There has been a rapid rise in cirrhosis-related mortality in the United States in the past decade.1 This significant increase in mortality has been observed mainly in patients with alcohol-related liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma (HCC).2 Racial and ethnic disparities have been linked to outcomes in patients with end-stage liver disease (ESLD).3,4 The highest prevalence of cirrhosis-related mortality was seen in non-Hispanic whites; followed by Hispanics, non-Hispanic blacks, and Asians.2 Ethnicity-based mortality rates in patients with ESLD revealed that the number of deaths due to HCC was higher than cirrhosis-related mortality among non-Hispanic blacks and non-Hispanic Asians.2
The association between Hispanic ethnicity and outcomes in patients with cirrhosis remains controversial. Comprehensive reviews of prevalence, natural history, and response to treatment in Hispanic patients indicate higher incidence, more severe pattern of disease, and adverse treatment outcomes in Hispanics compared to the non-Hispanic white population.1,5 In contrast to these studies, annual age-standardized mortality rates for HCC was lower in Hispanics living in the United States, between 2007 and 2016, compared to non-Hispanic blacks and Asians.2 This survival benefit in the Hispanic race has also been observed in patients with cardiovascular and renal disease6 and has been labeled as the “Hispanic paradox.”
In this issue of Transplantation, Atiemo et al7 provide important information regarding the relevance of Hispanic ethnicity to mortality considering the etiology of cirrhosis. Using a retrospective cohort of over 20 000 patients, Atiemo and colleagues7 conducted multivariate Cox regression analysis to determine whether this “Hispanic paradox” exists in patients with cirrhosis. The study population consisted of 16% Hispanics, 45% non-Hispanic Whites (NHW), 22% African Americans, 3% Asians, and 14% other races/ethnic groups. In multivariate Cox analysis adjusted for age, sex, insurance status, etiology of cirrhosis, and comorbidities, mortality risk was higher in NHW and African Americans when compared to Hispanics. When survival analysis was stratified by etiology of cirrhosis, a survival benefit for Hispanics over NHW was observed in patients with alcohol-related cirrhosis and cirrhosis related to hepatitis B and C, whereas no difference in mortality risk was observed between Hispanics and NHW patients with HCC. Similar results were obtained using competing-risk analysis, despite a very low rate of liver transplantation (LT) in this cohort (5%), suggesting survival advantage of Hispanic ethnicity exists even in the presence of LT as a potential outcome. This analysis of a large cohort of a US population for ethnicity-based mortality rates in patients with cirrhosis adjusted for multiple confounders is commendable.
Interestingly, this study shows a survival advantage of female sex. This is contrary to the previous studies showing higher waitlist mortality in female patients with cirrhosis due to lower serum creatinine and subsequently lower model for end-stage liver disease (MELD) scores in females.8 It should be noted that sex differences also exist with regards to body composition and other clinical features of liver disease such as etiology, presence of liver tumors, and creatinine levels, which may contribute to disease burden.9
Although this study adds to our growing understanding of etiology- and racial-related mortality in cirrhosis, some words of caution are in order. The authors conclude that Hispanic race has a survival advantage in cirrhosis after adjusting for various confounding variables. However, the choice of reference category may change the interpretation of the results. For example, when compared to African American patients, the risk is lower in Hispanic and Asians. Therefore, we think Hispanic ethnicity should be compared to the non-Hispanics (taking as reference the absence of Hispanic ethnicity) to provide a more clear idea of the potential benefit of Hispanic ethnicity rather than comparing each ethnicity to Hispanics as the reference.
Although the authors explored the importance of MELD score in mortality prediction, other confounding factors remained unaccounted for. Low serum albumin is associated with mortality, poor outcomes,10 and advanced fibrosis11 in patients with cirrhosis. Inclusion of other major predictors of outcomes such as albumin or hepatic decompensation in multivariate analysis would have strengthened the independent association of Hispanic race with mortality in cirrhosis.
In this study, HCC was less prevalent in the Hispanic group in comparison to the NHW and Asian groups. This may in part contribute to the survival benefit seen in the Hispanic group. Lastly, a significant proportion of Hispanic patients, mainly those who are undocumented, may not have been registered in the healthcare databases used for analysis. Despite these confines, the results of this study are interesting because they emphasize the impact of age, sex, insurance status, etiology of cirrhosis, and comorbidities on outcomes in patients with cirrhosis.
In conclusion, the current study by Atiemo et al7 underlines the importance of ethnicity and cirrhosis-etiology in predicting adverse outcomes in patients with cirrhosis. However, prospective studies are required to overcome the difficulties in our present understanding of the predictive value of ethnicity in patients with cirrhosis. More importantly, the significance of genetic, geographical, and environmental disparities in studies assessing ethnicity-related cirrhosis mortality as well as the rationale behind this association requires further investigation. These studies will get us one step closer to individualized medicine, where screening and therapeutic strategies are tailored to sex, race, and etiology in patients with ESLD.
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8. Mindikoglu AL, Regev A, Seliger SL, et al. Gender disparity in liver transplant waiting-list mortality: the importance of kidney function.Liver Transpl2010161147–1157
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10. Walayat S, Martin D, Patel J, et al. Role of albumin in cirrhosis: from a hospitalist’s perspective.J Community Hosp Intern Med Perspect201778–14
11. Torres-Valadez R, Roman S, Jose-Abrego A, et al. Early detection of liver damage in Mexican patients with chronic liver disease.J Transl Int Med2017549–57