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HCV Increases Risk for Comorbid Conditions
  from Jules: numerous studies over many years provide evidence that HCV increases immune activation & disturbances in the immune system. HCV increases mortality and morbidity & has a doubling affect in HIV/HCV connected regarding risk for mortality & comorbidity - HCV increases risk for bone disease & fractures with many studies in HIV showing HCV increases risk beyond that from HIV alone, this is particularly true in HIV+ WIHS women. in the 2nd link below there are numerous links to studies regarding HCV increasing risk for bone, cardiovascular, diabetes, kidney and brain diseases. Achieving SVR improves immunity & inflammation but some questions renin whether SVR completely restores immunity. Several studies show SVR can reduce or eliminate for some kidney disease. Numerous studies report HCV increases risk for many different cancers including of course HCC, but also NASH increases risk for HCC and other cancers and NASH gets little attention by HIV care providers. Many people with HIV have liver disorders reflected by ALT elevations that are not related to viral hepatitis but these patients do not get evaluated for NASH or fatty liver. HIV+ have many of the important risk factors associated with NASH but again HIV providers are not attune to this. I have reported studies on this which are on the NATAP website in the Fatty Liver Section HCV has been a leading cause of death among HIV+ until the recent availability of DAAs with cure rates of 96% to 100% equally in HIV+ as well as HIV-negative, but what are the legacy affects in HIV+ of having had HCV for many years. The affects of HCV caused added immune activation & consequent inflammation do not completely disappear by an SVR. Damage has been caused and likely has an affect that has not yet been looked at in studies as far as I know.
HCV Extrahepatic Diseases / Manifestations - kidney, cardiovascular, bone - inflammation - brain - increased mortality - (10/17/16)
HCV+ Have Lots of Extra-Hepatic Manifestations & Increased Consequent Mortality: kidney, cardiovascular, brain, inflammation, bone disease, HIV+, cancers, affect on persons on Dialysis....HCV+ have more of these comorbid conditions & SVR has been found to improve conditions
EACS: Non-viral Liver Disease Burden in HIV Mono-infected Individuals: A Prospective Cohort Study - (12/07/17)
CROI: Hepatitis C and the Risk of Non-Liver-Related Morbidity and Mortality in HIV+ Persons....kidney, bone, cardiovascular - (04/4/16)
HCV & active IDU associated with immune activation - CROI/2016: Understanding the Relative Contributions of IDU and HCV on Systemic Immune Activation...... .....HCV should be aggressively treated in current IDUs even more if HIV and/or HCV positive - (04/4/16) HCV treatment should be aggressive in IDUs
because their immune system is activated, immune activation can lead to inflammation which can have poor long-term outcomes, we know that the onset of & early & accelerated & premature onset of comorbidities like heart disease, neurologic impairment, and perhaps kidney disease, bone disease & frailty are all associated with immune activation & to inflammation
Hypertension, proteinuria, and progressive renal failure are the main clinical manifestations of HCV-associated CKD--HCV RNA and related proteins have been found in mesangial cells, tubular epithelial cells, and endothelial cells of glomerular and tubular capillaries. The presence of HCV-related proteins in the mesangium was associated with higher proteinuria (16), possibly reflecting direct mesangial injury by HCV infection. -.......http://cjasn.asnjournals.org/content/4/1/207.long
Extrahepatic Complications of Hepatitis C Virus Infection in HIV and the Impact of Successful Antiviral Treatment
.....Chronic hepatitis C virus (HCV) infection exerts its main effects on the liver, promoting hepatic inflammation and fibrosis and increasing the risk of cirrhosis, hepatic decompensation, and hepatocellular carcinoma [1]. However, chronic HCV infection also affects organ systems outside of the liver and can contribute to the development of a variety of extra hepatic diseases, most notably atherosclerosis, metabolic alterations (eg, insulin resistance, diabetes mellitus, hepatic steatosis), renal disease (eg, proteinuria, membranoproliferative glomerulonephritis), bone disease (eg, arthralgias, osteoporosis, fractures), neuropsychiatric manifestations (eg, fatigue, cognitive impairment), B-cell non-Hodgkin’s lymphoma, cutaneous disorders (eg, lichen planus, porphyria cutanea tarda), and autoimmune and immune-mediated conditions (eg, mixed cryoglobulinemia, thyroid disease, sicca syndrome) [2, 3]. Some studies have suggested that the incidence of these diseases might be higher for human immunodeficiency virus (HIV)/HCV-connected individuals than for those with HCV alone [4, 5]. Regardless of HIV status, HCV-related extrahepatic conditions contribute to morbidity and could increase the risk of nonliver-related mortality [6-9].......The mechanisms for the extra hepatic comorbidities associated with chronic HCV infection are incompletely understood but are likely multifactorial. HCV replication in extrahepatic cells, interactions between HCV proteins and intracellular signaling pathways, HCV-induced stimulation of B-lymphocytes, and immune activation leading to chronic inflammation have all been hypothesized to play a role in the development of these conditions [2, 3]. Lifestyle factors, such as drug and alcohol abuse, smoking, and poor nutrition, may also be important contributors to the development of HCV-related extrahepatic diseases.
