Statin-Based Palliative Therapy for Hepatocellular Carcinoma

Most hepatocellular carcinoma (HCC) patients worldwide do not receive curative treatments. Alternative treatments for most HCC patients include palliative treatments, such as transarterial chemoembolization (TACE), chemotherapy, and radiotherapy. Although statins may be a chemopreventive treatment option for reducing hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related HCC risks, their therapeutic effects are unknown. This study evaluated the effects of statin on HCC patients receiving palliative treatment. Data from the National Health Insurance claims database and cancer registry databases of The Collaboration Center of Health Information Application, Taiwan, were analyzed. We included HCC patients who were treated between January 1, 2001, and December 31, 2010, and followed them from the index date to December 31, 2012. The inclusion criteria were presence of HBV carrier-related HCC, age >20 years, and having received TACE, radiotherapy, or chemotherapy as palliative treatment. The exclusion criteria were cancer diagnosis before HCC was confirmed, surgery, liver transplantation, radiofrequency ablation, or percutaneous ethanol injection as curative treatment, missing sex-related information, HCC diagnosis before HBV, and age <20 years. We enrolled 20,200 HCC patients. The median follow-up duration was 1.66 years (interquartile range, 0.81). In total, 1988 and 18,212 patients received palliative treatment with and without statin use, respectively. HCC patients who received palliative treatment with statin use had lower HCC-specific deaths in all stages than those who received palliative treatment without statin use (P = 0.0001, 0.0002, 0.0012, and 0.0002, and relative risk (RR) = 0.763, 0.775, 0.839, and 0.718, for stages I–IV, respectively). In all-cause and HCC-specific deaths, decreasing trends (P for trend <0.0001) of adjusted hazard ratios (aHRs) were observed in all stages with no treatment, statin use only, palliative treatment only, and palliative treatment plus statin use. The aHRs of all-cause and HCC-specific deaths increased with the progress in cancer stage and reduced with the use of advanced therapeutic modalities (P for trend <0.0001). Differences in HBV- and non-HBV-related HCC were solely due to statin use. Statin use alone reduced HCC-specific deaths by 36% in non-HBV-related HCC in stage I and 50% in HBV-related HCC in stages II and III. With a relatively substantial reduction in mortality, the therapeutic effects of statin use were stronger in HBV-related HCC than in non-HBV-related HCC. Palliative treatments are critical for HCC patients. Multiple therapeutic methods with statin use reduced the mortality risk. Statins prolong the survival of patients with advanced HCC receiving palliative treatment, thus demonstrating its therapeutic value as an adjuvant treatment. Furthermore, statin-based palliative treatment in early stage HCC remarkably reduced the number of deaths. For patients who cannot tolerate palliative treatments, statin use only might possibly reduce mortality, particularly in HBV-related early stage HCC patients (>50% reduction in HCC deaths).