Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic <scp>HBV</scp> infection

Cao, Zhujun; Li, Ziqiang; Wang, Hui; Liu, Yuhan; Xu, Youyong; Mo, Ruidong; Ren, Pengfei; Chen, Lichang; Lu, Jie; Li, Hong; Zhuang, Yan; Liu, Yunye; Wang, Xiaolin; Zhao, Guijun; Tang, Weiliang; Xiang, Xiaogang; Cai, Wei; Liu, Longgen; Bao, Shisan; Xie, Qing

doi:10.1111/liv.13536

Cited by 41 publications

(44 citation statements)

References 39 publications

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“…However, it should be noted that just as other tests, such as LS, APRI and FIB‐4, the diagnostic accuracy of serum GP73 was influenced by the magnitude of intrahepatic inflammation which renders this biomarker less accurate in CHB patients. Therefore, strategies such as combining different tests with serum GP73 might improve the overall accuracy . Moreover, the importance of serum GP73 as a predictor of fibrosis was substantially reduced in patients with ongoing antiviral therapy compared with antiviral‐naïve patients.…”

Section: Discussionmentioning

confidence: 98%

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Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection

Wang

Liu

et al. 2017

Journal of Viral Hepatitis

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Transient elastography (TE) is accurate in staging fibrosis noninvasively. However, a reliable serum biomarker with comparable accuracy is also important, especially when TE is unreliable/unavailable. Therefore, we aimed to evaluate the diagnostic performance of serum Golgi protein 73 (GP73) for significant fibrosis in patients with chronic HBV infection. A total of 801 patients with chronic liver disease (CLD; 492 chronic HBV infection and 309 non-HBV liver disease) with liver biopsy performance were enrolled. Healthy controls (n = 180) and hepatocellular carcinoma (HCC) patients (n = 85) were included for comparisons. Liver biopsy was used as the reference method for fibrosis staging. Serum GP73 level was measured in duplicate in double-blind fashion. Serum GP73 was highest in HCC but also significantly higher in chronic hepatitis B than in healthy controls. The elevation of serum GP73 in non-HCC patients was significantly associated with the presence of significant fibrosis independently of ALT level, liver stiffness (LS) value, inflammation grade and other confounding factors. The diagnostic performance of serum GP73 was accurate in antiviral-naïve HBV patients (area under the receiver operating curve [AUROC], 0.76 95% CI: 0.72-0.81) but not in patients with ongoing antiviral treatment (AUROC, 0.60). The utility of serum GP73 was also confirmed in non-HBV CLD (AUROC, 0.80 95% CI: 0.75-0.85). Serum GP73 was comparable to LS (AUROC, 0.78 95% CI: 0.73-0.82) and significantly better than AST to platelet ratio index (APRI) (AUROC, 0.67 95% CI: 0.62-0.72) and FIB-4 (AUROC, 0.68 95% CI: 0.63-0.73). In conclusion, serum GP73 is an accurate serum marker for significant fibrosis in chronic HBV infection, with higher accuracy than APRI and FIB-4. Serum GP73 is potentially a complementary tool for TE when evaluating the necessity of antiviral treatment, particularly in patients without definite antiviral indication.

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Section: Discussionmentioning

confidence: 98%

“…Such diagnostic performance suggested that it is not accurate enough for clinical practice, using serum GP73 alone. Thus, a combination strategy is needed to optimize the application of serum GP73 in selected patients …”

Section: Discussionmentioning

confidence: 99%

Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection

Wang

Liu

et al. 2017

Journal of Viral Hepatitis

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“…However, it is important to point out that the study by Cao and co‐workers looked at a relatively “healthy” population of HBV‐infected patients, in which this GP73‐LS algorithm was developed, applied and validated. About half of the patients had no significant fibrosis at all, and ALT levels were within normal range or only mildly elevated . It is therefore difficult to rule out necro‐inflammation as a confounding factor for GP73 levels based on this cohort, especially since inflammation had been demonstrated to affect GP73 levels in a prior study .…”

mentioning

confidence: 87%

“…In this issue of Liver International , Cao and colleagues demonstrate that Golgi protein 73 (GP73) correlated with histologically proven liver fibrosis, independent of hepatic inflammation or comorbidities, in a large cohort of treatment‐naïve chronic HBV‐infected patients. They propose a novel algorithm, tested and validated in two cohorts, in which GP73 in conjunction with liver stiffness could accurately diagnose liver fibrosis in the majority of cases …”

mentioning

confidence: 99%

Combining GP73 with liver stiffness measurements: A proof‐of‐concept for non‐invasive fibrosis assessment in antiviral‐naïve HBV patients

Weiskirchen

Tacke

2017

Liver International

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“…These patients were used as a subset to investigate the kinetics of cell death in association with disease course and outcome. All serum samples were stored according to the standard protocol of our biobank as described earlier . Measurements of serum K18 and cK18 were performed using ELISA kits: M65 EpiDeath® (#10040 Peviva AB) or M30‐Apoptosenses® (#10011 Peviva AB), respectively.…”

Section: Methodsmentioning

confidence: 99%

Serum keratin‐18 fragments as cell death biomarker in association with disease progression and prognosis in hepatitis B virus‐related cirrhosis

Chen

Liu

et al. 2019

Journal of Viral Hepatitis

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Extensive hepatocyte death leads to hepatic inflammation and contributes to systemic inflammation in decompensated cirrhosis. We aimed to investigate the prognostic value of serum cell death markers in patients with hepatitis B virus (HBV)‐related acute decompensation (AD) of cirrhosis with and without acute‐on‐chronic liver failure (ACLF). We studied two cohorts—cohort 1: 201 outpatients with stable chronic hepatitis B (49 cirrhosis); cohort 2: 232 inpatients with HBV‐related cirrhosis admitted for AD. Cell death was determined with serum keratin‐18 (K18) for total death and serum caspase‐cleaved‐K18 (cK18) for apoptosis. Survival analyses were performed using competing risk method. We found that serum K18 and cK18 were significantly (P < 0.001) higher in patients from cohort 2 than those from cohort 1. Among cohort 2, ACLF patients had significantly (P < 0.001) increased K18 and cK18 comparing to those without ACLF. Increased K18 and cK18 were mainly attributed to HBV flare and were associated with liver and coagulation failure. HBV‐AD patients without ACLF who admitted with upper tertile of K18 or cK18 were at higher risk of developing ACLF during follow‐up. Baseline serum K18 or cK18 was significantly associated with transplant‐free 90‐day survival independent of leucocytes, HBV DNA, bacterial infection, encephalopathy and severity scores. The combination of cell death biomarkers significantly improved the prognostic value of the currently established prognostic scores. The reduction of cell death level after standard treatment was associated with increased short‐term survival. In conclusion, measurements of serum K18 or cK18 in HBV decompensated cirrhosis are a promising tool for predicting ACLF and risk stratification of short‐term outcome.

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Algorithm of Golgi protein 73 and liver stiffness accurately diagnoses significant fibrosis in chronic HBV infection

Abstract: Serum GP73 is a robust biomarker for significant fibrosis diagnosis. GP73-LS algorithm provided better diagnostic accuracy than currently available approaches. More than 60% antiviral naïve CHB patients could use this algorithm without resorting to liver biopsy.

Cited by 41 publications

References 39 publications

Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection

Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection

Combining GP73 with liver stiffness measurements: A proof‐of‐concept for non‐invasive fibrosis assessment in antiviral‐naïve HBV patients

Serum keratin‐18 fragments as cell death biomarker in association with disease progression and prognosis in hepatitis B virus‐related cirrhosis

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