Electronically Retrieved Cohort Of HCV Infected Veterans Research Articles

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

BackgroundImpact of SARS‐CoV‐2 infection upon hospitalization, intensive care unit (ICU) admissions and mortality in persons with hepatitis C virus (HCV) infection is unknown.MethodsWe 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.ResultsWe 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.ConclusionsHCV+ 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.

BackgroundRate of SARS‐CoV‐2 infection and impact of liver fibrosis stage upon infection rates in persons with hepatitis C virus (HCV) infection are unknown.MethodsWe 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.ResultsAmong 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.ConclusionsTesting 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.

285. Fibrosis Progression and Clinical Outcomes in HCV/HBV Coinfected Persons in the ERCHIVES Cohort

BackgroundProgression of liver disease and clinical outcomes in HCV/HBV coinfected persons and how they differ from HCV monoinfected persons and HCV infected persons with resolved HBV infection are not well characterized. We compared incidence of cirrhosis, hepatic decompensation and overall mortality in these three groups.MethodsUsing the Electronically Retrieved Cohort of HCV-infected Veterans (ERCHIVES), we identified those with HCV infection only, HCV/HBV coinfection (HbsAg or HBV DNA or both positive) or HCV with resolved HBV (HbcAb+ in absence of HbsAg or HBV DNA positivity). We excluded those with HIV coinfection or hepatocellular carcinoma at or before baseline, and those who received any HCV or HBV treatment. Incident rates (95% CI) were determined for cirrhosis, first hepatic decompensation event and overall mortality in the three groups.ResultsWe identified 60,368 HCV monoinfected (Gp A), 151 HCV/HBV coinfected (Gp B) and 19,802 HCV infected with resolved HBV infection (Gp C). Mean age was 61.0, 60.9, and 63.0 years in the three groups and 96.5%, 96.0%, and 97.9% were males. Median baseline FIB-4 index was 2.0, 2.2, and 2.1, respectively. Incident cirrhosis (among those without cirrhosis at baseline) was increased 2- to 2.5-fold in HCV/HBV coinfected persons with baseline FIB-4 of 1.46–3.25. Hepatic decompensation and mortality were also increased several-fold in the HCV/HBV coinfected who had minimal or mild/moderate fibrosis at baseline. However, among those with cirrhosis at baseline, the difference was small among HCV/HBV coinfected and the other groups.ConclusionHCV/HBV coinfected persons with minimal or mild/moderate fibrosis at baseline have a much higher risk of developing cirrhosis, hepatic decompensation and mortality. However, once cirrhosis has is established, the difference is diminished. This underscores the need to intervene early when HCV/HBV coinfected persons still have minimal or mild/moderate fibrosis. Disclosures All authors: No reported disclosures.

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).

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. 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. 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. DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefits are more pronounced in persons with more advanced liver fibrosis.

930. HCV Treatment Is Associated With a Reduced Risk of Cardiovascular Disease Events: Results From ERCHIVES

BackgroundStudies reporting on the association between HCV and cardiovascular disease (CVD), and effect of HCV treatment upon future risk of CVD have shown mixed results.MethodsWithin ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans), we identified all persons treated for ≥7 weeks and propensity-score-matched group who never received HCV treatment. We excluded those with HIV, HBV, or previously diagnosed CVD. Incidence rate (per 1,000 person-years) and risk factors for CVD events (Cox proportional hazards analysis) were determined for various treatment groups. CVD events were identified using ICD-9CM/ICD-10 codes. Kaplan–Meier plots were generated to show and compare CVD-free survival by treatment status and attainment of SVR.ResultsAmong 32,575 treated and same number of untreated persons in the final dataset, median age was 58 years, 27% were Black race, and 96% were male. The incidence rate for CVD events/1,000 person-years (95% CI) among the treated was 19.10 (17.79, 20.50) vs. 32.37 (30.51, 34.33) among the untreated (P < 0.01). Treatment with a DAA regimen (vs. PEG/RBV; HR [95% CI] 0.68 [0.53,0.88]) and achieving SVR (HR [95% CI] 0.76 [0.63,0.92]) were associated with a lower risk of incidence CVD event (table). Kaplan–Meier curves demonstrated that untreated persons had a shorter CVD event-free survival during 30 months of follow-up compared with the treated persons. (figure; log-rank P < 0.0001)ConclusionHCV treatment is associated with a reduction in incident CVD events. Directly acting antiviral regimens (vs. PEG/RBV) and attainment of SVR (vs. no SVR) are associated with a lower risk of incident CVD events. Disclosures A. Ajwad Butt, Gilead: Grant Investigator, Research grant.

