Search

Background: Direct-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated. Methods: We analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018. We compared the following hypothetical interventions using causal inference methods: 1) initiation of DAA and 2) no DAA initiation. For patients with normal kidney function at baseline (eGFR>90 ml/min/1.73m2), we estimated and compared the risk for reaching Stage 3 chronic kidney disease (CKD) (eGFR≤60 ml/min/1.73m2) under each intervention. For patients with baseline CKD Stages 2–4 (152), we estimated and compared the mean change in eGFR at 2 years after baseline under each intervention. We used the parametric g-formula to adjust our estimates for baseline and time-varying confounders. Results: First, among 1390 patients with normal kidney function at baseline the estimated 2-year risk difference (95% CI) of reaching Stage 3 CKD for DAA initiation versus no DAA was -1% (-3, 2). Second, among 733 patients with CKD Stage 2–4 at baseline the estimated 2-year mean difference in change in eGFR for DAA initiation versus no DAA therapy was -3 ml/min/1.73m2 (-8, 2). Conclusions: We found no effect of DAA initiation on kidney function, independent of baseline renal status. This suggests that DAAs may not be nephrotoxic; furthermore, in the short-term, HCV clearance may not improve CKD. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) results from chronic inflammation/cirrhosis. Unfortunately, despite use of radiological/serological screening techniques, HCC ranks as a leading cause of cancer deaths. Our group has used alterations in high order chromatin as a marker for field carcinogenesis and hence risk for a variety of cancers (including colon, lung, prostate, ovarian, esophageal). In this study we wanted to address whether these chromatin alterations occur in HCC and if it could be used for risk stratification. Experimental design: A case control study was performed in patients with cirrhosis who went on to develop HCC and patients with cirrhosis who did not develop cancer. We performed partial wave spectroscopic microscopy (PWS) which measures nanoscale alterations on formalin fixed deparaffinized liver biopsy specimens, 17 progressors and 26 non-progressors. Follow up was 2089 and 2892 days, respectively. Results: PWS parameter disorder strength Ld were notably higher for the progressors (Ld = 1.47 ± 0.76) than the non-progressors (Ld = 1.00 ± 0.27) (p = 0.024). Overall, the Cohen’s d effect size was 0.907 (90.7%). AUROC analysis yielded an area of 0.70. There was no evidence of confounding by gender, age, BMI, smoking status and race. Conclusions: High order chromatin alterations, as detected by PWS, is altered in pre-malignant hepatocytes with cirrhosis and may predict future risk of HCC. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis C virus (HCV) is a common cause of increased morbidity and mortality in kidney transplant patients. It is associated with posttransplant glomerulonephritis, chronic allograft nephropathy, and New Onset Diabetes after Transplant (NODAT). In the past, HCV was difficult to treat due to the presence of interferon alpha‐based therapies that were difficult to tolerate and were associated with adverse side‐effects, such as the risk of rejection. With the advent of oral directly acting antiviral therapies, the landscape for HCV and transplantation has changed. These agents are highly effective and well tolerated with minimal side‐effects. Sustained viral response rates in excess of 90% are achieved with most current treatment regimens active against all HCV genotypes. These new agents may show an improvement in graft and patient survival while essentially eliminating the risk of acute rejection from the use of prior interferon‐based HCV therapies. These agents may also result in an improvement in organ allocation for HCV donor/HCV recipient transplantation. This review is meant to discuss the epidemiology of HCV, the new oral direct‐acting antiviral agents (DAAs) and future opportunities for research in the field of HCV related transplantation. [ABSTRACT FROM AUTHOR]

Background The effect of alcohol on liver disease in HIV infection has not been well characterized. Methods We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, ' FIB-4,' which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index (' APRI'), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg). Results Subjects ( n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus ( HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm3. Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis ( FIB-4 <1.45) (adjusted odds ratio [ AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis ( FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection. Conclusions In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population. [ABSTRACT FROM AUTHOR]

