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Last Update:  April 13, 2018
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General Reports
 

     Internet Documents
 
  FULL-TEXT PDF DOCUMENT
What HIV Clinicians Should Know (and Do) About HCV Coinfection
Mascolini, M   RITA Summer 2014

HCV infection remains among the most difficult-to-manage comorbidities in people with HIV. But care for HCV-coinfected people changed dramatically with
the advent of direct-acting antivirals (DAAs), as it has for everyone with HCV. This issue of Research Initiative, Treatment Action (RITA) examines how
DAAs have already transformed treatment of HCV infection and considers how they may continue to do so. A practice-oriented interview with HCV/HIV expert
Douglas Dieterich
offers nuts-and-bolts advice on prescribing DAAs for coinfected people and encourages more involvement by HIV clinicians in HCV management.
A second review article dissects perhaps the most controversial question about HCV/HIV coinfection—does HCV make HIV infection worse? Scores of studies
addressing different aspects of this question are almost evenly split in their conclusions. The RITA article suggests how HIV clinicians with coinfected patients may
work their way out of this data maze.]
A final review analyzes sexual HCV transmission among gay and bisexual men. Early research rated sexual HCV
transmission a rare event. But that thinking—still echoed in some online CDC material—stands starkly at odds with an explosive HCV epidemic documented in gays
and bisexuals who do not inject drugs.
Document

          Journal Papers, Abstracts, and Commentaries

 
FULL-TEXT ARTICLE
Circulating MiRNA-122 Levels Are Associated with Hepatic Necroinflammation and Portal Hypertension in HIV/HCV Coinfection.
Jansen C, Reiberger T, Huang J, et al
PLoS One
. 2015 Feb 3;10(2):e0116768.
Paper

Low risk of liver decompensation among human immunodeficiency virus/hepatitis c virus-coinfected patients with mild fibrosis in the short-term.
Macías J, Mancebo M, Márquez M, Merino D, et al

Hepatology
. 2014 Dec 24.
Abstract

Long-term Evaluation of Partial Splenic Embolization Followed by Interferon Therapy in Patients with Hepatitis C Virus (HCV) Cirrhosis and Thrombocytopenia.
Shimizu H, Takatsuka K, Nakano H, et al
Intern Med. 2014;53(9):925-931..
Abstract

Hepatic Decompensation in Antiretroviral-Treated Patients Co-Infected With HIV and Hepatitis C Virus Compared With Hepatitis C Virus-Monoinfected Patients: A Cohort Study.
Lo Re V 3rd, Kallan MJ, Tate JP,  et al
Ann Intern Med
. 2014 Mar 18;160(6).
Abstract

Risk of Liver Decompensations Among Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Individuals with Advanced Fibrosis: Implications for the Timing of Therapy.
Macías J, Márquez M, Téllez F, et al

Clin Infect Dis
. 2013 Aug 14.
Abstract

FULL-TEXT  ARTICLE
Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients.
Peters L, Mocroft A, Soriano V, et al
PLoS One. 2013 May 27;8(5):e64283.
Paper

Liver stiffness predicts liver-related complications and mortality in HIV patients with chronic hepatitis C on antiretroviral therapy.
Fernández-Montero JV, Barreiro P,  et al

AIDS
. 2012 Dec 29..
Abstract


Hepatopulmonary Syndrome
 

          Journal Papers, Abstracts, and Commentaries

  Hepatopulmonary Syndrome in HIV-Hepatitis C Virus Coinfection: A Case Report and Review of the Literature.
Torno MS, Witt MD, Sue DY.
Clin Infect Dis. 2004 Aug 1;39(3):E25-9.
Abstract

Liver Fibrosis
 

          Journal Papers, Abstracts, and Commentaries

 
Mechanisms of accelerated liver fibrosis in HIV-HCV coinfection.
Chrysanthidis T, Loli G, Metallidis S, Germanidis G.
AIDS Rev. 2017 Sep 19;19
Abstract

