Liver cancer in Hidalgo State, Mexico: analysis of the status, risk factors and regional public health policy requirements: a cross-sectional correlational study

ABSTRACT BACKGROUND: In Latin America, liver cancer is one of the top causes of cancer mortality. It is the fifth most common cause of death among malignant tumors in Mexico and is the leading cause in Hidalgo State (43.8% of the population living in poverty). OBJECTIVE: To conduct a correlational analysis on the main risk factors for liver cancer in Hidalgo State, Mexico, including municipal disaggregation and comparison with the national level. DESIGN AND SETTING: Cross-sectional, correlational, descriptive and comparative epidemiological study using Mexican governmental databases covering 1990-2019. METHODS: A comprehensive review of the databases of the General Directorate of Health Information (DGIS) was performed to analyze official death figures, hospital discharges and national and municipal population projections, using specific search criteria defined in the Global Burden of Disease classification, based on the risk factors for liver cancer. RESULTS: Liver cancer rates showed an evident rise in Hidalgo (183%), moving from 21st place in Mexico in 1990 to 9th place in 2019. This increase was correlated with alcoholism. An increasing trend for liver cancer deaths, of 133.89%, is projected for 2030. Females and the population over 60 years of age are more affected. There are some critical regions with liver cancer death rates twice the national rate or more. CONCLUSION: Targeted effective public health strategies should be structured by identifying, characterizing and regionalizing critical marginalized municipalities that are vulnerable to alcoholism and other risk factors for liver cancer. This approach may be helpful for other states in Mexico or similar countries.


INTRODUCTION
There has been an increase in the global incidence of liver cancer, which became the sixth most common cancer and the third leading cause of cancer death in the world in 2020. 1 This has also raised interest in studying its clinical and epidemiological aspects in Latin America. [2][3][4] Hepatocellular carcinoma (HCC) is the most frequent form of liver cancer, accounting for 75% to 85% of primary hepatic neoplasms. 1 It is also between the second and fourth most important cause of cancer-related mortality worldwide and is the leading cause of cancer among patients with cirrhosis. 2,3,5 HCC occurs more frequently in men than in women, and about one million new cases are diagnosed every year. 3,6,7 In Mexico, complications from liver cirrhosis have remained the third most common cause of death over the last decades, and the future trend is worrying. The incidence of HCC continues to rise in Mexico, especially affecting older people in the sixth decade of life, and the mortality rate used to be higher among males. The most common underlying chronic liver diseases that cause HCC in the Mexican population are alcoholic liver disease (ALD) and hepatitis C virus (HCV). However, non-alcoholic steatohepatitis (NASH) is increasingly a cause of HCC: the incidence of this disease is rising at an alarming rate because of complications from metabolic syndrome (MetS), which is present in a high proportion of Mexicans. 8,9 Although the epidemiological characteristics of HCC in Mexico are similar to those in other Latin American countries, such as Argentina, Brazil and Colombia, 4 comprehensive information concerning the diagnosis, treatment and surveillance of HCC in Mexico is scarce. Better information might improve early detection and thus decrease morbidity and mortality among HCC patients. 7

OBJECTIVE
The aims of this study were to conduct a correlational and descriptive analysis on the main risk factors for liver cancer in Hidalgo State (hepatic fibrosis/cirrhosis, ALD and HCV), including municipal disaggregation and comparison with the national level; and to study trends of liver cancer deaths and projections to 2030, using data covering the period from 1990-2019.

Study design
This study was designed as a correlational, descriptive, cross-sectional and comparative epidemiological study. This work did not require institutional review board (IRB) approval, given that it used anonymized and publicly available data.

