Sharon L. Hunt

Effects of Sofosbuvir-Based Treatment, With and Without Interferon, on Outcome and Productivity of Patients With Chronic Hepatitis C

BACKGROUND & AIMS Interferon-based treatment of chronic hepatitis C virus (HCV) infection can negatively affect patient-reported outcomes (PROs) and work productivity (WP). We assessed these factors in patients with chronic hepatitis C treated with sofosbuvir and ribavirin, with or without pegylated interferon. METHODS The HCV-specific Quality of Life (Chronic Liver Disease Questionnaire-HCV version [CLDQ-HCV]), Functional Assessment of Chronic Illness Therapy-Fatigue, and Work Productivity and Activity Index: Specific Health Problem questionnaires were completed before, during, and after treatment of patients infected with HCV genotypes 2 or 3 who received sofosbuvir and ribavirin for 16 or 12 weeks (the FUSION study, n = 201) or patients infected with HCV genotype 1 who received pegylated interferon, sofosbuvir, and ribavirin for 12 weeks (the NEUTRINO study, n = 327). RESULTS Patients in each group of the FUSION study had similar PRO and WP scores at each time point (all comparisons, P > .05). Compared with baseline, patients had modest reductions in fatigue, HCV-specific quality of life, and WP and Activity Index scores during treatment (P = .02 to <.0001). However, by 4 weeks after treatment, all scores returned to baseline levels or higher. Subjects in the NEUTRINO study had greater reductions in these scores during treatment; most remained significant through 4 weeks after treatment (P < .05). Significant improvements in PROs were observed among patients with sustained virologic responses 12 weeks after treatment in the FUSION and NEUTRINO studies (all P < .05). In multivariate analyses after adjustment for confounders, interferon therapy was independently associated with worse PROs after 12 weeks of treatment. CONCLUSIONS On the basis of an analysis of 2 large clinical trials (FUSION and NEUTRINO), patient outcome and productivity are more negatively affected by the inclusion of pegylated interferon in treatment than by interferon-free regimens. Patients with sustained virologic responses 12 weeks after treatment had significant improvements in PROs in both studies.

Strict versus liberal target range for perioperative glucose in patients undergoing coronary artery bypass grafting: A prospective randomized controlled trial

OBJECTIVE The purpose of this study was to test the hypothesis that a liberal blood glucose strategy (121-180 mg/dL) is not inferior to a strict blood glucose strategy (90-120 mg/dL) for outcomes in patients after first-time isolated coronary artery bypass grafting and is superior for glucose control and target blood glucose management. METHODS A total of 189 patients undergoing coronary artery bypass grafting were investigated in this prospective randomized study to compare 2 glucose control strategies on patient perioperative outcomes. Three methods of analyses (intention to treat, completer, and per protocol) were conducted. Observed power was robust (>80%) for significant results. RESULTS The groups were similar on preoperative hemoglobin A(1c) and number of diabetic patients. The liberal group was found to be noninferior to the strict group for perioperative complications and superior on glucose control and target range management. The liberal group had significantly fewer patients with hypoglycemic events (<60 mg/dL; P < .001), but severe hypoglycemic events (<40 mg/dL) were rare and no group differences were found (P = .23). These results were found with all 3 methods of analysis except for blood glucose variability, maximum blood glucose, and perioperative atrial fibrillation. CONCLUSIONS This study demonstrated that maintenance of blood glucose in a liberal range after coronary artery bypass grafting led to similar outcomes compared with a strict target range and was superior in glucose control and target range management. On the basis of the results of this study, a target blood glucose range of 121 to 180 mg/dL is recommended for patients after coronary artery bypass grafting as advocated by the Society of Thoracic Surgeons.

Patient-reported outcomes in chronic hepatitis C patients with cirrhosis treated with sofosbuvir-containing regimens

