Mortality is not increased in SARS-CoV-2 infected persons with hepatitis C virus infection.

BACKGROUND: Impact of SARS-CoV-2 infection upon hospitalization, intensive care unit (ICU) admissions and mortality in persons with hepatitis C virus (HCV) infection is unknown. METHODS: We used the Electronically Retrieved Cohort of HCV infected Veterans (ERCHIVES) database to determine the impact of HCV infection upon the rates of acute care hospitalization, ICU admission and all-cause mortality. We identified Veterans with chronic HCV infection and propensity score matched controls without HCV in ERCHIVES. We excluded those with HIV or hepatitis B virus coinfection. RESULTS: We identified 975 HCV+ and 975 propensity score matched HCV- persons with SARS-CoV-2 infection. Mean FIB-4 score (±SD) was higher in those with HCV (1.9 ± 2.1 vs 1.2 ± 0.9; P < .0001) and a larger proportion of those with HCV had cirrhosis (8.1% vs 1.4%; P < .0001). A larger proportion of HCV+ were hospitalized compared to HCV- (24.0% vs 18.3%; P = .002); however, those requiring ICU care and mortality were also similar in both groups (6.6% vs 6.5%; P = .9). Among those with FIB-4 score of 1.45-3.25, hospitalization rate/1000-person-years was 41.4 among HCV+ and 20.2 among HCV-, while among those with a FIB-4 > 3.25, the rate- was 9.4 and 0.6 (P < .0001). There was no difference in all-cause mortality by age, gender, FIB-4 score, number of comorbidities or treatment with remdesivir and/or systemic corticosteroids. CONCLUSIONS: HCV+ persons with SARS-CoV-2 infection are more likely to be admitted to a hospital. The hospitalization rate also increased with higher FIB-4 score. However, admission to an ICU and mortality are not different between those with and without HCV infection.

Rates and characteristics of SARS-CoV-2 infection in persons with hepatitis C virus infection.

BACKGROUND: Rate of SARS-CoV-2 infection and impact of liver fibrosis stage upon infection rates in persons with hepatitis C virus (HCV) infection are unknown. METHODS: We retrospectively analysed the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established database of HCV-infected Veterans in care. We excluded those with missing FIB-4 score and those with HIV or hepatitis B virus co-infection. We determined the number of persons tested, proportion who tested positive for SARS-CoV-2 and the infection rate by age and liver fibrosis stage. RESULTS: Among 172,235 persons with HCV, 14,305 (8.3%) were tested for SARS-CoV-2 infection and 892 (6.2%) tested positive. Those with SARS-CoV-2 infection were older, more likely to be Black (55.2% vs 37.8%), obese (body mass index >30 kg/m2 36.2% vs 29.7%) and have diabetes or stroke (P < .0001 for all comparisons). Mean FIB-4 scores and proportion of persons with cirrhosis (based on a FIB-4 > 3.25) were similar in both groups. Incidence rate/1,000 tested persons was much higher among Blacks (88.4; 95% CI 81.1, 96.2) vs Whites (37.5; 95% CI 33.1, 42.4) but similar among those with cirrhosis (FIB-4 > 3.25). The rates were also similar among those who were untreated for HCV vs those treated with or without attaining a sustained virologic response. CONCLUSIONS: Testing rates among persons with HCV are very low. Persons with infection are more likely to be Black, have a higher body mass index and diabetes or stroke. The degree of liver fibrosis does not appear to have an impact on infection rate.

Treatment of HCV reduces viral hepatitis-associated liver-related mortality in patients: An ERCHIVES study.

BACKGROUND & AIMS: Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown. METHODS: We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR). RESULTS: Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27-0.30) for Group A; 1.44 (1.38-1.49) for Group B; and 0.06 (0.05-0.06) for Group C; (p <0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05-0.06) for those with SVR vs. 0.78 (0.74-0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09-0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08-0.11) were associated with reduced hazards of liver-related mortality. CONCLUSIONS: Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies. LAY SUMMARY: Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.

Hepatitis C virologic response in hepatitis B and C coinfected persons treated with directly acting antiviral agents: Results from ERCHIVES.

