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Improved Survival in Hepatocellular Carcinoma Patients with Cardiac Arrhythmia by Amiodarone Treatment through Autophagy.

ABSTRACT: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. In basic studies, the regulation of autophagy has offered promising results for HCC treatment. This study aimed to address the question of whether amiodarone can improve survival rates in HCC patients associated with autophagy. Using datasets from the National Health Insurance Research Database, we enrolled patients over 18 years of age that had been diagnosed with HCC between January 1997 and December 2010. Amiodarone and non-amiodarone users were matched at a 1:1 frequency, according to all variables. Additionally, HepG2 cells treated with amiodarone were evaluated by cell viability and autophagic change. Autophagic signaling was examined by immunoblotting and tissue array immunohistochemistry. Of the 10,946 patients diagnosed with HCC, each cohort included 221 patients after 1:1 propensity score matching. The median survival was 36.70 months for the amiodarone users, and 24.48 months for the non-amiodarone users. After adjusting for age, gender, comorbidities and treatment, amiodarone users had a significantly lower risk of mortality. Amiodarone users also demonstrated an improved 3-year survival rate. Furthermore, amiodarone treatment-induced autophagy in HepG2 cells was demonstrated by autophagosome formation associated with increasing LC3B-II, P62, and Beclin-1 expression. Autophagic flux also increased following amiodarone treatment with bafilomycin A1. SiRNA of LC3B knocked down endogenous LC3B formation and restored HepG2 cell viability. This study provides epidemiologic evidence that amiodarone via autophagic degradation machinery may offer survival benefits for HCC patients with a history of arrhythmia. Further randomized, blinded, and placebo-controlled trials are warranted for patients with HCC.

SUBMITTER: Huang ST

PROVIDER: S-EPMC6720201 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Improved Survival in Hepatocellular Carcinoma Patients with Cardiac Arrhythmia by Amiodarone Treatment through Autophagy.

Huang Sheng-Teng ST Hsu Wei-Fan WF Huang Hung-Sen HS Yen Jia-Hau JH Lin Mei-Chen MC Peng Cheng-Yuan CY Yen Hung-Rong HR

International journal of molecular sciences 20190815 16

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. In basic studies, the regulation of autophagy has offered promising results for HCC treatment. This study aimed to address the question of whether amiodarone can improve survival rates in HCC patients associated with autophagy. Using datasets from the National Health Insurance Research Database, we enrolled patients over 18 years of age that had been diagnosed with HCC between January 1997 and December 2010. Amiodarone and non- ...[more]

PMID: 31443312

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Project description:BackgroundMore than 70% of patients with hepatocellular carcinoma (HCC) are not candidates for curative therapy or recur after curative-intent therapy. There is growing evidence on the use of ablative radiation therapy (RT) for liver tumors. We aimed to analyze outcomes of HCC patients treated with conventional versus ablative RT.MethodsWe retrospectively analyzed medical records of HCC patients treated with liver RT from 2001 to 2019. We defined ablative RT as biologically effective dose (BED) ≥80 Gy. RECIST 1.1 was used to define early responses at 3-6 months after RT, and local control (LC) at last follow-up (FU). Data was analyzed using Fisher exact test, Kaplan-Meier, cumulative incidence rates, Cox proportional hazards model and Fine-Gray competing risks.ResultsForty-five patients were identified, of whom 14 (31.1%) received ablative RT using a stereotactic technique. With median FU of survivors of 10.1 months, 1-year cumulative incidence of LC was 91.7% for ablative and 75.2% for BED <80 Gy. At early FU, patients treated with ablative RT had better responses compared to BED <80 Gy, with 7% progressing versus 19%, and 21.4% with complete response versus none (P=0.038). On univariate analysis (UVA), Child-Pugh (CP) score [hazard ratio (HR): 3 for CP-B, HR: 16 for CP-C] and BED (HR: 7.69 for BED <80 Gy) correlated with deterioration of liver function, leading to liver failure. Most liver failure cases were due to disease progression. No RT-related liver failure occurred in the ablative RT group. On UVA, only BED ≥80 Gy was associated with improved overall survival (OS) (HR: 0.4; P=0.044). Median OS (mOS) and 1-year OS were 7 months and 35% respectively for BED <80 Gy compared to 28 months and 66% for BED ≥80 Gy. No grade 3+ bowel toxicity was reported in either group.ConclusionsGreater than 90% LC was achieved after stereotactic ablative RT, which was associated with minimized tumor- and treatment-related liver failure and improved survival for highly selected inoperable HCC patients.

Dataset Information

Improved Survival in Hepatocellular Carcinoma Patients with Cardiac Arrhythmia by Amiodarone Treatment through Autophagy.

Publications

Improved Survival in Hepatocellular Carcinoma Patients with Cardiac Arrhythmia by Amiodarone Treatment through Autophagy.

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