Effects of Antiviral Therapy on HBV Reactivation (HBV-DNA(-))

Effects of Antiviral Therapy on HBV Reactivation and Liver Function After Hepatectomy for HBV-DNA Negative HBV-related Hepatocellular Carcinoma

Hepatitis B virus (HBV) reactivation happens after liver resection for HBV-related hepatocellular carcinoma (HCC) patients, particularly for those with positive serum HBV-DNA . The incidence rate and risk factors of HBV reactivation after hepatectomy for serum HBV-DNA negative HBV-related HCC are unclear.

Hepatitis B virus (HBV) reactivation happens after liver resection for HBV-related hepatocellular carcinoma (HCC) patients, particularly for those with positive serum HBV-DNA . The incidence rate and risk factors of HBV reactivation after hepatectomy for serum HBV-DNA negative HBV-related HCC are unclear.From July 2012 to December 2015, 174 consecutive patients with serum HBV-DNA negative HBV-related HCC underwent resection were prospectively enrolled in the studied. There are 66 patients received preoperative antiviral therapy (antiviral group) and 108 patients did not receive any antiviral therapy (non-antiviral group). The incidence of HBV reactivation, risk factors of liver function were analyzed in perioperative period. HBV reactivation developed in 30 patients (27.8%) in the non- antiviral group and 2 patients (3.0%) in the antiviral group, respectively (P < 0.001). Multivariate analysis revealed that minor hepatectomy (HR, 4.695; 95% CI, 1.257-17.537, P = 0.021) and without antiviral therapy (HR, 8.164; 95% CI, 1.831-36.397, p =0.006) were risk factors attributed to HBV reactivation. Patients in antiviral group and non-antiviral group or reactivation group and without reactivation group have similar ALT, TBil, ALB, and PT in 7 days after resection. However, patients in antiviral group have significantly better ALT and ALB on day 30th after resection than those in control group. Moreover, similar phenomenon were observed when comparing those with or without HBV reactivation. Resection could lead to HBV reactivation during the perioperative period for serum HBV DNA negative HBV-related HCC, especially in patients who did not receive any antiviral therapy. Anti-HBV therapy can reduce the risk of reactivation, thus improving liver function after hepatectomy.

Patients who received entecavir (zhengda Tianqing Co., Ltd, Lianyungang, Jiangsu Province, China; 0.5 mg/d) were submitted to antiviral group. Patients in the antiviral group received entecavir begin in the first 3 days before surgery for at lest 1 month. No immunological therapy in perioperative period will be submitted to any included patients.

Patients who did not receive any antiviral therapies were submitted as non-antiviral group. Patients in the non-antiviral group who underwent HBV reactivation will receive entecavir therapy. No immunological therapy in perioperative period will be submitted to any included patients.

Patients in the antiviral group received entecavir begin in the first 3 days before surgery for at lest 1 month.

Inclusion Criteria: underwent initial hepatectomy; preoperative serum HBsAg positive serum HBV DNA negative serum ALT in normal range Child-Pugh A liver function HCC was confirmed by histopathology patients in the treated group received Entecavir (ENT) while patients in the control group did not receive any antiviral therapy. Exclusion Criteria: underwent preoperative TACE or other anti-tumor treatments underwent preoperative antiviral treatment for nearly a year with autoimmune disease, other organ malignant tumor, or other severe disease.

Li X, Zhong X, Chen ZH, Wang TT, Ma XK, Xing YF, Wu DH, Dong M, Chen J, Ruan DY, Lin ZX, Wen JY, Wei L, Wu XY, Lin Q. Efficacy of Prophylactic Entecavir for Hepatitis B Virus-Related Hepatocellular Carcinoma Receiving Transcatheter Arterial Chemoembolization. Asian Pac J Cancer Prev. 2015;16(18):8665-70. doi: 10.7314/apjcp.2015.16.18.8665.

Xie ZB, Zhu SL, Peng YC, Chen J, Wang XB, Ma L, Bai T, Xiang BD, Li LQ, Zhong JH. Postoperative hepatitis B virus reactivation and surgery-induced immunosuppression in patients with hepatitis B-related hepatocellular carcinoma. J Surg Oncol. 2015 Nov;112(6):634-42. doi: 10.1002/jso.24044. Epub 2015 Sep 30.

Jang JW, Kim YW, Lee SW, Kwon JH, Nam SW, Bae SH, Choi JY, Yoon SK, Chung KW. Reactivation of hepatitis B virus in HBsAg-negative patients with hepatocellular carcinoma. PLoS One. 2015 Apr 20;10(3):e0122041. doi: 10.1371/journal.pone.0122041. eCollection 2015.

Sohn W, Paik YH, Cho JY, Ahn JM, Choi GS, Kim JM, Kwon CH, Joh JW, Sinn DH, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. Influence of hepatitis B virus reactivation on the recurrence of HBV-related hepatocellular carcinoma after curative resection in patients with low viral load. J Viral Hepat. 2015 Jun;22(6):539-50. doi: 10.1111/jvh.12356. Epub 2014 Nov 7.

Lee JI, Kim JK, Chang HY, Lee JW, Kim JM, Chung HJ, Kim YS, Lee KS. Impact of postoperative hepatitis B virus reactivation in hepatocellular carcinoma patients who formerly had naturally suppressed virus. J Gastroenterol Hepatol. 2014 May;29(5):1019-27. doi: 10.1111/jgh.12472.

Huang L, Li J, Yan J, Sun J, Zhang X, Wu M, Yan Y. Antiviral therapy decreases viral reactivation in patients with hepatitis B virus-related hepatocellular carcinoma undergoing hepatectomy: a randomized controlled trial. J Viral Hepat. 2013 May;20(5):336-42. doi: 10.1111/jvh.12036. Epub 2012 Dec 5.

Lao XM, Luo G, Ye LT, Luo C, Shi M, Wang D, Guo R, Chen M, Li S, Lin X, Yuan Y. Effects of antiviral therapy on hepatitis B virus reactivation and liver function after resection or chemoembolization for hepatocellular carcinoma. Liver Int. 2013 Apr;33(4):595-604. doi: 10.1111/liv.12112. Epub 2013 Feb 13.