Hepatotoxicity during legacy cancer chemotherapy in patients infected with hepatitis C virus: A retrospective cohort study.

BACKGROUND: The rates and causes of significant hepatotoxicity with cancer chemotherapy (CCT) in patients infected with hepatitis C virus (HCV) are incompletely characterized. METHODS: We compared rates of grade 3 or 4 hepatotoxicity, defined as elevated transaminases, during CCT in patients who are mono-infected with HCV compared with rates in controls matched on demographics, diagnosis, and rituximab use. We excluded patients with hepatobiliary cancers, hepatitis B virus or human immunodeficiency virus infection. Hepatotoxicity was attributed to a medical cause, cancer progression, or CCT, including HCV flare. RESULTS: Patients with HCV (n = 196) had a higher rate of cirrhosis than the 1,130 matched controls (21.9% versus 4%; P <0.001). Their higher rate of overall hepatotoxicity (8.7% versus 4.5% of controls, P = 0.01) was due to higher rate of CCT-related hepatotoxicity (4.1% versus 1.2%, P = 0.01). On multivariable analysis, the largest risk factor for overall hepatotoxicity was cirrhosis, and the only risk factor for CCT-related hepatotoxicity was HCV infection. Among those with HCV, the only significant risk factor for hepatotoxicity was rituximab use. Hepatotoxicity caused by CCT delayed or altered treatment in only 3 HCV patients and 1 control (1.5% versus 0.1%, P = 0.01). CONCLUSIONS: Most patients with HCV can safely be treated with cancer chemotherapy. Cirrhosis and HCV infection contributed to increased hepatotoxicity in subjects on CCT. Among HCV patients, rituximab use was the major risk factor for increased hepatotoxicity. Hepatotoxicity due to CCT itself rarely altered or delayed CCT. Nonetheless, HCV-positive patients should be monitored carefully during CCT.

Disparities in Initiation of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection in an Insured Population.

OBJECTIVES: The cost of direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection may contribute to treatment disparities. However, few data exist on factors associated with DAA initiation. METHODS: We conducted a retrospective cohort study of HCV-infected Kaiser Permanente Northern California members aged ≥18 during October 2014 to December 2016, using Poisson regression models to evaluate demographic, behavioral, and clinical factors associated with DAA initiation. RESULTS: Of 14 790 HCV-infected patients aged ≥18 (median age, 60; interquartile range, 53-64), 6148 (42%) initiated DAAs. DAA initiation was less likely among patients who were non-Hispanic black (adjusted rate ratio [aRR] = 0.7; 95% confidence interval [CI], 0.7-0.8), Hispanic (aRR = 0.8; 95% CI, 0.7-0.9), and of other minority races/ethnicities (aRR = 0.9; 95% CI, 0.8-1.0) than among non-Hispanic white people and among those with lowest compared with highest neighborhood deprivation index (ie, a marker of socioeconomic status) (aRR = 0.8; 95% CI, 0.7-0.8). Having maximum annual out-of-pocket health care costs >$3000 compared with ≤$3000 (aRR = 0.9; 95% CI, 0.8-0.9) and having Medicare (aRR = 0.8; 95% CI, 0.8-0.9) or Medicaid (aRR = 0.7; 95% CI, 0.6-0.8) compared with private health insurance were associated with a lower likelihood of DAA initiation. Behavioral factors (eg, drug abuse diagnoses, alcohol use, and smoking) were also significantly associated with a lower likelihood of DAA initiation (all P < .001). Clinical factors associated with a higher likelihood of DAA initiation were advanced liver fibrosis, HCV genotype 1, previous HCV treatment (all P < .001), and HIV infection ( P = .007). CONCLUSIONS: Racial/ethnic and socioeconomic disparities exist in DAA initiation. Substance use may also influence patient or provider decision making about DAA initiation. Strategies are needed to ensure equitable access to DAAs, even in insured populations.

Effectiveness of telaprevir and boceprevir triple therapy for patients with hepatitis C virus infection in a large integrated care setting.

