Interview with Professor Ruben Hernaez of Baylor Medical College in Houston, USA
Editor：Jiamo Ren
Editor's note: Chronic acute liver failure (ACLF) is often used to describe acute decompensation on the basis of chronic liver disease. It is different from chronic liver disease or decompensated cirrhosis. It is one of the important types of liver disease, often accompanied by multiple organ failure, with a high short-term mortality. The pathophysiological mechanism of ACLF is still unclear. At present, it is believed that the imbalance of immune regulation and excessive inflammatory reaction play an important role in the development of ACLF. From November 4 to 8, 2022, the 2022 American Association for the Study of Liver (AASLD) Annual Conference, an annual academic event in the field of hepatology, was held at the Convention and Exhibition Center in Washington, D.C. We specially invited the experts present - Professor Ruben Hernaez of Baylor Medical College in Houston, USA, to conduct an in-depth interview on the mechanism and feasibility of immunotherapy for ACLF patients.
iHepatology: What happens to the patient's immune function during the development and progression of ACLF? Are there any differences among patients with different etiologies or at different stages?
Dr Hernaez: As far as the immunology, what happens is patients get immune paralysis. The immune system of patients with acute-on-chronic liver failure (ACLF) is overwhelmed with a massive inflammatory response. The immune system is basically paralyzed. There are some effects on the mitochondria that we see, that are not present in patients without ACLF.
iHepatology: In clinical practice, how to evaluate the immune function of ACLF patients?
Dr Hernaez: One of the things we hope to do is look at the differential white cell count, and look for the presence of an increase in viral cell count. We also look at C-reactive protein. We also look at interleukin-6 and interleukin-8 and a few others.
iHepatology: What are the main immunomodulatory strategies for the treatment of ACLF?
Dr Hernaez: Regardless of the definition, both definitions are pinpointing that these are critically ill patients with chronic liver disease and/or cirrhosis. The idea is to look at the virus cell count and to investigate what is happening with a hepatitis virus infection, or bacterial or fungal, and then after applying either criteria, the idea is to treat effectively as we have discussed here at this meeting.
iHepatology: There are differences in the definition or diagnostic criteria of ACLF between the East and the West. How to evaluate and compare the clinical outcomes and treatment effects of ACLF patients reported from different regions?
Dr Hernaez: In Asia, and particularly in India, there are data for the use of granulocyte-colony stimulating factor (G-CSF). This has been shown to be invalid in the US. There are some randomized clinical trials and meta-analyses showing it is not that effective. The concept is to make the stem cells more effective, but to date, that has not been shown to be clinically efficacious.
iHepatology: What immunomodulatory measures have been validated or are under clinical trials that have shown therapeutic efficacy in the treatment of ACLF?
Dr Hernaez: That goes back to my prior comment. G-CSF could be used (and actually is being used) in Asia and India, for instance. But in the US, the trials did not succeed. Plasmapheresis or plasma exchange can help a little bit in some patients, but is not a long-term solution. The other thing is albumin exchange, which may help, because albumin has some immunomodulatory effects. As far as diet, unfortunately I don’t know much about it, but there have been studies into the immunomodulatory effects of diet. But all-in-all, as far as immunomodulatory approaches are concerned there is nothing strong to recommend.
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