Prediction of hepatic fibrosis in HIV/HCV co-infected patients using serum fibrosis markers: The SHASTA index
Introduction
Chronic hepatitis C is characterized by slowly progressive hepatic fibrosis. The fibrogenic stimulus transforms the quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells which degrade normal extracellular matrix (ECM) with accumulation of collagen [1]. Collagen accumulation results in architectural distortion with portal fibrosis leading to bridging fibrosis and eventually cirrhosis. The currently accepted gold standard in fibrosis determination is liver biopsy [2], [3]. Although widely performed and accepted in diagnosing hepatic fibrosis, liver biopsy has many inherent shortcomings.
Percutaneous liver biopsy is invasive with associated morbidity. Approximately 1–3% of patients require hospital admission following biopsy for an associated complication [4]. Furthermore, even with experienced physicians performing the biopsy and expert pathologists interpreting them, our so called gold standard has up to a 20% error rate in staging disease predominantly related to sampling error [5], [6].
Ideally serum markers of fibrosis could either replace the need for liver biopsy or identify those patients with more advanced liver disease who may benefit from a liver biopsy. Features essential of such proposed markers include hepatic specificity, ease of determination and ability to discriminate between degrees of fibrosis. Ultimately serum markers may even have the ability to determine response to various therapies and evaluate disease progression [1].
No single marker fulfills all of the proposed criteria to merit routine clinical use. A combination of markers including those that reflect alterations in hepatic synthetic function and markers of extracellular matrix turnover are emerging as useful diagnostic tests for differentiating early from advanced fibrosis [7], [8].
Hepatitis C and HIV co-infection is estimated to affect 200,000 people in the US alone [9], [10]. Co-infection is associated with more rapid progression of fibrosis, liver failure and hepatocellular carcinoma [11], [12], [13], [14], [15]. Consequently, there is an urgent need for reliable markers of fibrosis progression in this patient group. In this study we report the sensitivity, specificity and predictive value of existing putative fibrosis markers in a cohort of HIV/HCV co-infected persons receiving treatment in an urban HIV clinic.
Section snippets
Study subjects
The population for this study derives from HIV/HCV co-infected members of the Johns Hopkins University (JHU) HIV clinic cohort in Baltimore, MD. To obtain an unbiased estimate of the prevalence and severity of liver disease among HIV–HCV co-infected persons treated with anti-retroviral therapy (ART), 137 subjects were randomly selected from a group of 630 HIV–HCV co-infected persons who had received ART for two or more years and had not yet received treatment for HCV infection [16]. Of the 137
Results
Among the 95 subjects, the median age was 45, 63% were male and 94% were African–American (Table 1). The median CD4 cell count was 340 (interquartile range [IQR], 155–523) and the median HIV RNA level was 235 copies/ml (IOR, 31–19,238). The median HCV RNA level was 3,740,000 IU/ml (IQR, 1,290,000–5,870,000). No patients were positive for HBV DNA.
Discussion
Liver biopsy is the predominant diagnostic test upon which determination of prognosis and indeed the need for antiviral therapy is made in patients with chronic hepatitis C although its performance in accurately staging liver disease has recently come into focus. A recent study on virtual liver biopsy has suggested that liver biopsies need to be 25 mm long and non-fragmented to accurately stage disease in 80% of patients [20]. However, that goal is rarely achieved in clinical practice (<25% even
Acknowledgements
Financial support for this study came from DA-11602, DA-16065 and DA-13806 from the National Institute on Injection Drug Abuse, grant HS 07-809 from the Agency for Health Care Policy and Research and MO1-RR00052.
References (33)
- et al.
The role of laparoscopy in the diagnosis of cirrhosis
Gastrointest Endosc
(1996) Diagnosing fibrosis in hepatitis C: is the pendulum swinging from biopsy to blood tests?
Hepatology
(2003)- et al.
Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model
Hepatology
(2002) - et al.
Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C. UK Haemophilia Centre Directors' Organisation
Lancet
(1997) - et al.
Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter hemophilia cohort study
Blood
(1994) - et al.
Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis
J Hepatol
(1997) - et al.
Histological grading and staging of chronic hepatitis
J Hepatol
(1995) - et al.
A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C
Hepatology
(2003) - et al.
Sampling variability of liver fibrosis in chronic hepatitis C
Hepatology
(2003) - et al.
Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection
Am J Gastroenterol
(2002)