HCV-uninfected Patients Research Articles

Early initiation of glecaprevir/pibrentasvir after transplantation of HCV-viremic kidneys into HCV-negative recipients is associated with normalization in the altered inflammatory milieu.

Our previous Multicenter Trial to Transplant HCV-infected Kidneys (MYTHIC) observed that 100% of hepatitis C virus (HCV)-uninfected patients who received a kidney from an HCV-infected deceased donor were cured of HCV with an 8-week regimen of glecaprevir and pibrentasvir (G/P) initiated 2-5 days after transplantation. Following acute and chronic infection with HCV, immune system perturbations have been reported to persist even after viral clearance. The aim of this study was to determine whether HCV viremic kidney recipients in the MYTHIC study experience sustained changes in the soluble inflammatory milieu associated with HCV infection. Among nine patients with HCV viremia at day 3 post-kidney transplant (post-KT D3), IP-10, IL-10, MIP-1β, and IL-8 were significantly elevated from baseline. However, over the subsequent visits, there was a rapid, dramatic reduction back to baseline levels. Among seven patients who were not HCV viremic at post-KT D3, the cytokine levels did not significantly change. HCV-uninfected patients who received a kidney from an HCV-viremic deceased donor and were treated with early G/P experienced only transient alterations in the soluble inflammatory milieu. These data provide reassuring evidence that there appear to be no persistent cytokine disturbances with transient HCV viremia accompanying HCV donor positive/recipient negative kidney transplant.

Virologic Impact of Radiotherapy in Hepatitis C Virus-Infected Patients With Hepatocellular Carcinoma.

Hepatitis B virus (HBV) reactivation had been reported following radiotherapy in patients with hepatocellular carcinoma (HCC) along with limited data focused on patients infected with hepatitis C virus (HCV). Herein, we aimed to examine the virologic impact of radiotherapy in HCV-infected patients with HCC. In this case-control study, we identified all patients with unresectable HCC who received radiotherapy directed to the liver at MD Anderson from March 2009 through November 2018. Cases were defined as patients with HCV infection; controls were defined as patients without HCV infection. The case to control ratio was 1:3, and the subjects were matched by age, radiation dose, and fractionation or biologically effective dose of the radiation to the normal liver (α/β=2.5) and tumor (α/β=10). Thirty-two patients were studied, including 8 cases and 24 controls. No HCV reactivation was observed among the cases. Hepatitis flare was observed in 2 (25%) of 8 cases and 2 (8%) of 24 controls (p=0.25). The peak alanine aminotransferase level within 6 months after radiotherapy did not differ significantly between the cases and controls. Radiotherapy completion rates were similar in the two groups. This is the first report analyzing changes in HCV RNA levels after radiation for HCV-associated HCC. Our results suggest that the effects of radiotherapy on the liver function of HCV-infected patients with HCC do not differ from the HCV-uninfected patients. Therefore, it may not be necessary to monitor for HCV replication in HCV-infected patients receiving radiotherapy for HCC or to incorporate a biological variable based on HCV infection status in mathematical models of liver dose-volume constraints that predict radiation-induced liver disease.

Impact of diabetes on the risk of serious liver events and liver-related deaths in people living with HIV and hepatitis C co-infection: data from the ICONA Foundation Cohort Study.

To investigate the association between diabetes and HCV infection in persons living with HIV and to determine the impact of diabetes on the occurrence of serious liver events (SLEs) and liver-related deaths (LRDs) among HIV/HCV-co-infected patients. Patients were included if they had at least one follow-up visit. In a cross-sectional analysis among all HIV patients, we have investigated the association between diabetes and HCV infection. A further longitudinal analysis was performed in the population of HIV/HCV-co-infected free from SLE with FIB-4 index < 3.25 at baseline, using the following endpoints: (A) first event between SLE and LRD; (B) liver fibrosis progression defined as the first of two consecutive FIB-4 > 3.25; (C) first event between SLE, LRD, and liver fibrosis progression. Data from 15,571 HIV patients were analyzed: 2944 (18.9%) were HCV-Ab positive, and 739 (4.7%) presented a diagnosis of diabetes at their last follow-up. Among HIV/HCV-co-infected population, 107 patients had a diagnosis of diabetes. Viremic HCV-co-infected patients had 3-fold risk of diabetes onset than HCV-uninfected patients. On HIV/HCV-co-infected population, 85 SLEs/LRDs occurred over 20,410 person-years of follow-up (PYFU), for an incidence rate of 4.2/1000 PYFU (95%CI 3.4-5.2). Diabetic patients had 3-fold risk of pooled SLE and LRD than patients without diabetes. Furthermore, viremic HCV infection was independently associated with a higher risk of SLE/LRD (aIRR 3.35 [95%CI 1.14-9.83]). In HIV-infected patients, viremic HCV co-infection is a strong predictor of diabetes. Among HIV/HCV-co-infected population, diabetic patients showed an increased risk of SLE/LRD compared with those without diabetes.

