Showing posts with label HIV/HCV. Show all posts
Showing posts with label HIV/HCV. Show all posts

Tuesday, November 20, 2018

Mavyret for HCV/HIV Coinfection and Genotype 3: A Report of Three Cases

Intern Med. 2018 Nov 19. doi: 10.2169/internalmedicine.1856-18.
[Epub ahead of print]

Glecaprevir and Pibrentasvir for Japanese Patients with Human Immunodeficiency Virus and Genotype 3 Hepatitis C Virus Coinfection: A Report of Three Cases
Takuya Sho1, Goki Suda1, Megumi Kimura1, Tomoe Shimazaki1, Osamu Maehara1, Taku Shigesawa1, Kazuharu Suzuki1, Akihisa Nakamura1, Masatsugu Ohara1, Machiko Umemura1, Takaaki Izumi1, Naoki Kawagishi1, Masaru Baba2, Masato Nakai1, Mitsuteru Natsuizka1, Kenichi Morikawa1, Koji Ogawa1 and Naoya Sakamoto1; for the NORTE Study Group

Abstract:
The efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with human immunodeficiency virus (HIV) and/or genotype 3 hepatitis C virus (HCV) infection is yet to be clarified. This is because no or only a few patients have been included in Japanese phase 3 trials. We herein report for the first time the successful treatment of glecaprevir and pibrentasvir in three Japanese patients with HIV and genotype 3 HCV coinfection as well as hemophilia. Glecaprevir and pibrentasvir treatment is safe and effective for Japanese patients with genotype 3 HCV and HIV coinfection.

Full-text article
Download PDF: https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_1856-18/_pdf/-char/en

Tuesday, November 13, 2018

Hepatitis C is detectable in rectal and nasal fluid

Conference Coverage @ infohep
Hepatitis C is detectable in rectal and nasal fluid

Keith Alcorn Published: 12 November 2018

High levels of hepatitis C virus (HCV) can be found in the rectal and nasal fluids of people with high hepatitis C viral loads even when blood is not present, Austrian researchers reported on Sunday at the 2018 AASLD Liver Meeting.

The findings reinforce the plausibility of HCV transmission through sharing up rolled-up bank notes or other equipment for snorting drugs.

The findings were presented by Dr David Chromy of the Medical University of Vienna on behalf of the Vienna HIV & Liver Study Group.


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Sunday, November 11, 2018

Liver Meeting® 2018 - SOF/VEL/VOX Successful for Hepatitis C Virus Retreatment in Patients With and Without HIV

The Liver Meeting® 2018 
San Francisco, CA. 
November 9-13, 2018

Meeting Coverage

SOF/VEL/VOX Successful for Hepatitis C Virus Retreatment in Patients With and Without HIV
NOVEMBER 10, 2018
Danielle Mroz
Treatment was also successful in patients with prior noncompletion or poor adherence to direct-acting antiviral therapy.

A fixed-dose combination therapy of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX, Vosevi, Gilead) was highly effective after 12 weeks in retreating direct-acting antiviral-experienced patients with hepatitis C virus infection, with and without HIV co-infection, including those with prior noncompletion of treatment or poor adherence, according to results of a new study.

Read More: https://www.mdmag.com/conference-coverage/aasld-2018/sofvelvox-successful-for-hepatitis-c-virus-retreatment-in-patients-with-and-without-hiv

Meeting Updates 
View all updates on this blog, (LINK), coverage elsewhere, (LINK).

Wednesday, October 10, 2018

The British HIV Association is calling for accelerated efforts to cure hepatitis C virus in all those living with HIV

BHIVA statement

The British HIV Association (BHIVA) calls for accelerated efforts to prevent and cure hepatitis C infection in all those living with HIV 
10 October 2018

The British HIV Association (BHIVA) is calling for accelerated efforts to cure hepatitis C virus in all those living with HIV. New treatments for hepatitis C, direct acting agents (DAAs,) have transformed the potential for cure in patients when compared to older, interferon based, therapies. Curing hepatitis C can not only reduce the risk of cancer and liver cirrhosis, but also reduces the risk of cardiovascular disease, diabetes and other associated conditions. Until recently, access to these expensive treatments was limited but with treatment now widely available on the NHS, the new priority is to ensure all those with the virus are diagnosed, linked to services and cured.

Ambitious targets
As part of a concerted and collective effort towards eliminating hepatitis C as a major public health threat, BHIVA will be working closely with local services over the coming year to ensure all patients co-infected with HIV and hepatitis C are linked to care and treatment. We propose the following ambitious targets:
80% of all patients with diagnosed HIV and hepatitis C co-infection cured of hepatitis C by April 2019 (with 100% of patients assessed for therapy)

90% of all patients cured of hepatitis C by April 2020

100% of all patients cured of hepatitis C by April 2021.

In contrast to recent rapid progress in treating the majority of those diagnosed with HIV and hepatitis C co-infection, we expect the achievement of 100 per cent cure to be slower. This is because services will have to treat a small number of particularly vulnerable patients who struggle to make appointments and take medicines. In the short term, many services are likely to need additional staff and new ways of delivering care to ensure all those with the virus can be cured. Achieving this is likely to require plans tailored to individuals being delivered in different settings across the UK.

At the same time as increasing the uptake of treatment, it is important to maintain hepatitis C prevention initiatives and regular testing in those at risk (see BHIVA guidelines bit.ly/2Ou8gGA), particularly given the potential of bridging networks between those most vulnerable in the HIV positive and other at-risk communities. Patients continue to be diagnosed with new HCV infection, even after cure, and in some settings there remain policies restricting treatment of these patients until chronic infection is established. These groups are particularly likely to pass on infection and such policies have the potential to undermine progress being made towards hepatitis C microelimination (elimination within a particular group of patients) within people living with HIV (PLWHIV). We would urge all health commissioners to ensure treatment continues to be available for all who need it to stop the epidemic re-emerging in PLWHIV.

BHIVA will work closely with public health agencies to monitor progress in all parts of the UK. For example, with support from Public Health England, BHIVA estimates there were approximately 3,300 people living with diagnosed HIV and hepatitis C in England at the beginning of 2016, and that over half of these patients have now been cured for hepatitis C as a result of treatment with DAAs. In some regions (for example, the North East of England and Tayside in Scotland) 100 per cent cure is already close to being achieved.

The UK can be the first country to achieve microelimination of hepatitis C in those living with HIV, well ahead of WHO targets. We should seize this opportunity. 


References
1. WHO Global health sector strategy on viral hepatitis 2016-2021. Geneva June 2016
http://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/

2. Stanaway et al The global burden of viral hepatitis from 1990-2013: findings from the Global Burden of Disease Study 2013 Lancet. 2016 Sep 10;388(10049):1081-1088. doi: 10.1016/S0140-6736(16)30579-7. Epub 2016 Jul

3. Platt et al Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016 Jul;16(7):797-808. doi: 10.1016/S1473-3099(15)00485-5

4. Cooke and Hallett HCV and HIV: shared challenges, shared solutions Lancet Infect Dis. 2016 Jul;16(7):755-756

5. Public Health England Hepatitis C in England 2018 report March 2018

6. Hepatitis C Trust Eliminating Hepatitis C in Scotland: a call to action
http://www.hcvaction.org.uk/resource/eliminating-hepatitis-c-scotland-call-action

Hepatitis C - Vosevi safe, effective in ‘triple-infected’ patients with HCV, HBV, HIV

Vosevi safe, effective in ‘triple-infected’ patients with HCV, HBV, HIV

PHILADELPHIA – The direct-acting antiviral Vosevi demonstrated an average sustained virologic response rate of 87% among patients who were “triple-infected” with hepatitis C genotype 3, hepatitis B and HIV, as presented at the American College of Gastroenterology Annual Meeting.

