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

Abstract

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.

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

“…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.…”

“…All serum samples were stored according to the standard protocol of our biobank as described earlier. 34,35 Measurements of serum K18 and cK18 were performed using ELISA kits: M65 EpiDeath® (#10040 Peviva AB) or M30-Apoptosenses® (#10011 Peviva AB), respectively. The M30-antibody detect the unique peptide exposed on caspase-cleaved cK18 and therefore is presumably used as hepatocyte apoptosis marker, whereas M65 is investigated as total cell death marker since it detects both full-length form and its caspase-cleaved form.…”

Drug targeting strategies for liver cancer and other liver diseases

“…16 Some drugs also used in the treatment of HCC like doxorubicin, cisplatin and 5fluorouracil, used alone or in combination. Grafted Xyloglucan with the doxorubicin (DOX) and galactosamine to target liver hepatocytes 1 . In vitro cytotoxicity experiment revealed that similar cytotoxicity as free DOX against HepG2 cells and when it incubated with HeLa cells there was no significant cytotoxicity change while in case of a human tumor xenograft nude mouse model, the prepared conjugates shown higher therapeutic effect than without conjugated and plain doxorubicin.…”

“…Liver diseases, particularly hepatitis-B (viral HBV infections), liver fibrosis and hepatocellular carcinoma (HCC) are the major causes of disability and mortality worldwide. 1 These require long-term drug therapy. Liver-specific drug delivery is helpful in decreasing side effects by reducing drug distribution in non-target organ and improves the therapeutic efficacy by concomitantly increasing the drug concentration in target cells.…”

Hepatic Arterial Blood Flow Index Is Associated with the Degree of Liver Fibrosis in Patients with Chronic Hepatitis B Virus Infection

“…However, this technique is ineffective in diagnosing mild and significant liver fibrosis. Also, several factors, such as ALT flares, cardiac insufficiency, extrahepatic cholestasis, inflammation, obesity, and presence of ascites associated with liver stiffness, can limit the applicability of TE (7)(8)(9). In fact, the extensive application of TE in the assessment of all patients with CHC is not realistic, and there is still a need to improve the existing predictive models for staging fibrosis as a complementary approach for TE.…”