Medical Intensive Care Unit Admission Among Patients With and Without HIV, Hepatitis C Virus, and Alcohol-Related Diagnoses in the United States: A National, Retrospective Cohort Study, 1997–2014

HIV, hepatitis C virus (HCV), and alcohol-related diagnoses (ARD) independently contribute increased risk of all-cause hospitalization. We sought to determine annual medical intensive care unit (MICU) admission rates and relative risk of MICU admission between 1997 and 2014 among people with and without HIV, HCV, and ARD, using data from the largest HIV and HCV care provider in the United States. Veterans Health Administration. Annual MICU admission rates were calculated among 155,550 patients in the Veterans Aging Cohort Study by HIV, HCV, and ARD status. Adjusted rate ratios and 95% confidence intervals (CIs) were estimated with Poisson regression. Significance of trends in age-adjusted admission rates were tested with generalized linear regression. Models were stratified by calendar period to identify shifts in MICU admission risk over time. Compared to HIV-/HCV-/ARD- patients, relative risk of MICU admission decreased among HIV-mono-infected patients from 61% (95% CI: 1.56 to 1.65) in 1997-2009% to 21% (95% CI: 1.16 to 1.27) in 2010-2014, increased among HCV-mono-infected patients from 22% (95% CI: 1.16 to 1.29) in 1997-2009% to 54% (95% CI: 1.43 to 1.67) in 2010-2014, and remained consistent among patients with ARD only at 46% (95% CI: 1.42 to 1.50). MICU admission rates decreased by 48% among HCV-uninfected patients (P-trend <0.0001) but did not change among HCV+ patients (P-trend = 0.34). HCV infection and ARD remain key contributors to MICU admission risk. The impact of each of these conditions could be mitigated with combination of treatment of HIV, HCV, and interventions targeting unhealthy alcohol use.

Impact of chronic hepatitis C virus infection on the survival of patients with oropharyngeal cancer.

Although an association between hepatitis C virus (HCV) infection and oropharyngeal cancers (OPCs) has been reported, to the authors' knowledge the clinical significance of this epidemiological finding remains unknown. Therefore, the authors analyzed the oncologic outcomes of HCV-infected patients with OPCs. In this retrospective cohort study, all patients with OPCs who were seen at The University of Texas MD Anderson Cancer Center between January 2004 and December 2015 were reviewed. HCV infection was defined as detectable HCV RNA in the serum. Five-year overall survival and progression-free survival rates were compared between patients infected with HCV and those not infected. A total of 161 patients were examined. The majority of the patients were white (141 patients; 88%) and male (132 patients; 82%) and had TNM stage III or IV disease (147 patients; 91%). The OPC involved the tonsils (83 patients; 52%), base of the tongue (67patients; 42%), or the soft palate (11 patients; 7%). The median follow-up after an OPC diagnosis was 3 years (range, 1-13 years). HCV-infected patients (25 patients) and HCV-uninfected patients (136 patients) were comparable with regard to smoking and alcohol status. In multivariate analysis, HCV was associated with increased cancer-specific mortality (hazard ratio, 2.15; 95% confidence interval, 1.08-6.85 [P = .02]) and risk of OPC progression (hazard ratio, 5.42; 95% confidence interval, 2.64-11.14 [P = .0008]) independent of age and cirrhosis status. Antivirals were administered after the diagnosis of OPC in 8 of the 25 HCV-infected patients (32%). HCV-infected patients who received antivirals were found to have better 5-year overall survival (70% vs 12%; P = .005) and progression-free survival (72% vs 19%; P = .005) compared with patients who did not. The early detection of HCV is important in patients with OPC because this infection may affect their oncologic outcomes. Cancer 2018;124:960-5. © 2017 American Cancer Society.

Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection

Hepatitis C virus (HCV) may increase the risk of hepatopancreaticobiliary tumors other than hepatocellular carcinoma (HCC). Previous case control studies indicated a possible association between HCV and intrahepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extrahepatic cholangiocarcinoma (ECC) or pancreatic cancer. We conducted a cohort study including 146,394 HCV-infected and 572,293 HCV-uninfected patients who received care at Veterans Affairs health care facilities. Patients with two visits between 1996 and 2004 with HCV infection were included, as were up to four matched HCV-uninfected subjects for each HCV-infected subject. Risks of ICC, ECC, pancreatic cancer, and HCC were assessed using proportional hazards regression. In the 1.37 million person-years of follow-up, which began 6 months after the baseline visit, there were 75 cases of ECC, 37 cases of ICC, 617 cases of pancreatic cancer, and 1679 cases of HCC. As expected, the risk of HCC associated with HCV was very high (hazard ratio [HR], 15.09; 95% confidence interval [95% CI], 13.44, 16.94). Risk for ICC was elevated with HCV infection 2.55; 1.31, 4.95), but risk for ECC was not significantly increased (1.50; 0.60, 1.85). Adjustments for cirrhosis, diabetes, inflammatory bowel disease, hepatitis B, alcoholism, and alcoholic liver disease did not reduce the risk for ICC below twofold. The risk of pancreatic cancer was slightly elevated (1.23; 1.02, 1.49), but was attenuated after adjusting for alcohol use, pancreatitis, and other variables. Findings indicated that HCV infection conferred a more than twofold elevated risk of ICC. Absence of an association with ECC was consistent in adjusted and unadjusted models. A significant association with pancreatic cancer was erased by alcohol use and other variables.

