HCV-infected Participants Research Articles

#1050 Diabetes mellitus mediates the association between chronic hepatitis C virus infection and incidence of end-stage kidney disease

Abstract Background and Aims Chronic infection with the hepatitis C virus (HCV) is known to lead to extra-hepatic complications, notably affecting the kidneys. While prior research has established a link between chronic HCV infection and chronic kidney disease (CKD), there remains ongoing debate regarding whether this association is influenced by the presence of diabetes mellitus. Method This study, part of the REVEAL-HCV project in Taiwan, investigated the relationship between chronic HCV infection and end-stage kidney disease (ESKD). Initially, 23,820 individuals aged 30-65 from Taiwan were enrolled since 1991-1992. Data included physical exams, blood tests, and questionnaires covering sociodemographics, lifestyle, and comorbidities. The cohort was linked to Taiwan's National Health Insurance Research Database, providing extensive patient data. Hepatitis C status was determined by HCV RNA testing. ESKD was identified using ICD-9-CM codes from the health database. Covariates like age, sex, lifestyle factors, comorbidities, and lab results were considered. The study emphasized accurate diagnosis of diabetes based on insurance claims with well validation. The mediation analysis was done by constructing 2 logistic regression models, with one regressing the risk of ESKD on chronic HCV infection status and the other regressing the risk of ESKD on diabetes status. The direct and indirect (mediated through the risk of diabetes) effects of chronic HCV infection on the risk of ESKD were estimated using odds ratios. Confidence intervals for direct and indirect effects were estimated using 5000 bootstrapping replicates. Results The study examined 22,800 participants, with a mean age of 46.9 years. Among them, 738 were chronically infected with HCV. These HCV-infected participants were generally older, more likely to be female, had lower education levels, and higher prevalence of diabetes, hypertension, and CKD. During the 16.8-year median follow-up, covering 319,474 person-years, 378 end-stage kidney disease (ESKD) events occurred. The incidence of ESKD was higher in HCV-infected subjects (2.6%) compared to non-HCV-infected (1.6%). The univariate and multivariate-adjusted odds ratios (ORs) and 95% confidence interval for ESKD in HCV-infected participants were 2.06 (0.90-2.08) and 1.57 (1.01-2.44), respectively. HCV infection also showed a significant association with diabetes mellitus. The multivariable-adjusted OR for diabetes in HCV-infected individuals was 1.53 (1.31-1.78). Further, the study identified a diabetes-mediated pathway linking HCV infection to ESKD. In this pathway, HCV infection increased the odds of ESKD by 0.8%. This indirect pathway mediated by diabetes accounted for 16% of the overall association between HCV infection and ESKD with statistically significant. The direct pathway, though not statistically significant, indicated a 57% increased odds of ESKD in HCV-infected individuals compared to those without HCV. Conclusion Chronic HCV infection is linked to higher incidences of diabetes and ESKD. The mechanisms are intricate, with diabetes serving as a significant mediator in the pathway from HCV infection to ESKD.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

Screening of hepatitis B and C viral infection, recognition of risk factors, and immunization of patients against hepatitis B virus: a module developed for effective hepatitis control.