“Chronic hepatitis C treatment is no longer challenging in the era of DAAs with an SVR of up to 97%. However, triple infection treatment with HCV, HIV and hepatitis B has not been explored in real life situations,” Nimy John, MD, from the University of Massachusetts Medical School, said during her presentation.

American College of Gastroenterology Annual Meeting 
October 5, 2018 - October 10, 2018
See more from American College of Gastroenterology Annual Meeting

Tuesday, September 18, 2018

Audio Ask the Experts: Optimizing Cotreatment of HCV and HIV Infection


Ask the Experts: Optimizing Cotreatment of HCV and HIV Infection
Susanna Naggie, MD, MHS
Listen as expert faculty answer clinicians’ questions about specific challenges in managing HCV/HIV coinfection, including how to apply guideline-based strategies, avoid common DAA and ART interactions, incorporate recent therapy approvals, and more. 

Download: Optimizing Cotreatment of HCV and HIV Infection

Friday, June 8, 2018

HCV/HIV-coinfection - Successful direct acting antiviral (DAA) treatment before and after liver transplantation

PLOS ONESuccessful direct acting antiviral (DAA) treatment of HCV/HIV-coinfected patients before and after liver transplantation
Julia M. Grottenthaler, Christoph R. Werner, Martina Steurer, Ulrich Spengler, Thomas Berg, Cornelius Engelmann, Heiner Wedemeyer, Thomas von Hahn, Wolfgang Stremmel, Anita Pathil, Ulrich Seybold, Eckart Schott, Usha Blessin, Christoph P. Berg

Published: June 6, 2018 https://doi.org/10.1371/journal.pone.0197544 

Links

Abstract
Objectives
The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively.

Methods
When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1); MELD range 7–21; HCC (n = 2); HCV genotype 1a (n = 8), 1b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1)).

Results
Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy; subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in follow-up. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation; in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up.

Conclusion
DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted.

Saturday, April 14, 2018

JIAS - Special Issue: Towards global viral hepatitis elimination for all patients in all income settings

Journal of the International AIDS Society
Published on behalf of the International AIDS Society

Special Issue: Towards global viral hepatitis elimination for all patients in all income settings
Guest Editors: Marina B Klein, Karine Lacombe

The complete supplement file is available at

First Published: 10 April 2018
Full text
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Commentary
Open Access
How far are we from viral hepatitis elimination service coverage targets?

Yvan J‐F Hutin Marc Bulterys Gottfried O Hirnschall e25050
First Published: 10 April 2018
Abstract
Full text
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Research Articles
Open Access
Hep‐CORE: a cross‐sectional study of the viral hepatitis policy environment reported by patient groups in 25 European countries in 2016 and 2017

Jeffrey V Lazarus Samya R Stumo Magdalena Harris Greet Hendrickx Kristina L Hetherington
Mojca Maticic Marie Jauffret‐Roustide Joan Tallada Kaarlo Simojoki Tatjana Reic Kelly Safreed‐Harmon the Hep‐CORE Study Group e25052
First Published: 10 April 2018
Abstract
Full text
PDF

Reviews
Open Access
Approaches for simplified HCV diagnostic algorithms

Slim Fourati Jordan J Feld Stéphane Chevaliez Niklas Luhmann e25058
First Published: 10 April 2018
Abstract
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Research
Open Access
Linkage and retention in HCV care for HIV‐infected populations: early data from the DAA era

Rachel Sacks‐Davis Joseph S Doyle Andri Rauch Charles Beguelin Alisa E Pedrana Gail V Matthews Maria Prins Marc van der Valk Marina B Klein Sahar Saeed Karine Lacombe
Nikoloz Chkhartishvili Frederick L Altice Margaret E Hellard e25051
First Published: 10 April 2018
Abstract
Full text
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Commentary
Open Access
Treatment advocate tactics to expand access to antiviral therapy for HIV and viral hepatitis C in low‐ to high‐income settings: making sure no one is left behind

Céline Grillon Priti R Krishtel Othoman Mellouk Anton Basenko James Freeman Luís Mendão
Isabelle Andrieux‐Meyer Sébastien Morin e25060
First Published: 10 April 2018
Abstract
Full text
PDF 

Research
Open Access
Is hepatitis C virus elimination possible among people living with HIV and what will it take to achieve it?

Natasha K Martin Anne Boerekamps Andrew M Hill Bart J A Rijnders e25062
First Published: 10 April 2018
Abstract
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Commentary
Open Access
Research gaps in viral hepatitis

Anders Boyd Léa Duchesne Karine Lacombe e25054
First Published: 10 April 2018
Abstract
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Tuesday, April 3, 2018

MAVIRET (Glecaprevir/pibrentasvir) treats hepatitis C in HIV-coinfected individuals

Glecaprevir/pibrentasvir treats hepatitis C in HIV-coinfected individuals
Last Updated: 2018-04-02
By Reuters Staff
NEW YORK (Reuters Health) - The direct-acting antiviral (DAA) combination glecaprevir/pibrentasvir is effective for treating hepatitis C virus (HCV) infection in individuals coinfected with HIV-1, according to results from the non-randomized, open-label phase 3 EXPEDITION-2 trial. As many as 3 million of the 80 million individuals infected with HCV worldwide are coinfected with HIV-1. Most guidelines recommend these patients be treated like those with HCV monoinfection, with careful monitoring for drug-drug interactions with antiretroviral therapy (ART)....
Continue reading article: http://www.chronicliverdisease.org/reuters/article.cfm?article=20180402Other1554755267

Wednesday, January 31, 2018

Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus: A retrospective cohort study

World J Gastroenterol. Feb 7, 2018; 24(5): 613-622
Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.613

Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus: A retrospective cohort study
Patrícia dos Santos Marcon, Cristiane Valle Tovo, Dimas Alexandre Kliemann, Patrícia Fisch, Angelo Alves de Mattos

Full Text

Abstract
AIM
To assess the incidence of hepatocellular carcinoma (HCC) in chronic liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfected with human immunodeficiency virus (HIV).

METHODS
A retrospective cohort study was performed, including patients with chronic liver disease due to HBV or HCV, with and without HIV coinfection. Patients were selected in the largest tertiary public hospital complex in southern Brazil between January 2007 and June 2014. We assessed demographic and clinical data, including lifestyle habits such as illicit drug use or alcohol abuse, in addition to frequency and reasons for hospital admissions via medical records review.

RESULTS
Of 804 patients were included (399 with HIV coinfection and 405 monoinfected with HBV or HCV). Coinfected patients were younger (36.7 ± 10 vs 46.3 ± 12.5, P < 0.001). Liver cirrhosis was observed in 31.3% of HIV-negative patients and in 16.5% of coinfected (P < 0.001). HCC was diagnosed in 36 patients (10 HIV coinfected and 26 monoinfected). The incidence density of HCC in coinfected and monoinfected patients was 0.25 and 0.72 cases per 100 patient-years (95%CI: 0.12-0.46 vs 0.47-1.05) (long-rank P = 0.002), respectively. The ratio for the HCC incidence rate was 2.98 for HIV-negative. However, when adjusting for age or when only cirrhotic are analyzed, the absence of HIV lost statistical significance for the development of HCC.

CONCLUSION
In this study, the presence of HIV coinfection in chronic liver disease due to HBV or HCV showed no relation to the increase of HCC incidence.


