Association between deacetylase Sirtuins and radiation-induced liver disease / 临床肝胆病杂志

Radiation-induced liver disease （RILD）， also known as radiation hepatitis， is subacute liver injury induced by radiation. As the focus of senescence-related studies， the deacetylase family Sirtuins （SIRTs） have the molecular functions including DNA repair and chromatin regulation， which makes SIRTs a hub for regulating genome and epigenome stability. Radiation-induced hepatic DNA damage and reaction is the primary physiological and pathological process of RILD， which is similar to the function of SIRTs. This article briefly introduces the structure and function of the SIRTs protein family， elaborates on the basic concepts and progress of the physical physiology of radiation therapy， discusses the internal relationship between SIRTs and RILD from the perspective of radiobiology， and points out the possibility of SIRTs as a target for the prevention and treatment of RILD.

Establishment of a RILD model in C57BL/6J mice treated with precise radiotherapy / 中国辐射卫生

Objective To provide a reliable and stable animal model for investigating the molecular pathogenesis of radiation-induced liver disease (RILD). Methods Ninety C57BL/6J mice were divided into control, 20 Gy, 25 Gy, 30 Gy and 35 Gy radiation groups. The mice were executed at 4 weeks after radiation and the levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the liver serum were measured. HE staining was performed on the pathological liver tissues. Masson staining was performed at 36 weeks after radiation. Results Compared with the control group, the fatality rate was higher in the 30 and 35 Gy radiation groups, and the body weight significantly decreased in the 20 and 25 Gy radiation groups. Compared with the control group, alanine aminotransferase significantly increased in mice exposed to 20 Gy, while aspartate aminotransferase and alanine aminotransferase increased in mice exposed to 25 Gy. No significant changes were observed in the livers of the mice in the 20 and 25 Gy radiation groups, but pathological examination showed liver damage induced by both 20 and 25 Gy radiation. Conclusion A stable and reliable mouse model of RILD was constructed for treatment with linear accelerator. The mouse model of RILD constructed for stereotactic body radiation therapy using linear accelerator has significant research implications for the exploration of RILD.

Clinical significance of radiation-induced liver disease after stereotactic body radiation therapy for hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to investigate parameters that predict radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to identify the clinical significance of RILD. METHODS: We retrospectively reviewed the medical records of 117 HCC patients who were treated by SBRT from March 2011 to February 2015. RILD was defined as elevated liver transaminases more than five times the upper normal limit or a worsening of Child-Pugh (CP) score by 2 within 3 months after SBRT. All patients were assessed at 1 month and every 3 months after SBRT. RESULTS: Median follow-up was 22.5 months (range, 3 to 56) after SBRT. RILD was developed in 29 of the 117 patients (24.7%). On univariate analysis, significant predictive factors of RILD were pretreatment CP score (p < 0.001) and normal liver volume (p = 0.002). Multivariate analysis showed that CP score was a significant predictor of RILD (p < 0.001). The incidence of RILD increased above a CP score of 6 remarkably. The rate of recovery from RILD decreased significantly above a CP score of 8. Survival analysis showed that CP score was an independent prognostic factor of overall survival (p = 0.001). CONCLUSIONS: CP score is a significant factor to predict RILD in patients with chronic liver disease. RILD can be tolerated by patients with a CP score ≤ 7. However, careful monitoring of liver function is needed for patients with a CP score 7 after SBRT.

Predictive Values of Child-Pugh Score and Albumin-bilirubin Score for Liver Injury and Prognosis After Stereotactic Ablative Radiotherapy in Patients With Hepatocellular Carcinoma / 胃肠病学