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.

Proton pump inhibitors are associated with accelerated development of cirrhosis, hepatic decompensation and hepatocellular carcinoma in noncirrhotic patients with chronic hepatitis C infection: results from ERCHIVES

Proton pump inhibitors are among the most commonly prescribed medications in the United States. Their safety in cirrhosis has recently been questioned, but their overall effect on disease progression in noncirrhotic patients with chronic liver disease remains unclear. To determine the impact of proton pump inhibitors on the progression of liver disease in noncirrhotic patients with hepatitis C virus (HCV) infection. Using the electronically retrieved cohort of HCV-infected veterans (ERCHIVES) database, we identified all subjects who received HCV treatment and all incident cases of cirrhosis, hepatic decompensation and hepatocellular carcinoma. Proton pump inhibitor use was measured using cumulative defined daily dose. Multivariate Cox regression analysis was performed after adjusting univariate predictors of cirrhosis and various indications for proton pump inhibitor use. Among 11 526 eligible individuals, we found that exposure to proton pump inhibitors was independently associated with an increased risk of developing cirrhosis (hazard ratio [HR]: 1.32; 95% confidence interval: [1.17, 1.49]). This association remained robust to sensitivity analysis in which only patients who achieved sustained virologic response were analysed as well as analysis excluding those with alcohol abuse/dependence. Proton pump inhibitor exposure was also independently associated with an increased risk of hepatic decompensation (HR: 3.79 [2.58, 5.57]) and hepatocellular carcinoma (HR: 2.01 [1.50, 2.70]). In patients with chronic HCV infection, increasing proton pump inhibitor use is associated with a dose-dependent risk of progression of chronic liver disease to cirrhosis, as well as an increased risk of hepatic decompensation and hepatocellular carcinoma.

The Incidence of Hepatocellular Carcinoma Is not Increased in Individuals with Chronic Hepatitis C After Treatment with Interferon-free Regimens: an ERCHIVES Study

BackgroundSustained virologic response (SVR) after interferon-based treatment for chronic hepatitis C virus (HCV) infection has been strongly linked with decreased incidence of hepatocellular carcinoma (HCC). Surprisingly, several recent studies have reported higher rates of HCC in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging due to the heterogeneous populations and methodologies of these reports. As such, we sought to investigate whether DAA use is associated with increased rates of incident HCC.MethodsUsing the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database, we identified 17,836 patients without a prior diagnosis of HCC and divided them into 3 groups based on treatment: (a) pegylated interferon and ribavirin (IFN) (n = 3,534); (b) DAA-based therapy (n = 5,734); and (c) an untreated control group (n = 8,468). Predictors of HCC were identified using multivariate Cox proportional hazards analysis. HCC-free survival in cirrhotics was assessed by Kaplan–Meier analysis.ResultsSVR was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. In our cohort, the incidence rate of HCC was not different between IFN and DAA groups (7.48/1000 vs. 7.92/1000 patient-years of follow-up; P = 0.72). Moreover, DAA treatment was not associated with an increased risk of HCC (HR 1.16; [95% CI: 0.79, 1.71]) compared to IFN treatment. Other risk factors for HCC included older age, alcohol abuse/dependance history, smoking history, HCV genotype 3 infection, proton-pump inhibitor use, AFP > 20, and cirrhosis. Notably, among cirrhotics who achieve SVR, HCC-free survival was not different between IFN and DAA treated groups, and both groups had significantly improved HCC-free survival compared with untreated patients.ConclusionAmong cirrhotic patients with HCV, DAA treatment is associated with a comparable risk of HCC to IFN treatment. Furthermore, the rate of HCC after SVR by any treatment was significantly lower than for those untreated or who failed to achieve SVR. Previously reported increases in HCC associated with DAA treatment appear to be explained by the presence of pre-existing risk factors for HCC.Disclosures R. T. Chung, Gilead: Investigator, Research grant; Abbvie: Investigator, Research grant; Merck: Investigator, Research grant; Janssen: Investigator, Research grant; A. Butt, Merck: Investigator, Grant recipient

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

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. 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. 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). Treatment with PrOD or LDV/SOF and SVR are associated with a significant mortality benefit, apparent within the first 18 months of treatment.