Evaluation of dried blood spot samples for screening of hepatitis C and human immunodeficiency virus in a real-world setting

Scientific Reports
volume 8, Article number: 1858 (2018)
doi:10.1038/s41598-018-20312-5

Evaluation of dried blood spot samples for screening of hepatitis C and human immunodeficiency virus in a real-world setting
Sonia Vázquez-Morón, Pablo Ryan, Beatriz Ardizone-Jiménez, Dolores Martín, Jesus Troya, Guillermo Cuevas, Jorge Valencia, María A. Jimenez-Sousa, Ana Avellón & Salvador Resino

Full Text
https://www.nature.com/articles/s41598-018-20312-5

Abstract
Both hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection are underdiagnosed, particularly in low-income countries and in difficult-to-access populations. Our aim was to develop and evaluate a methodology for the detection of HCV and HIV infection based on capillary dry blood spot (DBS) samples taken under real-world conditions. We carried out a cross-sectional study of 139 individuals (31 healthy controls, 68 HCV-monoinfected patients, and 40 HCV/HIV-coinfected patients). ELISA was used for anti-HCV and anti-HIV antibody detection; and SYBR Green RT-PCR was used for HCV-RNA detection. The HIV serological analysis revealed 100% sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The HCV serological analysis revealed a sensitivity of 92.6%, specificity of 100%, PPV of 100%, and NPV of 79.5%. Finally, the HCV-RNA detection test revealed a detection limit of 5 copies/µl with an efficiency of 100% and sensitivity of 99.1%, specificity of 100%, PPV of 100%, and NPV of 96.9%. In conclusion, our methodology was able to detect both HCV infection and HIV infection from the same DBS sample with good diagnostic performance. Screening for HCV and HIV using DBS might be a key strategy in the implementation of national programs for the control of both infections.

Friday, January 19, 2018

Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients

Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients
Evrim Anadol , Kristina Lust , Christoph Boesecke, Carolynne Schwarze-Zander, Raphael Mohr, Jan-Christian Wasmuth, Jürgen Kurt Rockstroh , Jonel Trebicka

Published: January 18, 2018
https://doi.org/10.1371/journal.pone.0191118

Full Text
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Abstract
Introduction
Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients.

Methods
This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE).

Results
83% were male with a median age of 45, while 131 were co-infected with viral hepatitis. Overall, 18% had significant fibrosis and 7.5% had cirrhosis. 11% of HIV mono-infected patients had significant fibrosis and 2% had cirrhosis. HCV infection (OR:5.3), history of exposure to didanosine (OR:2.7) and HIV load below 40copies/mL (OR:0.5) were independently associated with significant fibrosis, while HCV (OR:5.8), exposure to didanosine (OR:2.9) and azidothymidine (OR:2.8) were independently associated with cirrhosis. Interestingly, in HIV mono-infected patients, a HIV-load below 40copies/mL (OR:0.4) was independently associated with significant fibrosis, and didanosine (OR:20.8) with cirrhosis.

Conclusion
In conclusion, history of exposure to didanosine and azidothymidine continues to have an impact on the presence of liver cirrhosis in HIV patients. However, HCV co-infection and ongoing HIV-replication have the strongest effect on development of significant fibrosis in these patients.

Full Text: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191118

Friday, January 5, 2018

Treatment of hepatitis C in special populations

First Online: 03 January 2018

Treatment of hepatitis C in special populations
Goki Suda, Koji Ogawa, Kenichi Morikawa, Naoya Sakamoto

Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is high and is moreover associated with a poor prognosis. In liver transplantation patients with HCV infection, recurrent HCV infection is universal, and re-infected HCV causes rapid progression of liver fibrosis and graft loss.

Additionally, in patients with HCV and human immunodeficiency virus (HIV) co-infection, liver fibrosis progresses rapidly. Thus, there is an acute need for prompt treatment of HCV infection in these special populations (i.e., hemodialysis, liver transplantation, HIV co-infection). However, until recently, the standard anti-HCV treatment involved the use of interferon-based therapy.

In these special populations, interferon-based therapies could not achieve a high rate of sustained viral response and moreover were associated with a higher rate of adverse events. With the development of novel direct-acting antivirals (DAAs), the landscape of anti-HCV therapy for special populations has changed dramatically. Indeed, in special populations treated with interferon-free DAAs, the sustained viral response rate was above 90%, with a lower incidence and severity of adverse events.

Full Text

Tuesday, October 31, 2017

VA's Updated - Chronic Hepatitis C Virus Infection:Treatment Considerations

Shared by @HenryEChang via Twitter

Chronic Hepatitis C Virus (HCV) Infection: Treatment Considerations from the Department of Veterans Affairs National Hepatitis C Resource Center and the HIV, Hepatitis, and Related Conditions Program in the Office of Specialty Care Services

This revision ( October 18 , 2017 ) incorporates updates to treatment regimens for chronic hepatitis C virus (HCV) infection, genotype s 1 -4, including re-treatment of patients who previously failed direct -acting antiviral therapy. A new table (Table 4) , “HCV Direct -Acting Antiviral Agents by Drug Class ” has been added. The section on “ Interpretation of Resistance -Associated Substitutions” has been revised , as have tables showing drug- drug interaction s to provide clinicians with guidance on the concomitant use of HCV drugs and other drugs, including HIV antiretroviral agents ( Table 23 and Table 24 ). The Panel continues to recommend that HIV/HCV-coinfected patients receive the same HCV antiviral regimen s as HCV - monoinfected patients unless ledipasvir/sofosbuvir is being considered, in which case a 12 -week regimen should be used (instead of an 8 -week regimen) . The previous revision included HBV testing and monitoring recommendations prior to starting HCV DAA , which can be found in Appendix D.

View: Updated Treatment considerations 

Friday, October 27, 2017

Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients

World J Hepatol. Oct 28, 2017; 9(30): 1190-1196
Published online Oct 28, 2017. doi: 10.4254/wjh.v9.i30.1190

Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients
Xiaoping He, Lynne Hopkins, George Everett, Willie M Carter, Cynthia SchroppDyce, Khalid Abusaada, Vincent Hsu

Core tip: This is a retrospective study to evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection in an urban HIV clinic. It demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV antiretroviral therapy (ART). Occasional HIV virologic rebound occurred but later resolved without the need to change ART.

Full-Text

Abstract
AIM
To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection in an urban HIV clinic.

METHODS
A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level. The primary end point was a sustained virologic response of HCV at 12 wk (SVR12) after the end of therapy.

RESULTS
Of the 40 patients enrolled, 55% were black, 22.5% had been previously treated for HCV, and 25% had cirrhosis. The patients were on a wide range of ART. Overall, 39 patients (97.5%) had a SVR 12 after the end of therapy, including rates of 97.1% in patients with HCV genotype 1a and 100% in those with HCV genotype 1b. One patient with HCV genotype 3a was included and achieved SVR12. Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis. Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn’t reveal any resistance associated mutation in the NS5A or NS5B region. Interestingly, 7 (17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen. Two (5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy, which resolved after resuming the same ART regimen. No severe adverse events were observed and no patient discontinued treatment because of adverse events. The most common adverse events included headache (12.5%), fatigue (10%), and diarrhea (2.5%).

CONCLUSION
This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART. Occasional HIV virologic rebound occurred but later resolved without the need to change ART.

Saturday, September 23, 2017

Gilead Receives Approval in Canada for Expanded Indication of EPCLUSA® for Chronic Hepatitis C in Patients Co-Infected with HIV

Gilead Receives Approval in Canada for Expanded Indication of EPCLUSA® (Sofosbuvir/Velpatasvir) for the Treatment of Chronic Hepatitis C in Patients Co-Infected with HIV

– New Data for First Approved Pan-genotypic Once-Daily Single Tablet Regimen for
Chronic Hepatitis C Virus Infection –
MISSISSAUGA, ON, Sept. 21, 2017 /CNW/ - Gilead Sciences Canada, Inc. (Gilead Canada) today announced that Health Canada has granted a Notice of Compliance (NOC) for updated labeling of EPCLUSA® (sofosbuvir 400mg/velpatasvir 100mg), the first all-oral, pan-genotypic, once-daily single tablet regimen (STR) for the treatment of adults with chronic hepatitis C virus (HCV) infection, to include use in patients co-infected with HIV-1. Health Canada granted EPCLUSA an NOC in July 2016, for the treatment of adults with genotype 1-6 chronic HCV infection without cirrhosis or with compensated cirrhosis, or with decompensated cirrhosis in combination with ribavirin.

