Exploring the Diagnostic Potential of Serum Golgi Protein 73 for Hepatic Necroinflammation and Fibrosis in Chronic HCV Infection with Different Stages of Liver Injuries

Exploring the Diagnostic Potential of Serum Golgi Protein 73 for Hepatic Necroinflammation and Fibrosis in Chronic HCV Infection with Different Stages of Liver Injuries Xiangjun Qian,1 Sujun Zheng,2 Leijie Wang,1 Mingjie Yao,1 Guiwen Guan,1 Xiajie Wen,1 Ling Zhang,3 Qiang Xu,1 Xiangmei Chen,1 Jingmin Zhao,4 Zhongping Duan,2 and Fengmin Lu1 1Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China 2Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China 3Department of Hepatopancreatobiliary Surgery, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou 450008, China 4Department of Pathology and Hepatology, the 5th Medical Centre, Chinese PLA General Hospital, Beijing 100039, China Correspondence should be addressed to Zhongping Duan; moc.361@7152naud and Fengmin Lu; Received 27 January 2019; Accepted 26 June 2019; Published 17 September 2019 Academic Editor: Mariann Harangi Copyright © 2019 Xiangjun Qian et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background and Aim. Serum Golgi protein 73 (GP73) is a promising alternative biomarker of chronic liver diseases, but most data are from patients with HBV infection rather than HCV. Materials and Methods. Two independent cohorts of chronic hepatitis C (CHC) patients from the 5th Medical Centre of the Chinese PLA General Hospital () and Beijing Youan Hospital () with different histories of HCV infection were enrolled. The correlations between serum GP73 and other biochemical indices, as well as its correlations with different stages of liver disease progression, were investigated. The receiver operating characteristic (ROC) curve was employed to evaluate the diagnostic potential of serum GP73 for liver necroinflammation and fibrosis, and comparisons of the diagnostic efficiency with traditional indices of hepatic liver injuries were further investigated. Results. Levels of serum GP73 were found significantly elevated in patients with moderate to severe inflammatory grade () and/or with advanced fibrotic stages () in both cohorts (, respectively), as compared to those with a normal or mild liver lesion. Further ROC analysis demonstrated that serum GP73 was comparable to serum ALT and AST in diagnosing the liver necroinflammation grade at , but its diagnostic values for advanced fibrosis () and cirrhosis () were limited when compared to APRI and FIB-4, and FIB-4 exhibited the best performance. Notably, an obvious elevation of serum GP73 was observed after patients received PEG-IFN and ribavirin treatment. Conclusions. Serum GP73 is an important biomarker in evaluating and monitoring the disease progression including liver necroinflammation and fibrosis in patients with chronic HCV infection, but the value is limited for diagnosing advanced fibrosis and cirrhosis in comparison with APRI and FIB-4. 1. Introduction About 80~150 million persons are chronically infected with hepatitis C virus (HCV) worldwide [1, 2]. Chronic HCV infection is the major cause of viral hepatitis, which finally progresses into hepatic fibrosis, cirrhosis, and hepatocellular carcinoma, and 350,000 deaths occur each year due to all HCV-related causes [3, 4]. Numerous studies have demonstrated that necroinflammation is a key component and contributor to hepatic wound healing and fibrogenesis [5–7], and the severity of liver fibrosis and cirrhosis is a significant predictor of disease progression and clinical prognosis for patients with chronic hepatic disease. Fortunately, antiviral treatment can reverse the fibrosis or even early cirrhosis [8–11]. To better manage the chronic hepatitis C (CHC) patients, it is critical to evaluate and monitor the grade of inflammation and the stage of liver fibrosis and cirrhosis. At present, though liver biopsy remains to be the gold standard for grading the activity of inflammation and histological lesions of the disease simultaneously [12, 13], it is not a feasible option because of potential risk of complications, sampling error, and interobserver variability [13–15]. Instead, several noninvasive methods for fibrosis assessment have been proposed as the alternatives to liver biopsy, such as the AST-to-platelet ratio index (APRI), fibrosis index based on four factors (FIB-4), and transient elastography (TE) which are based on blood indices and imaging modalities, respectively [12, 13]. They are relatively inexpensive and commonly accessible in most hospitals but can be affected by many factors like steatosis and cholestasis [16–18]. Golgi protein 73 (GP73) is a 73 kDa transmembrane glycoprotein mainly expressed in biliary epithelial cells but rarely in hepatocytes in normal liver [19]. The expression of GP73 was found significantly enhanced in acute and chronic liver disease [20]. Recently, studies from others and our laboratory have shown that serum GP73 levels were positively correlated with the progression of chronic liver disease, including inflammation and fibrosis/cirrhosis [21–25]. Since previous researches about GP73 were mainly focused on HBV infection-related liver disease, the diagnostic potential of serum GP73 in chronic HCV infection-related disease remains to be investigated. In the present study, we aimed to explore the correlations between serum GP73 and other biochemical indices among the chronic hepatitis C patients. Then, the diagnostic potential of serum GP73 for liver lesions was evaluated. Its performance was compared with that of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for identifying hepatic necroinflammation, as well as with that of APRI and FIB-4 models for fibrosis in different cohorts. 2. Materials and Methods2.1. Patients Two independent cohorts (Cohort A and Cohort B) with different histories of HCV infection were included in this retrospective study. Cohort A is composed of 174 inpatients from the 5th Medical Centre of the Chinese PLA General Hospital (PLAGH) between 2012 and 2017, including 96 patients with precirrhotic CHC, 35 cases with compensated liver cirrhosis (CLC), and 43 cases with decompensated liver cirrhosis (DLC). The demographics, biopsy results, and laboratory data including levels of serum GP73 of these patients were collected (Table 1). Cohort B from Beijing Youan Hospital had been detailed in prior research [26]. In brief, Cohort B including 120 patients, which belong to the Chinese Han ethnicity from rural villages in Dingxi City, suffered from HCV infection through regular plasma donations with repeated blood retransfusions between 1992 and 1995. All of them received a comprehensive examination including drawing cubital vein blood under the fast and accepting liver biopsy from July 2010 to June 201 (...truncated)