The continually increasing incidence of hepatitis, a worldwide health issue, in Pakistan, has highlighted the need to investigate the epidemiology factors and implement preventive measures accordingly. The purpose of this study was to scrutinize the prevalent and significantly associated risk factors of hepatitis in students and employees, screening them for hepatitis B and C virus and vaccinating them against HBV to make IUB hepatitis free. A total of 12,912 participants including students (n = 10,948) and employees (n = 1964) were screened for HBV and HCV via immunochromatographic test. Hepatitis- positive participants' blood samples were further tested and viral load was estimated by quantitative PCR. All the hepatitis-negative participants were vaccinated against HBV. The demographic and risk factors-related data were collected using the questionnaire. Statistical analysis (Chi-square test and bivariate regression analysis) was performed using SPSS software to explore any association between risk factors and hepatitis. Results indicated that 662/12912 participants (students = 478/10,948, employees = 184/1,964) tested positive for hepatitis. Among them, HCV was observed to be more prevalent than HBV among the study participants, employees, and students, and viral count was low in both HBV and HCV-infected participants. However, men were more affected than women. The studied risk factors represented higher frequency among hepatitis-positive participants relative to the hepatitis-negative participants. The Chi-square test revealed that students' gender, history of hepatitis in the family and relatives, dental treatment, sharing cosmetics and shaving blades were significant (p > 0.005) risk factors of hepatitis while in the employees group surgery and age were significant. Moreover, the reused of syringes was found to be associated with hepatitis in both groups. The bivariate analysis helped to identify various new risk factors which were independently, either positively or negatively, associated with hepatitis. Our study enabled us to recognize different risk factors of hepatitis among the target population. The information thus generated can be usefully applied in planning hepatitis awareness, targeted screening, and effective control programs for other target populations. In general, this module can be further utilized for any other disease.

Pharmacokinetics, Tolerability, and Safety of Glecaprevir/Pibrentasvir Co-formulated Bilayer Tablet Following Repeated Administration in Healthy Chinese Adults.

Glecaprevir (GLE)/pibrentasvir (PIB) is an all-oral, interferon- and ribavirin-free, pan-genotypic fixed-dose combination regimen approved for the treatment of all major genotypes of hepatitis C virus (HCV) infection in many countries worldwide. To support clinical development in China, an open-label, single-center phase 1 study was conducted to evaluate the pharmacokinetics, safety, and tolerability of GLE/PIB in healthy Chinese adults in Mainland China. Eighteen participants received 3 tablets of coformulated GLE/PIB 100/40mg once daily (QD) for 7 days. Following GLE/PIB 300mg/120mg administration, GLE and PIB reached maximum concentration in 4-5 hours with a terminal elimination half-life of 5.9 and 25 hours, respectively. Both GLE and PIB reached steady state by day 5, with no-to-minimal accumulation (≤17% higher). GLE/PIB exposures in healthy Chinese participants were similar to historical observations across phase 1 studies in healthy Western participants. GLE/PIB was safe and well-tolerated, with most adverse events being mild. These pharmacokinetics and safety data, together with existing global efficacy and safety data in healthy and HCV-infected Western participants, support the use of GLE/PIB 300mg/120mg QD in adult Chinese patients with chronic HCV infection.

Endotoxemia Associated with Liver Disease Correlates with Systemic Inflammation and T Cell Exhaustion in Hepatitis C Virus Infection.

Both acute and chronic hepatitis C virus (HCV) infections are characterized by inflammation. HCV and reduced liver blood filtration contribute to inflammation; however, the mechanisms of systemic immune activation and dysfunction as a result of HCV infection are not clear. We measured circulating inflammatory mediators (IL-6, IP10, sCD163, sCD14), indices of endotoxemia (EndoCab, LBP, FABP), and T cell markers of exhaustion and senescence (PD-1, TIGIT, CD57, KLRG-1) in HCV-infected participants, and followed a small cohort after direct-acting anti-viral therapy. IL-6, IP10, Endocab, LBP, and FABP were elevated in HCV participants, as were T cell co-expression of exhaustion and senescence markers. We found positive associations between IL-6, IP10, EndoCab, LBP, and co-expression of T cell markers of exhaustion and senescence. We also found numerous associations between reduced liver function, as measured by plasma albumin levels, and T cell exhaustion/senescence, inflammation, and endotoxemia. We found positive associations between liver stiffness (TE score) and plasma levels of IL-6, IP10, and LBP. Lastly, plasma IP10 and the proportion of CD8 T cells co-expressing PD-1 and CD57 decreased after initiation of direct-acting anti-viral therapy. Although associations do not prove causality, our results support the model that translocation of microbial products, resulting from decreased liver blood filtration, during HCV infection drives chronic inflammation that results in T cell exhaustion/senescence and contributes to systemic immune dysfunction.