BACKGROUND: There are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. METHODS: All HCV infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. Logistic regression model was used to determine factors associated with SVR. RESULTS: Among 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pre-treatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). CONCLUSION: HBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. Though not statistically significant, the virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores.

Liver Fibrosis Progression and Mortality in Hepatitis B- and C-Coinfected Persons Treated With Directly Acting Antiviral Agents: Results From ERCHIVES.

For persons with baseline Fibrosis-4 1.46-3.25, cirrhosis incidence/1000 patient-years was 49.3 among hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfected and 18.2 among HCV monoinfected (P = .03). Cirrhosis risk was numerically higher but statistically nonsignificant among HBV/HCV coinfected (hazards ratio [HR] 1.51; 95% confidence intervals [CI], .37-6.05) but lower among those who attained sustained virologic response (HR, .52; 95% CI, .42-.63).

Hepatitis C Virus (HCV) Treatment With Directly Acting Agents Reduces the Risk of Incident Diabetes: Results From Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES).

BACKGROUND: The effects of interferon-based therapies for hepatitis C virus (HCV) upon the risk of diabetes are controversial. The effects of newer, directly acting antiviral agents (DAA) upon this risk are unknown. We sought to determine the effects of HCV treatment upon the risk and incidence of diabetes. METHODS: Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database for persons with chronic HCV infection (n = 242 680), we identified those treated with a pegylated interferon and ribavirin regimen (PEG/RBV, n = 4764) or a DAA-containing regimen (n = 21 279), after excluding those with diabetes at baseline, those with a human immunodeficiency virus or hepatitis B virus coinfection, and those treated with both PEG/RBV and DAA regimens. Age-, race-, sex-, and propensity score-matched controls (1:1) were also identified. RESULTS: Diabetes incidence rates per 1000 person-years were 20.6 (95% confidence interval [CI] 19.6-21.6) among untreated persons, 19.8 (95% CI 18.3-21.4) among those treated with PEG/RBV, and 9.89 (95% CI 8.7-11.1) among DAA-treated persons (P < .001). Among the treated, rates were 13.3 (95% CI 12.2-14.5) for those with a sustained virologic response (SVR) and 19.2 (95% CI 17.4-21.1) for those without an SVR (P < .0001). A larger reduction was observed in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for fibrosis severity score [FIB-4] < 1.25; 5.7 for FIB-4 1.26-3.25; 9.8 for FIB-4 >3.25). DAA treatment (hazard ratio [HR] 0.53, 95% CI .46-.63) and SVR (HR 0.81, 95% CI .70-.93) were associated with a significantly reduced risk of diabetes. DAA-treated persons had longer diabetes-free survival rates, compared to untreated and PEG/RBV-treated persons. There was no significant difference in diabetes-free survival rates between untreated and PEG/RBV-treated persons. The results were similar in inverse probability of treatment and censoring weight models. CONCLUSIONS: DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefits are more pronounced in persons with more advanced liver fibrosis.

Trends in Treatment Uptake and Provider Specialty for Hepatitis C Virus (HCV) Infection in the Veterans Affairs Healthcare System: Results From the Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES).

Between 2001 and 2017, 108133 persons (45.7% of diagnosed cases) were initiated on anti-hepatitis C virus treatment in the Veterans Affairs healthcare system. In 2017, nonphysician clinicians accounted for 22.2% of prescriptions, infectious diseases specialists for 14.9%, and gastroenterologists/hepatologists for 10.3%. In the pre-direct-acting antiviral era, they accounted for 7.2%, 26.7%, and 11.6%, respectively.

Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events.

