High HBV-DNA Titer in Surrounding Liver Rather Than in Hepatocellular Carcinoma Tissue Predisposes to Recurrence After Curative Surgical Resection

Choi, Jong Gi; Chung, Young‐Hwa; Kim, Jeong‐A; Jin, Young–Joo; Park, Wonhyung; Lee, Danbi; Shim, Ju Hyun; Lee, Yoon Seon; Seo, Dong Dae; Jang, Myoung Kuk; Kim, Kang Mo; Lim, Young‐Suk; Lee, Han Chu; Lee, Yung Sang; Yu, Eunsil; Lee, Young Joo

doi:10.1097/mcg.0b013e3182371285

Cited by 5 publications

(8 citation statements)

References 33 publications

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“…Chronic hepatitis B virus (HBV) infection results in liver fibrosis/cirrhosis and development of hepatocellular carcinoma (HCC) [1], [2]. Establishment of chronic HBV infection is inversely associated with patient's age with neonatal and infants most susceptible, while adults are mostly resistant to chronic infection [3], [4].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B Virus Infection and Immunopathogenesis in a Humanized Mouse Model: Induction of Human-Specific Liver Fibrosis and M2-Like Macrophages

et al. 2014

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The mechanisms of chronic HBV infection and immunopathogenesis are poorly understood due to a lack of a robust small animal model. Here we report the development of a humanized mouse model with both human immune system and human liver cells by reconstituting the immunodeficient A2/NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice with human HLA-A2 transgene) with human hematopoietic stem cells and liver progenitor cells (A2/NSG-hu HSC/Hep mice). The A2/NSG-hu HSC/Hep mouse supported HBV infection and approximately 75% of HBV infected mice established persistent infection for at least 4 months. We detected human immune responses, albeit impaired in the liver, chronic liver inflammation and liver fibrosis in infected animals. An HBV neutralizing antibody efficiently inhibited HBV infection and associated liver diseases in humanized mice. In addition, we found that the HBV mediated liver disease was associated with high level of infiltrated human macrophages with M2-like activation phenotype. Importantly, similar M2-like macrophage accumulation was confirmed in chronic hepatitis B patients with liver diseases. Furthermore, gene expression analysis showed that induction of M2-like macrophage in the liver is associated with accelerated liver fibrosis and necrosis in patients with acute HBV-induced liver failure. Lastly, we demonstrate that HBV promotes M2-like activation in both M1 and M2 macrophages in cell culture studies. Our study demonstrates that the A2/NSG-hu HSC/Hep mouse model is valuable in studying HBV infection, human immune responses and associated liver diseases. Furthermore, results from this study suggest a critical role for macrophage polarization in hepatitis B virus-induced immune impairment and liver pathology.

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Section: Introductionmentioning

confidence: 99%

Hepatitis B Virus Infection and Immunopathogenesis in a Humanized Mouse Model: Induction of Human-Specific Liver Fibrosis and M2-Like Macrophages

et al. 2014

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“…The second stage was an RCT carried out to validate the findings. Of these studies, nine were conducted in Mainland China [12,18,21,22,24,26,29,31,32], four in Taiwan [19,23,28,30], three in Korea [6,20,25], two in Hong Kong [5,13], and one in Japan There was significant heterogeneity between the studies regarding recurrence (I 2 = 69 %; P = 0.02), but not between the studies regarding DFS and OS (Fig. 1).…”

Section: Eligible Studiesmentioning

confidence: 99%

Antiviral Therapy Decreases Recurrence of Hepatitis B Virus‐related Hepatocellular Carcinoma after Curative Resection: A Meta‐analysis

et al. 2014

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“…This is consistent with a randomized clinical trial that showed that nucleotide/nucleoside analog treatments decreased HBV-HCC recurrence [ 10 ]. Some studies indicated that serum HBV DNA status is a more sensitive criterion compared with HBV DNA titre in liver tissues [ 8 , 11–15 ]. In this current study, we refer to serum HBV DNA.…”

Section: Discussionmentioning

confidence: 99%

Preoperative serum hepatitis B virus DNA was a risk factor for hepatocellular carcinoma recurrence after liver transplantation

et al. 2022

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Background Tumour characteristics and orthotopic liver transplantation (OLT) criteria are risks for recurrence of hepatocellular carcinoma (HCC). In Asia, most HCC is caused by chronic hepatitis B infection. Whether hepatitis B virus DNA (HBV DNA) is a risk factor for HCC recurrence after OLT is not clear. Patients and methods In this retrospective study, we classified patients into groups of detectable and undetectable HBV DNA, non-HCC recurrence, and recurrence and performed analyses on differed characteristics between groups and risk factors for HCC recurrence after OLT. Results Among patients who underwent OLT for HCC, 117 were secondary to CHB infection. CHB was not a risk, but advanced tumour characteristics were risk factor for HCC recurrence. In patients with CHB-HCC, 24 (20.5%) of 117 patients had HCC recurrence. Compared to patients with HBV DNA undetectable ( n = 75), patients with detectable HBV DNA ( n = 42) had higher AFP concentration ( p < .001), higher proportion of macrovascular invasion ( p = .014), greater tumour diameter ( p < .001), poorer TNM stage ( p = .017), and higher proportion of extended OLT criteria ( p = .011) and HCC recurrence ( p = .036). Preoperative HBV DNA >2000 IU/mL was an independent risk factor for HCC recurrence (OR = 8.35, 95% CI 1.40, 50.00, p = .020). HBV DNA detectable was not a risk for HCC-related death. Conclusion Individuals with preoperative undetectable HBV DNA had advanced tumour characteristics and a higher proportion of HCC recurrence. Antiviral treatment for HCC should be performed, and HBV DNA undetectable should be obtained before OLT. But for an urgent OLT, preoperative detectable HBV DNA may not affect long-term survival. KEY MESSAGES Patients with HBV DNA detectable had advanced tumour characteristics, a higher proportion of extended OLT criteria, and HCC-recurrence. HBV DNA >2000 IU/mL was a risk factor for HCC recurrence. HBV DNA detectable was not a risk for HCC related death; extended OLT criteria affected long-term survival.

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High HBV-DNA Titer in Surrounding Liver Rather Than in Hepatocellular Carcinoma Tissue Predisposes to Recurrence After Curative Surgical Resection

Abstract: In patients with HBV-associated HCC, high HBV-DNA titer in surrounding liver rather than in the HCC itself is associated with posthepatectomy HCC recurrence after curative surgical resection.

Cited by 5 publications

References 33 publications

Hepatitis B Virus Infection and Immunopathogenesis in a Humanized Mouse Model: Induction of Human-Specific Liver Fibrosis and M2-Like Macrophages

Hepatitis B Virus Infection and Immunopathogenesis in a Humanized Mouse Model: Induction of Human-Specific Liver Fibrosis and M2-Like Macrophages

Antiviral Therapy Decreases Recurrence of Hepatitis B Virus‐related Hepatocellular Carcinoma after Curative Resection: A Meta‐analysis

Preoperative serum hepatitis B virus DNA was a risk factor for hepatocellular carcinoma recurrence after liver transplantation

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