HCV treatment initiation in the era of universal direct acting antiviral coverage - Improvements in access and persistent barriers.

Barriers to HCV treatment initiation persisted after the introduction of direct-acting antivirals (DAAs) in Canada among people who inject drugs (PWID); whether DAA universal coverage lifted these barriers remain unknown. We assessed the evolution of HCV treatment initiation and associated factors among PWID in Montreal, Canada, comparing eras of IFN-based regimens (2011-2013), of DAA restricted access (2014-02/2018), and universal coverage (03/2018-03/2020). We included chronically HCV-infected participants followed in a community-based PWID cohort in Montreal, Canada between 2011 and 03/2020 and collected data at 3-month intervals. Time-updated Cox regressions were conducted to examine 9 variables of interest associated with treatment initiation overall and for each of the three eras. Of 276 participants, 126 initiated treatment during follow-up. Yearly initiation increased from 3% in 2011 to 19% in 2016, and 54% in 2018. PWID aged >40 (vs. ≤40) were twice as likely to initiate treatment in 2014-02/2018 (HR: 2.02 95%CI: [1.24-3.28]) but not in other periods (2011-2013: 0.55 [0.25-1.22]; 03/2018-03/2020: 1.14 [0.59-2.22])). Odds of initiation were lower for men than women in all periods, with women three times more likely to be treated under universal coverage (0.30 [0.11-0.77] vs 2011-2013: 0.67 [0.25-1.78] and 2014-02/2018: 0.75 [0.42-1.35]). Recent incarceration was negatively associated with initiation throughout all periods (2011-2013: 0.57 [0.13-2.43]; 2014-03/2018: 0.39 [0.17-0.91]; 03/2018-03/2020: 0.25 [0.07-0.83]). Barriers associated with high injection frequency appear to have diminished since DAA introduction (2014-02/2018: 0.71 [0.42-1.20]; 03/2018-03/2020: 1.05 [0.52-2.11] vs. 2011-2013: 0.26 [0.08-0.88]). Contact with a primary care physician and engagement in opioid agonist therapy were positively associated with treatment initiation, though estimates were attenuated under universal coverage relative to previous eras. Treatment initiation rates have increased since the introduction of universal DAA coverage, though barriers such as incarceration persist.

Continued Low Rates of Hepatitis C Virus (HCV) Recurrence in HCV/HIV- and HCV-Infected Participants Who Achieved Sustained Virologic Response After Direct-Acting Antiviral Treatment: Final Results From the AIDS Clinical Trials Group A5320 Viral Hepatitis C Infection Long-term Cohort Study (V-HICS).

Final results from the long-term Viral Hepatitis C Infection Long-term Cohort Study (V-HICS) found low rates of hepatitis C virus (HCV) recurrence after direct-acting antiviral therapy in both HCV/human immunodeficiency virus (HIV)–coinfected (0.67/100 person-years) and HCV-infected (0.2/100 person-years) groups with >500 person-years of follow-up. Confirmed reinfections were in participants with HIV who reported high-risk behaviors.

End-stage liver disease in persons with hemophilia and transfusion-associated infections

