The result of the first PubMed MeSH search was 7166 peer-reviewed published articles about climate change and human health during the period between 1976 and 2022. After specifying peer-reviewed published articles that focused on the impacts of CC on liver, 33 peer-reviewed published articles were found during the period between 1991 and 2021.
The second PubMed MeSH search to select the peer-reviewed published articles discussing the relationship of CC on liver health problems caused by exposure to environmental toxins or pollutants revealed that only one article was published in the last 5 years. PubMed MeSH search for the effect of mycotoxins on the liver resulted into 31 articles, and after filtration only five peer-reviewed published articles were detected discussing the role of CC on mycotoxins affecting the liver.
The results of Google and Medline searches and the manual selection of peer-reviewed published articles focusing on the relationships between the various parameters of CC, such as temperature, precipitation salinity, the different toxins and pollutants, and human hepatic health problems, resulted in 10 peer-reviewed published articles.
This review discusses the role of CC on the mapping of some common communicable and non-communicable liver diseases and highlights the importance of considering CC as risk factor for remapping of hepatic diseases and the impacts of CC on the different hepatotoxic or hepato-carcinogenic causative agents mentioned in Table 1. Therefore, the main results from the included articles were presented as communicable and non-communicable liver diseases.
Table 1 Studies on the impact of climate changes on different liver diseases Communicable Diseases
Vector-Borne Diseases (VBDs)
Vectors transmitting parasitic or viral diseases are extremely sensitive to CC, as heat waves, extreme weather events, and salinity have direct effects on breeding rates and sites, survival rates and activities of these vectors, and indirect effects on the pathogens such as shortness or elongation of the incubation period inside the vectors. Therefore, CC will change the geographic distribution, intensity of transmission, and seasonality of VBDs [4]. In addition, the uncontrolled movement of livestock and people increases the risk of development of VBD outbreaks such as dengue and Rift Valley hemorrhagic fever [9].
Extreme weather events are favorite for mosquito breeding and cause rapid proliferation of several species of mosquitoes, including Aedes, Culex, and Anopheles spp. Aedes aegypti is a mosquito vector notorious for spreading different viruses causing hepatic complications such as yellow fever, dengue, Rift Valley hemorrhagic fever, chikungunya (CHIKV), and Zika.
CHIKV, as an example, is transmitted through the bite of the infected mosquitoes, mostly Aedes aegypti and Aedes albopictus. After infection with CHIKV, the virus replicates in many organs including liver and persists in it. Meanwhile, the main reservoir for persistent CHIKV infection is macrophages. CHIKV could also be affected by people and vector movements, as CHIKV outbreaks spread from Indian Ocean to Europe to be registered in Italy [10] and autochthonous cases in France [11].
Malaria transmission is nonlinear as a response to CC. When maximum temperature is close to the upper limit for vector and pathogen, this leads to reduction of transmission, while daily temperature near the minimum boundary increases the transmission. Infection of the liver cells can cause organ congestion, sinusoidal blockage, and cellular inflammation [12]. Moreover, cumulative amounts of rainfall and the increase in humidity affect mosquito breeding and survival, leading to the rapid development of infective sporozoites in the mosquitoes [12].
Water and Food-Borne Infectious Diseases
Ambient temperature, precipitation, floods, and humidity may have a significant role in distribution of intermediate hosts and pathogens that cause digestive diseases. In China, severe flood events due to CC were found to be associated with increase in the incidence of hepatitis A viral infections (HAV). Based on the data between 2005 and 2010 and flood event scenarios, the incidence of HAV infections was projected to be increased for the year 2030 to be between 0.382/105 and 0.399/105 [13]. Moreover, eradicated diseases, such as cholera and poliomyelitis, seemed to be re-emerging in Europe, due to the migration of infected population from their endemic areas [14].
Parasitic Diseases
Pseudamphistomum truncatum is a newly emerging zoonotic liver trematode affecting Baltic grey seals, with the roach (Rutilusrutilus) as a paratenic host. Accidentally, human may ingest fish with metacercariae, which develop to adults in the bile ducts. This accidental ingestion is of potential risk for humans and will be associated with chronic inflammation, fibrosis, and liver failure [15]. Global warming and the development of the toxic algae blooms linked to warm climate will affect the patterns of this infectious disease, which may decrease the risk of these accidental infections to human. In addition, it will impact the distribution, migration, diet and behavior of marine mammals and birds, and the changes in food web dynamics [16].
