【摘要】：目的對(duì)乙型肝炎病毒(HBV)相關(guān)性原發(fā)性肝癌(HCC)術(shù)后患者發(fā)生核苷(酸)類(lèi)似物(NAs)耐藥后其臨床特征及生存期等預(yù)后因素進(jìn)行分析并與同期NAs不耐藥和未服用NAs的病人相比較;檢測(cè)此類(lèi)患者是否存在預(yù)存耐藥,并因此探討臨床醫(yī)生抗病毒治療的決策。方法隨訪(fǎng)2011年1月至2014年7月在我院反復(fù)住院的482例漢族HBV相關(guān)HCC根治性切除術(shù)后患者資料,這些患者在術(shù)前均未使用NAs抗病毒治療。收集患者病史、血清學(xué)、影像學(xué)及病理學(xué)檢查資料;收集患者血清,同一患者進(jìn)行一次乙型肝炎病毒基因型檢測(cè)及用藥前、用藥后兩次耐藥突變位點(diǎn)檢測(cè)。分析這些患者是否存在預(yù)存耐藥;根據(jù)用藥情況及用藥后耐藥位點(diǎn)檢測(cè)結(jié)果將患者分為術(shù)后NAs耐藥組、NAs未耐藥組、術(shù)后未用NAs組。用SPSS 21.0統(tǒng)計(jì)學(xué)軟件進(jìn)行包括卡方檢驗(yàn)、T檢驗(yàn)、秩和檢驗(yàn)兩兩比較其數(shù)據(jù)差異,用累積生存函數(shù)曲線(xiàn)進(jìn)行生存分析。結(jié)果術(shù)后使用NAs抗病毒治療不耐藥的患者的轉(zhuǎn)氨酶水平、HBV-DNA水平、HBs Ag滴度、Child-Pugh評(píng)分、無(wú)瘤生存率及總生存率明顯均優(yōu)于不用NAs治療(P0.05)和對(duì)NAs耐藥的患者(P0.05);值得注意的是,術(shù)后使用NAs發(fā)生耐藥的患者的上述指標(biāo)均明顯差于不用NAs治療的患者(P0.05)。存在預(yù)存耐藥的少數(shù)患者中84.6%的患者因NAs選用不當(dāng)導(dǎo)致預(yù)后不佳(P㩳0.05)。結(jié)論相比較NAs不耐藥和不用NAs的患者,發(fā)生NAs耐藥的HCC患者的生存率顯著降低。因此,為了提高HBV相關(guān)性HCC術(shù)后患者的預(yù)后,選擇高效、低耐藥的抗病毒藥物很重要。并且用藥前進(jìn)行預(yù)存耐藥檢測(cè)可能是必要的。
[Abstract]:Objective to analyze the prognostic factors of nucleoside analogue (NAS) resistance in patients with hepatitis B virus (HBV) associated primary liver cancer (HCC) after operation, and to compare the clinical characteristics and survival time between patients with NAS insensitivity and those who did not take NAS at the same time. To detect the presence of pre-drug resistance in such patients, and therefore to explore clinicians' decision-making for antiviral therapy. Methods from January 2011 to July 2014, 482 patients with HBV-associated HCC received radical resection in our hospital from January 2011 to July 2014. None of these patients were treated with NAS antiviral therapy before operation. The patient's history, serological, imaging and pathological data were collected, and the same patient's serum was collected for the detection of hepatitis B virus genotypes and two drug resistance mutation sites before and after medication. The patients were divided into two groups according to the drug use and the results of the drug resistance locus test: the NAS resistant group was not resistant to NAS and the NAS group was not used after the operation. The statistical software SPSS 21.0 was used to carry out the T-test including chi-square test, the rank sum test was used to compare the data difference, and the cumulative survival function curve was used to analyze the survival. Results the level of transaminase and the Child-Pugh score of HBs Ag titer were significantly better than those without NAS therapy (P0.05) and NAS-resistant patients (P0.05) in the patients who received NAS antiviral therapy, and the patients who were resistant to NAS were significantly better than those who were not treated with NAS (P0.05), and those who were resistant to NAS (P0.05) were significantly better than those who were not treated with NAS (P0.05) and those who were resistant to NAS. The above indexes of patients who developed drug resistance after NAS use were significantly lower than those without NAS therapy (P0.05). 84.6% of the patients with preexisting drug resistance had poor prognosis due to improper selection of NAS (P0. 05). Conclusion the survival rate of NAS-resistant HCC patients was significantly lower than that of NAS-resistant patients and non-NAS resistant HCC patients. Therefore, in order to improve the prognosis of patients with HBV-associated HCC, it is important to select effective, low drug resistant antiviral drugs. And it may be necessary to test for pre-drug resistance before medication.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R512.62;R735.7

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