Data sources
A comprehensive review of the databases of the DGIS was per- To determine whether the hospital discharges relating to liver cancer were correlated with the hospital discharges relating to pathological conditions that were considered to be causes of HCC (which was our hypothesis), data from all municipalities were studied using the Spearman correlation test. However, the data did not follow normal distribution (P < 0.0001). Since not every municipality had similar hospital discharge relating to liver cancer, that hypothesis was tested again but considering only the municipalities in which the death rate was higher than the mean (5.02) + one standard deviation (5.49). These corresponded to municipalities with at least twice the national death rate due to HCC. These data followed normal distribution (P > 0.05), and the Spearman correlation test was thus applied. Finally, normality was tested using the Shapiro-Wilk test. These analyses were performed using the GraphPad Prism 6.01 software (California, United States).
The inclusion criteria were that these municipalities of Hidalgo State needed to have the following: a) records of MLT as the primary cause of death; and b) records of hospital discharges from the SS of Hidalgo relating to liver diseases. The exclusion criteria were situations of the following: a) death and hospital discharge records that stated a country of residence other than Mexico or reported the country as unspecified; and b) for data analysis at the state level, death and hospital discharge records declaring a state of residence other than Hidalgo or reporting this as unspecified.
Descriptive analysis on the data was carried out by determin- After the municipal mortality rates for liver cancer had been calculated, differential mapping was used to identify regions of Hidalgo with higher liver cancer rates. In addition, the 2010-2019 municipal population projections for Mexico compiled by CONAPO were used.

RESULTS
The relative weight (%), mortality rates for malignant tumors and their ranks as the primary cause of mortality were calculated for Mexico and Hidalgo based on the death figures for malignant tumors according to the GBD classification ( Table 1). MLTs are a public health problem at both the national and the state level, considering that they are the fifth largest cause of death in Mexico and the leading cause in Hidalgo. This state's liver cancer mortality rate is 6.4 deaths per 100,000 inhabitants, which is 1.1 points greater than the national rate; its relative weight is at least 1.4% higher than that of other tumors in the state and Mexico.   since then, it has always been among the top ten. Hidalgo occupies the ninth place in the national ranking of liver cancer deaths considering the cumulative death rate of 2010-2019 as the period analyzed for mortality. Furthermore, the ECI index in 2021 for each state is presented to contextualize their economic development. As observed, the situation of the financial resources of most of these states has the implication that their ability to improve their healthcare services and prevention programs may be limited.
The MLT mortality rate was 31.43% higher than the national rate between 1990 and 2019 (151.42% for Mexico and 182.85% for Hidalgo). Since 2005, the mortality rates in Hidalgo have always been higher than national rates ( Figure 1A). The death records comprising the period from 1985 to 2019 formed the basis to construct a functional linear model of data trend (Figure 1B), which showed a positive association between time and liver cancer death (y   Given the high prevalence of MLT in the state, municipal disaggregation was a necessity in order to analyze their death rates over  The relationship between hospital discharge rates relating to HCC and hospital discharge rates relating to ALD, CVH and fibrosis/cirrhosis as the leading risk factor for the disease in Hidalgo (2010-2019) was studied. The correlation analysis did not show any significant difference between hospital discharges relating to HCC and hospital discharges relating to ADL (ρ = -0.13, P > 0.05), CVH (ρ = -0.19, P > 0.05) or fibrosis/cirrhosis (ρ = 0.16, P > 0.05) ( Figure 2B). Nevertheless, among the municipalities with the highest HCC death rates, only nine with a mean hospital discharge rate for HCC + one standard deviation were considered for calculating Pearson's coefficient. This analysis revealed that there was a significant positive correlation between HCC and ALD (R 2 = 0.49, P < 0.05) in these critical municipalities ( Figure 2C).  and Colombia (0.09 ECI, 0.51 GINI), have lower mortality rates for liver cancer, which was ranked between sixth and tenth place in 2020. 12 MLTs are the leading cause of death in Hidalgo; identification and characterization of critical municipalities provide better understanding of the current situation of this disease in the state. In the population studied, the highest mortality rates were observed in the group aged > 60 years, which agrees with earlier data for Mexico. 8,10 In addition, both sexes seemed to suffer equally from HCC in 2014, 8 although most authors have reported higher mortality rates for men in Mexico 5,6 and Latin America. 2 In the present study in 2019, a higher death rate among women aged < 60 years was found in Hidalgo, although men were more affected than women in the three municipalities with the highest HCC death figures. Epidemiological reports have shown an equal ratio of male/female mortality due to HCC in countries like Mexico; however, current trends indicate a rise in the number of female deaths, such that in Mexico liver cancer was the third largest cause of death among women and the fifth among men in 2020. 9,12,14 Conversely, the estimated death rates due to liver cancer in Argentina, Brazil and Colombia for both sexes ranked sixth to tenth among cancers in 2020. 12 Scientific evidence confirms that ALD, CVH and fibrosis/ cirrhosis are the major risk factors for developing liver cancer. [1][2][3] Several studies carried out in South America have reported that HCV infection is the most frequent risk factor, but also that HCV/ HBV coinfection, alcoholic cirrhosis and non-alcoholic fatty liver disease (NAFLD) are also widespread risk factors. 4 Indeed, the Mexican population has been found to be more susceptible to ALD because of genetic and environmental factors. 15 In addition to the mortality data, our analysis on hospital discharges among Hidalgo inhabitants provided a gross indicator of morbidity. Hospital discharges can represent either demand for or provision of healthcare services, thus providing a valuable tool for identifying the morbidity profile. Moreover, hospital discharges indicate the level of hospital services for resolving the needs of patients. 16 For the present study, hospital discharges in which the municipality of residence was not specified were eliminated from the results, given that the objective was to analyze municipalities; otherwise, precise information might improve the municipal analysis.