MAIT-cell frequency and function in blood and liver of HCV mono- and HCV/HIV co-infected patients with advanced fibrosis. [The Netherlands{
B
eudeker BJB, van Oord GW, Arends JE, 
Liver Int
. 2017 Aug 9
Abstract

Trends in HCV treatment uptake, efficacy and impact on liver fibrosis in the Swiss HIV Cohort Study.
Béguelin C, Suter A, Bernasconi E, et al
Liver Int
. 2017 Jul 25. doi: 10
Abstract

FULL-TEXT ARTICLE
A prognostic model for development of significant liver fibrosis in HIV-hepatitis C co-infection.
Moqueet N, Kanagaratham C, Gill MJ, et al

PLoS One
. 2017 May 3;12(5):e0176282
Paper

Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women's interagency HIV study.
Desai SN, Dodge JL, Landay AL,  et al
Medicine (Baltimore). 2016 Aug;95(33):e4483
Abstract

Improving treatment and liver fibrosis outcomes with metformin in HCV-HIV co-infected and HCV mono-infected patients with insulin resistance: study protocol for a randomized controlled trial. 
Doyle MA, Singer J, Lee T, et al
Trials. 2016 Jul 20;17(1):331.
Abstract

A new 3p25 locus is associated with liver fibrosis progression in HIV/HCV co-infected patients.
Ulveling D, Le Clerc S, Cobat A, et al
Hepatology
. 2016 Jun 23.
Abstract

HLA-B18 as a risk factor of short-term progression to severe liver fibrosis in HIV/HCV co-infected patients with absent or minimal fibrosis: implications for timing of therapy.
Frías M, Rodríguez-Cano D, Cuenca-López F,  et al 

Pharmacogenomics J
. 2016 May 31..

Abstract

FULL-TEXT ARTICLE
High Proportion of HIV-HCV Coinfected Patients with Advanced Liver Fibrosis Requiring Hepatitis C Treatment in Haiphong, Northern Vietnam (ANRS 12262).
Nguyen Truong T, Laureillard D,  et al
PLoS One
. 2016 May 5;11(5):e0153744.

Paper

Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.
Kliemann DA, Wolff FH, Tovo CV, et al
Ann Hepatol
. 2015 Jan-2016 Feb;15(1):27-32.
Abstract

Enhanced liver fibrosis marker as a non-invasive predictor of mortality in HIV/HCV-coinfected women from the women's Interagency HIV study.
Peters MG, Bacchetti P, Boylan R, et al
AIDS
. 2015 Nov 20
Abstract

Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact.
Sagnelli C, Martini S, Pisaturo M,  et al

World J Hepatol
. 2015 Oct 28;7(24):2510-21
Abstract

FULL-TEXT ARTICLE
Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy.
Schmid P, Bregenzer A, Huber M,
PLoS One. 2015 Sep 29;10(9):e0138838.
Paper

Progression of liver fibrosis and modern combination antiretroviral therapy regimens in HIV-hepatitis C co-infected persons.
Brunet L, Moodie EE, Young J,  et al
Clin Infect Dis. 2015 Sep 23.
Abstract

Understanding the Mechanisms of Fibrogenesis in HIV/HCV-Coinfected Patients: Implications for Clinical Practice.
Sacchi P, Cima S, Zuccaro V, et al
AIDS Re
v
. 2015 Jul-Sep;17(3):159-70.
Abstract

Opioid use and risk of liver fibrosis in HIV/hepatitis C virus-coinfected patients in Canada.
Brunet L, Moodie E, Cox J, et al
HIV Med
. 2015 Jul 3.
Abstract

Fibrosis Regression Explains Differences in Outcome in HIV-/HCV-Coinfected Patients with Cirrhosis After Sustained Virological Response.
Casado JL, Esteban MA, Bañón S, et al
Dig Dis Sci. 2015 Jun 26.
Abstract

FULL-TEXT ARTICLE
Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection - The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index.
Rollet-Kurhajec KC, Moodie EE, et al

PLoS One
. 2015 Jun 19;10(6):e0129868.
Paper

Delayed liver fibrosis in HTLV-2-infected patients co-infected with HIV-1 and hepatitis C virus with suppressive antiretroviral therapy.
Abad-Fernández M, Moreno A, Dronda F, et al.

