Mac‐2‐binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C

Abstract

Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non‐HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non‐HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct‐acting antiviral (DAA) treatment were analyzed. The cumulative post‐SVR incidence of non‐HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non‐HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac‐2‐binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post‐SVR incidence of non‐HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post‐SVR incidence of non‐HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post‐SVR incidence of non‐HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival.

Fib-4 index predicts prognosis after achievement of sustained virologic response following direct-acting antiviral treatment in patients with hepatitis C virus infection

“…This new discovery, the Fib-4 index, which is known to reflect the degree of progression of liver fibrosis, significantly correlates not only with HCC incidence but also with all mortality rates. In contrast, regarding non-HCC malignancies, their incidence did not increase significantly, even in the high Fib-4 group, although we previously reported that M2BPGi measurements at baseline and SVR12 may help predict the post-SVR incidence of non-HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment [13,15]. Moreover, similar analyses of deaths, excluding those due to malignant tumors, did not exhibit a significant difference.…”

“…SVR, sustained virologic response. and SVR12 may help predict the post-SVR incidence of non-HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment [13,15]. Moreover, similar analyses of deaths, excluding those due to malignant tumors, did not exhibit a significant difference.…”

“…Considering that the Fib-4 > 3.25 group presented a considerably high carcinogenic rate, a close HCC surveillance by performing CT or MRI seems to be indispensable, as discussed in a recent report [14]. In addition, since analysis through lowering the boundary value that separates the Fib-4 index from 3.25 to 3.07 or raising it to 3.67 at other facilities has been reported [15,16], we also attempted to divide it by 3.45. On the contrary, in the Fib-4 < 1.45 group, no HCC outbreak cases were observed, as reported previously [12].…”

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

“…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 ].…”