Lauren A. Beste

Similar Effectiveness of Boceprevir and Telaprevir Treatment Regimens for Hepatitis C Virus Infection on the Basis of a Nationwide Study of Veterans

BACKGROUND & AIMS We investigated the real-world effectiveness of triple therapy regimens against hepatitis C virus (HCV) and compared rates of sustained virologic response (SVR) between telaprevir-based and boceprevir-based regimens in a population-based study. METHODS We analyzed data on all patients in the Veterans Administration healthcare system who were infected with HCV genotype 1 and began treatment with pegylated interferon, ribavirin, and either boceprevir (n = 3696, 83%) or telaprevir (n = 759, 17%) from June 2011 to February 2013. RESULTS Patients treated with telaprevir were more likely to have baseline characteristics associated with not achieving SVR than patients treated with boceprevir. Fewer than half of patients eligible for short-duration regimens (28 weeks for boceprevir, 24 weeks for telaprevir) successfully completed treatment (37% for boceprevir, 27.5% for telaprevir); ∼25% discontinued early, and the remaining patients were treated for longer durations. Of the patients who were supposed to complete 48-week regimens, only 35% of boceprevir-treated and 34% of telaprevir-treated patients completed >44 weeks. The rate of SVR was 51.5% overall, 42.7% among patients with cirrhosis, 56.8% among treatment-naive patients, 64.2% among prior relapsers, 31.7% among prior partial responders, and 29.8% among prior null responders. There were no significant differences in rate of SVR between patients given boceprevir or telaprevir in the entire population or among subgroups. The most important predictors of failure to achieve SVR were IL28B genotype, high viral load, black race, diabetes, high aspartate aminotransferase to platelet ratio index or FIB-4 scores, low platelet counts, or low levels of low-density lipoprotein cholesterol. Erythropoietin use was not associated with SVR. CONCLUSIONS In a nationwide analysis of veterans with HCV genotype 1 infection, rates of SVR were similar for those treated with boceprevir vs telaprevir. However, rates of treatment completion and SVR in real clinical practice were substantially lower than those in clinical trials.

Prevalence and Treatment of Chronic Hepatitis C Virus Infection in the US Department of Veterans Affairs

Chronic hepatitis C virus (HCV) is the most common blood-borne pathogen in the United States. HCV disproportionately affects Veterans Affairs (VA) health-care users: 174,302 HCV-infected veterans were in VA care in 2013, making the VA the worlds largest HCV care provider. This systematic review identified 546 articles related to HCV in the VA. After assessment by 2 independent reviewers, 28 articles describing prevalence and treatment of HCV in VA users ultimately met inclusion criteria. Most VA patients currently living with HCV infection were born between 1945 and 1965 and were infected with HCV between 1970 and 1990. To prevent HCV-related complications such as cirrhosis, hepatocellular carcinoma, and death, medical personnel must identify and treat HCV. However, antiviral therapy has historically been limited by medication side effects, contraindications, and patient acceptance. Although treatment initiation rates are higher in the VA than in the general United States, only 23% of VA HCV patients have received treatment and, of those, only a minority were cured. Recent development of more effective and tolerable antiviral agents represents a major pharmacological breakthrough. Eradication of HCV is theoretically possible for the majority of HCV patients for the first time, although new barriers, such as high drug costs, may limit future uptake.

Predictors of Early Treatment Discontinuation Among Patients With Genotype 1 Hepatitis C and Implications for Viral Eradication

BACKGROUND & AIMS A significant proportion of patients with hepatitis C virus (HCV) infection discontinue antiviral treatment prematurely. Risk factors for discontinuation before 48 weeks among patients with genotype 1 HCV vary over the course of therapy. We investigated the rates and risk factors for treatment discontinuation within 12 weeks, 12-24 weeks, and 24-48 weeks. METHODS We retrospectively evaluated data from all Veterans Affairs (VA) patients with genotype 1 HCV who initiated pegylated interferon and ribavirin therapy from 2002-2007 (n = 11,019). We accounted for appropriate discontinuation because of viral nonresponse. RESULTS Overall, 53% of patients completed at least 38.4 weeks of therapy (80% of the projected 48 weeks), 16.5% discontinued early in the setting of viral nonresponse, and 30.9% discontinued despite viral response or in the absence of virologic data. Cirrhosis, diabetes, pretreatment substance use disorder, hemoglobin, and lack of hematopoietic growth factor use independently predicted discontinuation before 12 weeks (P < .05 for all). Among patients with documented early virologic responses, higher baseline levels of creatinine, depression, and lack of growth factor use predicted discontinuation from 12-24 weeks. No factors independently predicted discontinuation from 24-48 weeks among patients responding to treatment at 24 weeks. CONCLUSIONS Early discontinuation of antiviral therapy is common. Use of growth factors was the strongest independent predictor of treatment retention before 24 weeks and should be evaluated prospectively. Early interventions may also be warranted for other risk factors for early discontinuation, such as pre-existing substance use, depression, cirrhosis, or diabetes.

