in referral centers using high-quality data. Methods We compared the performance characteristics of several such indexes with liver biopsies in a cohort of 490 diverse veterans with chronic hepatitis C from 24 centers. All laboratory tests including interpretation of the liver biopsy were done locally. The following indexes were calculated and correlated with a 5-point fibrosis stage (F0-F4) on liver biopsies: platelet counts (<100 or <150×109/L), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), Pohl score, AST-to-platelet ratio index (APRI) and “Loks model.” Results Our cohort was predominantly male with 24% blacks, and fibrosis stages of 0, 1, 2, 3, and 4 in 11%, 24%, 28%, 24%, and 13%, respectively. All indexes performed better in predicting advanced (F3-4) than significant (F2-4) fibrosis. When patients with F3-4 were compared to those with F0-2, the area under the receiver operating characteristics curve were 0.534 and 0.641 for platelet count <100 and <150×109/L, respectively, 0.524 for AAR, 0.534 for Pohl score, 0.693 for Loks model, and 0.765 for APRI. The sensitivity, specificity, and predictive values of APRI and Loks model were only slightly lower than those reported by the authors using the recommended cutoffs in clinical trial settings. Alcohol use within 12 months, normalization of AST, ALT, and race (blacks/non-blacks) had minimal impact on the performance. Conclusions AAR, Pohl, and platelet counts <100×109/L have limited ability to predict significant/advanced fibrosis with area under the receiver operating characteristics curve similar to 0.5. However, platelet counts <150×109/L, Loks model and APRI performed well for advanced fibrosis in our daily practice setting.

Hepatitis C treatment candidacy and outcomes among 4318 US veterans with chronic hepatitis C virus infection : Does a history of injection drug use matter?

Background/Goals Many patients with a history of injection drug use (IDU) are excluded from hepatitis C virus (HCV) treatment. This prospective multicenter study aimed to determine the impact of IDU history on HCV treatment candidacy and outcomes. Study Between 1999 and 2001, 4318 HCV-infected patients seen at 24 VA Medical Centers were evaluated for HCV treatment candidacy and followed prospectively. Univariate and multivariate logistic regression analyses were used to determine whether an IDU history was associated with HCV treatment candidacy, HCV treatment acceptance, early treatment discontinuation, and virologic response. Results Of 4318 participants, 2611 (61%) reported an IDU history. IDU history was not significantly associated with HCV treatment candidacy, acceptance, early discontinuation of therapy, or virologic response (all P values nonsignificant). Instead, reduced HCV treatment candidacy was independently associated with low-income [odds ratio (OR)=1.46, 95% confidence interval (CI)=1.22-1.74), education ≤12 years (OR=1.23, 95% CI=1.03-1.46), and alcohol consumption ≥3 drinks/d (OR=2.08, 95% CI=1.68-2.57), whereas early discontinuation of HCV therapy was independently associated with low-income and consuming ≥3 alcoholic drinks/d. Conclusions A history of IDU was not associated with HCV treatment candidacy or outcomes, supporting national guidelines to evaluate former IDUs on a case-by-case basis for HCV treatment.

National multicenter study of HIV testing and HIV seropositivity in patients with chronic hepatitis C virus infection

Background Although HIV testing is recommended for persons with hepatitis C virus (HCV) infection who are at risk for HIV, little is known about HIV testing in this population. Methods Data were prospectively collected in 4364 HCV-infected patients at 24 Veterans Affairs medical centers across the United States, including demographics, risk factors for HIV infection, and self-reported information on HIV testing. Results Overall, 76.8% had been tested for HIV at least once, 14.8% were never tested, 6.6% did not know if they were tested, and 1.8% declined to answer. Multivariable analysis identified injection drug use, needlestick injury, sex with a same-sex partner, a greater number of lifetime sexual partners, and sex with an injection drug user as factors that were independently associated with HIV testing. At least one risk factor for HIV infection was present in 84.5% of the 646 patients who were never HIV tested. Among the 3350 subjects who were tested for HIV, 8.4% were positive, 88.3% were negative, 2.4% did not know the results of their test, and 0.9% declined to answer. Multivariable analysis identified African American and Hispanic race/ethnicity, income ≤

Liver Disease in Injection Drug Users with Hepatitis C, With and Without HIV Coinfection

10,000, sex with a same-sex partner, and sex with an injection drug user as the only variables that were independently associated with HIV seropositivity. Conclusions Although a substantial proportion of HCV-infected patients have been tested for HIV, missed opportunities for early diagnosis of HIV infection exist. Public health strategies to improve HIV testing among patients with chronic HCV infection are needed.

A prospective study to examine persistent HCV reinfection in injection drug users who have previously cleared the virus.

Abstract Liver disease is a major health problem for individuals with a history of injection drug use. This is mainly from the hepatitis C virus (HCV), with or without co-infection with HIV. HCV-associated liver disease takes decades to develop into cirrhosis, from which it can adversely affect health. HIV coinfection is among the factors that are often associated with liver disease progression, and efforts to understand liver disease progression in HIV-HCV coinfected patients remain important. Maintaining high CD4 counts and avoiding alcohol intake are associated with slower liver disease progression. Pegylated interferon and ribavirin combination therapy has the potential to clear HCV, which provides the strongest health benefit to patients affected by the virus, although this can be difficult to accomplish for many reasons. Steatosis, fat within the liver, may also have important pathological implications for liver disease related to HCV. Limiting liver disease progression in IDUs with hepatitis C may well be best accomplished through promoting their full utilization of health care.