"HCV co-infection remains a major cause of morbidity in HIV-infected individuals. With this expanded indication, EPCLUSA provides co-infected patients with a much-needed one-pill-a-day regimen that works across all HCV genotypes and at all stages of disease. Being compatible with most widely-used antiretroviral regimens adds to its convenience," said Dr. Brian Conway, President and Medical Director, Vancouver Infectious Diseases Centre. "With EPCLUSA, physicians have an important new treatment option for their HCV/HIV co-infected patients."
The supplemental new drug submission was supported by data from the open-label, Phase 3 ASTRAL-5 study, which evaluated 12 weeks of treatment with EPCLUSA in 106 subjects with genotype 1-4 HCV infection who were co-infected with HIV and on stable antiretroviral therapy. In the study, 95 per cent (101/106) of patients achieved the primary endpoint of SVR12, defined as an undetectable viral load 12 weeks after completing therapy. The study also included patients with compensated cirrhosis.

The safety profile of EPCLUSA in HCV/HIV co-infected patients was similar to that observed in HCV mono-infected patients. The most common adverse events (in at least 10 per cent of subjects) were fatigue (22 per cent) and headache (10 per cent).

"Canada has committed to eliminating hepatitis C by 2030. To accomplish this goal, it is imperative that steps be taken to increase treatment rates in Canada, including treatment for people who are co-infected with hepatitis C and HIV," said Dr. Morris Sherman, Chairperson, Canadian Liver Foundation and Hepatologist at Toronto General Hospital. "Hepatitis C progresses faster in individuals who are co-infected with HIV, often increasing and speeding up the onset of liver damage. Today, with pan-genotypic curative hepatitis C therapies approved for treatment in hepatitis C and HIV co-infected patients, it is an important time for patients to discuss treatment options with their health care providers."

"EPCLUSA has already helped further simplify HCV treatment among mono-infected patients, and we are pleased that HCV/HIV co-infected patients can benefit from this pan-genotypic single tablet regimen," said Kennet Brysting, General Manager, Gilead Canada. "This approval advances the commitment we've made to the HCV and HIV communities to deliver innovative new treatments that address their unmet medical needs."
http://www.newswire.ca/news-releases/gilead-receives-approval-in-canada-for-expanded-indication-of-epclusa-sofosbuvirvelpatasvir-for-the-treatment-of-chronic-hepatitis-c-in-patients-co-infected-with-hiv-646369933.html

Tuesday, August 1, 2017

FDA Approves Expanded Labeling for Epclusa® for Hepatitis C in Patients Co-Infected with HIV

U.S. FDA Approves Expanded Labeling for Epclusa® (Sofosbuvir/Velpatasvir) for the Treatment of Chronic Hepatitis C in Patients Co-Infected with HIV

- New Data for First Approved Pan-genotypic Once-Daily Single Tablet Regimen for Chronic Hepatitis C Virus Infection -

FOSTER CITY, Calif.--(BUSINESS WIRE)--Aug. 1, 2017-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved updated labeling for Epclusa® (sofosbuvir 400mg/velpatasvir 100mg), the first all-oral, pan-genotypic, once-daily single tablet regimen (STR) for the treatment of adults with chronic hepatitis C virus (HCV) infection, to include use in patients co-infected with HIV. Epclusa received regulatory approval for the treatment of adults with genotype 1-6 chronic HCV infection without cirrhosis or with compensated cirrhosis, or with decompensated cirrhosis in combination with ribavirin, in the United States on June 28, 2016.

Epclusa has a boxed warning in its product label regarding the risk of hepatitis B virus (HBV) reactivation in HCV/HBV co-infected patients. See below for important safety information.
"HCV co-infection remains a major cause of morbidity in HIV-infected individuals. With this expanded use, Epclusa provides co-infected patients with a much needed one-pill-a-day regimen that works across all HCV genotypes and is compatible with widely-used antiretroviral regimens," said David Wyles, M.D., Chief, Division of Infectious Disease, Denver Health Medical Center; Associate Professor of Medicine, University of Colorado School of Medicine. "With Epclusa, physicians have an important new treatment option for their HCV/HIV co-infected patients."

The supplemental new drug application (sNDA) was supported by data from the open-label, Phase 3 ASTRAL-5 study, which evaluated 12 weeks of treatment with Epclusa in 106 subjects with genotype 1-4 HCV infection who were co-infected with HIV and on stable antiretroviral therapy. In the study, 95 percent (101/106) of patients achieved the primary endpoint of SVR12, defined as an undetectable viral load 12 weeks after completing therapy.

The safety profile of Epclusa in HCV/HIV co-infected patients was similar to that observed in HCV mono-infected patients. The most common adverse events (in at least 10 percent of subjects) were fatigue (22 percent) and headache (10 percent).

"Epclusa has already helped further simplify HCV treatment among mono-infected patients, and we are pleased that HCV/HIV co-infected patients can benefit from this pan-genotypic single tablet regimen," said John F. Milligan, PhD, Gilead's President and Chief Executive Officer. "This approval advances the commitment we've made to the HCV and HIV communities to deliver innovative new treatments that address their unmet medical needs."

U.S. Patient Support Program
To support these patients and their families, Gilead's U.S. Support Path® program provides information regarding access and reimbursement coverage options to patients in the United States who need assistance with coverage for their medications, including Epclusa. Support Path conducts benefits investigations and provides patients with information regarding their insurance options.
Further, the Epclusa Co-pay Coupon Program offers co-pay assistance for eligible patients with private insurance who need assistance paying for out-of-pocket medication costs.
To learn more about Support Path for Epclusa, please visit www.MySupportPath.com or call 1-855-7-MYPATH (1-855-769-7284) between 9:00 a.m. and 8:00 p.m. (Eastern), Monday through Friday.

Global Availability
The prevalence of HCV genotypes varies regionally throughout the world. In resource-limited settings genotype testing can often be costly or unreliable, posing yet another barrier to treatment. As a pan-genotypic therapeutic option, Epclusa may help eliminate the need for genotype testing and has the potential to accelerate access to treatment for patients worldwide.
Gilead is committed to helping enable access to Epclusa around the world. Gilead works with a network of regional business partners, generic licensing partners and other stakeholders to expand treatment globally. Epclusa is already licensed to Gilead's 11 Indian manufacturing partners who produce and distribute generic versions of this medicine for 101 developing countries.

Important U.S. Safety Information for Epclusa

BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV CO-INFECTED PATIENTS
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with Epclusa. HBV reactivation has been reported in HCV/HBV co-infected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
Contraindications
  • If Epclusa is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.
Warnings and Precautions
  • Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Epclusa due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect Due to Concomitant Use of Epclusa with P-gp Inducers and/or Moderate to Potent Inducers of CYP2B6, CYP2C8 or CYP3A4: Rifampin, St. John's wort, and carbamazepine are not recommended for use with Epclusa as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations.
Adverse Reactions
  • The most common adverse reactions (=10%, all grades) with Epclusa were headache and fatigue; and when used with RBV in decompensated cirrhotics were fatigue, anemia, nausea, headache, insomnia, and diarrhea.
Drug Interactions
  • Coadministration of Epclusa is not recommended with topotecan due to increased concentrations of topotecan.
  • Coadministration of Epclusa is not recommended with proton-pump inhibitors, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir.
Consult the full Prescribing Information for Epclusa for more information on potentially significant drug interactions, including clinical comments.