Background: Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a substantial medical and public health concern due to its increasing prevalence and complex patient management. Alcohol use may worsen HCV-related liver disease and interfere with adherence to antiretroviral therapy (ART) and medical care. We therefore studied the association between HCV infection and markers of HIV disease progression in adults with alcohol problems. Methods: This is a longitudinal study of 396 HIV-infected persons with alcohol problems, 199 (50%) of whom were coinfected with HCV (positive HCV RNA test). CD4 cell counts and HIV RNA levels were assessed at baseline and then every 6 months for up to 42 months. Hepatitis C virus RNA status was determined at study enrollment. We examined the relationship between HCV infection and laboratory markers of HIV progression (CD4 cell count and log10 HIV RNA) by fitting multivariable longitudinal regression models for each outcome. Results: Among subjects who were adherent to ART, the presence of HCV infection was associated with a lower CD4 cell count (adjusted mean difference −46.0 cells/ μL, p=0.03). There was no association observed between HCV infection and CD4 cell count among those not adherent to ART or those not taking ART. No significant association was observed between HCV infection and HIV RNA regardless of ART status. Conclusions: Hepatitis C virus infection has an adverse effect on CD4 cell count in patients with alcohol problems who are adherent to ART. Addressing HCV coinfection among these patients may confer additional immunologic benefit for this patient population. [ABSTRACT FROM AUTHOR]

Background. Ongoing substance use is a potential confounder for immunological studies on hepatitis C virus (HCV), but there is little in the literature regarding the effects of injection drug use (IDU) or alcohol on HCV-specific immune responses. We wanted to determine whether IDU or alcohol affected immune responses in HCV-infected and human immunodeficiency virus (HIV)/HCV coinfected subjects. Methods. Eight-four subjects with HIV/HCV and 57 with HCV were classified as either injection drug users, drinkers, or nonusers based on questionnaire results. Immune responses were studied with enzyme-linked immunosorbent spot assay for interferon (IFN)-γ, interleukin (IL)-10, and tumor necrosis factor (TNF)-α against HCV proteins Core, NS3, and NS5 and recall antigens. Results. Subjects with HIV/HCV, in aggregate, had significantly lower HCV-specific IFN-g and TNF-aresponses than subjects with HCV. However, HIV/HCV injection drug users had HCV specific IFN-γ and IL-10 responses that were similar to those of HCV injection drug users and were significantly higher than in nonusers with HIV/HCV. Conversely, subjects who drank alcohol had similar immune responses to those who were abstinent, among both subjects with HIV/HCV and subjects with HCV. Conclusions. Studies that examine IFN-γ or IL-10 immune responses in HIV/HCV-coinfected or HCV-infected persons need to consider current IDU. Alcohol, at levels consumed in this cohort, does not appear to have as much of an effect on antigen-specific immune responses. [ABSTRACT FROM AUTHOR]

The article reports on the HIV infection that does not affect the performance of noninvasive markers of fibrosis for the diagnosis of Hepatitis C virus related in liver disease. The diagnostic performance of the evaluated noninvasive markers of liver fibrosis is equivalent in HCV/HIV-coinfected and HCV-infected subjects.

We estimate that only one-third of patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are eligible for therapy for HCV with interferon (IFN) and ribavirin, and, of those who are eligible, two-thirds decline treatment. To date we have initiated treatment with IFN and ribavirin for 8% of coinfected patients evaluated, and <1% of patients have had a sustained virological response. During this process, we have identified many problems that significantly limit our ability to initiate and complete treatment with IFN in this population and have categorized these difficulties into 4 main challenges. They include access to care, contraindications or barriers to treatment, patients' reluctance to start treatment with IFN, and the low tolerability of treatment. If patients coinfected with HCV and HIV are to be treated for hepatitis C in greater numbers, these issues will need to be addressed. [ABSTRACT FROM AUTHOR]

