摘要
Background:Severe liver disease(SLD),including cirrhosis and liver cancer,constitutes a major disease burden in China.We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD.Methods:The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years.The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline.Cox regression was used to estimate adjusted hazard ratios(HRs)for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors(smoking,alcohol,physical activity,and central adiposity).Additionally,the contribution of genetic risk for hepatitis B virus(HBV,assessed by genetic variants in major histocompatibility complex,class II,DP/DQ[HLA-DP/DQ]genes)was also estimated.Results:Compared with those with 0-1 healthy lifestyle factor,participants with 2,3,and 4 factors had 12%(HR 0.88[95%confidence interval[CI]0.85,0.92]),26%(HR 0.74[95%CI:0.69,0.79]),and 44%(HR 0.56[95%CI:0.48,0.65])lower risks of SLD,respectively.Inverse associations were observed among participants with both low and high genetic risks(HR per 1-point increase 0.83[95%CI:0.74,0.94]and 0.91[95%CI:0.82,1.02],respectively;P_(interaction)=0.51),although with a non-significant trend among those with a high genetic risk.Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk.Despite the limited power,healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk(HR 0.59[95%CI:0.37,0.96]).Conclusions:Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk.Moreover,it is also important for improving the prognosis of SLD in individuals with a low genetic risk.Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis,particularly among individuals with a high ge
基金
supported by grants from the National Natural Science Foundation of China(Nos.91846303 and 81941018)
The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong,China.The long-term follow-up is supported by grants(Nos.2016YFC0900500,2016YFC0900501,and 2016YFC0900504)
from the National Key Research and Development Program of China,and Chinese Ministry of Science and Technology(No.2011BAI09B01)
Dr.Pang acknowledged support from the China Postdoctoral Science Foundation(Nos.2019TQ0008 and 2020M670071)
the Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation(No.BMU2022 RCZX022)
the Fundamental Research Funds for the Central Universities,and the Peking University Start-up Grant(No.BMU2022PY014)