AIDS
. 2015 Jan 5.
Abstract

Liver fibrosis, microbial translocation and immune activation markers in HIV and HCV infections and in HIV/HCV co-infection.
Sacchi P, Cima S, Corbella M,  et al
Dig Liver Dis. 2014 Nov 29
Abstract

Liver fibrosis progression despite HCV cure with antiviral therapy in HIV-HCV-coinfected patients.
Labarga P, Fernandez-Montero JV, de Mendoza C, et al
Antivir Ther. 2014 Nov 5.
Abstract

FULL-TEXT ARTICLE

PRO-C3-Levels in Patients with HIV/HCV-Co-Infection Reflect Fibrosis Stage and Degree of Portal Hypertension.
Jansen C, Leeming DJ, Mandorfer M,. et a
PLoS One. 2014 Sep 29;9(9):e108544
Paper

Comparison of liver fibrosis progression in HIV/HCV co-infected and HCV mono-infected patients by transient elastometry.
Mazzocato S, Orsetti E, Gesuita R, et al
Scand J Infect Dis
. 2014 Sep 22:1-6. [
Abstract

FULL-TEXT ARTICLE
Liver Fibrosis, Host Genetic and Hepatitis C Virus Related Parameters as Predictive Factors of Response to Therapy against Hepatitis C Virus in HIV/HCV Coinfected Patients.
Corchado S, López-Cortés LF, Rivero-Juárez A, et al
PLoS One
. 2014 Jul 11;9(7):e101760.
Paper

Progression to advanced liver fibrosis in HIV/HCV-coinfected patients and prioritization of new hepatitis C therapies.
Labarga P, Fernández-Montero JV, López M, et al
Antivir Ther. 2014 Jun 25.
Abstract

Increased incidence of antiretroviral drug discontinuation among patients with viremic hepatitis C virus coinfection and high hyaluronic acid, a marker of liver fibrosis.
G
rint D, Peters L, Rockstroh JK, et al
AIDS. 2014 Feb 20;28(4):577-87.
Abstract

Regression of liver fibrosis is progressive after sustained virological response to HCV therapy in patients with hepatitis C and HIV coinfection.
Casado JL, Quereda C, Moreno A, Pérez-Elías MJ, et al

J Viral Hepat
. 2013 Dec;20(12):829-37.
Abstract

Liver fibrosis progression in HIV-HCV-coinfected patients treated with distinct antiretroviral drugs and impact of peginterferon-ribavirin therapy.
Fernández-Montero JV, Barreiro P,  et al
Antivir Ther
. 2013 Nov 5..
Abstract

FULL-TEXT ARTICLE
The progression of liver fibrosis in prison inmates co-infected by HIV and HCV who started on boosted protease inhibitor therapy

Saiz de la Hoya Zamácola P, Alía Alía C,  et al
Rev Esp Sanid Penit. 2013 Oct;15(2):54-62.
Paper

Factors influencing liver fibrosis and necroinflammation in HIV/HCV coinfection and HCV monoinfection.
Sagnelli C, Uberti-Foppa C, Pasquale G,  et al
Infection. 2013 Jul 10.
Abstract

Prediction of hepatic fibrosis in patients coinfected with human immunodeficiency virus and hepatitis C virus based on genetic markers.
Fernández-Rodríguez A, Berenguer J, Jiménez-Sousa MA,  et al
J
Acquir Immune Defic Syndr
. 2013 Jun 21.

Abstract

FULL-TEXT ARTICLE
Predictive Value of Liver Enzymes and Inflammatory Biomarkers for the Severity of Liver Fibrosis Stage in HIV/HCV Co-Infected Patients.
Charpentier C, Champenois K, Gervais A,  et al

PLoS One
. 2013;8(3):e59205
Paper

Effect of HIV on Liver Fibrosis among HCV-Infected African Americans.
Silver D, Karnik G, Osinusi A, Silk R, et al

Clin Infect Dis
. 2013 Feb 1 [
Abstract

FULL-TEXT ARTICLE
HIV-1 Tropism and Liver Fibrosis in HIV-HCV Co-Infected Patients.
Abravanel F, Raymond S, Pambrun E, Winnock M,  et al

PLoS One
. 2012;7(11):e50289.