Many persons with hemophilia were infected with hepatitis C and B viruses (HCV, HBV) and HIV, but the consequences of these transfusion-acquired infections are poorly defined. We estimated the risk of HCV-related end-stage liver disease (ESLD) and the associations of age, HBV, and HIV with that risk. All 1816 HCV-seropositive hemophilic patients at 16 centers were followed for up to 16 years. Of these, 624 were HIV(-) and 1192 were HIV-coinfected; 135 had persistent HBV surface antigenemia, 1374 had resolved HBV infection, and 287 were HBV-uninfected. ESLD was defined as bleeding esophageal varices, hepatic encephalopathy, persistent ascites, or death excluding nonhepatic causes of these conditions. Competing risk models were used to estimate the annual hazard rate and cumulative incidence of ESLD. Proportional hazards models were used to estimate relative hazards of ESLD with covariates. ESLD developed in 127 of the HCV/HIV-coinfected participants, with an estimated 16-year cumulative incidence of 14.0% (95% confidence interval [CI], 11.6%-16.4%). Without HIV, 10 HCV-infected participants developed ESLD, for a significantly lower cumulative incidence of 2.6% (95% CI, 1.0%-4.3%, P <.0001). ESLD risk increased steeply with age in both groups. With HIV, ESLD risk was increased 8.1-fold (95% CI, 1.9-35.2) with HBV surface antigenemia, 2.1-fold (95% CI, 1.3-3.3) with fewer than 0.2 x 10(9)/L (200/microL) CD4(+) lymphocytes, and 1.04-fold (95% CI, 1.03-1.06) per year of age. Thus, HIV is associated with a markedly increased risk of HCV-related ESLD for persons with hemophilia, particularly with HBV infection, low CD4(+) lymphocytes, or older age.

Motivations, facilitators and barriers to accessing hepatitis C treatment among people who inject drugs in two South African cities

BackgroundTreatment of hepatitis C (HCV) among people who inject drugs (PWID) is a critical component of efforts to eliminate viral hepatitis. A recent study found high HCV prevalence among PWID in two cities, Pretoria (84%) and Cape Town (44%). Very few (< 5%) HCV-infected individuals attended follow-up appointments. This sub-study explores differences between stated desire for cure and appointment attendance in light of perceived facilitators and barriers to HCV treatment and care access among PWID.MethodTwo sets of semi-structured interviews were implemented in a group of HCV-infected participants opportunistically sampled and recruited at harm reduction service sites. Initial interviews, conducted before the planned hospital appointment date, asked participants (N = 17, 9 in Pretoria and 8 in Cape Town) about past experiences of healthcare provision, plans to attend their referral appointment and perceived barriers and facilitators to seeking hepatitis treatment. Second interviews (n = 9, 4 in Pretoria, 5 in Cape Town), conducted after the planned referral appointment date, asked about appointment attendance and treatment experience. Trained social scientists with experience with PWID conducted the interviews which were recorded in detailed written notes. Data was thematically analysed in NVivo 11.ResultsDespite routine experiences of being stigmatised by the healthcare system in the past, most participants (n = 16, 94%) indicated a desire to attend their appointments. Attendance motivators included the desire to be cured, fear of dying and the wish to assist the research project. Perceived barriers to appointment attendance included fear of again experiencing stigmatisation and concerns about waiting periods and drug withdrawal. Perceived facilitators included the knowledge they would be treated quickly, and with respect and access to opioid substitution therapy. In the end, very few participants (n = 5) went to their appointment. Actual barriers to attendance included lack of finances, lack of urgency and forgetting and fatalism about dying.ConclusionsSouth Africa can learn from other countries implementing HCV treatment for PWID. Successful linkage to care will require accessible, sensitive services where waiting time is limited. Psychosocial support prior to initiating referrals that focuses on building and maintaining a sense of self-worth and emphasising that delayed treatment hampers health outcomes is needed.

Direct acting antiviral HCV treatment does not influence renal function.

HCV infection is associated with chronic kidney disease due to several mechanisms. Patients treated with interferon-based regimens demonstrate improved renal function and reduced incidence of chronic kidney disease. There is scarce evidence on the effect of direct acting antiviral regimens (DAAs) on renal function.We evaluated serial measures of renal function in a cohort of HCV-infected participants following completion of DAA-based treatment regimens.Measures of glomerular filtration rate (GFR) were estimated by the CKD-EPI equation. Data was recorded at end of treatment, and at 6-12 months, 12-24 months, and greater than 24 months following treatment completion. Group-based trajectory modeling was used to determine distinct GFR trajectories. Predictors of group membership were determined by multinomial regression analysis.Six trajectories were identified. One trajectory comprising 27% of the cohort demonstrated declining renal function and the others demonstrated no change in renal function over time. Baseline GFR did not predict SVR. Diabetes was associated with lower post-treatment GFR but patients with diabetes did not demonstrate a decrease in GFR over the period of evaluation. Cirrhosis and SVR were not significant predictors of GFR or GFR trajectory.There is no clinically relevant change in renal function among the majority of HCV-infected patients following completion of DAA-based treatments. Renal function does not influence the efficacy of DAA-based regimens. No consistent effect of DAA treatment and/or SVR on renal function was observed over a 2-year period following treatment completion.