Fasciola hepatica is a real example of the impact of CC on the change in the distribution and the magnitude of parasitic infestations. Fasciola hepatica is mainly a sheep liver-fluke but could be transmitted to human if they ingest infested liver. Wet and mild warm climate is essential for the parasitic free-living stages and the intermediate snail host to grow on grassland and needs approximately 3 months for parasite stages to develop from the eggs and for the release of the infective metacercariae [17]. With global warming, the prevalence of infections increased in endemic countries, as climatic conditions became more suitable for the survival and expansion of the free-living cercaria and the intermediate snails; also, the increase of grazing season enhanced the exposure of the grazing animals to the parasite [17].
Non-Communicable Diseases
The main classes of toxicants of clinical significance discussed in this review are the chemicals that could be affected by CC and have toxic impacts on the liver or/and gastrointestinal tract (GIT), including particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), and heavy metals, in addition to the mycotoxins including aflatoxins and aquatic toxins such as cyanobacteria. The increase in the concentrations of these chemicals may have significant impacts in changing of the health map of some non-communicable hepatic diseases, such as hepatotoxicity or cancers. Biomass combustion associated with heating and cooking needs is a major source of household air pollution, such as PM, PAHs, and different gases [18].
Particulate Matter (PM)
Mostly, PM occurs naturally in the environment as desert dust, forest fire, sea salt, and sulfates from volcanoes; however, PM concentrations were projected to increase with CC in the atmosphere as a result of chemical reactions between the different pollutants due to the global warming, which could cause mutations and cancers of liver and lungs [6]. Artificially, PM is emitted from industrial sources and heavy traffic. The potential shift of the conditions of subtropical desert to higher latitudes is linked to climate change and desertification. PM concentrations in North Africa and the Middle East are among the highest in the world due to dust events [19].
During the 3-day Saharan episode in Texas in 2008, the total dust contribution increased to 64% for PM2.5 and 85% for PM10 [20]. It was found that long-term exposure to ambient PM2.5 air pollution was associated with adverse effects on liver enzymes [21] and shortens the survival of cases of liver cancer. The liver is affected by PM due to the detoxifying role of xenobiotics absorbed from PM [21].
Moreover, aflatoxigenic producing fungi may by carried on PM, which increases hepatic cancers [22]. Hepatotoxicity was reported in school-aged children due to exposure to air pollution in the vicinity of a petrochemical complex [23]. Another animal study found that exposure of C57Bl/6J mice for 24 h to vinyl chloride metabolites induced significant liver inflammation and injury [24]. In a recent study, it was found that soluble vanadium, as a soluble metal present in the vicinity of a petrochemical complex, contributed to PM2.5-induced oxidative stress in the liver [25]. However, it remains unclear the effects of released metals from petrochemical industries on hepatotoxicity. This finding suggests potential increase in the risk of hepatotoxicity and carcinogenicity, as PM concentrations were projected to increase with CC [6], due to air pollution episodes that are expected to be associated with stagnation events and heat waves [21].
Polycyclic Aromatic Hydrocarbons (PAHs)
PAHs are found in coal and in tar sediments and produced from incomplete combustion of organic matter as in the cases of forest fires, incineration, and engines. Climate change may increase the emission of toxic environmental chemicals from biomass combustion associated with heating and cooking needs [18]. The amounts of PAHs removed from the atmosphere by wet deposition are more easily from the atmosphere than the vapor phase. Thus, precipitation is more effective in removing the sorbed PAHs rather than the vapor phase, while the vapor phase is more efficiently removed from the atmosphere under cold conditions as compared to warm conditions. The removed PAH may contaminate surface water and the soil. Most of the PAH compounds are recognized as toxic, mutagenic, and carcinogenic substances, and long-term exposure may cause liver damage [26]. Therefore, CC may have a significant role in persistence of PAHs in the atmosphere, which may increase the hepatic damaging and carcinogenic effects.
