The changing epidemiology of liver diseases in Asia.

Abstract

The Asia-Pacific region is the largest continent, carrying more than half of total world population, which is disproportionally affected by liver disease. Globally, this region accounts for 62.6% of deaths due to all types of liver diseases and, in particular, for 54.3% of cirrhosis related deaths and 72.7% of HCC related deaths. More than two-thirds of the global burden of acute viral hepatitis was reported in this region in 2015.1 The underlying causes of liver diseases in the Asian-Pacific region is quite different from the rest the world. In 2015, chronic hepatitis B (CHB) caused 49.1% of all deaths due to liver cancer in Asia-Pacific region (vs 12.7% in USA and 20.4% in Europe), whereas chronic HCV infection was responsible for 10.8% of deaths due to liver cancer (37.1% in USA and 37.2% in Europe). On the other hand, 29.8% of liver-related mortality due to liver cancer was related to alcohol consumption (vs 38.1% in USA and 37.1% in Europe), and 10.1% was related to nonalcoholic fatty liver disease (NAFLD) and other diseases (12.1% in USA and 5.3% in Europe).1 Looking back to the previous decades, it can be appreciated a progressive change in the etiology of hepatitis, cirrhosis and liver cancer, which is also influenced by specificities in disease epidemiology in single countries. To help our readers to understand more in details the changing epidemiology of liver diseases in Asia, the Editorial Board of Liver International launched a “Special Issue 2021”, and invited a panel of hepatologists, virologists, epidemiologists and scientists from the Asia-Pacific region to share their expert opinion and review the past experience and challenges, covering the topic of viral hepatitis, metabolic and alcoholic liver diseases, drug induced liver diseases, rare liver diseases, liver cancer, liver failure and liver transplantation. This special issue documents the prevalence, incidence, and mortality of liver diseases, the progress towards the World Health Organization (WHO) 2030’s elimination goals and addresses the barriers, challenges, and continuing gaps. This special issue also highlights the advancement of basic, clinical, and diagnostic sciences and research, up-to-date therapeutic approaches and preventive measures to viral hepatitis and liver cancer. Here, we briefly summarized the key messages of each topic. At the World Health Assembly (WHA) in 2015, as a part of the sustainable development goals for 2030, the world health organization (WHO) set specific targets to achieve in order to control and eradicate viral hepatitis, specifically HBV and HCV infection, recognizing them as public health threats. Linh-Vi Le et al2 measured the progress in Asia and Pacific in achieving key impact targets for 2020 by modelling disease burden and the cascade of care. Between 2015 and 2020, chronic HBV prevalence declined from 4.69% to 4.30%, and HCV prevalence declined from 0.64% to 0.58%. However, the incidence of hepatocellular carcinoma (HCC) related to HBV and HCV infections still increased by 9% and 7%, respectively. Liver-related deaths from HBV rose by 8%, and mortality attributable to HCV plateaued. It is worrisome that only 13% of chronic HBV infections were diagnosed and 25% treated, and that 21% of chronic HCV infections were diagnosed and 11% treated. In summary, while Asia Pacific region is on track for reducing new HBV infections, it is late in reducing HCV incidence and witnessing a rise in deaths attributable to HBV and HCV. It is therefore far from achieving testing and treatment targets. National action plans will be essential for accelerating the region towards reaching elimination goals by 2030. Although we have safe and effective combination therapies with direct antiviral agents (DAA) against multiple HCV genotypes and nearly all patients can be successfully treated, clinical challenges remain on the road to HCV elimination. These include: (1) there is a subset of patients who still do not respond to available therapies and harbor mutations against which few current DAAs are effective; (2) only a small proportion of HCV patients have been diagnosed and treated; (3) patients remain at increased risk of HCC even after the elimination of HCV, especially in they are treated at the cirrhotic stage.3 Dual HBV/HCV co-infection is commonly encountered in endemic areas. Liu et al. re-visited the prevalence of dual HBV/HCV infection in certain Asia-Pacific countries.4 With the implementation of HBV vaccination programs, the incidence of new HBV infection will decrease. On the other hand, HCV can be cured in the majority of patients with DAA. Therefore, the proportion of dual HBV/HCV infection is expected to be decreasing. However, there still remains a risk of HBV reactivation in patients receiving DAA for HCV therapy. Co-administration of nucleos(t)ide analogues (NUC) concomitantly with DAA therapy for chronic HCV infection is recommended in dually infected subjects. In Asia, the prevalence and presentation of non-alcoholic fatty liver disease (NAFLD) vary widely across regions because of the substantial diversity in ethnicity, socioeconomic status and environmental triggers. In this special issue, Takuma Nakatsuka et al. reviewed the epidemiological trends, clinical features, optimal assessment and current management practices for NAFLD in Asia.5 Approximately 7%–20% non-obese Asians with body mass index (BMI) less than 25 kg/m2 are estimated to have NAFLD. Furthermore, the dual etiology of fatty liver, particularly with viral hepatitis in Asia, makes it complex and challenging to manage. Lifestyle modification remains the cornerstone for managing NAFLD as there are still no approved drugs. Regarding pediatric NAFLD, Zou et al. implemented a systematic review and found that more than one-third of children with NAFLD had elevated levels of ALT, indicating high proportion of possible nonalcoholic steatohepatitis (NASH) in children.6 Boys were more prone to have NAFLD than girls after 10 years