LiverScreen

LiverScreen

Screening for liver fibrosis – population-based study across European countries

The progression process of liver diseases

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. Liver fibrosis (Figure 1) represents the common consequence of any chronic liver injury, including fatty liver due to metabolic risk factors. This leads to a persistent liver inflammation, which stimulates a wound healing response in which extracellular matrix proteins, such as collagens and hyaluronic acid, accumulate in the liver and form scar tissue (fibrosis).

liver_fibrosis_stages
Figure 1. Liver fibrosis stages (from F0: normal liver to F4: cirrhosis) 1,2

Efffective treatment options are only available for early stages of liver disease

As prognosis and management of patients with chronic liver diseases depend critically on liver fibrosis stage and progression, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up3. Treatment options for liver fibrosis usually depend on both the underlying cause and the stage of the fibrosis. Figure 2 shows the progression from a normal liver towards cirrhosis  and decompensation or liver cancer in later stages, which takes place slowly over decades4.

liver_cirrhosis_progression
Figure 2. Progression from normal liver towards liver cirrhosis4

When liver disease is detected at an early stage, several effective treatment options are available. For example, intensive behavioral intervention targeting weight loss, either with diet, exercise programs or bariatric surgery has been proven to be an effective treatment in patients with NAFLD5. Avoiding alcohol consumption is also effective in stop liver damage, improve liver function tests, improve liver fibrosis in patients with alcoholic liver disease. Additionally, early detection is also beneficial for patients with HBV and/or HCV, as pharmaceutical discoveries have yielded ground-breaking treatment options for both HBV and HCV. As a consequence, we can now eliminate the virus (HCV) or suppress its replication (HBV) in the vast majority of patients6. However, only a timely disease detection will allow curative treatment, leading to elimination of chronic viral hepatitis7, thus preventing the development of liver-related complications. Thus, an important remaining challenge is to identify the patients who are not aware to have chronic HCV and/or HBV because they are asymptomatic. When detected on time, improvement on liver fibrosis stage is also achievable by immunosuppressive therapy in patients with autoimmune disease,  and by removing iron overload in those with hemochromatosis disease8. When advanced cirrhosis has developed, etiological treatments, when still applicable, cannot always prevent the onset or the progression of the complications. Beyond the strategies to prevent or to treat the complications, liver transplantation (LT) is the only way to cure advanced liver cirrhosis, but LT is only available for a small group of patients. In Europe, less than 2,000 liver transplants are performed each year, which should be compared to the 170,000 annual deaths due to cirrhosis.  Thus, the fibrosis stage is strongly associated with the probability of survival (Figure 3).

patients_conditional_survival
Figure 3. The conditional survival of patients as a function of their fibrosis staging and diagnosis. At 10-year survival, the greatest improvement is between diagnosed and undiagnosed patients with F2-F3 stages. The fact that fibrosis progression is not linear results in differential survival estimates given an initial diagnosis at the age of 45-years old (unpublished data).

Possible solutions

Transient elastography (TE, , FibroScan®, Echosens, Paris, France, Figure 4),  is the most accurate and validated point-of-care technique for detecting the stage and progression of liver fibrosis and cirrhosis in patients with known chronic liver disease with immediate results (<5 min)9. The technique itself is proven to be safe, with low inter- and intra- variability10. Moreover, it is widely used in specialist liver centers across Europe. TE is a ultrasound – based technique that measures the velocity of a low-frequency elastic shear wave propagating through the liver and correlates with the stiffness of the liver tissue, therefore correlating with fibrosis11. TE can be performed in any outpatient clinic by trained nurses or physician assistants due to the short learning curve and is already widely available in clinics across Europe.

te_in_action
Figure 4. TE in action. The left part shows the Fibroscan instrument and the right part shows a close-up of the results from the Firboscan. It can be seen that the results from the instrument are very easily interpreted and is perfectly suited for us.

References

  1. Schuppan, Detlef, and Nezam H. Afdhal. “Liver cirrhosis.” The Lancet 371.9615 (2008): 838-851.
  2. Lee, Youngmin A., Michael C. Wallace, and Scott L. Friedman. “Pathobiology of liver fibrosis: a translational success story.” Gut 64.5 (2015): 830- 841.
  3. Friedrich-Rust et al. Critical comparison of elastography methods to assess chronic liver disease. Nat Rev Gastroenterol Hepatol. 2016; 13: 402-411
  4. Pellicoro et al. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat Rev Immunology. 2014; 14: 181-194
  5. Thursz, Mark, et al. “EASL Clinical Practice Guidelines: Management of alcohol-related liver disease.” Journal of hepatology 69.1 (2018): 154-181.
  6. European Association For The Study Of The Liver. “EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.” Journal of hepatology 67.2 (2017): 370-398.
  7. Lazarus, 2017, Nature Rev Gas Hep, Many European countries ‘flying blind’ in their efforts to eliminate viral hepatitis
  8. Rockey et al. Fibrosis–A Common Pathway to Organ Injury and Failure, New Engl J Med. 2015; 373:96
  9. Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis. Hepatol.2015;63,237-64
  10. EFSUMB guidelines for the use of elastography 2017
  11. Sandrin, Laurent, et al. “Transient elastography: a new noninvasive method for assessment of hepatic fibrosis.” Ultrasound in medicine & biology 29.12 (2003): 1705-1713.