Gaps in Viral Hepatitis Awareness in the United States in a Population-based Study

The benefits of highly effective therapies for chronic hepatitis B virus (HBV) or HCV infection can only be realized if infected individuals are identified and linked to care. We sought to identify gaps in awareness of diagnosis of HBV or HCV infection in a population-based sample of adults living in the United States (US). Using National Health and Nutrition Examinations Surveys data, we examined factors associated with HBV and HCV awareness. Participants surveyed from 2013 through 2016, age ≥20 years, with complete serologic analyses were included. HBV and HCV infections were defined by detection of serum HBsAg and anti-HCV, respectively. The primary outcome was awareness of infection-if participants replied "yes" to the question: "Has a doctor or other health professional ever told you that you have hepatitis B or C?" Of 14,745 participants, 68 had HBV and 211 had HCV infection, corresponding to prevalence values of 0.7% and 1.8%, respectively. Among HBV-infected persons, 32% reported awareness, and 28% of aware persons reported treatment. Among HCV-infected persons, 49% reported awareness, 45% of aware persons were treated, and 59% of treated patients achieved a sustained virologic response. Factors associated with greater awareness in multivariable models included US citizenship, higher education, and abnormal level of alanine aminotransferase for HBV-infected participants and non-Hispanic race, income above the poverty line, not married, and history of injection drug use for HCV-infected participants. Fewer than half of US adults with HBV or HCV infection are aware of their infection. Opportunities to increase awareness include provider education on cut-off values for abnormal level of alanine aminotransferase that should prompt screening, and expansion of existing screening interventions to under-recognized at-risk groups.

Abstract P064: Hepatitis C Infection Does Not Confer Elevated Risk of Chronic Kidney Disease Among Hispanics/Latinos: Findings From the Hispanic Community Health Study/Study of Latinos

Background: Chronic kidney disease (CKD) is estimated to affect 14% of adults in the US, and there is a continued need to identify actionable risk factors for impaired kidney function. Viral infections, including hepatitis C, have been demonstrated to cause secondary glomerular nephropathies, such as cryoglobulinemia. However, there has been conflicting evidence of causal associations between hepatitis C infection (HCV) and incident CKD. Furthermore, this relationship has not been well-studied in individuals of Hispanic or Latino descent. Hypothesis: We hypothesized that hepatitis C infection would be positively associated with incident CKD among Hispanics/Latinos. Methods: The study population was comprised of 11,120 participants of the Hispanic Community Health/Study of Latinos (HCHS/SOL), a cohort of adults sampled from four regions across the US. The cohort was 63% female, and mean age at baseline (2008-2011) was 47 years. HCV seropositivity was defined by detectable HCV antibodies and confirmation with either recombinant immunoblot assay (RIBA) testing or detectable HCV RNA. Individuals were determined to have CKD if they had estimated glomerular filtration rate &lt;60 mL/min/1.73 m 2 and albumin/creatinine ratio &gt;30mg/g. Those with prevalent CKD at baseline were excluded from the analysis. Logistic regressions were performed to estimate the odds ratios (OR) and 95% confident intervals [95% CI] of CKD at Visit 2 (2015-2017). Estimates were adjusted for demographic factors including age, gender, and self-reported heritage/background. Adjustments were also made for baseline educational attainment, smoking behaviors, body mass index, prevalent diabetes, and prevalent hypertension. Results: Over a median follow-up of 5.9 years, 202 cases of CKD occurred. Incident CKD was proportionally, more common among HCV infected individuals: 8 of 116 (6.9%) HCV seropositives experienced CKD, in contrast to 194 cases (1.8%) among the 11,004 non-infected individuals. The crude odds ratio of CKD among HCV infected participants was more than 4 times that of uninfected participants (OR 4.51 [1.97-10.34]). After adjustment for demographic factors, such as age and self-reported heritage, HCV infection continued to be associated with increased risk (OR 2.45 [1.02-5.89]). However, after further controlling for comorbid conditions, the odds ratio of CKD among HCV seropositives was attenuated and no longer significant (OR 2.25 [0.87-5.84]). Diabetes (OR 4.91 [2.73-8.83]) and hypertension (OR 2.22 [1.32-3.74]) were significantly associated with incident CKD. Conclusion: Among individuals of Hispanic/Latino origin, hepatitis C infection does not appear to be associated with increased risks of CKD. These results imply that primary and secondary prevention of diabetes and hypertension may hold higher priority than treatment HCV infection in efforts to prevent CKD among Hispanics/Latinos.