The Common Hepatotoxic Heavy Metals
Heavy metals, such as lead, chromium, arsenic, mercury, nickel, and cadmium, may cause hepatotoxicity, in addition to ultrastructural changes in the hepatocytes, that is induced by oxidative stress reactions [27]. Some studies have also reported a relation between chronic arsenic (As) exposure and development of pre-neoplastic liver lesions, abnormal liver function, hepatomegaly, liver sclerosis, fibrosis, cirrhosis, and liver cancer [28]. Several potential mechanisms of hepatocarcinogenesis of As have been proposed, including genotoxicity, generation of free radicals and oxidative stress, disturbance of signal transduction and cellular proliferation, massive alteration in DNA methylation, and direct cytotoxicity; however, the exact mechanism requires further elucidation [29, 30].
Cadmium (Cd), another heavy metal, has been associated with hepatocarcinogenic potential via multiple mechanisms as shown in animal studies [31]. This mandates conducting human case-control studies to compare individuals with cirrhosis and/or HCC with different Cd body burden, perhaps as indicated by urinary Cd. Nardi et al. [32] proved that CC influences ecotoxicological effects of environmental contaminants, due to the interactions between temperature, pH, and Cd had significant effects on induction of metallothioneins and responses of the antioxidant system, causing oxidative damages, which was tissue dependent. But, future climate scenarios in Visser et al. [33] study project lower concentrations of Cd and Zn in surface water. The reduced leaching of heavy metals, due to drying of the catchment, showed a positive impact of CC on a limited aspect of surface water quality.
Repeated occurrence of extreme events as flooding due to climate change leads to inundation of contaminated land with heavy metals which will be transported in floodwater reaching the freshwater and marine environment and finally to human beings [34]. Alternate floods and droughts due to climate changes have been associated with the release of arsenic and contamination of groundwater. Climate change causes increase in air temperature and high rainfall events (high river discharge rates) at some locations which will increase resuspension of contaminated suspended sediment and chemical reactions, thereby will increase total concentrations of heavy metals with high adsorption capacities to suspended solids in surface waters, which leads to deteriorations in the quality of freshwater ecological status [35].
Global warming and acidification in sea water may increase the methylation rates of heavy metals, such as mercury in tuna and tuna-like species [36]. Moreover, soil acidity, resulting from acidic rains, may lead to movement of heavy metals into the watery environment [37, 38]. In Beijing, the undergoing increased temperature and heavy rainfall frequency affect water quality related to fluoride and arsenic concentrations of most urban lakes, which become worse under climate change trend [39].
Aquatic Toxins of Cyanobacteria
Freshwater harmful cyanobacterial blooms (CyanoHABs) are recognized to produce a wide range of toxins and bioactive compounds, which are secondary metabolites. The most commonly occurring cyanobacterial toxins are the microcystin and nodularin which are hepatotoxic [40]. These toxins may induce oxidative stress and metabolic disorder [41]. Exposure to microcystins may also alter microRNA (miRNA) expression in the liver and induce liver injury and promote liver tumor [42], which will lead to development of liver cancer, hepatocyte necrosis, cell fragmentation, glycogen depletion, and vacuolization [43].
Climate change plays a significant role in the development of CyanoHABs in fresh water, due to the alteration of temperature and light of the ecosystem that could support the growth of CyanoHAB species. Global warming and the change in the pattern of precipitation will increase the frequency of CyanoHAB, which increases the magnitude and the duration of blooms. Furthermore, high atmospheric temperature leads to increase in the stratification and lowers the viscosity of seawater which is favorable to CyanoHAB growth [40]. Thus, there is a synergism between global warming and eutrophication, which is simultaneous with intensification of CyanoHAB [44]. It has been reported, in a multi-lake analysis, that cyanobacteria appeared more sensitive to the interaction of nutrients and temperature in more eutrophic lakes [45]. Therefore, global warming stimulates growth of hepatotoxic cyanobacteria and increases the cellular toxicity levels directly and indirectly [46].
