Another Asymptomatic Epidemic?

Alcohol related liver disease can be preventable through education programmes. The significant improvement and introduction of Hepatitis C antiviral agents and vaccination programmes for hepatitis B will eventually result in a reduced prevalence of endstage liver disease secondary to chronic viral hepatitis. Non-alcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disease in western countries. NAFLD is strongly related to metabolic syndrome and insulin resistance seems to play a crucial role. NAFLD is defined by the presence of liver fat accumulation exceeding 5% of hepatocytes in the absence of significant alcohol intake (20 g per day for men and 10 g per day for women), viral infection, or any other specific aetiology of liver disease.¹

NAFLD encompasses a histological spectrum ranging from simple steatosis to NASH. Various stages of fibrosis can exist, ranging from absent (stage F0) to cirrhosis (stage F4). Simple steatosis can progress to NASH and clinically significant fibrosis and thus progressive liver disease and hepatocellular carcinoma.²

More than 50% of adults in the 27 European Union (EU) countries are considered to be overweight (36.4%) or obese (15.5%). Obesity presents greater health risks than being overweight. The prevalence of obesity varies among these EU countries, from less than 10% in Romania, Switzerland and Italy to over 20% in the United Kingdom, Ireland and Malta. NAFLD also has reached epidemic proportions among populations typically considered at low risk, such as China (15%) and Japan (14%).

In an Italian study, NAFLD prevalence was 26%. In a multi-centre European study it was 30.4% and in a southern European study 33% of patients had a high probability of having the disease.^3-5 A study in Greece revealed evidence of NAFLD in 31% and of NASH in 40% of autopsied cases of ischaemic heart disease or traffic accident death.⁶ Two major European studies reported NAFLD prevalence rates of 42.6-69.5% in patients with type 2 diabetes.^7-8

Moving on to mortality, data from the Danish National Registry of Patients revealed NAFLD- associated age-adjusted standardized mortality ratios (SMR) (After adjustment for sex, diabetes and cirrhosis at the baseline) were 2.3 (95% CI 2.1- 2.6) for all causes, 19.7 (95% CI 15.3- 25.0) for hepatobiliary disease, and 2.1 (95% CI 1.8-2.5) for cardiovascular disease.⁹

In a cohort of Swedish NAFLD patients, the age, sex, and calendar-period adjusted mortality ratio was 1.69 (95% CI 1.24-2.25) for NAFLD compared to the general population.¹⁰

With regards to the economic burden, a German study demonstrated that the average annual overall health-care costs were significantly higher at baseline and at follow-up measurements for individuals with evidence of NAFLD.¹¹

Based on data from the USA adult liver transplantation databases, since 2004 NASH is the second leading cause for liver transplantation. In the USA, NAFLD and NASH related cirrhosis is anticipated to become the leading cause for chronic liver disease and transplantation within the next 1-2 decades.¹²

What can we do about it? In the absence of a universal protocol and effective therapy to treat these patients, general lifestyle interventions including dietary changes and increased physical activity remains the main treatment modality for this group of patients.¹³

References

1. McPherson S, Hardy T, Henderson E, Burt AD, Day CP, Anstee QM. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol. 2015;62:1148-55. 

2. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202-1219. 

3. Haring R, Wallaschofski H, Nauck M, Dorr M, Baumeister SE, Volzke H. Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels. Hepatology 2009;50:1403-11. 

4. Castellares C, Barreiro P, Martin-Carbonero L, Labarga P, Vispo ME, Casado R, et al. Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. J Viral Hepat 2008;15:165-72. 

5. Bedogni G, Miglioli L, Masutti F, Castiglione A, Croce LS, Tiribelli C, et al. Incidence and natural course of fatty liver in the general population: the Dionysos study. Hepatology 2007;46:1387-1391. 

6. Zois CD, Baltayiannis GH, Bekiari A, Goussia A, Karayiannis P, Doukas M, et al. Steatosis and steatohepatitis in postmortem material from Northwestern Greece. World J Gastroenterol 2010;16:3944-9. 

7. Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30:1212-8. 

8. Williamson RM, Price JF, Glancy S, Perry E, Nee LD, Hayes PC, et al. Prevalence of and risk factors for hepatic steatosis and nonalcoholic Fatty liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes Care 2011;34:1139-44. 

9. Jepsen P, Vilstrup H, Mellemkjaer L, Thulstrup AM, Olsen JH, Baron JA, et al. Prognosis of patients with a diagnosis of fatty liver--a registry-based cohort study. Hepatogastroenterology 2003;50:2101-4. 

10. Soderberg C, Stal P, Askling J, Glaumann H, Lindberg G, Marmur J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010;51:595-602. 

11. Baumeister SE, Volzke H, Marschall P, John U, Schmidt CO, Flessa S, et al. Impact of fatty liver disease on health care utilization and costs in a general population: a 5-year observation. Gastroenterology 2008;134:85-94. 

12. Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547-555.
13. Milic S, Mikolasevic I, Krznaric-Zrnic I, Stanic M, Poropat G, Stimac D, et al. Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options. Drug Des Devel Ther. 2015;9:4835- 4.

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