DISCUSSION
A significant increase in hospital discharges among cirrhosis patients was observed in Hidalgo from 2010 to 2019. Other authors have also reported high incidence and prevalence of cirrhosis over a similar period, which was related to high alcohol consumption and viral infections. 9,17 Hospital discharges relating to HCV also increased in this state, since chronic HCV infection has emerged as a health problem in Mexico 18,19 and Latin America. 3,4 ALD is the most important cause of chronic liver disease and accounts for one-third of all HCC cases globally. 20 Furthermore, the increase in alcohol consumption in the young Mexican population is alarming, while Unexpectedly, the municipality of Pachuca, the state capital of Hidalgo, had a high mortality rate for liver cancer and was ranked third. Pachuca had a GINI index of 0.397 in 2015 and an illiteracy rate of 1.59% in 2020. Use of alcohol and illegal drugs is increasing in Pachuca, although 54.8% of the Hidalgo population has been exposed to prevention programs. 22 Hence, these municipalities require a profound status analysis and regional strategies to improve future public health policies.
These findings suggest that national or state prevention programs aimed at reducing alcohol and drug consumption or at providing care for underserved communities have not significantly improved the social and health conditions in those municipalities. This may be considered to be a social failure despite the many governmental strategies that have been implemented to improve Mexico's poverty and social lag indicators. [22][23][24][25] Consequently, the prevalence of non-communicable diseases is high among marginalized communities. Moreover, these communities are exposed to unhealthy environments, and the socioeconomic inequalities and exclusion from formal labor markets to which these communities are exposed in Mexico and Latin America restrict their access to healthcare services. 26 Although local or regionalized public health policies are often overdue, application of such policies is required urgently because they can have profound positive effects on community health and can ameliorate health disparities, lessen administrative paperwork within healthcare systems and diminish governmental dysfunction. 27 Two areas of opportunity and challenges are recognized: implementation of a population-based cancer registry with reliable data; and creation of a national cancer plan to guide control programs and strategies. 28,29 Unfortunately, local or regional healthcare policy strategies depend on government budgets at the state or national level, but community and municipal populations cannot quickly manage these resources and demand their uncorrupted use.

CONCLUSION
This study provided a detailed epidemiological view of the sta-