Yada Masayoshi, Miyazaki Masayuki, Motomura Kenta, Masumoto Akihide, Nakamuta Makoto, Kohjima Motoyuki, Sugimoto Rie, Aratake Yoshifusa, Higashi Nobuhiko, Morizono Shusuke, Takao Shinichiro, Yamashita Naoki, Satoh Takeaki, Yamashita Shinsaku, Kuniyoshi Masami, Kotoh Kazuhiro
Department of Hepatology, Iizuka Hospital, Iizuka, Japan ;
Department of Gastroenterology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan ;
J Gastrointest Oncol. 2016 Aug;7(4):615-23. doi: 10.21037/jgo.2016.03.10.
Serum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis.
Eighty-nine consecutive patients with HCC (Child-Pugh class A) who were treated using sorafenib were enrolled into this study. Pretreatment characteristics and changes in hepatic functional tests based on early response to sorafenib and serum LDH levels were analyzed. The degree of fibrosis was estimated using the aspartate aminotransferase (AST) to platelet ratio index (APRI), and the tumor response was evaluated after 3 months of sorafenib treatment.
Overall, five patients discontinued sorafenib within 4 weeks. For the other 84 patients, those with progressive disease (PD) had significantly high pretreatment LDH levels, which correlated with the APRI score but not with the tumor stage. Multivariate logistic analysis revealed that older age and lower pretreatment LDH levels were independent prognostic factors for a better response to sorafenib. In patients who discontinued sorafenib early, three experienced acute liver failure accompanied with an increase in serum LDH.
We demonstrated that baseline serum LDH levels in HCC patients were affected by liver fibrosis but not by the tumor stage, and these LDH levels could be a marker for early response to sorafenib. A marked increase in serum LDH levels during sorafenib administration might also indicate subsequent acute liver failure. Close observation of serum LDH levels before and during sorafenib treatment could be useful in managing treatment of patients receiving this therapy.
血清乳酸脱氢酶（LDH）水平可能是多种实体瘤患者接受索拉非尼治疗的预后因素，因为它反映了侵袭性肿瘤中的缺氧情况。然而，对于肝细胞癌（HCC），LDH的预后作用一直存在争议。肝纤维化可能导致肝脏缺氧，此前尚未在晚期HCC患者中进行过研究。因此，我们旨在分析基于纤维化程度的LDH的预后作用。
连续89例接受索拉非尼治疗的HCC患者（Child-Pugh A级）纳入本研究。分析了基于索拉非尼早期反应的治疗前特征和肝功能检查变化以及血清LDH水平。使用天冬氨酸转氨酶（AST）与血小板比值指数（APRI）评估纤维化程度，并在索拉非尼治疗3个月后评估肿瘤反应。
总体而言，5例患者在4周内停用索拉非尼。对于其他84例患者，疾病进展（PD）患者的治疗前LDH水平显著升高，这与APRI评分相关，但与肿瘤分期无关。多因素逻辑分析显示，年龄较大和治疗前LDH水平较低是索拉非尼反应较好的独立预后因素。在早期停用索拉非尼的患者中，3例经历了急性肝衰竭并伴有血清LDH升高。
我们证明，HCC患者的基线血清LDH水平受肝纤维化影响，但不受肿瘤分期影响，这些LDH水平可能是索拉非尼早期反应的标志物。索拉非尼给药期间血清LDH水平的显著升高也可能表明随后的急性肝衰竭。密切观察索拉非尼治疗前和治疗期间的血清LDH水平可能有助于管理接受该治疗的患者。