About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk that physicians may not see the benefits of prescribing Epclusa for the treatment of adults with chronic HCV infection, for expanded use in patients co-infected with HIV. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. Full Prescribing Information for Epclusa, including BOXED WARNING, is available at www.gilead.com.

Epclusa is a registered trademark of Gilead Sciences, Inc., or its related companies.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Monday, July 31, 2017

Really Rapid Review — Paris IAS 2017

HIV and ID Observations
An ongoing dialogue on HIV/AIDS, infectious diseases, all matters medical, and some not so medical.

Really Rapid Review — Paris IAS 2017
Paul E. Sax, MD

Last week, the International AIDS Society meeting returned to Paris for the first time since 2003.

Here’s a Really Rapid Review® of some of the conference highlights, roughly ordered by “cure”, prevention, treatment, and complications....

Continue reading.....

Saturday, June 10, 2017

CROI 2017: Highlights of Advances in Viral Hepatitis and Liver Fibrosis.

Top Antivir Med. 2017 May/Jun;25(2):84-92.

CROI 2017: Highlights of Advances in Viral Hepatitis and Liver Fibrosis.
Luetkemeyer AF1, Wyles DL2.

ABSTRACT:
At the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington, hepatitis C virus (HCV) infection was a major focus in the context of HIV-associated liver disease. Well-tolerated direct-acting antiviral (DAA) regimens have enabled effective treatment of the populations that are hardest to cure, including those with decompensated cirrhosis, and many studies examined the impact of HCV cure on hepatitis and extrahepatic outcomes. Scaling up access to DAAs and the impact that their universal availability can have on reducing prevalence were key topics. There was much discussion of what is needed to eliminate HCV on local and global levels and a focus on ensuring that the populations hardest to reach can access treatment. Prevention of new infections and reinfection will be key to sustaining the benefits of scaled-up HCV treatment, with particular attention to populations at elevated risk for HCV reinfection, including HIV-infected men who have sex with men (MSM) as well as some HIV-uninfected MSM on preexposure prophylaxis. In the hepatitis B virus (HBV) arena, a landmark phase III trial demonstrated that tenofovir disoproxil fumarate given to HBV-infected pregnant women at week 28 of gestation, in combination with postpartum HBV vaccination and hepatitis B immunoglobulin, resulted in zero mother-to-child transmissions of HBV.

Keywords: CROI, 2017, hepatitis, HBV, HCV, viral hepatitis, direct acting antivirals  

Authors Bio: Dr Luetkemeyer is Associate Professor at the University of California San Francisco. Dr Wyles is Chief of the Infectious Diseases Division at Denver Health in Colorado. Send correspondence to Anne F. Luetkemeyer, MD, 995 Potrero Ave, Box 0874, San Francisco, CA 94110.

Selected Topics
HCV Natural History and Markers of Clinical Fibrosis
HCV Treatment Outcomes: Impact of Generics and Genotype
Toxicity and Drug Interactions During DAA Treatment
HCV Treatment in Cirrhosis and Post-Liver Transplant
Impact of HCV on Extrahepatic Disease, Lipid Profiles, and Overall Mortality
Hepatocellular Carcinoma


All cited abstracts appear in the CROI 2017 Abstracts eBook, available online at www.CROIconference.org.

Recommended Links
CROI 2017 - Conference on Retroviruses and Opportunistic Infections (CROI)
February 13-16, 2017, Seattle WA

Friday, November 4, 2016

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections
World J Hepatol. Nov 8, 2016; 8(31): 1295-1308
Published online Nov 8, 2016. doi: 10.4254/WJH.v8.i31.1295
Daniel Fuster, Arantza Sanvisens, Ferran Bolao, Inmaculada Rivas, Jordi Tor, Robert Muga    

Abstract
Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus (HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.

Key Words: Hepatitis C virus, Human immunodeficiency virus, Hepatitis C virus/human immunodeficiency virus co-infection, Liver, Alcohol

Core tip: The present review is focused on alcohol use disorder and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection, as well as HCV/HIV co-infection.
Citation: Fuster D, Sanvisens A, Bolao F, Rivas I, Tor J, Muga R. Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections.

INTRODUCTION
Alcohol abuse is a major cause of preventable liver disease worldwide, and alcohol use disorder (AUD) is associated with substantial disease burden in western countries[1]. According to 5th edition of the Diagnostic and Statistical Manual of Mental Disorders[2], AUD encompasses both alcohol abuse and alcohol dependence. Table 1 presents the diagnostic criteria for AUD and other definitions of unhealthy alcohol use, such as the recommendations of the United States National Institute on Alcohol Abuse and Alcoholism.

In the United States, almost 9% of the adult population meets the AUD criteria and alcohol contributes to 79000 deaths annually[3]. Within the European Union, alcohol misuse causes 14% of deaths in men and nearly 8% of deaths in women, with alcohol-related mortality disproportionally impacting young people[4]. In Spain, unhealthy alcohol use is exhibited by 5% of the population between 15 and 64 years old, and 15% report at least one binge drinking episode within the prior year[5]. Moreover, the pattern of binge drinking is becoming increasingly prevalent, mainly among young individuals.

Per capita alcohol consumption is strongly correlated with liver cirrhosis mortality rates globally[6]. However, the short- and long-term impacts of binge drinking with regards to the development and severity of alcoholic liver disease (ALD) are not yet known. Per capita alcohol consumption is strongly correlated with liver cirrhosis mortality rates across countries[5]. Notably, the medical literature reveals wide heterogeneity in the methods used to assess alcohol exposure, and it can be challenging to analyze time-varying exposures like alcohol consumption over time[7].

Epidemiology of AUD in hepatitis C virus and human immunodeficiency virus infection
Addressing alcohol use is critical in the management of hepatitis C virus (HCV)-infected patients, as AUD is associated with poor clinical outcomes and liver-related deaths in this patient group[8]. Compared to the general population, HCV-infected adults tend to consume greater amounts of ethanol[9], being over twice as likely to consume more than one alcoholic drink per day (34% vs 14%) and almost 8 times more likely to consume over three drinks per day (19% vs 2%)[10].

Moreover, alcohol abuse is associated with concomitant use of illegal substances, and 30% to 50% of patients with a history of substance abuse consume alcohol[11]. This is highly important since 2/3 of new HCV infections in the western world are associated with drug injection[12]. Accordingly, the prevalence of HCV infection is higher among patients with AUD who are current or past injecting drug users[13]. Within a cohort of patients with AUD admitted for hospital detoxification in the Barcelona area, HCV prevalence was as high as 20%[14]. However, other researchers in Spain reported a much lower prevalence of 3.5%[13], possibly due to differences in patient selection.

The prevalence of HCV infection is confounded by the degree of liver disease. Cross-sectional studies performed in hepatology clinics showed that HCV prevalence was higher among patients with advanced liver fibrosis, and almost universal among HCV-infected patients with hepatocellular carcinoma[15,16]. On the other hand, HCV prevalence ranged from 1% to 10% in community-oriented studies of individuals with AUD but without clinically apparent liver disease[17,18]. A recent meta-analysis including 24 studies reported that the average weighted prevalence of HCV infection among patients with AUD was 16.3%[13].