Similar Low Rates of HCV Recurrence in HCV/HIV- and HCV-Infected Participants who Achieved SVR After DAA Treatment: Interim Results From the ACTG A5320 Viral Hepatitis C Infection Long-term Cohort Study (V-HICS).

Hepatitis C virus (HCV) recurrence rates were similar between those with HCV/HIV co-infection (0.35/100 person-years) and HCV infection (0.42/100 person-years). Low rates of recurrence likely represent enrollment of an HIV population at low risk for recurrence. Care should be taken not to label all HCV/HIV co-infected patients as being at high risk for HCV recurrence.

Aflatoxin B1 exposure increases the risk of hepatocellular carcinoma associated with hepatitis C virus infection or alcohol consumption

BackgroundHepatocarcinogenicity of aflatoxin B1 (AFB1) has rarely been studied in populations with hepatitis C virus (HCV) infection and those without hepatitis B virus (HBV) and HCV infection (non-B-non-C). This case-control study nested in a community-based cohort aimed to investigate the HCC risk associated with AFB1 in HCV-infected and non-B-non-C participants. MethodsBaseline serum AFB1-albumin adduct levels were measured in 100 HCC cases and 1767 controls seronegative for anti-HCV and HBsAg (non-B-non-C), and another 103 HCC cases and 176 controls who were anti-HCV-seropositive and HBsAg-seronegative. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. ResultsIn 20 years of follow-up, the follow-up time to newly developed HCC was significantly shorter in participants with higher serum AFB1-albumin adduct levels in non-B-non-C (p = 0.0162) and HCV-infected participants (p < 0.0001). Within 8 years of follow-up, HCV infection and AFB1 exposure were independent risk factors for HCC. Elevated serum AFB1-albumin adduct levels were significantly associated with an increased risk of HCC newly developed within 8 years of follow-up in non-B-non-C participants with habitual alcohol consumption [crude OR (95% CI) for high vs. low/undetectable levels, 4.22 (1.16–15.37)] and HCV-infected participants [3.39 (1.31–8.77)], but not in non-B-non-C participants without alcohol drinking habit. AFB1 exposure remained an independent risk predictor for HCV-related HCC after adjustment for other HCC predictors (multivariate-adjusted OR [95% CI], 3.65 [1.32–10.10]). ConclusionsAFB1 exposure contributes to the development of HCC in participants with significant risk factors for cirrhosis including alcohol and HCV infection.

