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Valuing the Prevention and Treatment of Liver Disease to Promote Human Wellbeing

Chen, Zhi

Editor(s): van der Veen, Stijn

Author Information
Infectious Microbes & Diseases: June 2022 - Volume 4 - Issue 2 - p 47-48
doi: 10.1097/IM9.0000000000000092
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Over 45 million people suffer from chronic liver disease globally,1,2 and an estimated 2 million deaths are caused by liver diseases globally each year, including 1 million deaths due to cirrhosis and 1 million deaths due to viral hepatitis and hepatocellular carcinoma.3,4 Acute liver failure, chronic viral hepatitis, metabolic dysfunction-associated fatty liver disease (MAFLD), drug-induced liver injury, liver fibrosis, liver cirrhosis, hepatocellular carcinoma, and autoimmune liver diseases (including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis and related diseases) are among the major causes of death.3 Various etiologies may lead to liver injury, including viral infection, autoimmune disorders, alcoholism, drug abuse, metabolic disorders, and nonalcoholic steatohepatitis.5

Over the past few decades, the development and application of vaccines for hepatitis A, B, and E, and the emergence of direct antiviral drugs for hepatitis C, have led to a dramatic reduction in the incidence of new viral hepatitis infections and mortality rate. However, the overall disease burden of viral hepatitis is still high, and comprehensive approaches, such as further strengthening vaccine-based immunization, improving early detection, and popularizing antiviral therapy, are still needed. The most economic and effective way to prevent hepatitis A virus (HAV) infections is HAV vaccination, and the most effective HAV vaccines include inactivated and live attenuated vaccines. Since 2008, China has implemented a nationwide expanded child immunization program for HAV, which has contributed to a decline in the incidence of hepatitis A from 100/100,000 in 1992 to 1.3679/100,000 in 2017. The mortality rate from hepatitis A currently stands at 0.003/1,000,000.6 Currently, there is no effective treatment for hepatitis E. Vaccination is an effective way to prevent and cure hepatitis E virus (HEV) infections. Developed HEV vaccines are mainly categorized as recombinant protein vaccines and DNA vaccines. Hecolin®, a recombinant capsid protein-based hepatitis E vaccine developed in China, has been marketed and commercialized. Early prevention can be achieved by vaccination of the susceptible population aged 16 and above following a 3-dose (0, 1, and 6 months) immunization schedule.

Hepatitis B and C are the two most common types of viral hepatitis, which commonly develop into chronic conditions. It has been estimated that there were over 257 million chronic hepatitis B patients worldwide in 2015.3 The continuous existence of covalently closed circular DNA, a persistent reservoir of viral DNA in the nucleus of infected cells, makes it difficult to eventually eradicate hepatitis B virus (HBV) from the environment and host populations. At present, the goal of HBV treatment is clinical cure, which refers to the state that chronic HBV patients who have been treated still maintain negative for HBV surface antigens (with or without hepatitis B surface antibodies), maintain undetectable HBV-DNA levels, and maintain normal liver function indexes after stopping treatment. Clinical practice shows that active antiviral therapy can reduce the risk of liver fibrosis, cirrhosis, and liver cancer. Antiviral therapy is required as long as HBV DNA remains positive and transaminase abnormalities caused by other reasons are excluded.

Current antiviral drugs include nucleoside (acid) analogs and interferon (IFN), which can effectively inhibit HBV replication, reduce or delay liver damage, and reduce the incidence of liver adverse prognosis. Most of the novel anti-HBV drugs are in clinical phases I and II, including direct antiviral drugs, viral entry inhibitors, nucleocapsid inhibitors, hepatitis B surface antigen (HBsAg) releasing inhibitors. The research of potent tools for gene-specific therapeutics, including RNA interference, antisense RNA, and gene editing, is developing rapidly for HBV treatment. Immunotherapy drugs and methods are also under active exploration or clinical research.7 In addition, host-specific therapies such as apoptosis inducers and cyclophilic inhibitors, as well as covalently closed circular DNA methylation or histone modification of HBV are expected to be new approaches for HBV treatment.

First described as “non-A and non-B” hepatitis in 1975, our understanding of hepatitis C virus (HCV) has achieved qualitative breakthroughs in recent decades. The emergence of direct-acting antiviral agents has replaced pegylated IFN-α therapy with ribavirin. Current IFN-free pangenotypic direct-acting antiviral therapies allow more than 95% of HCV patients to be cured.8 However, low detection rate, high recurrence rate of certain HCV subtypes (eg, 3b), and high treatment costs are still global public health problems. The ultimate elimination of HCV may still require the development of a preventive vaccine. HCV vaccine development is still ongoing, with three vaccine candidates already in preclinical and clinical trials in humans; a prototype vaccine consisting of the HCV core protein and an adjuvant, an adenovirus-based vector vaccine that can express NS3-5B protein and induce long-lived T cell responses, and a recombinant form of the E1E2 envelope glycoprotein. However, these vaccines have not achieved the expected effects required for subsequent clinical promotion. The emergence of vaccines and antiviral drugs has significantly reduced the incidence of viral hepatitis.

Along with lifestyle modification and improvement of living standards, the prevalence of metabolic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease in the population is increasing. Statistically, the global prevalence of NAFLD can be as high as 25%.9 Past NAFLD was defined by the absence of excessive alcohol consumption or other clearly defined factors of liver damage. It is a clinicopathological syndrome with hepatocyte steatosis of more than 5% as the main histological feature. However, this definition lacks consideration of disease heterogeneity and hinders the study of precision therapy. In 2020, the consensus of an international expert group recommended changing the name of NAFLD to MAFLD.10 The new diagnostic criteria are based on histological (liver biopsy), radiographic, and blood biomarker evidence of hepatic fat accumulation (hepatocellular steatosis) in combination with one of the following conditions; overweight, obesity, type 2 diabetes, or metabolic dysfunction.11 Diagnosis is based on the presence of metabolic dysfunction, which is a positive diagnostic criterion, not an exclusion-based diagnosis, and absence of excessive alcohol consumption is no longer a diagnostic criterion. The new naming and definition will help increase the diagnosis rate of MAFLD.12 Further stratification and subgroup analysis of the disease is helpful to study the changes of liver histology during the development of the disease and its influence on the course of disease. Currently, clinical treatment for MAFLD is still limited to lifestyle change, treatment of metabolic diseases, and liver transplantation for advanced patients, and there is a lack of precise and effective drugs to inhibit the process of MAFLD. Future research more likely focuses on screening and identification of specific markers, disease typing, and drug development. Accurate diagnosis and disease stratification are the premise of symptomatic treatment.

Liver cancer has become one of the most common malignancies and is globally the second leading cause of morbidity and mortality.13,14 Because of lack of specific symptoms and effective early diagnostic methods, liver cancer tends to be diagnosed at late stages, with limited therapeutic options and poor prognosis.15 Serum alpha-fetoprotein is a widely used diagnostic marker for liver cancer, but its sensitivity and specificity are not sufficient in the early stage of the disease.16 Therefore, it is urgent to find a more valuable marker for the early diagnosis of liver cancer. Cheng et al. applied quantum dot nanoprobes to simultaneously detect multiple biomarkers for early diagnosis of liver cancer, which has great potential for realizing early diagnosis of liver cancer.17

The prevention and treatment of chronic liver disease can significantly promote human wellbeing, especially through strengthened vaccination and effective detection methods, and interventional measures. At the same time, it is necessary to actively carry out further basic and translational studies related to liver disease, which can clarify the mechanisms and lay the foundation for early diagnosis and better treatment.


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liver disease; prevention; treatment

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.