AUDIT-C Alcohol Screening Results and Postoperative Inpatient Health Care Use.

BACKGROUND Alcohol screening scores ≥5 on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) up to a year before surgery have been associated with postoperative complications, but the association with postoperative health care use is unknown. This study evaluated whether AUDIT-C scores in the year before surgery were associated with postoperative hospital length of stay, total ICU days, return to the operating room, and hospital readmission. STUDY DESIGN This cohort study included male Veterans Affairs patients who completed the AUDIT-C on mailed surveys (October 2003 through September 2006) and were hospitalized for nonemergent noncardiac major operations in the following year. Postoperative health care use was evaluated across 4 AUDIT-C risk groups (scores 0, 1 to 4, 5 to 8, and 9 to 12) using linear or logistic regression models adjusted for sociodemographics, smoking status, surgical category, relative value unit, and time from AUDIT-C to surgery. Patients with AUDIT-C scores indicating low-risk drinking (scores 1 to 4) were the referent group. RESULTS Adjusted analyses revealed that among eligible surgical patients (n = 5,171), those with the highest AUDIT-C scores (ie, 9 to 12) had longer postoperative hospital length of stay (5.8 [95% CI, 5.0-6.7] vs 5.0 [95% CI, 4.7-5.3] days), more ICU days (4.5 [95% CI, 3.2-5.8] vs 2.8 [95% CI, 2.6-3.1] days), and increased probability of return to the operating room (10% [95% CI, 6-13%] vs 5% [95% CI, 4-6%]) in the 30 days after surgery, but not increased hospital readmission within 30 days postdischarge, relative to the low-risk group. CONCLUSIONS AUDIT-C screening results could be used to identify patients at risk for increased postoperative health care use who might benefit from preoperative alcohol interventions.

Improved surveillance for hepatocellular carcinoma with a primary care-oriented clinical reminder

BACKGROUND & AIMS Surveillance of patients with cirrhosis for hepatocellular carcinoma (HCC) with liver ultrasound every 6 months has been linked to longer survival and greater use of definitive treatment. However, less than 20% of patients typically undergo routine surveillance. METHODS We conducted a quasi-experimental study to assess whether a primary care-oriented, point-of-care clinical reminder improves HCC surveillance. Our study included patients with cirrhosis who made 1 or more primary care visits to 8 Veterans Affairs (VA) facilities over 18 months. Clinicians at 1 facility were sent a reminder to perform liver ultrasound assessments for patients with cirrhosis who had not received surveillance in the preceding 6 months. Outcomes included the proportion of patients receiving adequate HCC surveillance (defined as >2 instances of liver imaging >6 months apart) and HCC diagnosis and stage. Because it was a quality improvement project, this study did not require approval by an institutional review board under Federal law and VA policy. RESULTS Baseline rates of adequate HCC surveillance were similar at all facilities (18.2% at the intervention site vs 16.1% elsewhere; P = .23). After the reminder was implemented, adequate surveillance at the intervention site (for 790 patients) increased by 51%, but was unchanged at the other facilities (for 2094 patients) (27.6% vs 17.5%; P < .001). Adequate surveillance occurred more often at the intervention site (adjusted odds ratio, 1.29; 95% confidence interval, 1.03-1.61; P = .02). A higher crude percentage of patients was diagnosed with HCC at the intervention site than elsewhere (3.2% vs 1.9%; P = .03). We detected no difference in tumor stage at diagnosis. CONCLUSIONS In a VA population, a clinical reminder system increased HCC surveillance in patients with cirrhosis.

Direct-acting antivirals are effective for chronic hepatitis C treatment in elderly patients: a real-world study of 17 487 patients.

Background The mean age of patients with chronic hepatitis C virus (HCV) infection in the USA has been increasing. Despite the increasing proportion of HCV-infected elderly patients, this group is under-represented in clinical trials of HCV treatment. Aim We aimed to describe the real-world effectiveness of direct-acting antivirals (DAAs) among elderly patients. Patients and methods We retrospectively identified 17 487 HCV-infected patients who were started on treatment with sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir-based regimens in the Veterans Affairs Healthcare System between 1 January 2014 and 30 June 2015. We ascertained sustained virologic response (SVR) rates in patients aged below 55, 55–59, 60–64, 65–69, 70–74, and 75 years or older and performed multivariable logistic regression to determine whether age predicted SVR. Results Overall unadjusted SVR rates were 91.2% [95% confidence interval (CI): 89.7–92.4], 89.8% (95% CI: 88.8–90.7), 90.8% (95% CI: 90.1–91.6), 91.1% (95% CI: 90.1–91.9), 90.0% (95% CI: 86.9–92.4), and 93.8% (95% CI: 88.8–96.7) in patients aged below 55, 55–59, 60–64, 65–69, 70–74, and 75 years or older. Unadjusted SVR rates were similar in all age groups after stratifying by genotype, treatment regimen, stage of liver disease, and treatment experience. In multivariate models, age was not predictive of SVR after adjusting for confounders. Conclusion DAAs produce high rates of SVR in all age groups, including patients in our oldest age category (≥75 years). Advanced age in and of itself should not be considered a barrier to initiating DAA treatment.