BACKGROUND & AIMS: Infection with hepatitis virus C (HCV) is associated with an increased risk of cardiovascular disease (CVD) events. It is not clear whether treatment with direct-acting antiviral (DAA) agents affects risk of CVD. METHODS: We searched the Electronically Retrieved Cohort of HCV-Infected Veterans database for patients with chronic HCV infection (n = 242,680) and identified patients who had been treated with a pegylated interferon and ribavirin regimen (n = 4436) or a DAA-containing regimen (n = 12,667). Treated patients were matched for age, race, sex, and baseline values with patients who had never received treatment for HCV infection (controls). All subjects were free of any CVD event diagnosis of HCV infection at baseline. The primary outcome was incident CVD events, identified by International Classification of Diseases, Ninth Edition, Clinical Modification or International Classification of Diseases, Tenth Edition code, in the different groups and in patients with vs without a sustained virologic response to therapy. RESULTS: There were 1239 (7.2%) incident CVD events in the treated groups and 2361 (13.8%) events in the control group. Incidence rates were 30.9 per 1000 patient-years (95% CI 29.6-32.1) in the control group and 20.3 per 1000 patient-years (95% CI 19.2-21.5) in the treated groups (P < .0001). Treatment with pegylated interferon and ribavirin (hazard ratio 0.78; 95% CI 0.71-0.85) or a DAA regimen (hazard ratio 0.57; 95% CI 0.51-0.65) was associated with a significantly lower risk of a CVD event compared with no treatment (controls). Incidence rates for CVD events were 23.5 per 1000 patient-years (95% CI 21.8-25.3) in the group treated with the pegylated interferon and ribavirin regimen, 16.3 per 1000 patient-years (95% CI 14.7-18.0) in the group treated with a DAA regimen, and 30.4 (95% CI 29.2-31.7) in the control group. A sustained virologic response was associated with a lower risk of incident CVD events (hazard ratio 0.87; 95% CI 0.77-0.98). CONCLUSIONS: In an analysis of a cohort of HCV-infected veterans, treatment of HCV infection was associated with a significant decrease in risk of CVD events. Patients treated with a DAA regimen and patients who achieved sustained virologic responses had the lowest risk for CVD events.

Tricyclic antidepressant use and the risk of fibrosis progression in hepatitis C-infected persons: Results from ERCHIVES.

Recent preclinical studies have suggested an antifibrotic role for tricyclic antidepressants (TCA). Using the Electronically Retrieved Cohort of hepatitis C virus (HCV) Infected Veterans, we aimed to evaluate the impact of TCA use on fibrosis progression and development of hepatocellular carcinoma (HCC) among HCV-infected persons. Subjects were categorized according to use of TCAs, selective serotonin reuptake inhibitors (SSRI) or no antidepressants. TCAs or selective serotonin uptake inhibitors use was defined according to cumulative defined daily dose (cDDD), and categories were mutually exclusive. Subjects with HIV coinfection, hepatitis B surface antigen (HbsAg) positivity, cirrhosis or HCC at baseline were excluded. Outcomes were liver fibrosis progression measured by APRI scores and incident HCC. We utilized Cox proportional hazards regression to determine predictors of cirrhosis, defined as APRI > 2, and incident hepatocellular carcinoma (iHCC). Among 128 201 eligible HCV+ persons, 4% received TCAs, 43% received selective serotonin uptake inhibitors, and 53% received no antidepressants. Fewer TCAs users had drug abuse (34% and 43%) and alcohol abuse (32% vs 42%) compared to selective serotonin uptake inhibitor users. After adjusting for age, baseline APRI score, diabetes, hypertension, alcohol use, drug abuse and HCV RNA levels, TCAs use was associated with decreased risk of cirrhosis (hazard ratio [HR] = 0.77, 95% CI = 0.60, 0.99) and delayed time to development of cirrhosis, but not with decreased iHCC. In conclusion among a large cohort of HCV-positive Veterans, TCAs use was associated with decreased fibrosis progression and lower risk of developing cirrhosis. These data provide supportive evidence for the beneficial effects of TCAs on progression of liver fibrosis in patients with chronic HCV infection.

HCV treatment initiation in persons with chronic kidney disease in the directly acting antiviral agents era: Results from ERCHIVES.

BACKGROUND: Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. METHODS: We identified HCV+ persons in ERCHIVES between October 1999 and July 2016. We excluded HIV+ and HBsAg+ and those with missing baseline HCV RNA and baseline eGFR data. We identified persons initiated on any approved DAA-regimen through July 2016, by CKD stage. Logistic regression analyses were used to determine factors associated with treatment initiation. RESULTS: Among 83 706 evaluable persons, 21.1% initiated treatment. Rates differed significantly by CKD stage: 22.1% for eGFR>90 mL/min/1.73 m2 and CKD stage-2; 14.9% for CKD stage 3; and 8.0% for CKD stage-4/5. Those with CKD stage-3 were 33% less likely and those with CKD stage-4/5 were 60% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90 mL/min/1.73 m2 . Treatment initiation was less likely in HCV genotype 2 (OR 0.59; 95%CI 0.53,0.66) or 3 (OR 0.53; 95%CI 0.47,0.61) and those with diabetes (OR 0.87, 95% CI 0.81,0.94), cardiovascular disease (OR 0.77, 95% CI 0.70,0.84), alcohol abuse or dependence (OR 0.74, 95% CI 0.70,0.79) or cirrhosis (OR 0.86, 95% CI 0.80,0.92) at baseline. CONCLUSIONS: Persons with more advanced CKD are less likely to receive treatment for HCV despite recent data on safety and efficacy. Strategies are needed to improve treatment rates in the HCV/CKD population.

Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared With Untreated Hepatitis C Virus-Infected Persons: Results From ERCHIVES.

BACKGROUND: Interferon-based regimens are associated with a substantial survival benefit for persons infected with hepatitis C virus (HCV). Survival data with direct-acting antiviral agents are not available. We conducted this study to quantify the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) regimens upon mortality. METHODS: In the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans, we identified HCV-infected persons initiated on PrOD or LDV/SOF, excluding those with human immunodeficiency virus, hepatitis B surface antigen positivity, hepatocellular carcinoma, or missing HCV RNA or FIB-4 scores. For each case, we identified a propensity score-matched control never initiated on treatment. Primary outcome was survival. Outcomes were assessed using frequency of events, Kaplan-Meier curves, and Cox proportional hazards regression analyses. RESULTS: We identified 1473 persons on PrOD, 5497 on LDV/SOF, and 6970 propensity score-matched untreated persons. Treated persons were more likely to be obese and have cirrhosis, but less likely to have stage 3-5 chronic kidney disease (CKD), alcohol or drug abuse or dependence diagnosis, and anemia. The proportion of persons who died was higher in the untreated group compared with either treatment group (PrOD, 0.3%; LDV/SOF, 1.4%; untreated controls, 2.5%; P < .001). A significantly larger percentage of treated patients survived to 18 months of follow-up, compared with untreated controls (P < .001). In multivariable Cox regression analysis, treatment with either regimen (hazard ratio [HR], 0.43; 95% confidence interval [CI], .33-.57) and attainment of sustained virologic response (SVR) were associated with significantly lower mortality (HR, 0.57; 95% CI, .33-.99). CONCLUSIONS: Treatment with PrOD or LDV/SOF and SVR are associated with a significant mortality benefit, apparent within the first 18 months of treatment.

Risk of Acute Myocardial Infarction Among Hepatitis C Virus (HCV)-Positive and HCV-Negative Men at Various Lipid Levels: Results From ERCHIVES.

BACKGROUND: Risk of acute myocardial infarction (AMI) among hepatitis C virus (HCV)-positive versus HCV-negative persons with similar lipid levels is unknown. We determined incident AMI rates among HCV-positive and HCV-negative men among various lipid strata. METHODS: We created a propensity score matched (PSM) cohort and a low cardiovascular disease (CVD) risk cohort. Primary outcome was incident AMI rates by HCV status in each lipid strata using National Cholesterol Program guidelines for lipid strata. RESULTS: We identified 85863 HCV-positive and HCV-negative men in the PSM population. The incidence rates/1000 patient-years (95% confidence interval [CI]) for AMI among total cholesterol (TC) 200-239 stratum were 5.3 (4.89, 5.71) for HCV-positive versus 4.71 (4.42, 5) for HCV-negative men (P = .02) and for TC >240 mg/dL were 7.38 (6.49, 8.26) versus 6.17 (5.64, 6.71) (P = .02). For low-density lipoprotein cholesterol (LDL) of 130-159 mg/dL, AMI rates were 5.44 (4.97, 5.91) for HCV-positive and 4.81 (4.48, 5.14) for HCV-negative men (P = .03). The rise in risk with increasing lipid levels was greater in younger HCV-positive than in HCV-negative men (e.g., TC > 240 mg/dL: age >50 HR 1.38 [HCV-positive] and 1.12 [HCV-negative]; age ≤50 HR 1.6 [HCV-positive] and 1.29 [HCV-negative]), and more profoundly altered in HCV-positive men by lipid lowering therapy (change in HR with lipid-lowering therapy for TC >240 mg/dL from 1.82 to 1.19 [HCV-positive] from 1.48 to 1.03 [HCV-negative]). CONCLUSIONS: HCV-positive men have a higher risk of AMI than HCV-negative men at higher TC/LDL levels; this risk is more pronounced at a younger age. Lipid lowering therapy significantly reduces this risk, with more profound reduction among HCV-positive versus HCV-negative men at similar lipid levels.

