non-invasive tool for assessing liver fibrosis in HIV/HCV patients

Transient elastography: A non-invasive tool for assessing liver fibrosis in HIV/HCV patients
ISSN 1007-9327 CN 14-1219/R
World J Gastroenterol 2010 November 7; 16(41): 5225-5232

BRIEF ARTICLE

Valentina Li Vecchi, Maurizio Soresi, Claudia Colomba, Giovanni Mazzola, Pietro Colletti, Maurizio Mineo, Paola Di Carlo, Emanuele La Spada, Giovanni Vizzini, Giuseppe Montalto
Valentina Li Vecchi, Maurizio Soresi, Giovanni Mazzola, Pietro Colletti, Maurizio Mineo, Emanuele La Spada, Giuseppe Montalto, Department of Clinical Medicine and Emerging Pathologies, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy
Claudia Colomba, Paola Di Carlo, Infectious Diseases Section, Department of Health Promotion Sciences, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy
Giovanni Vizzini, Department of Gastroenterology and Hepatology, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IsMeTT), University of Pittsburgh Medical Center, Via Tricomi 1, 90127 Palermo, Italy
Author contributions: Montalto G, Li Vecchi V and Mazzola G designed the research; Li Vecchi V, Mazzola G, La Spada E, Colletti P, Mineo M, Colomba C and Di Carlo P performed the research; Soresi M analyzed the data; Li Vecchi V and Montalto G wrote the paper; Montalto G, Soresi M and Vizzini G reviewed the paper.
Correspondence to: Giuseppe Montalto, Professor, Department of Clinical Medicine and Emerging Pathologies, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy. gmontal@unipa.it
Telephone: +39-91-6552991 Fax: +39-91-6552977
Received: April 14, 2010   Revised: June 1, 2010
Accepted: June 8, 2010
Published online: November 7, 2010

Abstract

AIM:
To assess the prevalence of advanced liver fibrosis (ALF) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV/HCV patients using transient elastography, and to identify factors associated with ALF.

METHODS:
Between September 2008 and October 2009, 71 HIV mono-infected, 57 HIV/HCV co-infected and 53 HCV mono-infected patients on regular follow-up at our Center were enrolled in this study. Alcohol intake, the main parameters of liver function, presence of HCV-RNA, HIV-RNA, duration of highly active anti-retroviral therapy (HAART) and CD4 cell count were recorded. ALF was defined as liver stiffness (LS) ≥ 9.5 kPa. To estimate liver fibrosis (LF) a further 2 reliable biochemical scores, aspartate aminotransferase platelet ratio index (APRI) and FIB-4, were also used.

RESULTS:
LS values of co-infected patients were higher than in either HIV or HCV mono-infected patients (c2MH = 4, P < c2 =" 5,"> 9.5 kPa. There was no significant correlation between extent of LF and HAART exposure or duration of HAART exposure, in particular with specific dideoxynucleoside analogues.

CONCLUSION:
ALF was more frequent in co-infected than mono-infected patients. This result correlated with lower CD4 levels. Protective immunological effects of HAART on LF progression outweigh its hepatotoxic effects.


Peer reviewer: Dr. Chao-Hung Hung, MD, Associate Professor, Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung, Kaohsiung 833, Taiwan, China

Li Vecchi V, Soresi M, Colomba C, Mazzola G, Colletti P, Mineo M, Di Carlo P, La Spada E, Vizzini G, Montalto G. Transient elastography: A non-invasive tool for assessing liver fibrosis in HIV/HCV patients. World J Gastroenterol 2010; 16(41): 5225-5232 Available from: URL: http://www.wjgnet.com/1007-9327/full/v16/i41/5225.htm DOI : http://dx.doi.org/10.3748/wjg.v16.i41.5225

INTRODUCTION

In the last few years, liver disease associated with hepatitis C virus (HCV) has emerged as a significant problem in human immunodeficiency virus (HIV)-infected patients, thanks to improved survival in the highly active anti-retroviral therapy (HAART) era[1]. It has been reported that HIV and HCV co-infection leads to a more rapid progression of liver disease to cirrhosis[2,3]. Other factors such as severe immune suppression and alcohol consumption accelerate the progression of HCV-related fibrosis[4,5]. Virologically successful HAART slows the progression of liver fibrosis (LF) and reduces hepatic necroinflammatory activity in HIV/HCV co-infected patients[2,6]. In contrast, antiretroviral-related liver toxicity could contribute to liver damage in HIV- and HIV/HCV-infected patients[7]. Mitochondrial toxicity of nucleoside analogues[8], and glucose or lipid abnormalities, such as hyperglycemia and lipodystrophy, which are particularly common when using some protease inhibitors[9], may produce or enhance LF progression in HIV mono- and HIV/HCV co-infected patients. Currently, in this respect, a growing number of cases of cryptogenetic liver disease in symptomatic and asymptomatic HIV-infected patients has been reported[10,11].

Percutaneous liver biopsy is the gold standard for assessing LF. However, it may be associated with sampling variability[12], is an invasive technique with rates of morbidity of 3% and mortality of 0.03%[13,14], and as a consequence, is not suitable for repeated assessment, which is required when monitoring LF.

For these reasons, new non-invasive methods for the assessment of LF have been developed. Transient elastography (TE) (Fibro-Scan®; EchoSens, Paris, France) is a rapid, reliable and tolerable imaging technique for the assessment of LF by measuring liver stiffness (LS)[15,16].

On the other hand, many biochemical markers have been implemented to estimate LF, with the aim of reducing the number of liver biopsies[14].

The advent of TE and biochemical markers has been demonstrated to be very helpful in the non-invasive measurement of LF, particularly in asymptomatic HIV-infected patients in whom liver biopsy is not recommended[11]. TE has already been validated for the measurement of LF in HIV and HCV seropositive patients[17,18].