Paper

Antiretroviral therapy and sustained virological response to HCV therapy are associated with slower liver fibrosis progression in HIV-HCV-coinfected patients: study from the ANRS CO 13 HEPAVIH cohort.
Loko MA, Bani-Sadr F, Valantin MA,et al

Antivir Ther
. 2012 Oct 10.

Abstract

Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels.
Pace FH, Ferreira LE, Silva AE, Ferraz ML.
Rev Soc Bras Med Trop. 2012 Aug;45(4):444-7.
Abstract

nsulin resistance is associated with progression to hepatic fibrosis in a cohort of HIV/HCV co-infected patients.
Hull MW, Rollet K, Moodie EE,  et al
AIDS. 2012 Jun 2
Abstract

Course of Liver Fibrosis in HIV /HCV Coinfected Patients Depending on the Course of HIV Therapy
Carton JA, Collazos J, DE LA Fuente B, Asensi V.
AIDS Res Hum Retroviruses. 2012 Jun 26..
Abstract

Effect of Liver Fibrosis on Long-Term Mortality in HIV/HCV Coinfected Individuals Who Are Evaluated to Receive Interferon Therapies in the HAART Era.
Sanmartín Sentañes R, De Felipe E, Tor J, et al

AIDS Res Hum Retroviruses
. 2012 Mar 25..
Abstract

Change in Fibrosis Score as a Predictor of Mortality Among HIV-Infected Patients with Viral Hepatitis.
Jain MK, Seremba E, Bhore R,  et al
AIDS Patient Care STDS
. 2012 Jan 12
Abstract

Gender Differences in liver Fibrosis and Hepatitis C Virus-related Parameters in Patients Coinfected with Human Immunodeficiency Virus.
Collazos J, Cartón JA, Asensi V., et al
Curr HIV Res
. 2011 Aug 9.

Abstract

Estimated Liver Fibrosis and its Impact on All-Cause Mortality of HCV-Monoinfected and HCV/HIV-Coinfected Drug Users.
Sanvisens A, Fuster D, Serra I, et al
Curr HIV Res. 2011 Jun 15.
Abstract

Similar Progression of Fibrosis between HIV/HCV- and HCV-Infected Patients: Analysis of Paired Liver Biopsy Samples.
Sterling RK, Wegelin JA, Smith PG,  et al
Clin Gastroenterol Hepatol.
2010 Aug 19.
Abstract

 

     Conference Reports, Abstracts, and Posters

 
Determinants of liver fibrosis among HCV-mono-infected and HIV/HCV-co-infected persons
G. Kirk, S. Mehta, J. Astemborski, et al

(XIX International AIDS Conference)
Abstract

HCV/HIV co-infection and the degree of liver fibrosis as risk factors of HAART-associated nephrotoxicity
M. del Palacio, A. Moreno, M. Martínez-Colubi, et al

(XIX International AIDS Conference)
Abstract

HCV/HIV co-infection and the degree of liver fibrosis as risk factors of HAART-associated nephrotoxicity
M. del Palacio, A. Moreno, M. Martínez-Colubi, et al
(XIX International AIDS Conference)
Abstract

 

Hepatic Steatosis
 

     Journal Papers, Abstracts, and Commentaries
 

 
TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype.
Sagnelli C, Merli M, Uberti-Foppa C,  et al
World J Gastroenterol. 2016 Oct 14;.
Abstract

Hepatic steatosis and steatohepatitis in human immunodeficiency virus/hepatitis C
virus-coinfected patients.
Macías J, Berenguer J, Japón MA, et al
Hepatology. 2012 Apr 16.
Abstract

Hepatic steatosis in HIV-HCV coinfected patients receiving antiretroviral therapy is associated with HCV-related factors but not antiretrovirals.
Martinez V, Ta TD, Mokhtari Z,  et al
BMC Res Notes. 2012 Apr 10;5(1):180
Abstract

Prospective evaluation of hepatic steatosis in HIV-infected patients with or without hepatitis C virus co-infection.
Li Vecchi V, Soresi M, Giannitrapani L, et al
Int J Infect Dis. 2012 Mar 17.

