The Liver

As the second largest organ in the body, the liver interacts with almost every organ system in the body. It serves a broad range of functions, such as alcohol/ chemical metabolism, blood filtration, bile production and much more [1].

About the Disease:

Acute-on-chronic liver failure (ACLF) is a deadly condition/syndrome that to this day does not have a truly efficient and effective solution [2,3].

ACLF in its simplest definition is a sudden amplification  of cirrhosis/chronic liver failure which can lead to short mortality.

    • Cirrhosis(liver)  – the degeneration of liver cells which can lead to permanent damage or even failure of the liver.The fibrogenic process and the unleashing of acute-on-chronic liver failure
  • There are 3 types, depending on how it begins and progresses [3]. 
    • A : liver function worsens in patient with chronic liver disease 
    • B : decompensation in patient with cirrhosis 
    • C : liver function worsens in decompensated cirrhotics
  • ACLF is often associated with extra-hepatic organ failure which is why ACLF is so dangerous [3]. 
    • The severity of ACLF is often determined on the number of surrounding organs that also get damaged.

Statistics:

Acute-on-chronic liver failure is a serious condition that affects a multitude of patients every year. 24 to 40 percent of patients are diagnosed with cirrhosis, yet ACLF may still be present [2]. 40 to 50 percent of cases of ACLF do not show symptoms, making the disease very dangerous [2]. Average affirmative diagnosis of ACLF takes 3-7 days [4]. This is enough time for the condition to get even worse. ACLF can cause damage to more organs than just the liver including the lungs, kidneys, etc. [4]. The image below shows just how severe ACLF and cirrhosis can be and the multitude of organs it can affect.

ACLF as well as cirrhosis have become an increasing risk for patients. In 2013 alone, 1.2 million people were diagnosed with liver disease and later died because of it [5]. Treatment remains hard to come by, and the waiting for certain treatments can be fatal. According to Scientific American, Nearly 18 people die a day in the United States waiting for an acceptable match of an organ [6].

Current Treatment- Liver Transplant:

Acute-on-Chronic Liver Failure (ACLF) progresses extremely quickly and generally speaking has a poor prognosis without transplantation [7]. So oftentimes, liver transplantation is the way to go as it has been suggested to drastically improve survival amongst ACLF patients.

However, there are several limitations due to the great lack of availability of donor organs. This makes it difficult for ACLF patients to have priority on the waitlist [8].

To determine priority, waitlists look at which patients have adequate post-transplant survival rate to justify the use of limited donor organs. Some issues that arise for priority with ACLF patients include:

  • Some patients have multi-organ failure which decreases their chance of survival post-transplant [7].
  • Studies done by Trebicka et al. show that patients with ACLF that are transplanted may have a higher rate of complications and lower survival rate as compared to other patients in need of a liver transplant [8].
  • In addition, active alcoholism is often the main precipitating factor involved in ACLF. This can further pose trouble for ACLF patients hoping to be admitted to the waitlist as many countries require abstinence for at least 6 months in order to be admitted to the list [8].

Even after the transplant, there is always the possibility of rejection of the graft. 

Current Treatment- Therapeutic Approaches

Therapeutic approaches are being explored due to the high short-term mortality rates and high costs for chronic liver diseases. There are two options of therapeutic approaches that show signs of working,  Granulocyte colony stimulating factor (G-CSF) transplantation and Mesenchymal stem cells (MSC) transplantation.

G-CSF stimulates the blood marrow to supply more granulocytes and stem cells. These products are then put circulation. This growth factor has been shown to have an effect on end-stage liver diseases by improving not only stem cells but also liver regeneration. Afterwards, patients had higher neutrophil counts and decreased sepsis/sepsis related deaths. G-CSF has shown potential in both acute and chronic liver failure patients. However, not enough studies have been done for us to be sure about the best time to administer G-CSF and at what dosages [10].

Mesenchymal stem cells have been shown to improve liver function in end-stage liver diseases. The study transfused MSC from umbilical cords and no significant adverse side effects were recorded. There were increased survival rates and increases in  serum albumin, cholinesterase, and prothrombin activity [9].

The studies are hopeful, but there have been very few studies with very small sample sizes for both treatments. More research has to be done if for reliable results of this treatment.

References 

  1. Kalra, A., et al., Physiology, Liver, in StatPearls. 2020: Treasure Island (FL).
  2. Shah, N. J., Mousa, O. Y., Syed, K., & John, S. (2020, September 10). Acute and Chronic Liver Failure. Retrieved September 19, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK499902/
  3. Arroyo, V., & Jalan, R. (n.d.). ACUTE-ON-CHRONIC LIVER FAILURE: DEFINITION, DIAGNOSIS AND … Retrieved September 20, 2020
  4. Hernaez R, Solà E, Moreau R, Ginès P, 2017
  5. Allen AM, Kim WR, 2016
  6. Vartan S, 2019
  7. Wu, T., & Sundaram, V. (2019, November 06). Transplantation for Acute‐on‐Chronic Liver Failure. Retrieved September 24, 2020, from https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/cld.852
  8. Trebicka, J., Sundaram, V., Moreau, R., Jalan, R., & Arroyo, V. (2020, July 02). Liver Transplantation for Acute‐on‐Chronic Liver Failure: Science or Fiction? Retrieved September 24, 2020, from https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/lt.25788
  9. Shi, M., Zhang, Z., Xu, R., Lin, H., Fu, J., Zou, Z., Zhang, A., Shi, J., Chen, L., Lv, S., He, W., Geng, H., Jin, L., Liu, Z., & Wang, F., 2012
  10. Yang, Q., Yang, Y., Lv, F., He, J., & Chen, Z., 2016

Figure 1: https://www.e-cmh.org/m/journal/view.php?number=1472

Figure 2: https://www.medicalindiatourism.com/blog/signs-symptoms-liver-damage.html

Figure 3: https://www.bioedge.org/bioethics/organ-donation-debate-continues/12344

Figure 4: https://i1.wp.com/coloradorehabilitation.com/wp-content/uploads/2014/08/denver-stem-cell-therapy.jpg