Therefore, due to CC, there is a projection that the frequency and duration of cyanobacteria bloom exposure will be increasing in the Baltic Sea within the coming years[44], as well as any aquatic area with the similar environmental conditions. This may cause change in the health map and increase the risk of development of hepatic toxicity and carcinogenicity among the coastal residents consuming contaminated water or sea foods with CyanoHAB toxins. Moreover, depletion of dissolved CO2 by dense CyanoHAB creates a concentration gradient across the air-water interface [47], which will affect the aquatic ecosystem and the aquatic life and will decrease the protein sources for coastal populations.
Fungal Mycotoxins
Mycotoxins are the secondary metabolites produced by certain fungal species including Aspergillus, Penicillium, and [48]. Mycotoxins of special interest are aflatoxins (AFs), fumonisins (FUMs), and ochratoxinA (OTA). Mycotoxins represent challenges regarding world-wide food safety and embody a substantial economic burden for many countries. Mycotoxins are natural contaminants of agricultural crops, and their prevalence may increase due to global warming [49]. There is a great evidence that global warming stimulates mycotoxins’ occurrence, and the interactions between gut microbiota and mycotoxins were found to play a significant role in the development of hepatocellular carcinoma secondary to mycotoxicosis [50].
Among all mycotoxins, the biggest attention has been given to aflatoxins (AFs), namely AFB1, because it is a well-known human carcinogen, as CC is considered to be an important predictor for the increase of AFs’ risk of crops’ contamination and improvement of predictive modeling, extension to the impact of CC on fungi and mycotoxin co-occurrence, both in crops and their value chains, up to consumers [51]. AFs are secondary metabolites produced by various Aspergillus species and infect crops including, e.g., peanut, cotton-seed, maize, nuts, cereals, spices, and dried fruits. AFs are highly liver carcinogenic and can also cause acute toxicity or even be fatal for both livestock and humans if ingested in sufficient amounts; the availability of mathematical models as risk assessment tools for prediction of the possibility of A. flavus infection and levels of AFs contaminations in maize within CC highlights the agricultural practices used to prevent or mitigate the deleterious consequences of AF contaminations [52].
In equatorial and sub-equatorial developing countries, traditional agriculture is usually carried out under optimum conditions and suitable climate for fungal growth and aflatoxin production. This situation is further worsened due to CC, which produces conditions increasingly suitable for the growth of aflatoxigenic producing fungi and mycotoxin production [22]. Tropical countries and warm areas are more suitable for the growth of fungi producing aflatoxin, but, in hot countries aflatoxin producing fungi will be inhibited [53]. Changes in climate could result in large fluctuations in the ambient temperature and precipitation that lead to fluctuation in the quantity of aflatoxin producers. These changes in climate are going to have a critical effect on the agricultural sector by altering the climatic conditions for mycotoxigenic fungal growth. That may result in geographical changes in the quantity and the types of mycotoxin producers, specially aflatoxins, that will result in remapping of the health problems resulting from the ingestion of contaminated crops by mycotoxins.
Amatoxin-Containing Mushroom
Mushrooms are important forest fungi in many ecosystems, being highly vulnerable to climate change [54]. Amatoxin-containing mushrooms are responsible for most fatal mushroom ingestions with the subsequent delayed-onset hepatocellular necrosis and are produced primarily by 3 species of mushrooms: Amanita, Lepiota, and Galerina [56]. Alday et al. reported that movement of mushroom and their fruiting bodies could be used to monitor the impact of early CC on forests, especially in the Mediterranean region [54].
Impacts of CC on liver disease in Africa
Africa is vulnerable to CC due to weak adaptive capacity, high dependence on ecosystem for livestock, and less developed agricultural systems. Expectations of changes in temperature, rainfall patterns, safe water, and man-made ecological changes of irrigation schemes will lead to increase the burden of schistosomiasis, as well as malaria in endemic areas in Africa. CC impacts also the infection control scenario of zoonotic infections including fascioliasis and the expansion of vectors or reservoirs of infection such as visceral leishmaniasis and the other parasitic liver diseases in Africa such as human echinococcosis and amebic liver abscess [55].