Research ArticleA diagnostic score for the prediction of spontaneous resolution of acute hepatitis C virus infection
Introduction
Chronic infection with hepatitis C virus (HCV) remains a major global health burden. Hepatitis C virus infection commonly runs asymptomatic with only a minority of patients presenting with symptomatic, acute hepatitis C (AHC). Spontaneous viral resolution occurs in about 20–40% of infected patients. Considerable evidence has accumulated that particularly those patients with an icteric, symptomatic course of AHC have higher chance to resolve HCV infection spontaneously [1], [2], [3], [4], [5], [6], [7], [8]. In this respect, it was shown that a fast decline of HCV-RNA during early stages of infection is indicative of viral clearance [9]. As a genetic marker, a single nucleotide polymorphism (SNP) on chromosome 19 (rs12979860) near the IL28B region was found to be associated with spontaneous resolution of AHC [8], [10], [11], [12]. Moreover, it was reported that in the early stages of hepatitis C infection, the appearance of HCV specific CD4(+)Th1 cells is more common in patients with consecutive viral clearance [13]. Recently, high serum levels of interferon-gamma inducible protein 10 (IP-10) were also shown to be associated with spontaneous resolution of acute HCV infection [8], [14], [15].
Taken together, spontaneous clearance of HCV is dependent on both host and pathogen related factors [16], [17], [18], [19]. Nevertheless, a proportion of patients, even with acute symptomatic presentation, develop chronic infection and, therefore, optimal therapy strategies to prevent this evolution are still under debate. Early antiviral therapy for AHC has been shown to exert a favorable outcome [20], [21], but is associated with substantial toxicity and costs and is dispensable in patients who would clear the virus spontaneously during the course of the disease.
However, discussion is ongoing if delayed treatment-initiation impairs response to antiviral treatment [22]. A study performed in Germany suggested comparable outcome for both, the early treatment intervention and delayed initiation of antiviral therapy [23].
Hence, the aim of this study was to develop a simple and reliable score, based on clinical and laboratory parameters, found to be predictive of spontaneous viral resolution, to discriminate patients needing early antiviral treatment from those who could be monitored by watchful waiting due to high probability of SC.
Section snippets
Patients
This retrospective study included 136 Caucasian patients (male: 74 [54.4%]; mean age at time of infection: 35 ± 15 years) with proven acute hepatitis C virus infection, diagnosed in Austrian tertiary referral centers. AHC was defined either by an elevation of alanine aminotransferase (ALT) serum levels of more than 5 times the upper limit of normal (ULN), with or without jaundice in anti-HCV antibody and HCV-RNA positive patients (N = 103), with exclusion of chronic hepatitis C and exclusion of other
Patient characteristics and clinical presentation
Seventy-four (54%) of all patients and twenty-nine (55%) of patients with SC were male. HCV-genotyping could be performed in 109 patients (80%) as follows: HCV-GT 1: 67 (61%); GT2: 6 (6%); GT3: 30 (28%); GT4: 4 (3%), GT6: 2 (2%), mixed GT (2/4): 1 (1%). Spontaneously clearing patients were younger than patients who developed viral persistence (31 ± 13 [17–81] vs. 37 ± 16 [16–81] years; mean ± SD [range]; p = 0.031). Quantitative HCV-RNA levels at first presentation were higher in patients developing
Discussion
In view of high sustained virologic response (SVR) rates reached by early initiation of antiviral therapy in patients with acute hepatitis C virus infection, identification of patients probably not clearing HCV spontaneously is of particular importance, as a delayed start of treatment may diminish efficacy of antiviral therapy [5], [19], [25], [26], [27], [28]. Thus, optimal timing and an appropriate patient selection are crucial in the treatment of patients with acute hepatitis C and still
Conflict of interest
PF is a member of the global advisory board and of the speaker’s bureau of ROCHE, Basel CH and Rottapharm-Madaus, Monza, Italy. He is also advisor to Böhringer-Ingelheim, Vertex/Tibotec, Idenix, Achilleon, Glaxo Smith-Kline, and MSD and receives an unrestricted research grant from ROCHE Austria and MSD Austria. HH, AM, CD, MS, and RS serve as speakers for Roche Austria, MSD Austria, Bristol-Myers Squibb, and Janssen Austria. All other authors have no financial disclosures to report.
Authors’ contributions
Sandra Beinhardt: acquisition, analysis and interpretation of data; statistical analysis; drafting of the manuscript. Berit Anna Payer, Michael Strasser, Emina Dulic-Lakovic, Evelyn Grilnberger-Franz, Hermann Laferl: acquisition of data. Andreas Maieron: acquisition of data; critical revision of the manuscript for important intellectual content. Christian Datz: acquisition of data; critical revision of the manuscript for important intellectual content. Rudolf Stauber: acquisition of data;
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2015, Current Opinion in VirologyCitation Excerpt :In addition, Grebely et al. identified IL28B genotype, female sex and HCV genotype 1 as independent predictors for spontaneous clearance [46]. On the basis of the IL28B genotype, peak-bilirubin, patients’ age and HCV-RNA decline within the first 4 weeks after onset, Beinhardt et al. [47] established a prognostic score for the prediction of spontaneous clearance in acute hepatitis C. A cut-off of ≥3 points (out of 5) predicted viral clearance with a sensitivity of 71% and a specificity of 87% (AUROC: 0.82).
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2015, Clinical Microbiology and InfectionCitation Excerpt :However, when the immune status of a patient can be restored by combined antiretroviral therapy, the chance of spontaneous clearance seems to increase [50]. Several models have been developed to prevent unnecessary pegylated IFN (pegIFN)-based treatment for patients who would have cleared HCV spontaneously [42,51–54]. These prediction algorithms rely on pathophysiological causative mechanisms, but also on clinical or biochemical findings, such as jaundice, bilirubin elevation, or the IP-10 level, which may be a reflection of a well-functioning immune system.
Hepatitis C
2015, The LancetCitation Excerpt :The early peak in HCV viral RNA load is sometimes followed by a transient decline,69 and approximately 15–20% of patients will clear acute infection.3,69,71 Factors that have been shown to be associated with spontaneous clearance of HCV infection include being female, IFNL3 polymorphisms, high alanine aminotransferase concentrations, presence of jaundice, speed of decline of HCV RNA, and high blood IP-10 concentrations.72 A balance has to be made between early treatment in patients who might spontaneously clear infection and delaying treatment, which will result in reduced treatment efficacy.
Management of acute and chronic HCV infection in persons with HIV coinfection
2014, Journal of HepatologyCitation Excerpt :However, following the identification of the importance of the IL28B polymorphism, several groups of investigators have developed clinical tools to predict the likelihood of spontaneous clearance for individual patients. At the time of acute HCV diagnosis, the presence of IL28B CC genotype, female sex and the presence of jaundice are strongly associated with subsequent HCV clearance [77,78]. In addition, significant decline in serum HCV RNA levels over the initial four weeks following HCV diagnosis has been associated with higher likelihood of spontaneous clearance [79].
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2014, Gastroenterologia y Hepatologia