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Serum Golgi protein 73 (GP73) is a diagnostic and prognostic marker of chronic HBV liver disease.

Xu Z, Liu L, Pan X, Wei K, Wei M, Liu L, Yang H, Liu Q - Medicine (Baltimore) (2015)

Bottom Line: In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis.Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy.Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels.

View Article: PubMed Central - PubMed

Affiliation: From the Clinical Liver Center (ZX, Liguan Liu, XP, HY, QL); Central Laboratory of Clinical Hepatology (KW, MW); and Department of Pathology (Lifei Liu), The 180th Hospital of the People's Liberation Army, Quanzhou, China.

ABSTRACT
Alanine aminotransferase (ALT) is the most commonly used marker of liver injury, but normal ALT levels are seen in a proportion of chronic hepatitis B virus (HBV)-infected patients with severe liver injury. Golgi protein 73 (GP73) is a promising alternative marker of liver injury. This study assessed the relation between GP73 levels and liver disease severity, monitored the kinetic changes in GP73 levels in chronic HBV patients receiving entecavir (ETV) therapy, and investigated the potential diagnostic and prognostic values of serum GP73 as a new liver injury biomarker in chronic HBV infections. This study enrolled 1150 patients with chronic HBV infections, 200 of whom were retrospectively enrolled in this study after receiving 1 year of ETV treatment. GP73 expression in liver tissue was detected by immunohistochemistry. GP73 levels in single or serial serum samples were measured by enzyme-linked immunosorbent assay. Immunohistochemical analysis indicated that GP73 protein expression in the liver increased progressively with pathologic progression from nonexistent or mild hepatitis to severe hepatitis and cirrhosis during chronic HBV infection. Serum GP73 levels were positively correlated with the disease severity of chronic HBV infections (r = 0.58, P < 0.001). In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis. Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy. Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels.

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Changes in serum GP73 concentration and intracellular GP73 protein expression level before and after 1 year of ETV therapy. (A) Changes in serum GP73 concentration during ETV antiviral therapy in patients with CHB. (B) Moderately positive GP73 hepatocytes detected before treatment. (C) Weakly positive GP73 detected after 1 year of ETV treatment. (Magnification, ×200). CHB = chronic hepatitis B, ETV = entecavir.
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Figure 3: Changes in serum GP73 concentration and intracellular GP73 protein expression level before and after 1 year of ETV therapy. (A) Changes in serum GP73 concentration during ETV antiviral therapy in patients with CHB. (B) Moderately positive GP73 hepatocytes detected before treatment. (C) Weakly positive GP73 detected after 1 year of ETV treatment. (Magnification, ×200). CHB = chronic hepatitis B, ETV = entecavir.

Mentions: In 200 CHB patients who received ETV treatment for more than 1 year, serum HBV DNA was decreased and biochemical indexes were returned to normal after 3 months. We monitored the dynamic changes in serum GP73 concentration at the start of treatment and 1, 3, 6, 9 and 12 months after initiating the treatment. Along with reduced liver necroinflammation, the serum GP73 concentration also gradually declined from 97.26 ± 42.52 ng/mL in the first month of treatment to 68.21 ± 33.65 ng/mL at month 3, 58.57 ± 29.52 ng/mL at month 6, 51.76 ± 25.39 ng/mL at month 9, and 53.37 ± 21.62 ng/mL at month 12. The average GP73 serum concentration fell significantly from its baseline level (113.09 ± 48.91 ng/mL) compared with its serum concentration after 12 months of treatment (P < 0.01). The largest serum GP73 concentration decrease occurred after 3 months of treatment, coinciding with ALT normalization (Figure 3A). GP73 levels continued to decline until stabilizing after month 9 (Figure 3A). Our ANOVA-repeated measures showed that the serum GP73 concentration linearly declined to the normal level during 1-year ETV treatment (linear F = 256.15, P < 0.001).


