Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Objective: Mental illnesses may be caused by genetic and environmental factors. Recent studies reported that mental illnesses were accompanied by higher oxidative stress level. However, the results were inconsistent. Thus, present meta-analysis aimed to analyse the association between oxidative DNA damage indicated by 8-hydroxy-2’-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), which has been widely used as biomarker of oxidative stress, and mental illnesses, including schizophrenia, bipolar disorder and depression. As oxidative DNA damage is caused by reactive oxygen species (ROS), systematic review and meta-analysis were also conducted to analyse the relationship between ROS and these three mental illnesses. Methods: Studies from 1964 to 2020 (for oxidative DNA damage) and from 1907 to 2021 (for ROS) in Pubmed and Scopus databases were selected and analysed using Comprehensive Meta-Analysis version 2 respectively. Data were subjected to meta-analysis for examining the effect sizes of the results. Publication bias assessments, heterogeneity assessments and subgroup analyses based on biological specimens, patient status, illness duration and medication history were also conducted. Results: This meta-analysis revealed that oxidative DNA damage was significantly higher in patients with schizophrenia and bipolar disorder based on random-effects models whereas in depressed patients, the level was not significant. Since heterogeneity was present, results based on random-effects model was preferred. Our results also showed that oxidative DNA damage level was significantly higher in lymphocyte and urine of patients with schizophrenia and bipolar disorder respectively. Besides, larger effect size was observed in inpatients and those with longer illness duration and medication history. Significant higher ROS was also observed in schizophrenic patients but not in depressive patients. Conclusion The present meta-analysis found that oxidative DNA damage was significantly higher in schizophrenia and bipolar disorder but not in depression. The significant association between deoxyguanosines and mental illnesses suggested the possibility of using 8-OHdG or 8-oxodG as biomarker in measurement of oxidative DNA damage and oxidative stress. Higher ROS level indicated the involvement of oxidative stress in schizophrenia. The information from this study may provide better understanding on pathophysiology of mental illnesses.

Objective: Mental illnesses may be caused by genetic and environmental factors. Recent studies reported that mental illnesses were accompanied by higher oxidative stress level. However, the results were inconsistent. Thus, present meta-analysis aimed to analyse the association between oxidative DNA damage indicated by 8-hydroxy-2’-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), which has been widely used as biomarker of oxidative stress, and mental illnesses, including schizophrenia, bipolar disorder and depression. As oxidative DNA damage is caused by reactive oxygen species (ROS), systematic review and meta-analysis were also conducted to analyse the relationship between ROS and these three mental illnesses. Methods: Studies from 1964 to 2020 (for oxidative DNA damage) and from 1907 to 2021 (for ROS) in Pubmed and Scopus databases were selected and analysed using Comprehensive Meta-Analysis version 2 respectively. Data were subjected to meta-analysis for examining the effect sizes of the results. Publication bias assessments, heterogeneity assessments and subgroup analyses based on biological specimens, patient status, illness duration and medication history were also conducted. Results: This meta-analysis revealed that oxidative DNA damage was significantly higher in patients with schizophrenia and bipolar disorder based on random-effects models whereas in depressed patients, the level was not significant. Since heterogeneity was present, results based on random-effects model was preferred. Our results also showed that oxidative DNA damage level was significantly higher in lymphocyte and urine of patients with schizophrenia and bipolar disorder respectively. Besides, larger effect size was observed in inpatients and those with longer illness duration and medication history. Significant higher ROS was also observed in schizophrenic patients but not in depressive patients. Conclusion The present meta-analysis found that oxidative DNA damage was significantly higher in schizophrenia and bipolar disorder but not in depression. The significant association between deoxyguanosines and mental illnesses suggested the possibility of using 8-OHdG or 8-oxodG as biomarker in measurement of oxidative DNA damage and oxidative stress. Higher ROS level indicated the involvement of oxidative stress in schizophrenia. The information from this study may provide better understanding on pathophysiology of mental illnesses.