BACKGROUND: In 2011, the FDA approved telaprevir (TVR) and boceprevir (BOC) for use with pegylated interferon and ribavirin to treat hepatitis C virus (HCV) genotype 1. We aimed to evaluate the real-world application, tolerability, and effectiveness of TVR- and BOC-based HCV treatment in a large integrated care setting. METHODS: We utilized Northern California Kaiser Permanente Medical Care Program (KPNC) electronic databases and medical records to study the experience of all KPNC patients who initiated TVR or BOC from June 2011 to March 2012. RESULTS: Compared with the pool of 5,194 treatment-eligible patients, the 352 treatment initiators were more likely to be cirrhotic (24 vs. 10%, p < 0.001) and treatment-experienced (44 vs. 22%, p < 0.001). Among the treatment initiators, 211 received TVR and 141 BOC. Overall, 31% discontinued treatment prematurely; 16% of patients stopped treatment early because of side effects. One patient with cirrhosis died of sepsis during treatment. Premature discontinuation was highest among TVR-treated cirrhotic patients (58%). Sustained virologic response (SVR) was achieved in 55% overall and was similar comparing the TVR (56%)- and BOC (53%)-treated groups. The only independent predictors of treatment failure were cirrhosis at baseline [odds ratio (OR) for SVR 0.44, p = 0.004] and prior partial or null response (OR for SVR 0.57, p = 0.02). CONCLUSIONS: In the initial application of TVR and BOC, patients with cirrhosis and prior treatment failure were prioritized for treatment. In this real-world experience, most patients successfully completed a full treatment course. However, side effect-related premature discontinuations were common, and SVR rates were lower than reported in clinical trials.

Characteristics and management of patients with chronic hepatitis B in an integrated care setting.

BACKGROUND: Few population-based studies have described characteristics and management of patients with chronic hepatitis B (CHB) in the USA. METHODS: We retrospectively studied adults with CHB in the Northern California Kaiser Permanente Medical Care Program (KPNC) from July 2009 to December 2010 (n = 12,016). Laboratory tests, treatment patterns, and hepatocellular carcinoma (HCC) surveillance were ascertained during a "recent" 18-month study window (July 2009-December 2010), or as "ever" based on records dating to 1995. RESULTS: The mean age was 49 years; 51 % were men, 83 % Asian, and 87 % KPNC members >5 years. Overall, 51 % had ≥ 1 liver-related visit, 14 % with gastroenterology or infectious disease specialists, and 37 % with primary care providers (PCP) only. Less than 40 % of patients had both hepatitis B virus (HBV) DNA and ALT testing conducted recently, while 56 % of eligible patients had received HCC surveillance. Recent laboratory testing and HCC surveillance were more frequent in patients seen by a specialist versus PCP only (90 vs. 47 % and 92 vs. 73 %, respectively, p values <0.001). During the study period, 1,649 (14 %) received HBV treatment, while 5 % of untreated patients had evidence of treatment eligibility. Among 599 patients newly initiated on HBV therapy, 76 % had guideline-based indications for treatment. CONCLUSIONS: Most patients initiated on HBV treatment met eligibility, and very few patients with evidence of needing treatment were left untreated. However, monitoring of ALT and HBV DNA levels, as well as HCC surveillance, were not frequent, underestimating the proportion of patients that warranted HBV therapy. Viral monitoring and cancer surveillance are therefore important targets for improving the scope of CHB care in the community setting.

Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial.

UNLABELLED: This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. CONCLUSION: PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics.

BACKGROUND: One type of fecal occult blood test (FOBT), the unrehydrated guaiac fecal occult blood test (GT), is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs, but it has relatively low sensitivity as a single test for detecting advanced colonic neoplasms (cancer and adenomatous polyps > or = 1 cm in diameter). Thus, improving the sensitivity of FOBT should make colon cancer screening programs that use these tests more effective. METHODS: We assessed prospectively the performance characteristics of two newer FOBTs in 5841 subjects at average risk for colorectal cancer in a large group-model managed care organization. The tests evaluated included a sensitive GT, a fecal immunochemical test (FIT), and the combination of both tests. Patients with positive and negative test results were advised to have colonoscopy and sigmoidoscopy, respectively. Sensitivity and specificity for detecting advanced neoplasms in the left colon within 2 years after the FOBT screening were evaluated for the two tests administered separately and in combination. RESULTS: A total of 139 patients were diagnosed with advanced colorectal neoplasms (n = 14 cancers, n = 128 adenomas) within the 2 years following their initial FOBT screening. Sensitivity for detecting cancer was 81.8% (95% confidence interval [CI] = 47.8% to 96.8%) for the FIT alone and 64.3% (95% CI = 35.6% to 86.0%) for the sensitive GT and the combination test. Sensitivity for detecting advanced colorectal adenomas was 41.3% (95% CI = 32.7% to 50.4%) for the sensitive GT, 29.5% (95% CI = 21.4% to 38.9%) for the FIT, and 22.8% (95% CI =16.1% to 31.3%) for the combination test. Specificity for detecting cancer and adenomas was 98.1% (95% CI = 97.7% to 98.4%) and 98.4% (95% CI = 98.0% to 98.7%), respectively, for the combination test; 96.9% (95% CI = 96.4% to 97.4%) and 97.3% (95% CI = 96.8% to 97.7%), respectively, for the FIT; and 90.1% (95% CI = 89.3% to 90.8%) and 90.6% (95% CI = 89.8% to 91.4%), respectively, for the sensitive GT. CONCLUSIONS: The FIT has high sensitivity and specificity for detecting left-sided colorectal cancer, and it may be a useful replacement for the GT.