Fibrosis Progression and Incidence of Cirrhosis and Hepatic Decompensation in Persons Treated with Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir: Results from ERCHIVES

Background Data are limited regarding the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir regimen (PrOD) upon the rate of liver fibrosis progression and incidence of cirrhosis and hepatic decompensation after treatment for HCV.Methods Within ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans), we identified HCV infected persons treated with PrOD and treatment-na•ve controls to determine the effect of PrOD treatment upon subsequent progression of fibrosis and incident cirrhosis and hepatic decompensation. Controls were propensity-score matched based on demographic and clinical characteristics. We excluded those with HIV coinfection, positive HBsAg, hepatocellular carcinoma at baseline and those with missing HCV RNA or FIB-4 scores. Fibrosis progression and liver cirrhosis were assessed using the FIB-4 score.ResultsThe final propensity score matched sample included 1,473 PrOD-treated individuals, and an equal number of matched, untreated controls. PrOD-treated patients had significantly reduced median FIB-4 scores over time, compared with controls (median absolute change in FIB-4 = -0.7 [IQR -1.51, -0.3] vs. +0.06 [IQR -0.38, 0.49]; P < 0.0001). Compared with matched controls, PrOD-treated patients had an 86% relative reduction in the risk of incident cirrhosis over 2,241 patient-years of follow-up (adjusted HR 0.14 [95% CI 0.08-0.23]). Treatment with PrOD was also associated with delayed time to first hepatic decompensation event (P < 0.001). In sensitivity analysis, the exclusion of patients with baseline cirrhosis did not materially alter the estimates of effect.Conclusion Treatment with PrOD is associated with a significant reduction in fibrosis progression, a longer time to the development of cirrhosis, and reduced risk of hepatic decompensation. Our results demonstrate the long-term anti-fibrotic benefits associated with PrOD therapy for chronic HCV.Disclosures J. Kort, Abbvie: Employee and Shareholder, Salary; A. Butt, Merck: Investigator, Grant recipient

Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES.

Statins are associated with delayed fibrosis progression and a reduced risk of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV). Limited data exist regarding the most effective type and dose of statin in this population. We sought to determine the impact of statin type and dose upon fibrosis progression and HCC in patients with HCV. Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database, we identified all subjects initiated on HCV antibody (anti-HCV) therapy from 2001 to 2014, and all incident cases of cirrhosis and HCC. Statin use was measured using cumulative defined daily dose (cDDD). Multivariable Cox's proportional hazard regression models were used to examine the relationship between statin use and development of cirrhosis and HCC. Among 9,135 eligible subjects, 1,649 developed cirrhosis and 239 developed incident HCC. Statin use was associated with a 44% reduction in development of cirrhosis (adjusted hazard ratio [HR]: 0.6; 95% confidence interval [CI]: 0.53, 0.68). The adjusted HRs (95% CI) of fibrosis progression with statin cDDD 28-89, 89-180, and >180 were 0.74 (0.59, 0.93), 0.71 (0.59, 0.88), and 0.6 (0.53, 0.68), respectively. Mean change in FIB-4 score with atorvastatin (n = 944) and fluvastatin (n = 34) was -0.17 and -0.13, respectively (P = 0.04), after adjustment for baseline FIB-4 score and established predictors of cirrhosis. Statin use was also associated with a 49% reduction in incident HCC (adjusted HR: 0.51; 95% CI: 0.36, 0.72). A similar dose-response relationship was observed. In patients with chronic HCV, statin use was associated with a dose-dependent reduction in incident cirrhosis and HCC. Atorvastatin and fluvastatin were associated with the most significant antifibrotic effects, compared with other statins. (Hepatology 2016;64:47-57).

