Does Fatty Liver Play a Role in the Risk of All-Cause and Cause-Specific Mortality in Patients with Gallstone Disease?

Abstract

We read with interest the article of Konyn et al1Konyn P. et al.Clin Gastroenterol Hepatol. 2022; (Epub 2022/06/02)Google Scholar in Clinical Gastroenterology and Hepatology, who performed a prospective cohort study, and concluded that gallstone disease was associated with increased all-cause mortality in individuals without nonalcoholic fatty liver disease (NAFLD) rather than in those with NAFLD. This is an interesting study. However, we have some concerns about this study. First, Konyn et al1Konyn P. et al.Clin Gastroenterol Hepatol. 2022; (Epub 2022/06/02)Google Scholar performed analyses after categorizing 4 groups (NAFLD [-]/gallstone disease [-] vs NAFLD [-]/gallstone disease [+] vs NAFLD [+]/gallstone disease [-] vs NAFLD [+]/gallstone disease [+]) in Table 3. They observed the association between gallstone disease and all-cause mortality only in individuals without NAFLD. Thus, they considered that NAFLD is not a statistically significant predictor of all-cause mortality. Nevertheless, combining the NAFLD (+) gallstone disease (-) and NAFLD (+) gallstone disease (+) groups, we were surprised that NAFLD increases all-cause mortality after adjusting for age and sex. This seems contradictory to their assumption. Furthermore, NAFLD was confirmed to be associated with high overall and liver-related mortality in previous studies from NHANES III and an impressive number of cohort studies.2Alvarez C.S. et al.Hepatology. 2020; 72: 430-440Crossref PubMed Scopus (25) Google Scholar, 3Ong J.P. et al.J Hepatol. 2008; 49: 608-612Abstract Full Text Full Text PDF PubMed Scopus (484) Google Scholar, 4Younossi Z.M. et al.Hepatology. 2016; 64: 73-84Crossref PubMed Scopus (5052) Google Scholar, 5Ekstedt M. et al.Hepatology. 2015; 61: 1547-1554Crossref PubMed Scopus (1265) Google Scholar, 6Paik J.M. et al.Hepatol Commun. 2019; 3: 1459-1471Crossref PubMed Scopus (78) Google Scholar It would be better if the authors could make a reasonable explanation for this result. Second, in the age- and sex-adjusted models, we noted that those with NAFLD and gallstone disease/cholecystectomy showed a significant association with all-cause mortality (hazard ratio, 1.31; P < .001; hazard ratio, 1.29; P = .003, respectively) compared with individuals without NAFLD or gallstone disease/cholecystectomy. Those with NAFLD and gallstones showed marginal association with all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 0.96–1.51), compared with individuals without NAFLD or gallstones. This provides some evidence of a correlation between gallstones and all-cause mortality even in a fatty liver population. The authors adjusted for up to 18 confounding factors in the multivariable models and found no association in NAFLD individuals subsequently. It could be inappropriate. The more confounding factors are included, the more cases of outcome events are required. It is generally accepted that at least 15–20 cases of nontruncated events per independent variable are required to guarantee the reliability of the estimates. That is, approximately 270 nontruncated events are required (18 confounding factors × 15). According to Table 1, there were approximately 855 individuals in the NAFLD (+) gallstone disease (+) group, 463 individuals in the NAFLD (+) cholecystectomy (+) group, and 396 individuals in the NAFLD (+) gallstone(s) (+) group. We did not find data on the number of deaths in each group. We are concerned that such a conclusion may be reached because of low validity caused by an inadequate sample population. We recommend that the authors report the number of people in each group and the number of deaths. Besides, we suggested that the authors perform multiple multivariable models to demonstrate the robustness of this result. Overall, we congratulate the authors for conducting this study. This is an interesting topic and a large number of future cohort studies will be needed to validate this result. Gallstone Disease and Its Association With Nonalcoholic Fatty Liver Disease, All-Cause and Cause-Specific MortalityClinical Gastroenterology and HepatologyPreviewPresence of gallstone disease may influence outcomes in patients with nonalcoholic fatty liver disease (NAFLD). We studied the impact of gallstone disease on mortality in individuals with and without NAFLD. Full-Text PDF ReplyClinical Gastroenterology and HepatologyPreviewWe thank Xie and their colleagues for their interest in our study and greatly appreciate their questions. We have carefully reviewed their letter and would like to address their remarks. Full-Text PDF