Background:Child-Pugh score(CPS)and albumin-bilirubin(ALBI)score have important predictive value for the assessment of survival of patients with hepatocellular carcinoma(HCC). Aims:To investigate the predictive values of CPS and ALBI score for radiation-induced liver disease(RILD)and long-term prognosis in patients with HCC receiving stereotactic ablative radiotherapy(SABR). Methods:A total of 152 HCC patients receiving SABR from June 2006 to June 2012 at Baoji Central Hospital were enrolled. CPS and ALBI score were determined,and the predictive values of CPS and ALBI score for RILD and prognosis were compared. Results:In 152 patients with HCC,CPS-A was noted in 119 patients, CPS-B in 33 patients;ALBI-1 was noted in 60 patients,ALBI-2 in 86 patients,ALBI-3 in 6 patients. The 5-year overall survival rate was significantly higher in CPS-A patients than in CPS-B patients(46.2% vs. 15.2%,P <0.001). Significant difference in 5-year overall survival rate was found among patients with ALBI-1,ALBI-2 and ALBI-3(P =0.002). CPS grade(HR=1.38,95% CI:1.18-1.94,P=0.008)and ALBI grade(HR=1.68,95% CI:1.32-2.03, P=0.003)were independent risk factors for 5-year survival of patients with HCC. RILD was found in 20 cases(13.8%) within 4 months after SABR. AUC of ALBI for prediction of RILD was significantly higher than that of CPS(0.784 vs. 0.611,P=0.028). Patients with CPS-A and ALBI< -2.76 were less likely to develop RILD after SABR(2.4%). Conclusions:ALBI can effectively predict the occurrence of RILD and long-term survival of HCC patients after SABR.

Reappraisal of Risk Factors Predicting Liver Complications from Radiotherapy for Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Determination of the optimal radiotherapeutic parameters for radiotherapy of hepatocellular carcinoma (HCC) is still under investigation. The purpose of this study is to identify the risk factors associated with radiation-related morbidity. METHODS: We evaluated one hundred fifty-eight patients, who were given radiotherapy for HCC between January 1992 and March 2000. Radiation-induced liver disease (RILD) was defined as the development of nonmalignant ascites without disease progression and an anicteric elevation of the alkaline phosphatase level by at least twofold. Gastrointestinal toxicity was assessed by using the RTOG-EORTC scale. RESULTS: Six patients (3.8%) displayed RILD. In these patients, three patients had not responded to other previous treatments. Two patients with portal vein thrombosis or huge sized mass, above 10 cm, showed liver toxicity and two other patients presented with Child-Pugh class B liver cirrhosis. Eight patients (5%) had gastro-duodenal ulcers. In one of these 8 patients, the left lobe close to the stomach was involved and two patients had been treated for gastro-duodenal ulcer. In two more patients, the radiation field, with using anterior/posterior radiation ports, covered a significant volume of the gastrointestinal tract. One of eight patients had been irradiated with a large fraction size (250 cGy). CONCLUSIONS: The efforts should be made to reduce the radiation-related complications for hepatocellular carcinoma by considering the volume and the function of remaining liver, the location of tumor, the tumor size and the severity of liver cirrhosis.

Lyman NTCP model analysis of radiaton-induced liver disease in hypofractionated conformal radiotherapy for primary liver carcinoma / 中华放射肿瘤学杂志

Objective To-identify the factors associated with radiation-induced liver disease (RILD) and to describe the probability of RILD using the Lyman normal tissue complication(NTCP) model for primary liver carcinoma(PLC) treated with hypofractionated conformal therapy (CRT).Methods A total of 109 PLC patients treated with hypofractionated CRT were prospectively followed according to the Child-Pugh classification for liver cirrhosis,93 patients in class A and 16 in class B.The mean dose of radi- ation to the isocenter was (53.5?5.5) Gy,fractions of (4.8?0.5) Gy,with interfraction interval of 48 hours and irradiation 3 times per week.Maximal likelihood analysis yielded the best estimates of parameters of the Lyman NTCP model for all patients;Child-Pugh A and Child-Pugh B patients,respectively.Results Of all the patients,17 developed RILD (17/109),8 in Child-Pugh A(8/93 ) and 9 in Child-Pugh B(9/ 16).By multivariate analysis,only the Child-Pugh Grade of liver cirrhosis was the independent factor (P= 0.000) associated with the developing of RILD.The best estimates of the NTCP parameters for all 109 pa- tients were n=1.1,m=0.35 and TD_(50) (1)=38.5 Gy.The n,m,TD_(50) (1) estimated from patients with Child-Pugh A was 1.1,0.28,40.5 Gy,respectively,compared with 0.7,0.43,23 Gy respectively,for patients with Child-Pugh B.Conclusions Primary liver cancer patients who possess Child-Pugh B cirrho- sis would present a significantly greater susceptibility to RILD after hypofractionated CRT than patients with Child-Pugh A cirrhosis.The predominant risk factor for developing RILD is the severity of hepatic cirrhosis in the liver of PLC patients.