Abstract

Hepatic steatosis in patients coinfected with human immunodeficiency virus/hepatitis C virus: A meta-analysis of the risk factors.
Machado MV, Oliveira AG, Cortez-Pinto H.
Hepatology
. 2010 Jul;52(1):71-8.
Abstract

Adipose Tissue and Metabolic Factors Associated With Steatosis in HIV/HCV Coinfection: Histology Versus Magnetic Resonance Spectroscopy.
Ghotb A, Noworolski SM, Madden E,  et al
J Acquir Immune Defic Syndr
. 2010 May 27
Abstract

Hepatic steatosis associated with increased central body fat by dual-energy X-ray absorptiometry and uncontrolled HIV in HIV/hepatitis C co-infected persons.
Brown TT, Mehta SH, Sutcliffe C, et al 
AIDS
. 2010 Feb 24.
Abstract


Cirrhosis
 

     Journal Papers, Abstracts, and Commentaries
 
 
FULL-TEXT ARTICLE
Prognostic value of liver stiffness in HIV/HCV-Coinfected patients with decompensated cirrhosis.
Pérez-Latorre L, Sánchez-Conde M, Miralles
BMC Infect Dis. 2018 Apr 11;18(1):
Paper

FULL-TEXT ARTICLE
The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients.
Núñez-Torres R, Macías J, Mancebo M,  et al

PLoS One
. 2016 Dec 14;11(12):e0168265
Paper

Incidence and Progression to Cirrhosis of New HCV infections in Persons Living with HIV.
Puoti M, Lorenzini P, Cozzi-Lepri A,  et al
Clin Microbiol Infect
. 2016 Dec 9.
Abstract

Liver stiffness predicts variceal bleeding in HIV/HCV-coinfected patients with compensated cirrhosis.
Merchante N, Rivero-Juárez A, Téllez F, et al

AIDS
. 2016 Dec 5.
Abstract

Statin drugs decrease progression to cirrhosis in HIV/HCV co-infected individuals.
Oliver NT, Hartman CM, Kramer JR, Chiao EY.
AIDS
. 2016 Aug
Abstract

Associations between lipodystrophy or antiretroviral medications and cirrhosis in patients with HIV infection or HIV/HCV coinfection.
Ioannou GN, Bryson CL, Weiss NS, Boyko EJ.
Eur J Gastroenterol Hepatol. 2015 Mar 12.
Abstract

Prediction of liver complications in patients with HCV-related cirrhosis with and without HIV coinfection: comparison of hepatic venous pressure gradient and transient elastography.
Pérez-Latorre L, Sánchez-Conde M, Rincón D, et al

Clin Infect Dis
. 2013 Nov 21.
Abstract

HIV/HCV co-infected patients and cirrhosis: how to diagnose it and what to do next?
Martel-Laferrière V, Wong M, Dieterich DT.
Clin Infect Dis. 2013 Oct 30.
Abstract

Liver stiffness measurement versus liver biopsy to predict survival and decompensations of cirrhosis among HIV/HCV-coinfected patients.
Macías J, Camacho A, Von Wichmann MA, López-Cortés LF, et al
AIDS
. 2013 Jun 3..

Abstract

The Diagnostic Accuracy of Fibroscan for Cirrhosis is Influenced by Liver Morphometry in HCV Patients with a Sustained Virological Response.
D'Ambrosio R, Aghemo A, Fraquelli M,  et al
J Hepatol
. 2013 Mar 22.
Abstract

Liver stiffness correlates with Child-Pugh-Turcotte and MELD scores in HIV/hepatitis C virus-coinfected patients with cirrhosis.
Recio E, Macías J, Rivero-Juárez A, Téllez F, et al
Liver Int
. 2012 Mar 9.
.
Abstract

 

