Chronic liver diseases must be reduced worldwide: it is time to act

Abstract

There were an estimated 1·5 billion cases of chronic liver disease worldwide in 2017,1GBD 2017 Disease and Injury Incidence and Prevalence CollaboratorsGlobal, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet. 2018; 392: 1789-1858Summary Full Text Full Text PDF PubMed Scopus (4905) Google Scholar including 10·6 million cases of decompensated cirrhosis and 112 million cases of compensated cirrhosis.2GBD 2017 Cirrhosis CollaboratorsThe global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2020; 5: 245-266Summary Full Text Full Text PDF PubMed Scopus (355) Google Scholar Cirrhosis accounted for an estimated 1·32 million deaths in the same year.2GBD 2017 Cirrhosis CollaboratorsThe global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2020; 5: 245-266Summary Full Text Full Text PDF PubMed Scopus (355) Google Scholar This burden, which is probably underestimated,2GBD 2017 Cirrhosis CollaboratorsThe global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2020; 5: 245-266Summary Full Text Full Text PDF PubMed Scopus (355) Google Scholar is highly concerning. Liver cirrhosis is largely due to chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), alcohol-related liver disease, and non-alcoholic steatohepatitis. In 2016, the World Health Assembly developed a global strategy for the elimination of viral hepatitis, focusing on HBV and HCV. Based on 2019 data, just 11 high-income countries are on course to eliminate HCV by 2030, with the USA only expected to eliminate it after 2050.3Gamkrelidze I Pawlotsky JM Lazarus JV et al.Progress towards hepatitis C virus elimination in high-income countries: an updated analysis.Liver Int. 2021; 41: 456-463Crossref PubMed Scopus (36) Google Scholar In WHO's 2021 global progress report on HIV, viral hepatitis, and sexually transmitted infections, it was stated that in 2019 there were 3 million new HBV or HCV infections, 0·8 million people died from HBV, and 0·3 million people died from HCV. At the beginning of 2020, the global prevalence of HBV infection was estimated to be 3·63% (279·9 million), with as few as 36·7 million infected individuals diagnosed and 6·6 million thought to have received an antiviral treatment.4Razavi-Shearer D, Blach S, Estes C, et al. Global HBV cascade of care: the pre-COVID-19 baseline. AASLD The Liver Meeting; Nov 12–15, 2021 (abstr 66).Google Scholar At the same time, the global prevalence of HCV infection was estimated to be 0·75% (59 million), with 13 million people diagnosed and just more than 10 million being treated since direct-acting antivirals became available in 2014.5Blach S, Dugan E, Razavi-Shearer D, et al. Global status update on the HCV prevalence and cascade of care entering 2020. AASLD The Liver Meeting; Nov 12–15, 2021 (abstr 100).Google Scholar In other words, only 2·4% of all people chronically infected with HBV and 16·9% of people chronically infected with HCV are thought to have been treated worldwide. This lack of treatment could also explain the high prevalence of hepatocellular carcinoma in 2018, with an estimated 661 000 cases and particularly high rates in east Asia, southeast Asia, and north Africa.6Rumgay H Ferlay J de Martel C et al.Global, regional and national burden of primary liver cancer by subtype.Eur J Cancer. 2022; 161: 108-118Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar In 2017, alcohol-related liver disease was responsible for 23·6 million cases of compensated cirrhosis, 2·46 million cases of decompensated cirrhosis, and more than 332 000 deaths.2GBD 2017 Cirrhosis CollaboratorsThe global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2020; 5: 245-266Summary Full Text Full Text PDF PubMed Scopus (355) Google Scholar Non-alcoholic steatohepatitis caused 9·42 million cases of compensated cirrhosis, 917 000 cases of decompensated cirrhosis, and 118 000 deaths in the same year.2GBD 2017 Cirrhosis CollaboratorsThe global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Gastroenterol Hepatol. 2020; 5: 245-266Summary Full Text Full Text PDF PubMed Scopus (355) Google Scholar Patients with end-stage liver disease are admitted to hospitals more often, stay longer, and have more readmissions compared with patients with other serious chronic diseases. In the USA, the hospital cost of diagnosis and treatment for patients with liver cirrhosis increased by 30·2% between 2008 and 2014 to US$7·37 billion, with particularly increased rates of admission for patients with decompensated cirrhosis.7Desai AP Mohan P Nokes B et al.Increasing economic burden in hospitalized patients with cirrhosis: analysis of a national database.Clin Transl Gastroenterol. 2019; 10e00062Crossref Scopus (34) Google Scholar To reduce this burden, we need to diagnose chronic liver diseases at an early stage, well before the development of decompensated cirrhosis or hepatocellular carcinoma. Currently, patients with chronic viral hepatitis often have advanced liver disease at the time of diagnosis; in the USA, 13·1% (47 466/363 532) of individuals screened for HCV antibodies, HCV RNA, or both in 2019 by two large laboratory companies had stage 4 liver fibrosis (ie, liver cirrhosis)8Reau N Sulkowski MS Thomas E et al.Epidemiology and clinical characteristics of individuals with hepatitis C virus infection in the United States, 2017–2019.Adv Ther. 2021; 38: 5777-5790Crossref PubMed Scopus (3) Google Scholar and, in Thailand, a country where HBV is endemic, patient awareness of their risk for developing hepatocellular carcinoma and adherence to regular surveillance for it are low. Transient elastography has been applied as a screening tool in population studies in both high-income and lower-middle-income countries,9Caballería L Pera G Arteaga I et al.High prevalence of liver fibrosis among European adults with unknown liver disease: a population-based study.Clin Gastroenterol Hepatol. 2018; 16 (e5): 1138-1145Summary Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 10Cainelli F Yi V Vento S Prevalence of liver fibrosis using transient elastography in the general population in Cambodia: a pilot study.Eur J Gastroenterol Hepatol. 2021; 331035Crossref PubMed Scopus (1) Google Scholar finding prevalences of 3·6–13·0% for liver fibrosis and 0·7–1·3% for cirrhosis. This technique, which is quite simple to use, should be used to assess liver fibrosis at least in the parts of the world where the prevalence of chronic liver diseases is high, such as India, Russia, southeast Asia, and sub-Saharan Africa. For HCV infection, where highly effective drugs are available, testing has largely focused on at-risk groups (eg, people who inject drugs or people who received blood transfusions before 1992) or on specific geographical areas. However, if elimination is to be achieved, all adults should be tested at least once (to begin with) in every country and those who are infected should be promptly treated. In fact, studies have shown that general population screening and treatment intervention for HCV is feasible and cost-effective in lower-middle-income countries. For chronic hepatitis B, non-alcoholic steatohepatitis, and alcohol-related chronic liver disease, a pre-symptomatic diagnosis would allow the early implementation of antiviral therapy for HBV, recommendation of dietary and behavioural modifications for non-alcoholic steatohepatitis, and strong advisement of alcohol abstinence for alcohol-related liver disease, improving outcomes for patients. Considerable increases in treatment rates are necessary to decrease HBV and HCV disease burden, and low-income and middle-income countries should get international help, as they did for HIV infection therapy. In conclusion, it is time to move from words to action and start widespread screening for chronic liver diseases in countries and areas where the burden is high, especially in low-income and middle-income countries, to finally identify liver fibrosis and viral hepatitis at an early stage and prevent end-stage liver disease and hepatocellular carcinoma. A Fibroscan was provided for free to the University of Puthisastra by Echosens outside the scope of the submitted work.

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