Health-related quality of life (HRQOL) is diminished in patients infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but the effect of HIV/HCV coinfection on HRQOL is unknown. We compared the HRQOL of urban HIV/HCV coinfected patients with that of patients infected with either HCV or HIV alone. We then compared the 3 groups with a US population sample, adjusting for demographic characteristics. HRQOL for the group of HIV/HCV coinfected patients was statistically similar to that of HRQOL in patients with either HCV or HIV alone, but the 3 groups had a significantly decreased HRQOL than did the adjusted US population. Using multivariate techniques, we determined that age, unemployment, injection drug use, and depression were associated with impaired HRQOL. These findings underscore the importance of a multidisciplinary approach to the treatment of these patient populations. [ABSTRACT FROM AUTHOR]

Reports that hepatitis C virus and human immunodeficiency virus coinfected people in an urban population in the U.S. had low eligibility for interferon and ribavirin treatment. Percentage of people eligible and ineligible for treatment out of the total number of people evaluated Barriers in treatment eligibility.

Background: The impact of Hepatitis C virus (HCV) RNA levels on the evolution of chronic HCV infection-related liver damage is controversial. Heavy alcohol use is believed to have a deleterious impact on the course of HCV disease, but current knowledge about the possible effect of alcohol use on HCV RNA levels in HIV/HCV coinfected patients is limited. Methods: We examined 107 HIV/HCV-infected individuals with current or past unhealthy alcohol use to assess the association between alcohol consumption (any drinking vs. abstinent) and HCV RNA levels. Results: Participants were 75% male, with a mean age of 43 years, and 63% were on antiretroviral therapy. Mean (SD) log HIV RNA was 3.1 (1.4) and mean (SD) log HCV RNA was 6.1 (0.8). Past-month alcohol use was present in 38% of participants. In a multivariable linear regression analysis we found no significant differences in mean log HCV RNA levels between those reporting alcohol use and those who were abstinent [β (95%CI): −0.04 (−0.34, 0.26), p = 0.79)]. There was no significant association between any heavy drinking day and HCV RNA level (0.07, 95% CI: (−0.24, 0.38), p = 0.66). Conclusions: We did not detect significant associations between alcohol use and HCV RNA levels among HIV/HCV coinfected patients. [ABSTRACT FROM AUTHOR]

Abstract: We examined the association of substance abuse treatment with access to liver specialty care among 231 persons coinfected with HIV and hepatitis C virus (HCV) with a history of alcohol problems who were recruited and followed up in the HIV-Longitudinal Interrelationships of Viruses and Ethanol cohort study from 2001 to 2004. Variables regarding demographics, substance use, health service use, clinical variables, and substance abuse treatment were from a standardized research questionnaire administered biannually. We defined substance abuse treatment services as any of the following in the previous 6 months: 12 weeks in a halfway house or residential facility, 12 visits to a substance abuse counselor or mental health professional, day treatment for at least 30 days, or any participation in a methadone maintenance program. Liver specialty care was defined as a visit to a liver doctor, a hepatologist, or a specialist in treating hepatitis C in the past 6 months. At study entry, most of the 231 subjects (89%, n = 205) had seen a primary care physician, 50% had been exposed to substance abuse treatment, and 50 subjects (22%) had received liver specialty care. An additional 33 subjects (14%) reported receiving liver specialty care during the follow-up period. In the multivariable model, we observed a clinically important although not statistically significant association between having been in substance abuse treatment and receiving liver specialty care (adjusted odds ratio = 1.38; 95% confidence interval = 0.9–2.11). Substance abuse treatment systems should give attention to the need of patients to receive care for prevalent treatable diseases such as HIV/HCV coinfection and facilitate its medical care to improve the quality of care for individuals with substance use disorders. The data illustrate the need for clinical care models that give explicit attention to the coordination of primary health care with addiction and hepatitis C specialty care while providing ongoing support to engage and retain these patients with complex health needs. [Copyright &y& Elsevier]