The aim of this study was to assess the prevalence of LF and cirrhosis in a group of HIV mono-infected, HCV mono-infected and HIV/HCV co-infected patients using TE and biochemical markers. In addition, we evaluated which of the factors studied correlated with advanced LF (ALF) and cirrhosis.

MATERIALS AND METHODS

Study population

Between September 2008 and October 2009 all consecutive HIV mono-infected and HIV/HCV co-infected patients on regular follow-up at the AIDS Center of the University of Palermo, as well as HCV mono-infected patients seen consecutively at the Outpatient Clinic of the Department of Clinical Medicine and Emerging Pathologies of the University of Palermo were enrolled in this study.

Information on age, gender, risk factors for HCV and HIV infections, cumulative exposure to non-nucleoside and nucleoside reverse-transcriptase inhibitors, protease inhibitors and specific antiretroviral drugs within each class were all recorded in a database designed for this study.

For all HIV-infected patients the absolute number of CD4+ T-cells and plasma HIV-RNA levels was assessed. In HCV-infected patients, HCV-genotype and plasma HCV-RNA levels were also recorded. In addition, at baseline, complete blood cell counts, alanine aminotransferase (ALT), aspartate aminotransferase (AST), g-glutamyl transferase (gGT), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and glycemia were measured.

Alcohol intake > 20 g/d either at the time of the study or in the past was recorded through patient interviews. Diabetes or impaired fasting glucose (IFG) were defined according to the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus criteria[19].

Patients with acute liver decompensation, hepatocellular carcinoma or chronic hepatitis B were excluded.

The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Patients were enrolled after written informed consent was obtained.

Assessment of LF

LF was assessed by a single certified operator (trained by the manufacturer) using TE (FibroScan®; EchoSens, Paris, France). TE provides an assessment of LS expressed in kPa units. In brief, an ultrasound transducer probe is mounted on the axis of a vibrator. Vibrations of mild amplitude and low frequency are transmitted by the transducer, inducing an elastic shear wave that propagates through the underlying tissues. The speed of propagation of this vibration across the liver is directly related to tissue stiffness.

The tip of the probe transducer was placed in the intercostal spaces at the right lobe of the liver. Only patients with 10 valid elastometric measures, interquartile ranges > 30% and ≥ 60% success rate (the number of validated measurements divided by the total number of measurements) were considered to be reliable. ALF (severe fibrosis and cirrhosis) was defined as a median LS of 9.5 kPa. As previously published, this cut-off value is strongly correlated with a Metavir score of F3, both in HCV mono-infected and HCV⁄HIV co-infected patients[17,18].

LF was also assessed biologically using 2 different well-validated indices, the aspartate aminotransferase platelet ratio index (APRI) index and the FIB-4 index. The APRI was calculated as follows: AST⁄upper limit of normal × 100⁄platelet count (109⁄L)[20,21]. The FIB-4 index was calculated as follows: age × AST (IU⁄L)⁄{[platelet count (109⁄L)] × [ALT (IU⁄L)]1⁄2}[22]. The prevalence of ALF was estimated using as a reference a FIB-4 index > 3.25 and an APRI index > 1.5[20,22].

Statistical analysis

When data distribution was Gaussian, values were expressed as mean ± SD and their differences were calculated using the Student t-test; otherwise, data were expressed as the median and range and analyzed using the Mann-Whitney U test. Fisher’s exact and c2 tests, the c2 test of Mantel Haenszel, Spearman’s rank correlations (r) and Pearson’s correlation (r) were used where appropriate. Multiple linear regression analysis was used to study the association between increased values of LS and variables statistically significant at univariate analysis. All analyses were performed using the SPSS software package (version 13.0; Chicago, IL, USA).

RESULTS

Study population

A total of 201 patients on regular follow-up at both our Centers were enrolled in the study.

In 11 patients (4 HIV mono-infected, 6 HCV mono-infected and one co-infected) a valid elastometric assessment could not be obtained because of truncular obesity, therefore 190 patients were finally included in this study. There were 137 HIV-infected patients, including 71 HIV mono-infected and 66 HIV/HCV co-infected, and 53 HCV mono-infected patients. Patient characteristics at the time of LS measurement are summarized in Table 1.

HIV patients were significantly younger than HCV mono-infected individuals (P < c2mh =" 4," c2 =" 5," r =" 0.5," b =" 0.47," b =" 0.25," b =" 0.34," b =" 0.4," b =" -0.21," r =" 0.60," r =" 0.64," r =" 0.50," r ="0.53,"> 20 g/d (P <> 20 g/d in both HCV mono-infected and co-infected patients, but we did not find any correlations between LF and duration of HCV infection, HAART exposure, duration of HAART exposure or cumulative exposure to any class of antiretroviral drugs.

Applications

A good adherence to antiretroviral therapy, when it is indicated, is important to reduce the risk of progression of LF in co-infected patients. In addition, HCV mono- and co-infected patients should modify negative habits and lifestyles, such as alcohol consumption, which could accelerate the progression of LF. Important fields for further study could include the use and evaluation of the applicability of FibroScan® for repeated assessment in the monitoring of LF.

Terminology

Transient elastometry (Fibro-Scan®; EchoSens, Paris, France) is a rapid, reliable and well-tolerated imaging technique for the assessment of LF by measuring LS.

Peer review

The authors aimed to assess the prevalence of advanced LF (ALF) in HIV, HCV and HIV/HCV patients using TE and to identify factors associated with ALF. They concluded that HIV/HCV co-infected patients had ALF more frequently at TE than HCV and HIV mono-infected patients. The title reflects accurately the contents of the article, and the abstract delineates concisely the research.

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