AUD may also be common among human immunodeficiency virus (HIV)/AIDS patients, with a prevalence ranging from 30% to 50%[19]. High prevalences of alcohol consumption have been reported in HIV/AIDS cohort studies from the United States[20,21], Europe[22-24], South Africa[25], and other parts of the world[26]. In the Women’s Interagency HIV Study, 14%-24% of female HIV/AIDS participants reported hazardous alcohol use within the past year[27]. On the other hand, patients with AUD show a lower prevalence of HIV infection than HCV infection[14], which is confounded by prevalence of injection drug use.

AUD AND CHRONIC HCV INFECTION
Effect of alcohol on HCV replication
Alcohol metabolites apparently enhance viral protein expression as well as the heterogeneity of HCV quasispecies[28]. Some authors describe RNA-HCV increases among patients who use alcohol[29]. However, a meta-analysis performed by Anand et al[30] in 2005 showed no association between RNA-HCV and alcohol consumption.

Impact of alcohol on HCV infection persistence
Spontaneous resolution of HCV infection requires an early and wide immune response against HCV viral proteins[31]. Once acute HCV infection is controlled, the presence of memory T-cell populations is associated with reduced persistence of infection in re-exposed individuals[32]. HCV infection persistence is also associated with loss of specific T-cell proliferation, and reduced migration of effector T cells to the liver[33]. HCV-infected patients with AUD show functional impairment of dendritic cells[34], which partly explains the association between alcohol use and lower odds of spontaneous HCV resolution[35,36].

Effect of alcohol on HCV-related immunity
Mice that are chronically exposed to ethanol exhibit diminished immune responses to HCV-core protein, mainly due to impaired maturation of dendritic cells[34]. In HCV-infected patients, dendritic cells present impaired allostimulation capacity, which is more apparent in the presence of alcohol[34]. Alcohol and HCV infection exert synergistic effects, suppressing major histocompatibility complex class II[37] via functional impairment of the proteasome (intracellular protein complexes that degrade unnecessary or damaged proteins) and alterations in interferon signaling[38]. This could partly explain the lower efficacy of interferon-based HCV treatment regimens among patients with AUD[39].

Effect of alcohol on cytotoxicity
Enhanced hepatocyte apoptosis is observed in HCV infection, which is apparently associated with impaired immune responses rather than directly attributable to the viral infection[40]. Hepatocyte apoptosis is mediated by cytotoxic T cells and natural killer cells via caspase activity[40]. BCL-2 protein is associated with mitochondrial permeability, and its expression is reduced in HCV-infected hepatocytes[41]. Alcohol seems to enhance hepatocyte apoptosis through down-regulation of BCL-2 expression[40].

Alcohol and oxidative stress
The HCV core viral protein is associated with higher oxidative stress. It binds the mitochondrial wall, facilitating calcium entrance, electron transport, and increased reactive oxygen species, which results in increased oxidative stress that damages the cell[42]. This protein also targets microsomal triglyceride transfer protein activity, thus modifying hepatic very-low-density lipoprotein particle assembly and secretion, which leads to liver steatosis[43]. Moreover, the HCV core viral protein alters the oxidant/antioxidant state of the liver in the absence of inflammation, consequently producing mitochondrial DNA damage[44].

In HCV-core transgenic mice, chronic ethanol administration is associated with higher lipid peroxidation and synergic induction of TGF-β1 and hepatic stellate cells[45]. The HCV-core protein cooperates with ethanol to activate some p38 mitogen-activated protein kinase pathways, resulting in polygene modulation, and contributing to liver disease pathogenesis[46]. In alcohol-fed NS5A transgenic mice, the synergistic effect between HCV infection and alcohol is dependent on mechanisms involving Toll-like receptor 4, which belongs to the innate immune system[47]. Alcohol consumption and HCV infection impact FOXO3 expression, thus impairing antioxidant capacity in the liver[48].

In humans, indirect evidence suggests that oxidative stress is associated with more extensive liver injury in patients with AUD and HCV infection, as they tend to show higher serum levels of malondialdehyde (a lipid peroxidation product), poor glutathione peroxidase activity, and stimulation of Th1 response cytokines[49]. Moreover, patients with AUD present major lipid peroxidation, and the loss of antioxidant capacity is associated with liver fibrosis[50]. Among HCV-infected patients who drink alcohol, liver fibrosis is independently associated with liver steatosis, oxidative stress, age, and iron deposits in the liver[51].

Alcohol and progression of HCV-related liver disease
Alcohol consumption is associated with more extensive progression of HCV-related liver damage[52,53]. No safe level of alcohol consumption has been described, as even HCV-infected patients who drink moderate amounts of alcohol (30 g/d) experience progressive liver fibrosis[54-56]. A meta-analysis assessed 20 studies that were published between 1995 and 2004, and found that the relative risk of progression to liver cirrhosis or decompensated liver disease among HCV-infected patients was 2.3 times higher, with a 95%CI of 1.7-3.3, among those who drank alcohol compared to abstainers[52]. However, the majority of included studies were performed in liver units, and thus might be biased towards patients with more severe forms of liver disease[52]. Alcohol consumption is also associated with higher risks of cirrhosis decompensation and liver-related death[57]. Moreover, alcohol consumption has a synergistic effect with chronic hepatitis C, increasing the risk of liver cancer[58].

Assessment of liver disease in patients with AUD and HCV infection
In both HCV infection and ALD, liver fibrosis is the main prognostic factor of liver disease progression[59,60]. Although liver biopsy is the gold standard for liver fibrosis assessment[61], it is associated with several rare complications and is not usually performed in patients with substance use disorders[62]. Recent reports describe the estimation of liver fibrosis using several non-invasive biological markers derived from laboratory parameters routinely used in clinical practice, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count.

Of these potential markers, FIB-4[63] and the aspartate aminotransferase/platelet ratio index (APRI)[64] have been validated against the gold standard of liver biopsy in HCV-monoinfected patients as well as HCV/HIV-coinfected patients[65-68]. These markers perform better for detecting either the absence of liver fibrosis or the presence of advanced liver fibrosis[63,64]. However, clinical experience using these markers in patients with AUD is limited[69], and concerns have been raised about the possibility of overestimating liver fibrosis in patients with alcoholic steatohepatitis. Moreover, ALD is a formal contraindication for the use of Pohl’s score[70]-an index that uses aminotransferase levels and platelet count. Transient elastography has also been used to assess liver fibrosis in ALD[71], but the presence of severe liver steatosis may distort results, leading to overestimation of advanced liver fibrosis[72].

In prior studies, we have defined alcohol-related liver disease (ARLD) as the presence of any two of the following criteria: Elevated AST to between 74 and 300 U/L, AST/ALT ≥ 2, and total bilirubin > 1.2 mg/dL[73,74]. Within a cohort of AUD patients admitted for hospital detoxification in metropolitan Barcelona, Spain, 14.6% met those criteria, and ARLD was associated with mid-term mortality[75].

Impact of HCV infection on hospitalizations and mortality of patients with AUD
As previously mentioned, alcohol use is associated with worse prognosis in HCV-related liver disease. It is estimated that 36% of liver cirrhosis among HCV-infected individuals is attributable to alcohol use[76]. HCV infection also has a deleterious impact on clinical outcomes among patients with AUD[77-80]. Tsui et al[77] identified 6354 AUD-related hospital admissions, and reported that the HCV-positive patients were twice as likely to die (4.4% vs 2.4%, P < 0.01), and showed significantly longer hospital stays (19% longer, 95%CI: 12%-27%). Another study included patients from the United States Nationwide Inpatient Sample Dataset who had a primary or a secondary discharge diagnosis of alcoholic hepatitis, and reported that HCV-positive patients had higher mortality with an odds ratio (OR) of 1.29 (95%CI: 1.12-1.49, P < 0.01)[78].

