NAFLD Related Liver Cancer Risk Screening and Intervention

             

                Interview with Professor Arun Sanyal of Virginia Commonwealth University

 

Editor's note: The global incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing, which is the main cause of chronic liver disease worldwide, covering a series of pathological manifestations from steatosis to inflammation and fibrosis to cirrhosis. More and more studies have shown that the incidence rate of NAFLD related liver cancer has also increased significantly, and has gradually become one of the main causes of liver cancer. At present, the pathogenesis of NAFLD related liver cancer is still unclear, and the risk screening and effective intervention of HCC in NAFLD patients has become a hot topic in this field. At the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in 2022, this magazine invited Professor Arun Sanyal of Virginia Commonwealth University to conduct an in-depth interview on the above issues. Now, the contents are organized into articles for the readers.

 

iHepatology: Would you please tell us what are the changes in the epidemiology and clinical outcomes of NAFLD in recent years?

Dr Sanyal: There are a couple of important trends that are developing within NAFLD. First of all, with the aging of the NAFLD population, we are seeing increasing numbers of people presenting with advanced fibrosis. The burden of patients with advanced fibrosis and cirrhosis from NAFLD is steadily increasing. In 2016, we had done modeling to show that the prevalence would double between 2015 and 2030, and the data appears to show we are on track for that doubling. This highlights the urgent need to tackle the public health problem of fatty liver disease.

 

iHepatology: In recent years, the number of HCC related to NAFLD has gradually increased. At present, what means can we use to identify the high-risk groups of HCC in NAFLD patients?

Dr Sanyal: You are absolutely correct. The incidence of HCC is increasing, and is very closely linked to the presence of underlying NAFLD. So let me go step by step. First thing, if there is a strong family history of HCC, then that is the population you should pay attention to. Number two, people who have advanced fibrosis are more likely to develop HCC. The risk of HCC increases exponentially as you go from stage 0 to 2, and then stage 3 and stage 4. A good simple way to identify that population is to use a test called FIB-4, which is not perfect, but correlates reasonably well with the presence of underlying fibrosis. FIB-4 is widely available, and requires you to know the age of the patient, and to get AST, ALT and platelet count. If you put these in your FIB-4 calculator on Google, it will give you a number. If that number is >2.6, then it enriches the likelihood of developing HCC in the future.

 

iHepatology: In order to prevent NAFLD related HCC, please give us some good suggestions?3. Does active treatment of NAFLD and NASH help reduce the risk of liver cancer?

Dr Sanyal: If NASH and NAFLD are etiologies for the development of HCC, it would logically follow that if you treat these conditions effectively, you will reduce the incidence of HCC. Is there evidence to that fact? We don’t have the long-term studies, because it still takes many years for HCC to develop. Particularly, most of the clinical trials are in patients with stage 2 and stage 3 disease, where, especially for stage 2, the incidence of HCC is still, as an absolute number, fairly low. So we need longer studies to have the evidence base to be able to say that. But it is the logical assumption that if you treat NASH, the incidence of NASH-related HCC will decrease.

 

iHepatology: In the future, what problems do you think need to be solved urgently in the field of NAFLD and related HCC?

Dr Sanyal: The first issue is in people with early stage fibrosis, because the incidence of HCC in people who have early stage disease is very low. For the individual who gets HCC, it’s a big deal, because it is HCC. So we need tools to enrich that population so we know within that early fibrosis stage population, who is particularly at risk and then to develop a more intensive surveillance and preventive strategy for that population. You cannot do trials of preventive strategies when the incidence of disease in the background is very low. For people with more advanced disease, we need these long-term trials with effective NASH therapies to show whether we can actually reduce the incidence of HCC. Now, once HCC develops, we also need better understanding of whether HCC in the setting of NASH behaves the same as HCC developing in the setting of viral hepatitis. There are emerging data that checkpoint inhibitors, for example, may not help all patients with NASH, and may actually cause worsening of HCC in some patients. We need much more clarity on that. In Asia, particularly where a lot of patients have comorbid viral hepatitis and NASH, we need to know what is the biology of the disease. We need more data, and this is an urgent need to further improve precision approaches for the treatment of HCC in those populations.