Serum Golgi protein 73 (GP73) is a diagnostic and prognostic marker of chronic HBV liver disease.

Xu Z, Liu L, Pan X, Wei K, Wei M, Liu L, Yang H, Liu Q - Medicine (Baltimore) (2015)

Changes in serum GP73 concentration and intracellular GP73 protein expression level before and after 1 year of ETV therapy. (A) Changes in serum GP73 concentration during ETV antiviral therapy in patients with CHB. (B) Moderately positive GP73 hepatocytes detected before treatment. (C) Weakly positive GP73 detected after 1 year of ETV treatment. (Magnification, ×200). CHB = chronic hepatitis B, ETV = entecavir.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554005&req=5

Figure 3: Changes in serum GP73 concentration and intracellular GP73 protein expression level before and after 1 year of ETV therapy. (A) Changes in serum GP73 concentration during ETV antiviral therapy in patients with CHB. (B) Moderately positive GP73 hepatocytes detected before treatment. (C) Weakly positive GP73 detected after 1 year of ETV treatment. (Magnification, ×200). CHB = chronic hepatitis B, ETV = entecavir.
Mentions: In 200 CHB patients who received ETV treatment for more than 1 year, serum HBV DNA was decreased and biochemical indexes were returned to normal after 3 months. We monitored the dynamic changes in serum GP73 concentration at the start of treatment and 1, 3, 6, 9 and 12 months after initiating the treatment. Along with reduced liver necroinflammation, the serum GP73 concentration also gradually declined from 97.26 ± 42.52 ng/mL in the first month of treatment to 68.21 ± 33.65 ng/mL at month 3, 58.57 ± 29.52 ng/mL at month 6, 51.76 ± 25.39 ng/mL at month 9, and 53.37 ± 21.62 ng/mL at month 12. The average GP73 serum concentration fell significantly from its baseline level (113.09 ± 48.91 ng/mL) compared with its serum concentration after 12 months of treatment (P < 0.01). The largest serum GP73 concentration decrease occurred after 3 months of treatment, coinciding with ALT normalization (Figure 3A). GP73 levels continued to decline until stabilizing after month 9 (Figure 3A). Our ANOVA-repeated measures showed that the serum GP73 concentration linearly declined to the normal level during 1-year ETV treatment (linear F = 256.15, P < 0.001).

Bottom Line: In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis.Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy.Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels.

View Article: PubMed Central - PubMed

Affiliation: From the Clinical Liver Center (ZX, Liguan Liu, XP, HY, QL); Central Laboratory of Clinical Hepatology (KW, MW); and Department of Pathology (Lifei Liu), The 180th Hospital of the People's Liberation Army, Quanzhou, China.

ABSTRACT
Alanine aminotransferase (ALT) is the most commonly used marker of liver injury, but normal ALT levels are seen in a proportion of chronic hepatitis B virus (HBV)-infected patients with severe liver injury. Golgi protein 73 (GP73) is a promising alternative marker of liver injury. This study assessed the relation between GP73 levels and liver disease severity, monitored the kinetic changes in GP73 levels in chronic HBV patients receiving entecavir (ETV) therapy, and investigated the potential diagnostic and prognostic values of serum GP73 as a new liver injury biomarker in chronic HBV infections. This study enrolled 1150 patients with chronic HBV infections, 200 of whom were retrospectively enrolled in this study after receiving 1 year of ETV treatment. GP73 expression in liver tissue was detected by immunohistochemistry. GP73 levels in single or serial serum samples were measured by enzyme-linked immunosorbent assay. Immunohistochemical analysis indicated that GP73 protein expression in the liver increased progressively with pathologic progression from nonexistent or mild hepatitis to severe hepatitis and cirrhosis during chronic HBV infection. Serum GP73 levels were positively correlated with the disease severity of chronic HBV infections (r = 0.58, P < 0.001). In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis. Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy. Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels.

Show MeSH
Related in: MedlinePlus