old. Therefore, pediatric NAFLD and its complications later in adulthood would likely impose a heavy financial burden on health systems in the following years. Finally, Yang et al. reviewed the epidemiology of concurrent NAFLD in Asian CHB patients focusing on the impact on clinical outcomes.7 CHB patients tend to have lower prevalence and incidence of NAFLD than the general population. Concurrent NAFLD can promote HBsAg seroclearance and might inhibit HBV replication. On the other hand, severe steatosis and steatohepatitis might exacerbate liver fibrosis in CHB patients. The impact of concurrent NAFLD on HCC risk, all-cause mortality, and antiviral treatment response in CHB patients remains controversial. The overall prevalence of alcoholic liver disease (ALD) in Asia is difficult to assess accurately because large-scale epidemiological surveys are not available for many countries or regions. In this special issue, Xu et al. provided the first meta-analysis of the overall prevalence of ALD and the alcohol-attributable proportions of liver cirrhosis and HCC in Asia.8 Results showed that the overall prevalence of ALD was 4.8%. The pooled alcohol-attributable proportions of liver cirrhosis and HCC were 12.6% and 8.3%, respectively. Of note, ALD prevalence and alcohol-attributable proportion of HCC in Asia increased over the past two decades, calling for the implementation of specific actions to invert this trend. The epidemiology and etiology of drug induced liver injury (DILI) vary across different countries and populations. Li et al. reviewed the incidence and potential risk factors of DILI comparing Asia to other regions of the world.9 The main conclusions were that antibiotics are the leading drugs implicated in DILI in the West, whereas traditional Chinese medicine is the primary cause implicated in DILI in the East. The incidence of herbal and dietary supplements-induced hepatotoxicity is increasing globally. There are no confirmed risk factors for all-cause DILI. The increased awareness and improved availability of specific laboratory tests are progressively facilitating the diagnosis of rare diseases such as autoimmune, cholestatic and genetic liver diseases. Katsumi et al. reviewed the epidemiological and clinical characteristics of autoimmune hepatitis (AIH) patients in Asia.10 Although cases of type 1 AIH showing a good treatment response are common in Asia, the overall percentage of cirrhosis observed in patients at the time of AIH diagnosis is still high, and more serious disease progression has been observed. In addition, Lv et al. reviewed the current clinical and epidemiological profiles of some rare liver diseases including primary biliary cholangitis, AIH, Wilson disease and Citrin deficiency etc.11 Well-designed epidemiological studies are still warranted to ascertain the incidence and prevalence of rare liver diseases at the population level. Zhang et al. reviewed the changing epidemiology of hepatocellular carcinoma (HCC) in Asia, focusing on the demographic characteristics, risk factors, as well as prevention and surveillance of HCC.12 HBV and HCV remain the most common risk factors with a slightly downward trend in most Asian countries. Metabolic factors and alcohol will play more important role in HCC development in the future. The survival time of Asian HCC patients was significantly prolonged in the past decades thanks to the development and implementation of new approaches based on surgery, locoregional therapy, radiation and systemic therapy. Three groups reviewed the current treatment strategies for HCC, addressing the rapid changes in the clinical management of HCC in Asia.13-15 Recently, the availability of new therapeutic options, with the development of new systemic therapies (molecular targeted agents and immune checkpoint inhibitors, ICIs), and new sequential therapies enabled a paradigm shift in the management of HCC. These advancements improved the overall survival of patients with advanced HCC, as well as of those with intermediate or early HCC. Atezolizumab plus bevacizumab became a first-line therapy in advanced HCC. Other combination therapies (e.g. ICIs, molecular targeted agents[MTAs], VEGF inhibitors) are undergoing clinical trials. Systemic therapy may be used in selected intermediate HCC patients, in either first-line, early-switch or neoadjuvant settings. Regarding HCC surveillance, Park et al. prospectively recruited 382 patients with cirrhosis who underwent 1–3 rounds of gadoxetic acid-enhanced magnetic resonance imaging (MRI) and ultrasound at 6-month intervals for HCC surveillance.16 They concluded that in high-risk patients, MRI-based surveillance approaches had higher sensitivities than ultrasound-only surveillance for early-stage HCC. Jindal et al. reviewed the current and changing epidemiological trends of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) in Asia-Pacific region.17 The definition of ALT and ACLF was not consistent among different counties. Viral hepatitis is the main cause of ALF and ACLF in Asia, but recent data suggest that incidence of ALF and ACLF secondary to drugs, herbs and alcohol is increasing. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of ALF and ACLF in the near future. Ling et al. reviewed the past and current status of liver transplantation (LT) due to liver failure in China.18 According to the China Liver Transplant Registry data, among all adult transplant recipients from 2015 to 2020, recipients with malignant liver tumors accounted for approximately 45.0% and those with liver failure accounted for 49.8%. The quantity and quality of LT have been improving progressively over the past two decades, because of the fruitful clinical studies and innovation. In summary, this special issue covered a comprehensive liver diseases spectrum with focus on the Asia-Pacific region, which is home to over 50% of patients with liver diseases in the world. We hope that this updated summary and scientific insights will help us fight liver diseases in this area and ultimately benefit patients.