Indefinite antiviral therapy may be required after surgical resection for hepatocellular carcinoma complicating chronic hepatitis B
A 66-year-old male patient was admitted to First Affiliated Hospital, Zhejiang University School of Medicine, China in January 2006. The patient who had a 15-year history of HBV infection and treated with lamivudine (LAM) (100 mg once daily, take orally, GlaxoSmithKline, UK), was found LAM-resistant mutation in the YMDD motif of the polymerase gene (rtM204I) in 2006; thus an additional adefovir (ADV) (10 mg once daily, take orally, GlaxoSmithKline, UK) was given. Five months later, the patient was admitted to our hospital for a high alpha-fetoprotein (AFP) level (642.2 ng/ml). HCC was highly suspected by the computed tomography (CT) []. Therefore, a local tumor resection was performed and the pathology confirmed the mass nature of HCC with high-moderate differentiation []. Serum AFP level decreased sharply after the operation and viral load was stable with persistent undetectable HBV DNA. During the following long-term follow-up, the patient was in a satisfactory status [].\nIn March 2009, the patient was found hepatitis B envelope antigen (HBeAg) seroconversion. He discontinued antiviral treatment after a 13-month consolidation therapy. One month later, the patient suffered fatigue, nausea, jaundice, abdominal distension and then hepatic encephalopathy. The initial serology showed high serum levels of total bilirubin (TB) (203 umol/L) (normal range: 3.4-17.1 umol/L), aminoleucine transferase (ALT) (808 IU/L) (normal range: 0-40 U/L), aspartate aminotransferase (AST) (1020 U/L) (normal range: 4-40 U/L) and international normalized ratio (INR) (2.2) (normal range: 2.0-2.5). Viral markers showed HBV reactivation (HBsAg 421.91 ng/ml (normal range: 0-0.18 ng/ml), HBeAg 11.7 ng/ml, antibody to hepatitis B core antigen 120.63 ng/ml and HBV DNA 4.68 × 107 copies/ml (normal range: <103 copies/ml). Both the AFP level and radiological assessment of liver were negative for HCC recurrence. The patient was diagnosed as HBV-related acute-on-chronic liver failure (ACLF) and treated with combined nucleoside analogs (LAM [100 mg once daily, take orally, GlaxoSmithKline, UK] and ADV [10 mg once daily, take orally, GlaxoSmithKline, UK]) and foscarnet sodium injection (3 g once daily, Chia-tai Tianqing Pharmaceutical Co., Ltd., China) besides other conservative therapies. Two weeks later, the patient was noted an obviously improved liver function (ALT/AST 68/81 IU/L, TB 71 umol/L, INR 1.3) and a decreased viral load (HBV DNA 6.31 × 104 copies/ml). A gradually resolution of hepatic encephalopathy and ascites was also achieved. After a 2-month conservative treatment, the patient gained a sustained clinical remission of ACLF with normal liver function and undetectable HBV DNA.\nIn September 2010, the patient was found two occupancies located in the right lobe of cirrhotic liver [] with normal serum AFP level. HCC recurrence was highly suspected and curative hepatic segmentectomy was performed. Both tumors were confirmed by pathology as poorly differentiated HCC and the immunohistochemistry showed different results from the initial one's []. In addition, real-time polymerase chain reaction revealed positive results of covalently closed circular DNA (cccDNA) and HBV-x gene levels in the recurrent HCC and primary one, although serum HBV DNA levels were undetectable []. The patient was subsequently discharged after 2 weeks of operation. CT scan performed post-operatively showed no evidence of disease recurrence up to now.