Comparing Child-Pugh, MELD, and FIB-4 to Predict Clinical Outcomes in Hepatitis C Virus-Infected Persons: Results From ERCHIVES.

BACKGROUND: Identifying hepatitis C virus (HCV)-positive persons at high risk of early complications can help prioritize treatment decisions. We conducted this study to compare Child-Turcotte-Pugh (CP), MELD, and FIB-4 scores for predicting clinical outcomes and to identify those at low risk of complications. METHODS: Within electronically retrieved cohort of HCV-infected veterans, we identified HCV-positive persons and excluded those with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), prevalent hepatic decompensation (HD), hepatocellular carcinoma (HCC), and those treated for HCV. We calculated incidence rates for HD, HCC, and all-cause mortality at 1, 3, and 5 years after HCV diagnosis. Using receiver operating characteristic (ROC) curves, we determined the optimal cut-off values for each score for these outcomes. RESULTS: Among 21 116 persons evaluated, 89.7% were CP Class-A, 79.9% had MELD<9, and 43.4% had FIB-4<1.45. AUROC for HD at 1, 3, and 5 years was higher for FIB-4 (0.84-0.86) compared with MELD (0.70-0.76) (P < .001). AUROC for HCC at 1, 3, and 5 years was 0.81-0.82 for FIB-4 but 0.61-0.68 for CP and MELD scores. (P < .001) AUROC for all-cause mortality at 3 and 5 years was 0.65-0.68. The optimal cut-off scores to identify persons at low risk of complications were as follows: CP <5; MELD <8; FIB-4 <3 for HD and HCC, and <2 for all-cause mortality, below which <1.5% developed HD and HCC and ≤2.5% died at 3 years. CONCLUSIONS: FIB-4 score is a better predictor of HD and HCC in HCV-positive persons. A score of <3 is associated with a low risk of HD and HCC 1 and 3 years after HCV diagnosis.

Treatment adherence and virological response rates in hepatitis C virus infected persons treated with sofosbuvir-based regimens: results from ERCHIVES.

BACKGROUND & AIMS: Role of non-adherence upon virological success with newer oral regimens is unknown. We sought to determine the impact of treatment adherence upon virological outcomes in hepatitis C virus (HCV) infected persons on sofosbuvir (SOF)-based regimens, using pharmacy prescription data as a measure of adherence. METHODS: We analysed HCV infected persons in Electronically Retrieved Cohort of HCV Infected Veterans, who were initiated on SOF-based regimens, excluding those with human immunodeficiency virus, positive hepatitis-B surface antigen, hepatocellular carcinoma and missing HCV RNA. RESULTS: The final dataset included following regimens: SOF+simeprevir (SIM) (n = 1050), SOF+ledipasvir (LDV) (n = 974), SOF+ribavirin (RBV) (n = 663, genotype 2 or 3), and SOF+pegylated interferon (PEG)+RBV (n = 519, genotype 1 or 4). Those treated with a SOF-based regimen were older and more likely to have cirrhosis, diabetes, chronic kidney disease, higher HCV RNA levels, higher body mass index, compared with 1652 controls receiving a boceprevir-based (BOC) regimen. Sustained virological response (SVR12) rates for the SOF+SIM and SOF+LDV groups did not decline significantly even when as low as 50% of the full course was prescribed (except SOF+LDV, 90-99% prescriptions had SVR12 of 84.6%; n = 13). SOF+RBV for genotype 2/3 who received 50-80% of the prescriptions, 23/34 (67.6%) achieved SVR12. For persons with genotype 1/4 infection treated with SOF+PEG+RBV, no declines in SVR12 were seen with lower rates of prescriptions (40/43, or 93% SVR12 rate). CONCLUSIONS: Sofosbuvir-based treatment regimens are highly effective in achieving SVR12. This efficacy is not significantly affected when treated persons receive less than a full prescribed course of treatment.