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

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. 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. 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. 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.

Liver Fibrosis Progression in Hepatitis C Virus Infection After Seroconversion

Knowing the rate of liver fibrosis progression in hepatitis C virus (HCV)-infected persons can help inform patients and providers (clinicians, medical institutions or organizations, and third-party payers) in making treatment decisions. To determine the rate and factors associated with liver fibrosis progression and hepatic decompensation in persons after acquiring HCV infection. Secondary data analysis of persons in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a national Veterans Affairs (VA) database, between 2002 and 2012. Among 610 514 persons in ERCHIVES (half were HCV positive), we identified those with an initial negative and subsequent positive test result for HCV antibody and positive HCV RNA test result (HCV+). Controls had 2 negative HCV antibody test results (HCV-) in a comparable time frame and were matched 1:1 on age (in 5-year blocks), race, and sex. We excluded persons with human immunodeficiency virus, hepatitis B, less than 24 months of follow-up, hepatocellular carcinoma, and cirrhosis at baseline. Progression of liver fibrosis as estimated by the Fibrosis-4 (FIB-4) index; development of cirrhosis, defined by a FIB-4 score greater than 3.5; and development of hepatic decompensation. The evaluable data set consisted of 1840 persons who were HCV+ and 1840 HCV- controls. The HCV+ persons were younger and had a lower mean (SD) body mass index (27.39 [5.51] vs 29.49 [6.16]; P < .001), a higher prevalence of alcohol and drug abuse and dependence diagnoses, and higher serum aminotransferase levels, but had a lower prevalence of diabetes and hypertension. Fibrosis progression started early after infection among HCV+ persons and tapered off after 5 years. A total of 452 cirrhosis and 85 hepatic decompensation events were recorded. After 10 years of follow-up, HCV+ persons were more likely to have a diagnosis of cirrhosis compared with HCV- controls (18.4% vs 6.1%). Nine years after diagnosis of cirrhosis, hepatic decompensation events were uncommon but had a higher rate in the HCV+ group (1.79% vs 0.33%). Persons who seroconverted for HCV have a more rapid progression of liver fibrosis and accelerated time to development of cirrhosis after seroconversion compared with HCV- controls. Fibrosis progression occurs early after infection; however, hepatic decompensation is uncommon after diagnosis of cirrhosis.

Predictors of Mortality among United States Veterans with Human Immunodeficiency Virus and Hepatitis C Virus Coinfection.

Background. Understanding the predictors of mortality in individuals with human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfection can be useful in management of these patients. Methods. We used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) for these analyses. Multivariate Cox-regression models were used to determine predictors of mortality. Results. Among 8,039 HIV infected veterans, 5251 (65.3%) had HCV coinfection. The all-cause mortality rate was 74.1 (70.4–77.9) per 1000 person-years (PY) among veterans with HIV/HCV coinfection and 39.8 (36.3–43.6) per 1000 PY for veterans with HIV monoinfection. The multivariable adjusted hazard ratio (95% confidence interval) of all-cause mortality for HCV infection was 1.58 (1.36–1.84). Positive predictors of mortality included decompensated liver disease (2.33 (1.98–2.74)), coronary artery disease (1.74 (1.32–2.28)), chronic kidney disease (1.62 (1.36–1.92)), and anemia (1.58 (1.31–1.89)). Factors associated with reduced mortality included HCV treatment (0.41 (0.27–0.63)) and higher CD4 count (0.90 (0.87–0.93) per 100 cells/μL higher count). Data were insufficient to make informative analyses of the role of HCV virologic response. Conclusion. HCV coinfection was associated with substantial increased risk of mortality among HIV infected veterans. HCV treatment was associated with significantly lower risk of mortality.