Exhausted T-cells and Inflammatory Monocytes are Linked to Brain Atrophy in HIV - (03/10/17)
HCV SVR Improves Quality of Life & Brain Function - (01/27/12)
SVR Reduces Kidney Disease Risks/ HCV Causes Increased Kidney Disease Risks - (09/13/17)
Direct-Acting Antiviral Therapy Restores Immune Tolerance to Patients With Hepatitis C Virus-Induced Cryoglobulinemia Vasculitis....http://www.natap.org/2017/HCV/PIIS0016508517302354.pdf
AASLD: Chronic Hepatitis C Virus Infection and Cancer Risks: A Population-Based Cohort Study - (11/14/16)
Eradication of HCV and non-liver-related non-AIDS-related events (CVD/diabetes/kidney/cancers) in HIV/HCV coinfection - (02/01/17) - After a median five-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR 0.57 [95% CI, 0.35 - 0.93] P= .024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR 0.43 [95% CI, 0.17 - 1.09], P=.075).
Extrahepatic manifestations of hepatitis C virus infection - Review......
http://www.natap.org/2006/HCV/042106_01.htm HEMATOLOGIC DISORDERS - HCV infection is associated with a number of hematologic disorders including essential mixed cryoglobulinemia, monoclonal gammopathies (which may be associated with multiple myeloma), and lymphoma and less commonly monoclonal gammopathies.
Chronic Hepatitis C Virus Infection Increases Mortality From Hepatic and Extrahepatic Diseases: A Community-Based Long-Term Prospective Study - (R.E.V.E.A.L.)-HCV study......http://www.natap.org/2012/HCV/071912_01.htm

"anti-HCV seropositives had higher mortality from both hepatic and extrahepatic diseases, showing multivariate-adjusted hazard ratio (95% confidence interval) of 1.89 (1.66-2.15) for all causes of death; 12.48 (9.34-16.66) for hepatic diseases; 1.35 (1.15-1.57) for extrahepatic diseases; 1.50 (1.10-2.03) for circulatory diseases; 2.77 (1.49-5.15) for [kidney] nephritis, nephrotic syndrome, and nephrosis; 4.08 (1.38-12.08) for esophageal cancer; 4.19 (1.18-14.94) for prostate cancer; and 8.22 (1.36-49.66) for thyroid cancer. Anti-HCV seropositives with detectable HCV RNA levels had significantly higher mortality from hepatic and extrahepatic diseases than anti-HCV seropositives with undetectable HCV RNA.”
Fracture risk in hepatitis C virus infected persons: results from the DANVIR cohort study; HIV & HCV/HIV Bone Loss - (03/19/14)
Bone Micro-Architectural Changes and Fracture Risk Prediction in HIV and HCV - (03/06/17)
Increased incidence of cancer and cancer-related mortality among persons with chronic hepatitis C infection, 2006-2010 - (09/18/15)
Extrahepatic Morbidity and Mortality of Chronic Hepatitis C Review - SVR Clears/Reduces Extrahepatic Manifestations - (11/05/15)
Heart Disease in HCV+......http://www.natap.org/2014/HCV/060314_02.htm
......HCV+ normotensive patients, in comparison with healthy normotensive subjects, have a significant increase in echocardiographic cardiac mass, totally similar to that observed in hypertensive patients.......IR/hyperinsulinemia HCV-related, by affecting cardiac remodeling, suggests considering chronic HCV infection as a possible new factor in the global cardiovascular risk burden
Hepatitis C Virus Infection is Associated With Increased Cardiovascular Mortality: A Meta-analysis of Observational Studies - (09/22/15)
EASL: Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients. ANRS CO12 CirVir Cohort - (04/26/17)
Hepatitis C virus infection: a risk factor for Parkinson's disease - (09/22/15)
AASLD: Cardiovascular risk in NAFLD- not an equal opportunity: implications for women's health - (11/29/17)
HIV and hepatitis C coinfection have consistently been reported to be associated with an increased fracture risk - both traumatic and fragility, compared with those with HIV monoinfection (Incidence rate ratio (IRR) 1.77, 95% CI 1.44-2.18) and uninfected individuals (IRR 2.95, 95% CI 2.17-4.01) in a systematic review....hepatitis C coinfection was found to be an independent significant predictor of incident fractures (hazard ratio = 1.27, 95% CI 1.08-1.50), which is possibly partly explained by the severity of chronic liver disease (cirrhosis) present (hazard ratio = 1.74, 96% CI 1.23-2.47). Several large cohort studies' elevated rates of bone fracture have been reported in PLWH compared with matched controls [1-4,5,6 ]. Comparison of fracture prevalence rates between HIV-infected and HIV-uninfected individuals in a large US Healthcare system reported a significantly increased prevalence in HIV-positive individuals (2.87 per 100 persons) compared with an HIV-negative group (1.77 per 100 person years). The increased fracture rates were observed for both men and women, and occurred predominantly at the hip, spine and wrist in the HIV-positive group [1]. Fragility fracture (hip, vertebra and arm) incidence in the Veterans Aging Cohort Study (VACS) cohort (over 40 000 HIV-positive men) was 2.6 per 1000 person-years [7]. For those with HIV and hepatitis C virus coinfection, the crude incidence rate of all fractures varies between 26.8 and 62.3 per 1000 person-years [8], whereas for fragility fractures 2.6 per 1000 person-years [9]. HIV infection was associated with a three-fold increased fracture risk, compared with age-matched and sex-matched individuals in Denmark [10].
EACS: How many HIV mono-infected or HBV or HCV co-infected patients with undetectable viremia should be monitored for liver disease severity in the presence of suspect NAFLD? - (12/08/17)
IAS: Fatty Liver in HIV+ at IAS - (08/05/17)

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