NAFLD, NASH, Drive Cirrhosis Rates and Liver Cancer Deaths

Global deaths from liver cancer related to nonalcoholic fatty liver disease (NAFLD) increased faster than liver cancer deaths related to other liver diseases during the decade 2010-2019, and nonalcoholic steatohepatitis (NASH) became the primary cause of cirrhosis as of 2017, according to the Global Burden of Disease (GBD) report on liver disease.

Chronic liver disease (CLD) and associated cirrhosis accounts for approximately 1 million deaths per year, according to the GBD, although other sources have estimated the death toll of CLD at twice this number. The 4 major drivers of chronic liver disease, the GBD authors state, are chronic hepatitis C (CHC), chronic hepatitis B (CHB), alcohol-related liver disease (ALD), and NAFLD. “In fact, given the pandemic of obesity, its associated liver disease, NAFLD, is increasing and is predicted to continue to do so,” they wrote.

The global rate of hepatocellular carcinoma (HCC) “appears to be decreasing at an overall APC of -1.93%, which is apparent with the age standardized incident rate of 6.5 (95% CI: 5.9–7.2) per 100,000 in 2019, a decrease of 27.5% (95% CI: -37.3 to -15.7) since 1990. Although the rates are decreasing, males continue to have a higher age standardized incident rate at 9.7 (95% CI: 8.7-10.8) compared with 3.6 (95% CI: 3.2–4.0) for females.” The authors attribute the decreased rate of HCC to the drop in cases of liver cancer associated with hepatitis virus B (HVB) and hepatitis virus C (HCV) and decreasing/stabilizing rates for NAFLD and ALD.

Cirrhosis caused by hepatitis virus B and hepatitis virus C decreased during the same period. The report notes that cases of cirrhosis for men and women increased at an annual percentage change of 0.78% and 0.71%, respectively, during 1990-2017. “Interestingly, according to etiology of liver disease, females had a higher APC for NASH (APC, 1.82% vs 1.69%) and ALD (APC, 0.97% vs 0.77%) than males.”

The World Health Organization (WHO) estimates that 58 million people have CHC, with approximately 1.5 million new infections and approximately 300,000 annual deaths, while 296 million are infected with CHB, which accounts for another 1.5 million new infections and an estimated 820,000 deaths.

ALD is another major cause of chronic liver disease, the authors reported, but “the diagnosis of ALD relies on the self-reporting of alcohol consumption, which is fraught with problems.” Using data from WHO and other sources, GBD investigators have estimated that alcohol misuse is responsible for 27% of deaths from liver disease and 30% of liver cancer deaths worldwide.

The global prevalence for NAFLD, derived through meta-analysis and systematic reviews, is estimated to be 30% of the adult population during 1990–2019. “However, when considering data only from 2016 to 2019, the NAFLD prevalence was estimated to be as high as 38%,” the authors of the GBD noted. Using new data now being provided on fatty liver disease, the authors note, “researchers have reported that the combined NAFLD prevalence for all ages has increased continuously from 10.5% (561.37 million) in 1990 to 16.0% (1, 235.70 million) in 2019, which provides an annual percent change (APC) of +1.47% (95% CI, 1.44%–1.50%). Among adults, the global prevalence of NAFLD was reportedly 23.4%, increasing annually by approximately 1.00% (95% CI: 0.97%–1.02%).”

The highest NAFLD prevalence rate (26.5%) has been found in the Middle East and North Africa, which highlights “the global shifting of disease burden from North American and European to Middle Eastern and North African, Asian, and Latin American areas. Nonetheless, North America still has a relatively high NAFLD prevalence rate of 15.78% (in 2019), with an APC of 1.15% (95% CI, 1.12–1.17) from 1990 to 2019.” Researchers have also found that during 2010-2019, “the global all-age, age-standardized deaths from liver cancer related to NAFLD increased faster than liver cancer deaths related to other liver diseases (NAFLD APC, 0.81%; ALD, 0.28%; HCV, -0.61%; and HBV, -0.04%).”

The report further stated that “NASH-related liver cirrhosis has been shown to be the dominant etiology of cirrhosis, accounting for 59.5% of cases.” NASH showed a 125.61% increase in the number of prevalent cases from 1990 to 2017.

“Despite the availability of a highly effective vaccine and antiviral regimens for treatment and cure, the global burden of CLD continues to increase, most likely owing to the increasing rates of NAFLD and ALD,” the GBD stated, noting that “cirrhosis cases related to HBV, HCV, NAFLD, and ALD are increasing while the burden of liver cancer appears to be decreasing in some regions of the world… In addition to its clinical burden, CLD also is associated with substantial quality of life and economic impact. Therefore, a comprehensive assessment for the burden of CLD is needed given that the regions of the world are impacted differently owing to a number of sociodemographic factors.”

Reference:

Younossi ZM, Wong G, Anstee QM, Henry L. The global burden of liver disease. Clin Gastroenterol Hepatol. 2023;21(8):1978-1991. DOI: https://doi.org/10.1016/j.cgh.2023.04.015