Whether the presence of cirrhosis influences patient‐reported outcomes (PROs), including health‐related quality of life, during treatment with newly available anti‐HCV (hepatitis C virus) regimens is unclear. Our aim was to assess the association of cirrhosis with PROs in patients treated with sofosbuvir (SOF)‐containing regimens. Four PRO questionnaires (Short Form‐36 [SF‐36], Functional Assessment of Chronic Illness Therapy‐Fatigue [FACIT‐F], Chronic Liver Disease Questionnaire‐HCV (CLDQ‐HCV), and the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI‐SHP]) were administered to subjects receiving SOF and ribavirin (RBV; FUSION trial, N = 201, 34% cirrhosis; VALENCE trial: N = 333, 21% cirrhosis) and SOF, RBV, and pegylated interferon (Peg‐IFN; NEUTRINO trial: N = 327, 17% cirrhosis). HCV patients with cirrhosis showed significant impairment of PROs before initiation of treatment. During treatment, patients with cirrhosis treated with the IFN‐free regimen experienced moderate decline in their PRO scores (0.6%‐5.2% on a normalized scale of the summary scores; all P > 0.02). In contrast, patients with cirrhosis treated with IFN‐containing regimen showed decline in PRO scores that ranged from 3.4% to 16.0% (all P < 0.005). Nevertheless, by follow‐up week 12, no PRO decrement from baseline was observed in patients with cirrhosis regardless of the treatment regimen. Furthermore, in patients with cirrhosis with HCV who achieved sustained virological response at 12 weeks (SVR‐12), some improvement in PROs from baseline was observed. During treatment, changes in PRO scores were similar between patients with and without cirrhosis for both treatment regimens (all P > 0.05). Independent predictors of lower PROs in patients with cirrhosis included baseline depression, anxiety, fatigue, high HCV viral load, female gender, and receiving IFN‐containing treatment. Conclusions: Treatment with SOF+RBV with or without Peg‐IFN is tolerated by HCV patients with and without cirrhosis in terms of their PRO scores. After achieving SVR‐12 with the IFN‐free regimen, patients with cirrhosis showed improvement in some aspects of their PROs. (Hepatology 2014;59:2161–2169)

The patient's journey with chronic hepatitis C from interferon plus ribavirin to interferon- and ribavirin-free regimens: a study of health-related quality of life

Interferon and ribavirin negatively impact health‐related quality of life (HRQL) during treatment.

Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported Outcomes

BACKGROUND Sofosbuvir-containing regimens have been approved for treatment of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients. We assessed the effect of treatment with sofosbuvir and ribavirin on patient-reported outcomes (PROs) in individuals with HIV/HCV coinfection. METHODS HIV/HCV-coinfected patients were treated for 12 or 24 weeks with sofosbuvir and ribavirin. Matched HCV-monoinfected controls were also evaluated. All subjects completed standard PRO questionnaires before, during, and after treatment. RESULTS Included were 497 participants from the PHOTON-1 and PHOTON-2 clinical trials. At baseline, more impairment in PRO scores was noted in HIV/HCV-coinfected patients, compared with HCV-monoinfected patients. During treatment, moderate decrements in PRO scores (change, up to -6.8% on a 0%-100% scale; P = .0053) were experienced regardless of treatment duration and were similar to those for HCV-monoinfected patients (all P > .05). In 413 HIV/HCV-coinfected patients with a virologic response sustained for 12 weeks after treatment cessation, most PRO scores improved (change, up to +7.6%; P < .0001), similar to findings for HCV-monoinfected patients. In multivariate analysis, in addition to clinico-demographic predictors, coinfection with HIV was associated with PRO impairment at baseline (beta, up to -7.6%; P < .002) but not with treatment-emergent changes in PRO scores (all P > .05). CONCLUSIONS Patients with HIV/HCV coinfection tolerate interferon-free sofosbuvir-based anti-HCV regimens well and, despite the presence of some baseline impairment, have treatment-emergent changes in PRO scores that are similar to those of patients with HCV monoinfection. CLINICAL TRIALS REGISTRATION NCT01667731 (PHOTON-1), NCT01783678 (PHOTON-2), NCT01604850 (FUSION), and NCT01682720 (VALENCE).

Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Co-infected with HIV: The Impact on Patient-Reported Outcomes