Effect of hepatitis C coinfection on discontinuation and modification of initial HAART in primary HIV care

To estimate the effect of hepatitis C (HCV) coinfection on time to first occurrence of either discontinuation or modification of initial HAART among previously antiretroviral therapy-naive HIV-infected patients. The analysis included antiretroviral therapy-naive patients who initiated HAART prior to November 2003 and were participating in the University of North Carolina Center for AIDS Research, HIV/AIDS observational clinical cohort. The effect of HCV status on time to first occurrence of either HAART discontinuation or modification was assessed using Kaplan-Meier survival estimates and multivariable proportional hazards regression was used to estimate hazard ratios. Of 296 patients initiating HAART, 22% were coinfected with HCV. During a median follow-up of 473 days [interquartile range (IQR), 167-940] from HAART initiation, 104 (35%) patients discontinued and 91 (31%) modified their first regimen. Reasons for discontinuation and modification were comparable by HCV serostatus and included treatment failure (12%), toxicity (41%), and barriers to adherence (47%). The median time to first occurrence of either discontinuation or modification among HCV-infected patients was 401 days (IQR, 128-821), and among HCV-uninfected patients was 493 days (IQR, 204-952) (P = 0.22). After adjustment for baseline demographic and clinical characteristics, the hazard ratio contrasting HCV-infected with HCV-uninfected patients was 1.39 (95% confidence interval, 0.95-2.03; P = 0.09). HCV coinfection was only marginally associated with a shorter duration of an initial HAART regimen, suggesting optimization of a first HAART regimen may not appreciably depend on HCV serostatus.

Treatment of Recurrent Hepatitis C in Liver Transplant Recipients

The course of hepatitis C is accelerated after transplantation, with an average of 25% of patients developing cirrhosis within 5 years of transplantation. Consequently, the 5- and 10-year graft survival rates in hepatitis C virus (HCV)-infected patients are significantly lower than in HCV-uninfected patients. Therapeutic interventions to prevent HCV recurrence and/or alter the rate of disease progression after transplantation are desirable. Prophylactic therapy in the form of polyclonal HCV antibodies has not been effective at prevention of HCV re-infection, but one study suggests that higher-dose therapy may modify the severity of early disease recurrence. Pre-emptive antiviral therapy has modest efficacy and generally is poorly tolerated. Live donor liver transplant recipients and recipients with low model of end-stage liver disease scores pretransplantation may tolerate pre-emptive therapy best. The treatment of recurrent established disease with a combination of interferon and ribavirin has been the mainstay of management. Similar to pre-emptive therapy, tolerance is reduced and dose reductions are frequent. The sustained virologic response rates are less than 45% in studies to date. Histologic and biochemical improvements generally are more frequent than virologic responses. Overall, the treatment of HCV disease in transplant recipients leaves much to be desired and there is an urgent need of new HCV therapies in this patient population.

Hepatitis C and progression of HIV disease.

Conflicting reports exist regarding the effect of hepatitis C virus (HCV) on the progression of human immunodeficiency virus (HIV) disease. To assess the effect of HCV infection on clinical and immunologic progression of HIV disease and immunologic response to highly active antiretroviral therapy (HAART). Prospective cohort study. University-based, urban HIV clinic in the United States. There were 1955 patients enrolled between January 1995 and January 2001 who were eligible for analysis because of having at least 1 return visit to the clinic and being free of acquired immunodeficiency syndrome (AIDS) at enrollment. Median (interquartile range) length of follow-up was 2.19 (1.00-3.50) years for HCV-infected and 2.00 (1.00-3.00) years for HCV-uninfected patients. Progression to an AIDS-defining illness, survival, and progression to a CD4 cell count below 200/microL; CD4 cell count change following initiation of effective HAART (resulting in a viral load of <400 copies/mL recorded at > or = 75% of measurements). No difference was detected in the risk of acquiring an AIDS-defining illness (HCV-infected patients, 231 events [26.4%] and HCV-uninfected patients, 264 events [24.4%]; relative hazard [RH], 1.03; 95% confidence interval [CI], 0.86-1.23) or in the risk of death (HCV-infected patients, 153 deaths [17.5%] and HCV-uninfected patients, 168 deaths [15.5%]; RH, 1.05; 95% CI, 0.85 -1.30). Although an increased risk of death was detected in the subgroup of 429 HCV-infected patients with a baseline CD4 cell count of 50/microL through 200/microL (RH, 1.51; 95% CI, 1.01-2.27), after adjustment for exposure to HAART and its effectiveness in a multivariate Cox regression analysis, death was not independently associated with HCV infection in this subgroup (RH, 1.01; 95% CI, 0.65-1.56). Similarly, in those receiving effective HAART (n = 208), there was no difference in the increase in CD4 cell count or CD4 percentage during HAART in HCV-infected compared with HCV-uninfected patients. Among patients in this urban US cohort, we did not detect evidence that HCV infection substantially alters the risk of dying, developing AIDS, or responding immunologically to HAART, especially after accounting for differences in its administration and effectiveness.