Sofosbuvir-based regimens in clinical practice achieve SVR rates closer to clinical trials: results from ERCHIVES.

BACKGROUND & AIMS: Sofosbuvir is widely prescribed for treatment of HCV infection. We compared the sustained virologic response rates (SVR12) and the haematologic toxicity of various sofosbuvir-based regimens in routine clinical practice. METHODS: We used ERCHIVES (Electronically Retrieved Cohort of HCV infected Veterans) to identify HCV-infected persons initiated on sofosbuvir-based regimens. Treatment duration and regimen were defined as per labelling guidelines. We excluded persons with HIV, positive hepatitis-B surface antigen, hepatocellular carcinoma and missing HCV RNA. RESULTS: Among 4257 sofosbuvir-treated persons, sofosbuvir/simeprevir (30%), sofosbuvir/ledipasvir (29%) and sofosbuvir/ribavirin (23%) were the most common combinations prescribed. The mean age (SD) was 60.22 (6.3) years, 96% were male, 22.4% were black, 37.2% had cirrhosis, 29.7% were treatment-experienced; baseline mean HCV RNA was 6.73 log lIU/ml. Comorbidities included: 40.2% alcohol abuse or dependence, 39.7% drug abuse or dependence, 25.1% diabetes and 14.4% stage 3-5 chronic kidney disease. Overall, 86.7% completed a full course of treatment. Overall, SVR12 rates were 88-98% in the sofosbuvir/simeprevir group and 93-98% in the sofosbuvir/ledipasvir group and did not vary based on previous treatment history or cirrhosis at baseline. For genotype 2/3 patients treated with sofosbuvir/ribavirin, SVR12 rates ranged from 69 to 87% with lowest rates in treatment-experienced cirrhotics. For the sofosbuvir/simeprevir and sofosbuvir/ledipasvir groups, grade3/4 haematologic adverse events were uncommon; these trended back close to baseline values after completion of treatment. CONCLUSIONS: Sofosbuvir-based regimens in clinical practice are associated with SVR rates comparable to those seen in clinical trials and low rates of grade 3/4 haematological adverse events.

Virologic response and haematologic toxicity of boceprevir- and telaprevir-containing regimens in actual clinical settings.

Effectiveness, safety and tolerability of boceprevir (BOC) and telaprevir (TPV) in actual clinical settings remain unknown. We determined rates of sustained virologic response (SVR) and haematologic adverse effects among persons treated with BOC- or TPV-containing regimens, compared with pegylated interferon/ribavirin (PEG/RBV). Using an established cohort of hepatitis C virus (HCV)-infected persons, Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), we identified those treated with a BOC- or TPV-containing regimen and HCV genotype 1-infected controls treated with PEG/RBV. We excluded those with HIV coinfection and missing HCV RNA values to determine SVR. Primary endpoints were SVR (undetectable HCV RNA ≥12 weeks after treatment completion) and haematologic toxicity (grade 3/4 anaemia, neutropenia and thrombocytopenia). We evaluated 2288 persons on BOC-, 409 on TPV-containing regimen and 6308 on PEG/RBV. Among these groups, respectively, 31%, 43% and 9% were treatment-experienced; 17%, 37% and 14% had baseline cirrhosis; 63%, 54% and 48% were genotype 1a. SVR rates among noncirrhotics were as follows: treatment naïve: 65% (BOC), 67% (TPV) and 31% (PEG/RBV); treatment experienced: 57% (BOC), 54% (TPV) and 13% (PEG/RBV); (P-value not significant for BOC vs TPV; P < 0.0001 for BOC or TPV vs PEG/RBV). Haematologic toxicities among BOC-, TPV- and PEG/RBV-treated groups were as follows: grade 3/4 anaemia 7%, 11% and 3%; grade 4 thrombocytopenia 2.2%, 5.4% and 1.7%; grade 4 neutropenia 8.2%, 5.6% and 3.4%. SVR rates are higher and closer to those reported in pivotal clinical trials among BOC- and TPV-treated persons compared with PEG/RBV-treated persons. Haematologic adverse events are frequent, but severe toxicity is uncommon.