Comparison of clinical outcomes following hepatic resection in non-alcoholic fatty liver disease-related hepatocellular carcinoma and hepatitis B-related hepatocellular carcinoma : propensity score-matched analysis

Abstract

Background/Aim Since it was first reported in 1990, the prevalence of Non-alcoholic fatty liver disease-related hepatocellular carcinoma(NAFLD-HCC) has increased in parallel with the incidence of metabolic syndrome. Studies report conflicting results regarding the prognosis for NAFLD- HCC. A previous comparison between NAFLD-HCC with hepatitis B virus-related HCC(HBV-HCC) is insufficient. The aim of this retrospective analysis was to compare the clinical characteristics and survival outcomes of NAFLD-HCC versus HBV-HCC. Methods The medical records of 432 patients who underwent hepatic resection for HCC at Severance Hospital between 2005 and 2015 were retrospectively reviewed. Metabolic syndrome was defined according to definition from the National Cholesterol Education Program: Adult Treatment Panel III(NCEP-ATP III). Occult HBV infection was identified by nested polymerase chain reaction(PCR) analysis, using known primers. Propensity analysis was carried out using logistic regression in order to minimize lead-time bias caused by lack of surveillance in NAFLD patients. Surgical and oncologic outcomes were compared between two groups. Results Thirty-two patients (7.4%) who underwent hepatic resection for HCC were diagnosed with NAFLD-HCC. Before matched analysis, cirrhosis was more frequently detected in HBV-HCC patients (55.0 vs 15.6%, p<0.001). Surgical outcomes were similar between the two groups, especially morbidity rates (18.0 vs 18.8%, p=0.596); hospital stay (12.2 vs 12.5 days, p=0.830); and in intraoperative blood loss volume (435 vs 554 mL, p=0.252). Average tumor size was larger in the NALFD-HCC group than the HBV-HCC group (4.4 vs 3.4 cm, p=0.014). After a median follow-up of 74.0 months (range 0-157 months), survival analyses before propensity-score matching showed better 5-year overall survival in HBV-HCC than NAFLD-HCC patients (80.7 vs 63.2%, p=0.041). However, survival analysis after propensity score-matching showed similar 5-year overall survival (60.8% vs 63.2%, p=0.978), There was no difference between the two groups in recurrence-free survival or disease-specific survival before and after matched analysis. Conclusion The NAFLD-HCC group had a larger tumor size and less cirrhosis at the time of diagnosis than the HBV-HCC group. The overall survival of the NAFLD-HCC group was worse than that of the HBV-HCC group, but after matched analysis, there was no significant difference in overall survival. There were no differences in recurrence-free survival or disease-specific survival between groups, before or after matched analysis.

대사 증후군의 증가와 더불어 비알코올성 지방간염에 동반한 간 세포암종의 발생이 증가하는 추세이나, 비알코올성 지방간염 동반 간세포암종과 B형 간염 동반 간세포암종과의 비교에 관한 많은 연구가 이루어지지 않은 상태로, 본 연구에서는 두 군간의 임상적 특성에 관한 비교를 위한 연구를 진행하였다. 단일기관에서 2005년부터 2015년까지 간세포암으로 간 절제술을 시행받은 총 432명의 환자를 대상으로 후향적 분석을 시행하였으며, B형 간염 보균자가 많은 국내의 특성을 고려하여 순수한 비알코올성 지방간염에 의한 간세포암종 환자군을 분류하기 위하여 이중 중합효소연쇄반응 기법을 이용하였다. 또한 B형 간염 환자에 비하여 비알코올성 지방간염 환자에서 나타나는 조기발견 바이어스를 줄이기 위하여 두 군간의 성향점수매칭을 통한 분석을 시행하였다. 총 432명의 환자 중 32명(7.4%)의 환자가 비알코올성 지방간염에 의한 간세포암종으로 간 절제술을 시행하였으며, 두 군 간의 수술 후 합병증 발생률 및 재원일수 등에서 유의한 차이는 보이지 않았다. 종양의 크기는 비알코올성 지방간염 그룹에서 더 크게 나타났으나(4.4 vs 3.4cm, p=0.014), 성향 점수를 이용한 매칭 후 두 군간의 5년 전체 생존률(60.8 vs 63.2%,p=0.978) 및 무재발생존률(40.6 vs 41.6%, p=0.738)의 차이는 보이지 않았다. 본 연구의 결과로 비알코올성 지방간염 발생 간세포암종이 B형간염 발생 간세포암종에 비하여 비슷한 예후를 보이며, 이는 정기적인 감시 검사의 부족에 따른 진단의 지연 및 대사성 질환에 의한 사망률 및 이환율의 증가에서 비롯되었음을 추론 가능하다.