Rates and predictors of response to anti‐viral treatment for hepatitis C virus in HIV/HCV co‐infection in a nationwide study of 619 patients

The effectiveness of anti‐viral treatment for hepatitis C virus (HCV) in HIV/HCV co‐infected patients in ‘real world’, clinical practice is unclear.

Specialty care and education associated with greater disease-specific knowledge but not satisfaction with care for chronic hepatitis C.

Background  Little is known about differences among hepatitis C virus (HCV) patients managed by generalists vs. specialists with respect to patient‐centred outcomes, such as disease‐specific knowledge, health‐related quality of life (HRQoL) and satisfaction with care.

Prevalence of alcohol misuse among men and women undergoing major noncardiac surgery in the Veterans Affairs health care system

BACKGROUND Patients who screen positive for alcohol misuse on the Alcohol Use Disorder Identification Test Consumption Questionnaire (AUDIT-C ≥5 points) have significantly increased postoperative complications. Severe alcohol misuse (AUDIT-C ≥9 points) is associated with increased postoperative health care use; however, little is known about the prevalence of alcohol misuse in demographic and clinical subgroups of surgical patients. METHODS The prevalence of alcohol misuse was evaluated among 10,284 patients (9,771 men and 513 women) who underwent major noncardiac surgery in Veterans Affairs (VA) hospitals during the fiscal years 2004 to 2006 and completed the AUDIT-C. Sex-stratified analyses evaluated prevalence rates of alcohol misuse (AUDIT-C ≥5) and severe misuse (AUDIT-C ≥9) across demographic and clinical subgroups. RESULTS Overall, 1,607 (16%) men and 24 (5%) women screened positive for alcohol misuse (AUDIT-C ≥5) in the year before operation, with 4% and 2% screening positive for severe misuse (AUDIT-C ≥9), respectively. Alcohol misuse was more common among men who were <60 years of age, divorced or separated, current smokers, or American Stoke Association class 1 or 2, and those with cirrhosis/hepatitis or substance use disorders. Among patients with alcohol misuse, 36% of men and 58% of women were American Society of Anesthesiologists class 1 or 2, and most did not have diagnoses that were commonly associated with alcohol misuse. CONCLUSION Alcohol misuse is relatively common in male surgical patients. Moreover, surgical patients undergoing operation who screen positive for alcohol misuse are often relatively healthy, without health problems that might alert providers to their alcohol misuse in the absence of screening.

Boceprevir and telaprevir-based regimens for the treatment of hepatitis C virus in HIV/HCV coinfected patients.

Background and aim Hepatitis C virus (HCV) treatment in patients coinfected with HIV has historically been limited by poor efficacy and medication toxicities. Direct-acting antivirals (e.g. boceprevir and telaprevir) improve treatment results in clinical trials, but little is known about the outcomes in community-based coinfected populations. This project aimed to describe the real-world effectiveness of boceprevir-based or telaprevir-based therapies in HIV/HCV coinfected patients. Materials and methods We identified HIV/HCV coinfected patients of all genotypes in the Veterans Affairs healthcare system who initiated pegylated interferon and ribavirin with or without boceprevir or telaprevir from June 2011 to November 2012 (n=134). Results Sustained virologic response (SVR) was higher in genotype 1 patients receiving boceprevir or telaprevir [n=62, SVR=50.0%, 95% confidence interval (CI) 37–63] versus pegylated interferon/ribavirin alone (n=48, SVR=33.3%, 95% CI 20–47). Patients with genotypes 2/3 treated with pegylated interferon/ribavirin (n=24) achieved an SVR of 41.7% (95% CI 20–63). Only a few patients (15–25%) of each genotype completed more than 44 of 48 projected weeks. Treatment with boceprevir or telaprevir was the only characteristic independently associated with SVR in genotype 1 (adjusted odds ratio 2.2, 95% CI 1.1–4.7). Conclusion Addition of boceprevir or telaprevir to pegylated interferon/ribavirin improves treatment response in genotype 1 HIV/HCV coinfected patients. Treatment response is similar to reports from HCV monoinfected Veterans Affairs patients but lower than those reported in clinical trials. Early treatment discontinuation was common.