Hepatitis C virus treatment and survival in patients with hepatitis C and human immunodeficiency virus co‐infection and baseline anaemia

The impact of pretreatment anaemia on survival in individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection is not known. Moreover, HCV treatment is offered less frequently to individuals with anaemia, due to haematological side effects of the treatment regimen. This study aimed to determine the effect of HCV treatment on survival among HCV/HIV co-infected individuals with pretreatment anaemia using the Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES). Individuals with HCV/HIV co-infection were included in current analyses. Participants were considered treated if they were prescribed ≥ 4 weeks of HCV treatment. All-cause mortality data were obtained using record linkage. Survival analyses were performed using Cox proportional hazard models. Among 5000 HCV/HIV co-infected individuals, 1671 (33.4%) had pretreatment anaemia. In a follow-up period of up to 7 years (19,500 person-years), individuals with anaemia had significantly higher mortality rate compared with those without anaemia [144.2 (95% CI: 134.5-154.7) vs 47.5 (44.0-51.2) per 1000 person-years, respectively]. Among individuals with anaemia, HCV treatment was associated with significantly lower mortality rate [66.6 (44.3-100.2) vs 149.6 (139.2-160.5) per 1000 person-years, for treated vs untreated, respectively]. Treatment remained associated with substantial survival benefit after taking into account the effect of multiple comorbidities (hazards ratio: 0.34, 95% CI: 0.21-0.62). These data suggest that HCV/HIV co-infected individuals with pretreatment anaemia have significantly higher mortality compared with those without anaemia. HCV treatment is associated with substantial survival benefit in this group. Additional studies are needed to determine strategies to improve HCV treatment rates among this group.

HCV Infection and the Incidence of CKD

The risk of hepatitis C virus (HCV) infection upon incident chronic kidney disease (CKD) in the presence of traditional risk factors and renal-modifying therapy is not well known. National cohort study. HCV-infected and -uninfected veterans in ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) in 2001-2006. HCV infection. Incident CKD stages 3-5. We identified 18,002 patients with HCV infection and 25,137 controls with estimated glomerular filtration rate >60 mL/min/1.73 m(2) at baseline. HCV-infected patients had a lower prevalence of several CKD risk factors, including diabetes (22.9% vs 26.6%), hypertension (52.4% vs 60.8%), and dyslipidemia (39.3% vs 73.9%; P < 0.001). HCV infection was associated with a higher risk of developing CKD stages 3-5 (HR, 1.30; 95% CI, 1.23-1.37). Increasing age, hypertension, and diabetes were associated with significantly higher risks of developing CKD in HCV-infected patients and controls. Decompensated liver disease was a strong predictor of CKD in HCV-infected patients (HR, 3.37; 95% CI, 3.10-3.66) and HCV-uninfected controls (HR, 2.04; 95% CI, 1.84-2.25). In Kaplan-Meier analysis, HCV-infected persons had a shorter time to CKD. Lack of proteinuria data; small number of women. HCV infection is associated with higher risk and shorter time to CKD despite having a lower prevalence of many CKD risk factors. HCV-infected persons should have targeted monitoring for the development and progression of CKD.

Effect of hepatitis C virus and its treatment on survival

The effect of hepatitis C virus (HCV) and its treatment on survival is not well defined. We undertook this study to determine the effect of HCV and its treatment on survival in a national cohort of HCV-infected veterans and uninfected controls. We used a national sample of HCV-infected persons and HCV-uninfected controls from the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) to compare survival between the two groups. We also compared the effect of treatment and treatment duration on survival in the HCV-infected group. We used matched Cox proportional hazards model to determine the predictors of mortality. Kaplan-Meier survival plots were generated to determine and compare survival among HCV-infected and HCV-uninfected persons, and among treated and untreated HCV-infected persons.We identified 34,480 matched pairs of HCV-infected subjects and controls. HCV infection was independently associated with a higher risk of mortality (hazards ratio, 1.37; 95% confidence interval, 1.31-1.47). Subjects treated for 48 weeks or longer had the lowest mortality among HCV-infected subjects (hazards ratio, 0.41; 95% confidence interval, 0.27-0.64), whereas those who received less than 48 week of treatment had intermediate mortality (hazards ratio, 0.71 and 0.60 for 0-23 weeks and 24-47 weeks of treatment, respectively) compared with untreated subjects. HCV infection is associated with a substantial increase in mortality. Subjects who are initiated on treatment, and particularly those who proceed to finish a full course of treatment, have significantly reduced risk of mortality. Further studies are warranted to determine the effect of virological control on survival.