Patients with AUD who are exposed to HCV infection probably differ from those who are not exposed with regards to co-morbidities or behaviors associated with poorer survival, such as the use of illicit drugs[81]. However, even in studies that have accounted for various lifestyle factors, HCV infection remains associated with both overall mortality, showing a hazard ratio (HR) of 2.55 (95%CI: 1.50-4.33, P < 0.01), and liver-related mortality (HR = 3.24, 95%CI: 1.18-8.94, P = 0.02)[79].

In our study of 675 AUD patients admitted for hospital detoxification, we examined the impact of HCV infection on mortality. Our results showed that HCV infection was associated with higher mortality, and that this effect was more apparent in patients with younger ages at admission (HR = 3.1, 95%CI: 1.3-7.3, P < 0.01) and those who were co-infected with HCV/HIV (HR = 3.9, 95%CI: 2.1-7.1, P < 0.01)[80]. In the same Barcelona cohort, we recently reported that AUD patients with HCV mono-infection showed an increased risk of liver-related death in comparison to AUD patients without HCV-infection (HR = 3.92, 95%CI: 2.03-7.59)[82].

Interferon-based treatment of HCV infection in patients with AUD
In the era of HCV antiviral therapy including interferon, infection treatment was challenging in individuals who consumed alcohol[8]. In fact, alcohol use was a major reason for a lack of HCV treatment[83,84]. Several researchers analyzed strategies to extend HCV treatment to patients with unhealthy alcohol use. Le Lan et al[85] performed an observational study of HCV treatment in alcohol-drinking patients, in which drinking in moderation was encouraged but not required. Of the study population, 30% continuously abstained, 34% consumed low-risk amounts of alcohol, and 36% continued to drink risky amounts. The overall sustained viral response (SVR) rate was 48% with no difference observed between abstainers and low-risk drinkers[85], confirming prior results in a Swiss HCV cohort[86].

Evon et al[87] performed a randomized clinical trial in the United States, which included 9-mo intervention comprising counseling, case management, and motivational interviewing for patients ineligible for HCV treatment (31% due to alcohol abuse). The intervention was associated with a 2.38 relative risk of being deemed eligible (95%CI: 1.21-4.68). The groups did not differ with regards to the proportion of patients that eventually received HCV antiviral therapy[87].

Interferon-free treatment of HCV infection in patients with AUD
The advent of direct-acting antivirals and interferon-free regimens has dramatically changed the landscape of HCV treatment, with most registration trials and pilot real-life experiences reporting SVR rates of over 90%[88]. Although treatment is now more feasible for patients with substance use disorders[89,90], to date, very few patients with AUD have been included in clinical trials[91-93].

The current American Association for the Study of Liver Diseases - Infectious Diseases of America guidelines for HCV treatment advocate abstinence from alcohol[94]. When appropriate, these guidelines suggest interventions to facilitate the cessation of alcohol consumption, ranging from brief interventions for patients with low alcohol intake[94], to referral to mutual help groups and specialty treatment for patients with established AUD[94]. While alcohol consumption is not a formal contraindication for HCV treatment, a year of abstinence from alcohol is thought to be necessary to achieve adequate treatment adherence[95].

There remains a need for a change in the provision of HCV treatment such that patients with AUD and HCV infection can benefit from viral eradication. Expansion of the capacity of primary care clinics or addiction clinics to provide HCV treatment has been successfully tested in several areas of the United States[96] and Australia[90]. These experiences should be replicated worldwide to more effectively treat difficult-to-reach populations[97].

AUD treatment in patients with HCV infection
Brief interventions involving feedback and discussion of the negative consequences of alcohol abuse are efficacious at motivating reduced alcohol consumption among among patients with unhealthy alcohol use[98], but not patients with alcohol dependence. Such brief interventions can be targeted towards patients with HCV infection, with delivery at the primary care level or in hepatology clinics[94,99]. More intensive treatments, such as motivational enhancement therapy, can also reduce the number of drinking days among patients with chronic HCV infection[100]. Other type of interventions, such as group therapy, can reportedly motivate abstinence from alcohol in 44% of patients in an HCV clinic[101].

Table 2 summarizes the various treatment strategies for patients with AUD. Specialty treatment should be favored in such cases, and patients should be offered detoxification; specific pharmacotherapy including disulfiram, acamprosate, naltrexone, or nalmefene; and psychosocial support[3]. Some researchers have reported satisfactory results with baclofene in patients with overt end-stage liver disease[102].

AUD AND HIV INFECTION
Effect of alcohol on the immune system
The combined effects of alcohol and HIV on the immune system have been investigated in simian models[103]. Alcohol and HIV infection show a synergistic impact on gastrointestinal tract integrity, causing initial depletion of intestinal CD4 cells[104,105]. Loss of intestinal wall integrity is associated with increased permeability, microbial translocation, and immune activation[106]. Immune activation is crucial for HIV disease progression[107], and is reportedly a better predictor of disease progression than HIV viral load[106,108]. While alcohol seems to impact the adaptive immune responses to HIV infection in animal models, the results in humans are mixed[103]. In a study of HIV-infected patients, blood alcohol levels relative to alcohol intake were higher before antiretroviral treatment compared to after treatment[109].

Alcohol and HIV disease progression
Prior to widespread use of antiretroviral therapy (ART), epidemiological data suggested that alcohol use was not associated with HIV disease progression[110,111]. However, following the advent of ART, several authors have reported reduced ART effectiveness among patients with AUD[19,112]. In 2003, Samet et al[113] investigated a cohort of HIV-infected patients, and reported cross-sectional data suggesting that alcohol consumption negatively impacted HIV disease progression. Alcohol consumption was associated with lower CD4 cell counts and higher HIV viral loads in patients receiving ART. A later longitudinal study of the same cohort demonstrated that heavy alcohol use in patients not receiving ART was associated with lower CD4 cell counts but not with HIV viral load[114].

Chander et al[115] at John Hopkins University reported that heavy alcohol consumption was associated with reduced viral suppression of HIV infection and lower treatment adherence. Wu et al[116] investigated 325 subjects receiving ART and found that, after adjusting for adherence, daily drinkers showed a nearly four-fold increase in the odds of detectable HIV viral load. This association was non-significant for regular drinkers. Their results further showed that alcohol use was not associated with CD4 cell count, and that alcohol consumption was not associated with HIV viral load among patients not receiving ART[116]. On the other hand, Baum et al[117] investigated HIV-infected patients receiving ART, and reported that alcohol use was associated with lower CD4 cell counts, greater risk of showing a CD4 cell count of < 200, and an increased HIV viral load over time.

More recent studies indicate that the benefits of ART seem to outweigh the detrimental effects of alcohol use, reinforcing the importance of initiating ART and ensuring adequate treatment adherence[118]. A study in a Swiss HIV cohort revealed no effect of alcohol consumption on either virological failure or CD4 cell count, both among ART-receiving and ART-naïve patients[119]. That study also demonstrated that heavy drinkers were more likely to interrupt ART; however, only 2.8% of participants were heavy drinkers[119]. A recent French study of HIV/AIDS patients reported that low levels of alcohol consumption (< 10 g/d) were associated with higher CD4 counts compared to in abstainers[120]. However, the beneficial effects of such low levels of alcohol consumption may be confounded by other healthier behaviors exhibited by moderate drinkers[121].

Overall, evidence acquired during the first decade of ART use suggested that AUD may impact HIV disease progression; however, more recent studies do not support those findings. These contradictory results may be partly explained by poor adherence to treatment and barriers to proper medical care associated with AUD.

Alcohol and comorbidities
Alcohol use is associated with unprotected sex and syringe sharing, thus elevating the risks of HIV acquisition and transmission[122-124]. Moreover, alcohol use is associated with higher prevalence of depressive symptoms[125], which can influence ART initiation[126], treatment adherence[127], treatment discontinuation[128], and disease progression[129,130]. Other substance use disorders frequently co-exist in patients who exhibit alcohol abuse[11], which is also associated with poorer treatment adherence, reduced HIV viral suppression, and lower retention in care[112,131].