Incidence and predictors of single drug discontinuation according to the presence of HCV coinfection in HIV patients from the ICONA Foundation Cohort Study

To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation. Inverse probability weighting method to control for potential informative censoring was applied. Data from 10,637 patients were analyzed and 1,030 (9.7%) were HCV-Ab positive. Overall, there were 15,464 ART discontinuations due to any reason in 82,415.9 person-years of follow-up (PYFU) for an incidence rate (IR) of 18.8 (95% confidence interval [95%CI] 18.5-19.1) per 100 PYFU. No difference in IR of ART discontinuation due to any reason between HCV-infected and -uninfected patients was found. In a multivariable Poisson regression model, HCV-infected participants were at higher risk of darunavir/r discontinuation due to any reason (adjusted incidence rate ratio = 1.5, 95%CI 1.01-2.22, p value = 0.045) independently of demographics, HIV-related, ART and life-style factors. Among DRV/r treated patients, we found that HCV-viremic patients had twice the risk of ART discontinuation due to any reason than HCV-aviremic patients. In conclusion, HIV/HCV coinfected patients had a marginal risk increase of DRV/r discontinuation due to any reason compared with those without coinfection.

Hepatitis C virus infection and risk of Parkinson's disease: a systematic review and meta-analysis.

Hepatitis C virus (HCV) infection is one of the most common infections worldwide. Recent epidemiologic studies have suggested that patients with HCV infection might be at an increased risk of Parkinson's disease. However, the data on this relationship remain inconclusive. This meta-analysis was conducted with the aim to summarize all available evidence. A literature search was performed using MEDLINE and EMBASE database from inception to May 2017. Studies that reported relative risks, odd ratios (ORs), or hazard ratios comparing the risk of Parkinson's disease among HCV-infected patients versus participants without HCV infection were included. Pooled OR and 95% confidence interval were calculated using a random-effect, generic inverse variance method. Of 468 studies, five studies with 323 974 participants met our eligibility criteria and were included in the analysis. We found a higher risk of Parkinson's disease among patients with chronic HCV infection compared with participants without HCV infection with the pooled OR of 1.35 (95% confidence interval: 1.19-1.52). The statistical heterogeneity of this study was insignificant (I=3%). The main limitation of this meta-analysis was the limited accuracy of diagnosis in the primary studies as they were coding-based studies. This study demonstrated a higher risk of Parkinson's disease among HCV-infected patients. Further studies are required to clarify how this risk should be addressed in the clinical picture.

Pre-vaccine plasma levels of soluble inflammatory indices negatively predict responses to HAV, HBV, and tetanus vaccines in HCV and HIV infection

BackgroundChronic hepatitis C virus (HCV) and HIV infections are associated with impaired responses to neo-antigens contained in hepatitis A virus (HAV)/hepatitis B virus (HBV) vaccines, yet responsible mechanisms are unclear. MethodsACTG 5232 and CFAR0910 were clinical trials where pre-vaccine levels of plasma IP10, IL-6, sCD163 and sCD14 were measured in viremic HCV- (n = 15) or HIV-infected participants (n = 24) and uninfected controls (n = 10). Accelerated dosing HAV/HBV vaccine and tetanus booster were administered and antibody response was measured at 0, 1, 3, 8, and 24 weeks. ResultsPre-vaccine plasma IP10, IL-6, and sCD14 levels were elevated in both HCV and HIV-infected participants, while sCD163 was also elevated in HCV-infected participants. Pre-immunization tetanus antibody levels were lower in HIV-infected than in uninfected participants, while vaccine induced antibody responses were intact in HCV and HIV-infected participants. After HAV/HBV vaccination, HCV and HIV-infected participants had lower and less durable HAV and HBV antibody responses than uninfected controls.Among HCV-infected participants, pre-vaccine plasma IP10, IL-6, sCD14, and sCD163 levels inversely correlated with HAV, HBV and tetanus antibody responses after vaccine. Low HAV/HBV vaccine responses in HIV-infected participants prohibited assessment of immune correlates. ConclusionsDuring HCV and HIV infection markers of systemic inflammation reflect immune dysfunction as demonstrated by poor response to HAV/HBV neo-antigen vaccine.