End Stage Liver Disease
 

  Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients.
Lo Re V 3rd, Kallan MJ, Tate JP, et al 
Open Forum Infect Dis
. 2015 Jul 9;2(3):ofv109
Abstract

Management of end-stage liver disease in HIV/hepatitis C virus co-infection.
Spengler U.
Curr Opin HIV AIDS
. 2011 Sep 13.
Abstract


Hepatocellular Carcinoma
 

     Journal Papers, Abstracts, and Commentaries

 

Hepatitis C-related hepatocellular carcinoma: diagnostic and therapeutic management in HIV-patients.
D'Aleo F, Ceccarelli M, Venanzi Rullo E, et a
l
Eur Rev Med Pharmacol Sci. 2017 Dec;21(24):5859-5867.
Abstract

Trends in incidences and risk factors for hepatocellular carcinoma and other liver events in HIV and hepatitis C virus co-infected individuals from 2001 to 2014: a multi-cohort study.
Gjærde LI, Shepherd L, Jablonowska E,  et al
Clin Infect Dis. 2016 Jun 15
Abstract

Imaging Features and Prognosis of Hepatocellular Carcinoma in Patients with Cirrhosis Who are Coinfected with Human Immunodeficiency Virus and Hepatitis C Virus.
Lewin M, Gelu-Simeon M, Ostos M,  et al

Radiology
. 2015 May 6:
Abstract

Incidence of hepatocellular carcinoma in hepatitis C cirrhotic patients with and without HIV infection: a cohort study, 1999-2011.
Di Benedetto N, Peralta M, Alvarez E,  et al
Ann Hepatol
. 2013 Jan-2014 Feb;13(1):38-44.
Abstract

HIV/hepatitis C virus-coinfected patients who achieved sustained virological response are still at risk of developing hepatocellular carcinoma.
Merchante N, Merino E, Rodríguez-Arrondo F, et al
AIDS. 2013 Sep 19
Abstract

Hepatocellular carcinoma in patients co-infected with hepatitis C virus and human immunodeficiency virus.
Dimitroulis D, Valsami S, Spartalis E,  et al

World J Hepatol
. 2013 Jun 27;5(6):323-327
Abstract

Uninodular combined hepatocellular and cholangiocarcinoma with multiple non-neoplastic hypervascular lesions appearing in the liver of a patient with HIV and HCV coinfection.
Uchino K, Tateishi R, Nakagawa H, et al

J Clin Virol
. 2013 Feb 19. .
Abstract

Primary liver cancer is more aggressive in HIV-HCV coinfection than in HCV infection. A prospective study (ANRS CO13 Hepavih and CO12 Cirvir)
Bourcier V, Winnock M, Ait Ahmed M, et al
Clin Res Hepatol Gastroenterol. 2011 Dec
Abstract

Insulin resistance is associated with a higher risk of hepatocellular carcinoma in cirrhotic HIV/HCV-coinfected patients: Results from ANRS CO13 HEPAVIH.
Salmon D, Bani-Sadr F, Loko MA,  et al
J Hepatol
. 2011 Dec 12
Abstract

 
  Conference Reports, Abstracts, and Posters
 
  Increased risk of hepatic decompensation and hepatocellular carcinoma in HIV/HCV-co-infected patients compared to HCV-mono-infected patients despite combination antiretroviral therapy
V. Lo Re, J Tate, M. Kallan, et al
(XIX International AIDS Conference)
Abstract

Portal Hypertension
 

          Journal Papers, Abstracts, and Commentaries

  FULL-TEXT ARTICLE
PRO-C3-Levels in Patients with HIV/HCV-Co-Infection Reflect Fibrosis Stage and Degree of Portal Hypertension.
Jansen C, Leeming DJ, Mandorfer M,. et al
PLoS One. 2014 Sep 29;9(9):e108544
Paper

HIV-HCV co-infected patients with low CD4+ cell nadirs are at risk for faster fibrosis progression and portal hypertension.
Reiberger T, Ferlitsch A, Sieghart W, et al
J Viral Hepat
. 2009 Sep 25.
Abstract

 


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