Jenna K. Kawamoto

Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c

AIM To determine whether successful treatment with directacting antivirals (DAA) is associated with improvements in hemoglobin A1c (HbA1c) and if type 2 diabetes mellitus (T2DM) or metabolic syndrome affects sustained virologic response (SVR). METHODS We performed a retrospective analysis of all hepatitis C virus (HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment (SVR12). RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2DM. Within that cohort, patients who achieved SVR12 had lower mean HbA1c pre treatment (7.35 vs 8.60, P = 0.02), and lower mean HbA1c post-treatment compared to non-responders (6.55 vs 8.61, P = 0.01). The mean reduction in HbA1c after treatment was greater for those who achieved SVR12 than for non-responders (0.79 vs 0.01, P = 0.03). In adjusted models, patients that achieved SVR12 were more likely to have a HbA1c decrease of ≥ 0.5 than those that did not achieve SVR12 (adjusted OR = 7.24, 95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2DM, successful treatment with DAA was associated with a significant reduction in HbA1c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore, the presence of T2DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.

Race affects SVR12 in a large and ethnically diverse hepatitis C‐infected patient population following treatment with direct‐acting antivirals: Analysis of a single‐center Department of Veterans Affairs cohort

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. HCV cure has been linked to improved patient outcomes. In the era of direct‐acting antivirals (DAAs), HCV cure has become the goal, as defined by sustained virological response 12 weeks (SVR12) after completion of therapy. Historically, African‐Americans have had lower SVR12 rates compared to White people in the interferon era, which had been attributed to the high prevalence of non‐CC interleukin 28B (IL28B) type. Less is known about the association between race/ethnicity and SVR12 in DAA‐treated era. The aim of the study is to evaluate the predictors of SVR12 in a diverse, single‐center Veterans Affairs population. We conducted a retrospective study of patients undergoing HCV therapy with DAAs from 2014 to 2016 at the VA Greater Los Angeles Healthcare System. We performed a multivariable logistic regression analysis to determine predictors of SVR12, adjusting for age, HCV genotype, DAA regimen and duration, human immunodeficiency virus (HIV) status, fibrosis, nonalcoholic fatty liver disease (NAFLD) fibrosis score, homelessness, mental health, and adherence. Our cohort included 1068 patients, out of which 401 (37.5%) were White people and 400 (37.5%) were African‐American. Genotype 1 was the most common genotype (83.9%, N = 896). In the adjusted models, race/ethnicity and the presence of fibrosis were statistically significant predictors of non‐SVR. African‐Americans had 57% lower odds for reaching SVR12 (adj.OR = 0.43, 95% CI = 1.5‐4.1) compared to White people. Advanced fibrosis (adj.OR = 0.40, 95% CI = 0.26‐0.68) was also a significant predictor of non‐SVR. In a single‐center VA population on DAAs, African‐Americans were less likely than White people to reach SVR12 when adjusting for covariates.

Impact of sustained virologic response on chronic kidney disease progression in hepatitis C

AIM To determine how sustained virological response at 12 wk (SVR12) with direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection affects chronic kidney disease (CKD) progression. METHODS A retrospective analysis was performed in patients aged ≥ 18 years treated for HCV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HCV from 2011-2013 who did not undergo HCV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for co-variates. RESULTS Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate (eGFR) one-year after HCV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 mL/min ± 0.75 mL/min per 1.73 m2 compared to a decline in eGFR of 11.0 mL/min ± 2.81 mL/min per 1.73 m2 in patients who did not achieve SVR12 (P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, CKD stage prior to treatment, diuretic use or other co-morbidities. The decline in eGFR in those with untreated HCV over 2 years was 2.8 mL/min ± 1.0 mL/min per 1.73 m2, which was not significantly different from the eGFR decline noted in HCV-treated patients who achieved SVR12 (P = 0.43). CONCLUSION Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.