HIV and hepatitis B and C co-infection among people who inject drugs in Zanzibar

BackgroundPeople who inject drugs are at high risk of acquiring hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV) due to risky injection and sexual practices. The objective of this study is to investigate the epidemiology of HIV, hepatitis B, and hepatitis C, and co-infection of these viruses among people who inject drugs in Zanzibar, Tanzania.MethodsWe used respondent-driven sampling to identify 408 participants, from whom we collected demographic data, information on sexual behaviours and injection drug practices, and blood samples for biological testing.ResultsPrevalence of hepatitis B surface antigenaemia, HCV, and HIV infection were 5.9, 25.4, and 11.3%, respectively. Of the participants who were hepatitis B surface antigen (HBsAg) positive, 33.5% were infected with HCV and 18.8% were infected with HIV. Of the HCV-infected participants, 29.3% were infected with HIV. Of the participants who were infected with HIV, 9.0% were HBsAg positive, 66.6% had HCV and 8.5% had both. None of the potential risk factors we measured were associated with HBsAg positivity. In contrast, older age and longer duration of injection drug use were independently associated with HCV infection. HCV infection among people who inject drugs is lower in Zanzibar than in other countries, but could rise without proper interventions.ConclusionsThese findings underscore the importance of screening people who inject drugs for HIV, HBsAg, and HCV; providing HBV vaccination to those who are eligible; initiating antiretroviral therapy for those who are co-infected with HIV/HBV and HIV/HCV; and introducing interventions that have high impact on reducing needle sharing.

High hepatitis C viral load and genotype 2 are strong predictors of chronic kidney disease

Associations between chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD) remain controversial. Here we aimed to clarify the association between HCV viral load, genotype, and CKD in 13,805 participants aged 30-65 years enrolled in the REVEAL-HCV Study, a community-based prospective study conducted in 1991-1992. CKD was defined by consecutive proteinuria oran estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2. Chronic HCV infection was defined by detectable HCV viral load. Logistic regression models were used to estimate prevalence odds ratio of CKD for chronic HCV infection after adjusting for other risk factors. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio (95% confidence interval) for CKD was significantly increased to 1.91 (1.27-2.88) for chronically HCV-infected participants. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio of CKD was 1.21 (0.54-2.70), 1.40 (0.66-3.00) and 3.44 (1.92-6.14) for chronically HCV-infected participants with low to high tertiles of serum HCV RNA, respectively. The adjusted prevalence odds ratios of CKD were 0.54 (0.17-1.75) for participants with low HCV RNA and genotype 1, 1.80 (0.84-3.87) for those with low HCV RNA and genotype 2, 2.62 (1.11-6.17) for those with high HCV RNA and genotype 1 and 4.99 (2.25-11.06) for those with high HCV RNA and genotype 2, compared with non-chronically HCV-infected participants. Thus, chronic HCV infection is associated with an increased risk of CKD. High HCV viral load and HCV genotype 2 are strong CKD predictors.

During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy

Immune activation predicts morbidity during hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, although mechanisms underlying immune activation are unclear. Plasma levels of autotaxin and its enzymatic product, lysophosphatidic acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown. We evaluated plasma levels of autotaxin, interleukin 6 (IL-6), soluble CD14 (sCD14), soluble CD163 (sCD163), and Mac2 binding protein (Mac2BP) during HCV infection, HIV infection, and HCV-HIV coinfection, as well as in uninfected controls, before and after HIV antiretroviral therapy (ART) initiation and during interferon-free HCV therapy. We observed greater plasma autotaxin levels in HCV-infected and HCV-HIV-coinfected participants, compared with uninfected participants, primarily those with a higher ratio of aspartate aminotransferase level to platelet count. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA levels in HCV-infected participants and with Mac2BP levels in HCV-HIV-coinfected participants, while in HIV-infected individuals, sCD14 levels correlated with Mac2BP levels. Autotaxin, LPA, and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting interferon-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting ART for HIV infection. In vitro, LPA activated monocytes. These data indicate that elevated levels of autotaxin and soluble markers of immune activation during HCV infection are partially reversible within 6 months of initiating interferon-free HCV treatment and that autotaxin may be causally linked to immune activation during HCV infection and HCV-HIV coinfection.