BACKGROUND Sofosbuvir-containing regimens have been approved for treatment of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients. We assessed the effect of treatment with sofosbuvir and ribavirin on patient-reported outcomes (PROs) in individuals with HIV/HCV coinfection. METHODS HIV/HCV-coinfected patients were treated for 12 or 24 weeks with sofosbuvir and ribavirin. Matched HCV-monoinfected controls were also evaluated. All subjects completed standard PRO questionnaires before, during, and after treatment. RESULTS Included were 497 participants from the PHOTON-1 and PHOTON-2 clinical trials. At baseline, more impairment in PRO scores was noted in HIV/HCV-coinfected patients, compared with HCV-monoinfected patients. During treatment, moderate decrements in PRO scores (change, up to -6.8% on a 0%-100% scale; P = .0053) were experienced regardless of treatment duration and were similar to those for HCV-monoinfected patients (all P > .05). In 413 HIV/HCV-coinfected patients with a virologic response sustained for 12 weeks after treatment cessation, most PRO scores improved (change, up to +7.6%; P < .0001), similar to findings for HCV-monoinfected patients. In multivariate analysis, in addition to clinico-demographic predictors, coinfection with HIV was associated with PRO impairment at baseline (beta, up to -7.6%; P < .002) but not with treatment-emergent changes in PRO scores (all P > .05). CONCLUSIONS Patients with HIV/HCV coinfection tolerate interferon-free sofosbuvir-based anti-HCV regimens well and, despite the presence of some baseline impairment, have treatment-emergent changes in PRO scores that are similar to those of patients with HCV monoinfection. CLINICAL TRIALS REGISTRATION NCT01667731 (PHOTON-1), NCT01783678 (PHOTON-2), NCT01604850 (FUSION), and NCT01682720 (VALENCE).

The impact of type 2 diabetes and obesity on the long-term outcomes of more than 85 000 liver transplant recipients in the US.

Type 2 diabetes is known to negatively impact the outcome of chronic liver disease.

The Impact of Surgical Ablation for Atrial Fibrillation in High-Risk Patients

BACKGROUND Data reported by The Society of Thoracic Surgeons adult cardiac surgery database demonstrate that only 38% of patients with atrial fibrillation (AF) underwent a concomitant surgical ablation. Surgeons are reluctant to add complexity and potential morbidity by including an additional procedure when performing surgery in higher operative risk patients. We investigated perioperative and long-term outcomes in high-risk patients who underwent open heart surgery with or without surgical ablation for AF. METHODS An additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) higher than 6 defined high-risk patients. Perioperative outcomes were captured prospectively, and long-term survival and quality of life were assessed. Propensity score matching using a 0.25 caliper was conducted between the surgical ablation group and the nonablation group (no history of AF). RESULTS The propensity score matching analysis included 178 patients per group. The groups were similar on preoperative characteristics including age, ejection fraction, EuroSCORE, and surgical procedures. The perioperative outcomes were similar between groups, including length of stay, permanent stroke, renal failure, 30-day readmissions, and operative (<30 days) mortality. Cumulative survival over 5 years also did not differ between groups (74.4% versus 69.7%, p=0.34). CONCLUSIONS The addition of an AF surgical ablation procedure did not add operative risk to patients considered high risk, and potentially improved long-term outcome for the subgroup of patients who had their AF ablated. This study suggests that the degree of surgical risk should not be the only decision factor when evaluating this challenging group of patients for surgical ablation.

The impact of chronic hepatitis C on resource utilisation and in-patient mortality for Medicare beneficiaries between 2005 and 2010

As baby boomers age, chronic hepatitis C (CHC) will become increasingly important in Medicare eligible group.

Health-related quality of life after coronary artery bypass grafting surgery and the role of gender☆

OBJECTIVE Heart disease is the leading cause of death for women. Previous studies suggest that women undergoing coronary artery bypass (CABG) surgery present with a higher severity of disease and that this may be an indicator of delays in treatment preceding diagnosis thus presenting challenges for recovery. The aim of this study was to examine gender differences in CABG morbidity and reported health-related quality of life (HRQL) at baseline and six months post-surgery. It was hypothesized that female gender would be an independent predictor for lower HRQL at six months following CABG surgery. METHODS Four hundred and ninety-six (n=496) adult patients who underwent a first-time, isolated CABG procedure with baseline and 6-month follow-up were included. Stepwise multivariate regressions were conducted to evaluate the factors predictive of 6-month HRQL scores. RESULTS Females had more preoperative co-morbidities and scored significantly lower on HRQL compared to males at both baseline (p values<0.01) and six months (p values<0.01) on all ten domains. Gender was a significant predictor of 6-month HRQL in regression models for 8 out of 10 HRQL domains including Physical Component Summary score (B=-2.54, p=0.02). CONCLUSIONS Female patients were at higher risk as reflected by their perioperative risk factors and baseline HRQL. These findings may reflect a delayed referral for surgery. Results indicated that female gender predicts lower HRQL 6-months post-CABG surgery, which can have an impact on recovery and outcomes. Efforts should be made to identify and treat female patients earlier to improve post-surgical outcomes.