Heavy alcohol use is related to liver disease among patients with HIV infection[132,133], and is also associated with cardiovascular disease[134] and exacerbations of chronic obstructive pulmonary disease[135]. A systematic review of 13 studies reported that heavy alcohol use was associated with elevated risk of cardiovascular disease, with a risk ratio of 1.78 (95%CI: 1.09-2.93)[134].

Alcohol and mortality in HIV infection
Alcohol is commonly regarded as an underappreciated modifiable risk factor in individuals with HIV infection, with or without HCV co-infection[116]. A retrospective study from northern California evaluated data from between 1996 and 2005, and found that higher mortality rates were associated with diagnosis of a substance use disorder (alcohol only, drug only, or alcohol and drug)[136]. In the HIV-LIVE cohort of HIV-positive patients with alcohol problems, short-term mortality was associated with homelessness and drug use[137], and long-term mortality was associated with HCV infection and high levels of inflammation markers[79,138]. A study from the VACS cohort revealed that even non-hazardous levels of alcohol consumption were associated with decreased survival[139]. Recent data from the same VACS cohort shows that among HIV-positive participants, alcohol use was associated with greater physiological injury. Moreover, within this cohort, a greater risk of mortality was associated with an Alcohol Use Disorders Identification Test value of ≥ 4 drinks/mo (HR = 1.25, 95%CI: 1.09-1.44), and of ≥ 30 drinks/mo (HR = 1.30, 95%CI: 1.14-1.50)[140].

HIV treatment in patients with AUD
Alcohol use co-existing with other substance use is associated with lower quality of HIV care[141] and poor retention in care[131]. A systematic review of 53 studies published between 2010 and 2015 showed that 77% of studies revealed that alcohol use was negatively associated with the HIV treatment cascade, i.e., access to care, ART prescription, and treatment adherence[142]. This suggests that unhealthy alcohol use should be targeted to increase the proportion of HIV/AIDS patients who achieve viral suppression.

Even modest alcohol consumption has been associated with poor ART adherence[139]. Hendershot et al[143] performed a meta-analysis of 40 studies, and showed that patients who drank relatively more were 50%-60% less likely to adhere to ART compared with those who abstained or drank relatively less. Alcohol consumption appears to be dose-dependently related to ART adherence[115], and shows a temporal relationship to missed ART treatments[144].
AUD treatment in HIV-infected patients

Among HIV/AIDS patients who drink alcohol, brief interventions are reportedly efficacious for reducing the frequency of alcohol use and the frequency of unprotected sex[145,146]. However, patients abusing alcohol might need more intensive treatment. Some authors report that the addition of motivational interviewing[147] and problem solving therapy may be necessary to improve ART adherence[148]. An intervention called retention through enhanced personal contact has also been tested to improve retention among HIV-positive patients with alcohol use or mental illness[149].

Chander et al[150] recently performed a cross-sectional survey among HIV care providers, and found that although the majority reported that they usually screen for alcohol use, only 10% used a formal screening tool. Moreover, knowledge of pharmacotherapy for AUD was low, and most care providers referred patients to outside resources for treatment[150].

AUD AND HCV/HIV CO-INFECTION
A proportion of patients with both AUD and HCV infection also have HIV infection. In fact, HCV/HIV co-infection is clinically relevant among individuals with history of injection drug use[151]. HIV infection is associated with faster progression of HCV-related liver fibrosis[152,153] as well as earlier occurrence of decompensated liver disease[154,155], liver cancer[156], and liver-related death[157]. During the interferon era, co-infection with HIV compromised HCV treatment response[158,159]. However, interferon-free regimens have greatly increased the efficacy of HCV antiviral treatment among co-infected patients, both in clinical trials[160] and in real-life scenarios[161,162]. On the other hand, HCV infection is associated with increased risk of ART-related liver toxicity[163], which is even higher with concurrent alcohol use[164]. In cases of HCV/HIV co-infection, alcohol use is also associated with poorer treatment adherence[165], and seems to increase HCV RNA levels[166,167].

Until recently, the impact of alcohol use on HCV-related liver disease in HIV-infected patients had not received much attention in the literature. Older studies suggest that alcohol use is associated with biopsy-proven liver fibrosis in cases of co-infection[152,168]. However, studies using non-invasive methods have produced mixed results, highlighting the shortcomings of non-invasive methods-including methods relying on ALT, AST, and platelets-in patients with ALD[70,69]. Table 3 summarizes the different studies that have used non-invasive methods to evaluate liver fibrosis in patients with AUD and HCV infection or HCV/HIV co-infection.

A cross-sectional study in an urban HIV/AIDS cohort revealed that heavy alcohol use was associated with advanced liver fibrosis measured using the APRI score[169]. However, when the patients were stratified by HCV infection, high APRI score was associated with hazardous alcohol use only among patients without HCV infection[169]. Blackard et al[170] investigated a cohort of women, and demonstrated that alcohol use was not associated with FIB-4 values among HCV/HIV co-infected patients. Within our cohort of AUD patients, FIB-4 was significantly higher among HCV/HIV co-infected patients compared to in HCV monoinfected patients[171]. In the HIV-LIVE cohort, lifetime alcohol consumption[172] was not associated with the absence of liver fibrosis (FIB-4 < 1.45), and similar results were found for the presence of advanced liver fibrosis (FIB-4 ≥ 3.25) and among patients with HCV infection[173]. A study in the VACS cohort-which included a larger number of patients and a different measure of alcohol consumption-reported greater risks of advanced liver fibrosis (measured based on FIB-4) among co-infected patients who exhibited nonhazardous drinking (OR = 14.2, 95%CI: 5.91-34.0) or hazardous/binge drinking (OR = 18.9, 95%CI: 7.98-44.8), or who had alcohol-related diagnoses (OR = 25.2, 95%CI: 10.6-59.7) relative to uninfected individuals who were nonhazardous drinkers[174]. The somewhat discordant results among studies may be partly due to differences in the methods used to describe alcohol use and other characteristics of the study population[169-174].

French researchers investigating HCV/HIV co-infected patients recently found that advanced liver fibrosis (measured with transient elastography) was more common among those with an alcohol-related diagnosis (OR = 3.06, 95%CI: 1.42-6.60) compared to non-hazardous drinkers[175]. Elastography may be more reliable than laboratory markers for assessing liver fibrosis in HCV/HIV co-infected patients with AUD. Additionally, the combination of HCV infection and alcohol use is associated with greater mortality within HIV/AIDS cohorts[79,176], highlighting the need to further address alcohol use in co-infection. Although it can be challenging, it is feasible to reduce alcohol use in the setting of HCV/HIV co-infection[177].

CONCLUSION
To reduce the impact of HCV, HIV and ethanol on liver disease, patients with AUD should be screened for HCV and HIV infection, and interventions should focus on both reducing alcohol consumption and treating viral infections. Moreover, patients with HCV infection or HCV/HIV co-infection should be screened for unhealthy alcohol use to prevent end-stage liver disease. Several treatment interventions are efficacious for reducing alcohol consumption among individuals with HCV infection or HCV/HIV co-infection.

In settings where AUD often coexists with other substance use and viral co-infections, higher levels of co-morbidities are expected. Health care facilities for treatment interventions and multidisciplinary approaches must be widely accessible for managing AUD and associated diseases.

Source - Full Text - World J Hepatol. Nov 8, 2016; 8(31): 1295-1308
Published online Nov 8, 2016. doi: 10.4254/WJH.v8.i31.1295