A clustered ground‐glass hepatocyte pattern represents a new prognostic marker for the recurrence of hepatocellular carcinoma after surgery

Abstract

BACKGROUND:The recurrence of hepatocellular carcinoma (HCC) after hepatectomy is a serious event. It has been demonstrated that different ground-glass hepatocyte (GGH) patterns harbor specific hepatitis B virus (HBV) pre-S deletion mutants and represent preneoplastic lesions in chronic HBV infection. In the current study, the authors investigated whether a specific GGH pattern in nontumorous liver tissues was associated with the recurrence of HBVrelated HCC after surgery. METHODS: Clinicopathologic data from 82 patients with HBV-related HCC were reviewed. GGH patterns were assessed on hematoxylin and eosin-stained sections. Tissue hepatitis B surface antigen (HBsAg) expression was evaluated by immunohistochemical staining. Serum profiles of pre-S status, viral load, and HBV genotype were determined and correlated with clinical recurrence and survival after surgery. RESULTS: The results indicated that the clustered pattern of GGHs or HBsAg expression was associated significantly with decreased local recurrence-free survival (LRFS) during a mean follow-up of 46.4 months (P<.001). This biomarker was comparable to or better than the prognostic value of other parameters, such as multifocal tumors (P ¼ .022), satellite nodules (P ¼ .005), small cell dysplasia (P ¼ .045), or elevated viral load (P ¼ .027), to predict recurrent HCC. Multivariate analysis also revealed that type II GGHs, which expressed marginal HBsAg and consistently clustered in nodules, were independent variables associated with LRFS (P<.001) and overall survival (P ¼ .003). CONCLUSIONS: The current results indicated that the assessment of GGH patterns or HBsAg expression in nontumorous liver tissues provides an easily recognized, new risk marker for the recurrence of HBV-related HCC after hepatic resection. Cancer 2011;117:2951-60.

Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver

“…Almost all the untreated CHB patients harbored HBsAg-negative hepatocytes in their livers, and the distribution of HBsAg-positive cells was scattered or clustered (Fig. 6A), which was consistent with previous reports121314. The frequency of HBsAg-positive hepatocytes was positively correlated with serum HBV DNA and HBsAg levels in treatment-naïve CHB patients (Fig.…”

Hepatitis B virus surface gene pre‐S2 mutant as a high‐risk serum marker for hepatoma recurrence after curative hepatic resection

“…The anti‐HBS antibody (clone T9; Thermo Fisher Scientific), which recognized the major HBS region, and the in‐house developed anti‐LHBS antibody, which recognized the pre‐S 1 region, were used as the primary antibodies. The protocol of the IHC staining analysis followed that described . Briefly, the procedures were done with the Benchmark XT autostainer (Ventana Medical Systems Inc.).…”

“…Type II GGH has therefore been hypothesized as a preneoplastic change in chronic carriers and in the peritumorous regions of HCC . We also recently reported that clustered type II GGHs in HCC are correlated with higher tumor recurrence rates in patients who underwent a hepatic resection, which indicates that the pre‐S 2 mutant LHBS is important for HCC progression . Other studies have also reported that HBV carriers who presented with pre‐S 2 mutant LHBS in serum were predisposed to advanced liver diseases, including liver cirrhosis and HCC.…”

Effects of Antiviral Therapy on the Recurrence of Hepatocellular Carcinoma After Curative Resection or Liver Transplantation

“…All these changes eventually result in hepatocarcinogenesis. In peritumoral tissues, a preS deletion at nt.107-141 and preS2 mutations are independently associated with poor DFS and OS after surgery (23, 30). A1762T/G1764A in liver tissue can independently predict postoperative survival (15).…”