Summary Abstract

September 2024

​In this study we investigate trends in death rates from Liver Diseases (ICD-10 codes K70-K76) in the USA using crude data from the CDC (Centers for Disease Control and Prevention). We perform a summary analysis for all age groups. In separate reports we also perform a detailed analysis for younger individuals (aged 35-44) and for older individuals (aged 75-84).  

We compare trends Liver Diseases deaths where these appear on multiple causes (MC) of death, or as the underlying cause (UC). To remove the effect of Covid-19, we also analyse trends in death rates from Liver Diseases where Covid-19-related deaths are also reported in the death certificate. 

For individuals aged 35 to 44, our results show that the excess UC death rates from liver diseases (K70-K76) were 38.5% (Z-Score of 16.2) in 2020, then rose to 54.2% (Z-Score of 22.8) in 2021, 38.7% (Z-Score of 16.3) in 2022 and 22.1% (Z-Score of 9.3) in 2023. 

For individuals aged 75 to 84, our results show that the excess UC death rates from liver diseases (K70-K76) were 2.4% (Z-Score of 3.9) in 2020, then rose to 8.8% (Z-Score of 14.4) in 2021, 7.3% (Z-Score of 11.9) in 2022 and 11.1% (Z-Score of 18.2) in 2023. We also observe that the rises of excess MC* death rates (where COVID-19-related deaths are excluded) from liver diseases in 2020, 2021, 2022 and 2023 mirror the excess UC death rates, suggests that a common underlying factor is at play. 

When investigating liver diseases as underlying cause for all age groups we observe that the rise in excess deaths occurred for all age groups, however, suggesting different patterns for younger and older individuals. For younger individuals, aged 65 or less, excess death rates from liver diseases appear to be related to rises in all-cause mortality in 2020, peaking in 2021 and subsequent normalisation in 2022 and 2023. For older individuals, excess death rates rose from 2020 to 2023.

​The results indicate that from 2020 a novel phenomenon leading to increased liver disease death rates appears to be present which is driven by alcoholic liver disease in younger individuals while for older individuals, cirrhosis and fibrosis of the liver is the pathology driving excess death rates. From 2021 onwards, excess death rates for older individuals could be explained by adverse effects from COVID-19 vaccinations or lingering effects of multiple SARS-CoV-2 exposures, which requires further research.
When investigating liver diseases as underlying cause for all age groups, we observe that the rise in excess deaths occurred for all age groups, however, suggesting different patterns for younger and older individuals.

Inside the Report:
Excess Multiple-Cause (except COVID-19) Death Rates from Liver Diseases

​In this section we compute, for all 10-year age groups, the excess MC* death rates from liver diseases (K70-K76) in 2020, 2021, 2022 and 2023, shown in the Figures below (MC* excess death rates). As a reminder, MC* death rates refer to MC deaths from liver diseases except for those where COVID-19 is also reported (either as underlying cause or a contributing cause). In the Figure (left or top in mobile view) we plot the excess MC* death rate (in percent) while Figure (right or bottom in mobile view) shows the respective Z-scores. For a detailed view of the results refer to section 8.1, in the appendix of the full paper.
After removing COVID-19-related deaths, the results show that the excess MC* death rates exhibit a similar pattern to UC excess death rates for the different age groups. This is likely due to the rise in MC* death rates being driven by the rises in UC death rates. 

​For older individuals, aged 75-84 and 85+, after removing COVID-19-related deaths, we observe statistically insignificant excess MC* death rates in 2020, in similarity to observed for UC death rates. Excess death rates rose substantially from 2021, remaining high in 2022 and 2023, with very high statistical significance. 
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For individuals aged 65 and younger, excess death rates peaked in 2020 and 2021 and then declined in 2022 and 2023. The excess death rates in general show very high levels of statistical significance, as shown in Figure (Right) above. For younger individuals, the brunt of the effect was felt in 2020 and 2021, while for older individuals, the excess death rates peaked in 2023.

Observations

  • When investigating excess death rates from liver diseases (ICD-10 codes: K70-K76) from 2020 to 2023 for the distinct 10-year age groups, we observe two different patterns of behaviour for individuals aged 65 and younger and for individuals aged 75 and older, with individuals aged 65-74 falling somewhere in the middle. The previously presented detailed analysis of excess death rates from liver diseases for younger individuals aged 35-44 and for older individuals aged 75-84 are case studies that exemplify each of these patterns of behaviour. 

