Non-alcoholic fatty liver disease affects 64 million people in the United States, but, currently, there is not a non-invasive method to measure treatment response in fibrotic liver disease.1 As the hepatology industry continues to search for treatments that may one day cure fibrotic disease in the liver, there is an important hurdle that has yet to be overcome in the diagnosis of those diseases: Advancing the biopsy.
A common method to diagnose fibrotic liver disease, a biopsy is the removal of a small piece of tissue for the examination and determination by a physician to diagnose a specific disease. This procedure is common not only in fibrotic liver disease, but also in many types of cancer. While it has been a helpful diagnostic tool and standard technique for a very long time, there are some key issues with this procedure that make it outdated and prime for advancement.
1. Biopsies are an invasive, surgical procedure
As it requires the removal of a piece of an organ, liver biopsies are a surgical procedure. If sterile drapes and a large needle aren’t intimidating enough, this invasive procedure has a level of risk associated with it. For example, when biopsying the lung, there is a risk of lung collapse. For the liver, there’s a risk of excessive bleeding. The discomfort and risk associated with a biopsy lead to patient non-compliance. More importantly, as it is invasive, it cannot be adequately repeated. For patients with changes in their disease state or receiving medication, this limitation is an important issue. The ability to frequently query the status of disease in a patient or the effectiveness of therapy state is an essential need for a diagnostic tool.
2. There are variables in analysis
After a biopsy has occurred, the removed tissue needs to be analyzed by two physicians to assess and define characteristics that are observed in the tissue that are associated with the disease. This requirement takes time and consensus between physicians. Additionally, the tissue sample may not be representative of the entire organ. For example, within a liver with fibrotic disease—notoriously heterogenous from one area of the liver to another—sampling the most severely affected lobe may not provide a full scope of the disease to the entire liver.2
These two major limitations of biopsies as a diagnostic tool leaves the field at a disadvantage, not only for assessing the disease, but also for monitoring the disease over time and evaluating a patient’s response to treatment. One cannot measure the liver, or any other organ, frequently enough to see if treatment is working. Monitoring disease trajectory is the only way to evaluate treatment. This archaic tool thus stymies both the monitoring of disease progression and the determination of patient response to treatment.
While there are limitations with biopsies, a greater understanding of disease states and new research may help us develop a new method. Recognizing a set of biomarkers, like in cancer, that can be identified through a blood sample is a way that could allow for a less invasive approach. In our current state of advanced technology, synthetic biomarkers that can measure and predict the trajectory of a disease in a non-invasive manner that could provide clinically actionable output would be more ideal.
With increasing understanding of proteases—a class of enzymes that drive critical disease pathways—and increasing development of synthetic biologics and nanotechnology, it is not outside the spectrum of reality to create accurate, sensitive, and specific biosensors for a given disease state. The systemic injection of these biosensors eliminates the limitation associated with biopsying just one lobe of the liver and allows for a less risky and intimidating procedure. Additionally, the readout could be standardized, eliminating the need for multiple opinions. Finally, the ability to repeatedly inject these biosensors would allow for a more efficient and effective method for tracking disease progression. It would also better patient treatment-response monitoring by allowing a method to more rapidly test a drug’s effectiveness on the disease state.
- Mitra, S., De, A. & Chowdhury, A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Translational Gastroenterology and Hepatology. vol. 5 16–16 (2020).
- Koch, L. K. & Yeh, M. M. Nonalcoholic fatty liver disease (NAFLD): Diagnosis, pitfalls, and staging. Ann. Diagn. Pathol. 37, 83–90 (2018).