Liver fibrosis improvement assessed by magnetic resonance elastography and Mac‐2‐binding protein glycosylation isomer in patients with hepatitis C virus infection receiving direct‐acting antivirals

Abstract

Aim Fibrosis regression has been observed in patients with chronic hepatitis C virus (HCV) infection treated with direct‐acting antivirals. This study was aimed at evaluating dynamic changes of serum Mac‐2‐binding protein glycosylation isomer (M2BPGi) in patients with HCV genotype 1 receiving elbasvir/grazoprevir. Methods M2BPGi were serially measured at baseline, during and after therapy. Its diagnostic performance at baseline and sustained virological response at 24 weeks after treatment (SVR24) were compared with transient elastography (TE) and the aspartate aminotransferase/platelet ratio index (APRI) using magnetic resonance elastography (MRE) as a reference. Results Overall, 60 HCV mono‐infected and 36 HCV/HIV co‐infected patients were included with SVR24 rates of 93.3% and 97.2%, respectively. At baseline, TE, M2BPGi and APRI were correlated with MRE (r = 0.788, r = 0.703 and r = 0.564, respectively, p < 0.001). The area under the receiver operator characteristics curves for TE, M2BPGi and APRI in differentiating significant fibrosis were 0.88 (95% confidence interval; 0.81–0.95, p < 0.001), 0.86 (0.79–0.94, p < 0.001) and 0.74 (0.64–0.83, p < 0.001), respectively. The corresponding figures for cirrhosis were 0.95 (0.90–1.00, p < 0.001), 0.96 (0.92–1.00, p < 0.001) and 0.88 (0.79–0.97, p < 0.001), respectively. Compared with baseline, all fibrosis markers significantly declined after achieving SVR24. The correlations of TE, M2BPGi and APRI with MRE at time of SVR24 were r = 0.587 (p < 0.001), r = 0.457 (p < 0.001) and r = 0.293 (p = 0.004), respectively. In multivariate analysis, high baseline alanine aminotransferase level, HCV mono‐infection and advanced fibrosis were factors associated with M2BPGi reduction. Conclusions HCV eradication is associated with liver fibrosis improvement. M2BPGi has a better performance than APRI in monitoring liver fibrosis in patients treated with direct‐acting antivirals. This marker is applicable in resource‐limited settings where imaging‐based modalities are not widely accessible.

Application of Mac-2 binding protein glycosylation isomer as a non-invasive biomarker for probing liver disease

“…In addition, M2BPGi levels are correlated with other markers of liver fibrosis and ultrasound. This is consistent with the results of previous studies in Vietnam 18 , Thailand 19 , Japan 20 , and Egypt 21 . However, these studies used surrogate markers of liver fibrosis instead of liver biopsy, which is the gold standard.…”

“…In fact, studies found that liver fibrosis regression occurs when DAAs are used for HCV treatment 14 , 19 , 21 and M2BPGi is a marker for patient survival after treatment with DAAs 17 . One paper even found that M2BPGi has a better performance than APRI in monitoring liver fibrosis 19 while another paper found that M2BPGi shows better performance than other markers in assessing liver fibrosis in HCV patients 22 . Most studies on M2BPGi levels and HCV were on patients treated with DAAs.…”

Serum Mac-2 Binding Protein Glycosylation Isomer to Predict the Severity of Hepatic Fibrosis in Patients with Hepatitis C Virus Infection

“…In line with the published reports, we confirmed that serum M2BPGi level was highly correlated with LSM and hepatic fibrosis stage as determined with TE in our large-scale study [ 19 , 20 , 22 , 23 , 24 , 25 ]. However, the AUROCs of serum M2BPGi level in predicting patients with fibrosis stages of ≥F2, ≥F3, and F4 varied significantly among various studies.…”

“…In addition to laying down ECM to promote hepatic fibrosis, these activated HSCs also secret M2BPGi, which serves as the juxtacrine-acting messenger to Kupffer cells during hepatic fibrogenesis [ 20 ]. Because there is a strong link between serum M2BPGi and hepatic fibrogenesis, studies have shown that serum M2BPGi levels are associated with fibrosis stage, dynamic fibrosis evolution, antiviral responses, presence of esophagogastric varices, risk of HCC occurrence or recurrence, extrahepatic malignancy, and survival in patients with HCV infection [ 19 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

“…Although serum M2BPGi levels are associated with the severity of hepatic fibrosis in patients with HCV infection, the diagnostic accuracy as well as the cutoff levels of M2BPGi selected to predict different stages of hepatic fibrosis vary significantly across studies, which may be attributed to sample size, hepatic fibrosis distribution, and the adoption of reference standards [ 19 , 22 , 23 , 24 , 25 , 32 ]. To this end, we conducted a large-scale study to confirm and validate the clinical utility of serum M2BPGi in diagnosing hepatic fibrosis in patients with HCV infection.…”