  • We show in Figure 11 that for younger individuals, aged 65 and lower, excess death rates from liver diseases started in 2020 and peaked in 2021, subsequently dropping in 2022 and 2023. The pattern of excess deaths from liver diseases for younger individuals tracks changes in all-cause mortality from 2020 to 2023. As we’ve shown in Figure 4, for younger individuals, the principal driver of changes in death rates from liver disease in 2020, 2021, 2022 and 2023 was alcoholic liver disease (ICD-10 code: K70). 

  • Consequently, the increased levels of alcohol consumption per capita that was observed in 2020, 2021 and 2022 (Slater & Alpert, 2024), was a likely contributory factor towards increased liver disease death rates during the period. Although not being within the scope of this paper, we performed a quick analysis of the changes in alcohol consumption per capita to see if it could fully explain the increases in death rates from alcoholic liver disease and our preliminary analysis suggested that it cannot. Interestingly, however, we observe that the increase in alcoholic liver disease death rates is mostly driven by increases in spirits consumption and less so by wine and beer. We noticed that accounting for increases in alcohol consumption per capita only explain a fraction of the increase in death rates, suggesting that other additional factors are at play. These factors could be either the societal lockdowns and pandemic-related changes in lifestyles (in 2020), sequalae from the COVID-19 disease (in 2020 through 2023), or COVID-19 vaccinations (from 2021 onwards).  

  • In particular, a significant body of evidence is now pointing towards the COVID-19 vaccinations playing a significant role in contributing towards the excess all-cause mortality in 2021, 2022 and 2023 that is observed in developed countries with high COVID-19 vaccine intake. For example, a recent paper from Alexandria et al. (Alessandria, Malatesta, Berrino, & Donzelli, 2024), show that individuals with 2 or more vaccine doses experienced about 20% higher excess all-cause mortality (measured as all-cause death hazard ratios) when compared to unvaccinated individuals in a province in Italy. The paper confirms previous suspicions that were already present in the Pfizer clinical trials (Michels, et al., 2023) where the authors show that of the 38 deaths reported in the 6-Month Interim Report of Adverse Events, 21 BNT162b2 vaccinated subjects died compared to 17 placebo subjects, which corresponds to 23.5% excess all-cause mortality. Even though the sample size was small and not possible to infer statistical significance, the recent paper from Italy provided confirmation of the signal at a population level. Furthermore, the analysis of serious adverse events (SAE) of special interest in the Moderna and Pfizer clinical trials (Fraiman, et al., 2022) showed to the Pfizer trial exhibited a 57% higher risk of an SAE of special interest in vaccinated participants relative to the placebo control and 36% higher risk for the Moderna trial. The estimated rate of SAEs of special interest for both clinical trials combined was 1 in 800 for the recipients of these vaccines. 

  • Finally, the Nonclinical Evaluation Report BNT162b2 [mRNA] COVID-19 vaccine submitted to the Australian TGA (TGA - Health Safety Regulation, 2021)show that the vaccine was not confined to the injection site but distributed across almost all important organs of the body with particular accumulation in the liver (page 45 of the report) as stated in the conclusions: “Slow but significant distribution of lipid nanoparticles from the site of injection with major uptake into liver”, which could explain the liver being particularly impacted by production of the toxic spike protein. 

  • The pattern of excess deaths was different for older individuals aged 75 and above, showing much lower excess death rates (in percentage terms) than those for younger age groups. For older individuals, excess deaths rose consecutively from 2020 to 2023, with the main increase in excess mortality starting in 2021 and not in 2020 as was the case for younger individuals. For the older age groups, excess deaths increased substantially in 2021, 2022 and 2023, showing extreme deviations from the prior 2013-2019 trend. Additionally, as illustrated by the detailed analysis of the 75-84 age group , even as excess all-cause deaths declined in 2022 and 2023, excess death rates from liver diseases continued to rise.

  • As we’ve mentioned previously, for older individuals, cirrhosis and fibrosis of the liver was the main contributor to changes in deaths rates from liver diseases from 2020 to 2023. Consequently, increased levels of alcohol consumption during the pandemic years, are unlikely to be a significant contributory factor towards increased liver disease deaths for older individuals.

  • The results suggest that COVID-19 pandemic lockdowns are also unlikely explanations for the rise in excess liver disease death rates, for older individuals, as excess death rates were subdued in 2020. As excess deaths continued to rise in 2022 and 2023, indicating a worsening of the phenomenon that is leading to excess liver disease deaths. As previously explained, there is more and more evidence that this could be related to continuous uptake of COVID-19 inoculations within the older age groups (Alessandria, Malatesta, Berrino, & Donzelli, 2024). 

  • One cannot exclude other possible contributing factors such as pandemic-related changes in lifestyles, inflammatory processes due to cumulative exposures to SARS-CoV-2, “Long COVID” (Jangnin, et al., 2024) or other factors.
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