With an incidence of 25%, what should I do when a high-risk patient refuses further histological testing?

Clinically, in the face of the following types of patients, what disease will you diagnose?

Mild elevation of transaminases is accompanied by increased blood pressure, increased fasting blood glucose, hyperlipidemia, hyperuricemia, and increased body mass index (BMI). Ask about the medical history, there are many histories of hypertension, diabetes, etc. in the past. Most of the patients' body size is mainly obese, especially the central obesity with a large belly. Liver ultrasound, on the other hand, is usually absent from obvious abnormalities, or sometimes simply suggests a low hepatic echo.

In the past, doctors often told patients that they were fatty liver.

And now, if you say that again, you may be wrong! A new concept of disease has been born, and that is metabolism-related fatty liver disease (MALFD).

What is the difference between MAFLD and NAFLD?

MAFLD, formerly known as non-alcoholic fatty liver disease (NAFLD), currently has a global prevalence of up to 25%[1], and there is some difference in the screening diagnosis between the two.

Table 1 Differences between MAFLD and NAFLD

It can be seen that MAFLD no longer uses the "exclusion method" diagnostic method, and no longer uses the "one-size-fits-all" management model, and pays more attention to the high risk of steatohepatitis and fibrosis.

Considering that MAFLD is not detected and intervened in time, the risk of all-cause death, especially from liver disease, increases significantly with the onset and severity of liver fibrosis [2], and no drug has been approved in the United States or the European Union to date [1]. Therefore, hepatic fibrosis screening in patients with MAFLD is important to improve prognosis.

At present, the accuracy of non-invasive MAFLD screening is not good, and patients with "biopsy" are not suitable for acceptance

Liver aspiration biopsy is the "gold standard" for assessment of liver fibrosis, and because of its invasive nature, it is often difficult for patients to accept and its clinical use is limited [3]. The current recommended non-invasive test methods, such as ultrasound, are affected by the technical level of the operator, the patient's condition such as ascites, flatulence and other factors, the diagnostic sensitivity is limited, and when the degree of hepatocyte steatosis < 20%, the accuracy of ultrasound is reduced[1]. There is an urgent need for more effective and accessible screening.

In this regard, at the second Global Liver Health Forum hosted by Sanofi Global Medicine not long ago, Professor Fan Jiangao of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine in China brought more effective non-invasive screening solutions.

The new screening tool is metabolically relevant, non-invasive, and improves accuracy

Professor Fan Jiangao believes that with the deepening of research on the cause and pathogenesis, it is recognized that the occurrence and development of MAFLD is closely related to metabolic factors (including obesity, hypertension, hyperglycemia, abnormal lipidism, etc.). Most patients with NAFLD have one or more metabolic abnormalities, known as metabolic syndrome (MetS), and previous studies have shown an increased risk of developing advanced fibrosis compared with those without metabolic abnormalities [4]. Advanced fibrosis is directly associated with liver-related events and may indicate a poor long-term prognosis for patients with MAFLD [5].

Therefore, the simultaneous consideration of metabolic disorders when screening for liver fibrosis has become a new way of thinking for screening fibrosis in patients with MAFLD, and the TOWARDS1 study[6] included 246 patients aged 18 to 65 years who were biopsy-confirmed with MAFLD in 14 Chinese mainland studies. The results showed that there was indeed a significant association between metabolic disorders and liver fibrosis, manifested by:

●Significantly higher rates of significant fibrosis (≥ F2, 38% vs. 23%, p= 0.014) and higher liver hardness measurement (LSM) values (9.2 kPa vs. 7.4 kPa, p= 0.002) were significantly higher in patients with MetS compared with those without MetS;

●Patients with more metabolic disorders have more severe fibrosis (p= 0.017) compared with patients with fewer metabolic disorders;

●Decreased hdL-cholesterol (HDL-C) (OR 2.241, 95% CI 1.004; 5.002, p= 0.049) and increased fasting glucose (FPG) (OR 4.500, 95% CI 2.083; 9.725, p

Based on the above results, and taking into account the need to improve the diagnostic performance, accessibility and cost-effectiveness of current non-invasive diagnostic measurements, Professor Fan Jiangao's research team developed a new noninvasive screening tool (MetDis) that uses HDL-C reduction and FPG elevation to screen for advanced fibrosis with a sensitivity of 92%, a specificity of 81%, and an accuracy of 83%.

By combining MetDis with the standard non-invasive test FIB-4, it provides a more accurate diagnosis of late fibrosis and, due to the highly negative predictive value of FIB-4 + MetDis, also reduces the number of patients requiring liver biopsy compared to FIB-4 alone (36% vs. 17%, p).

Early intervention improves long-term outcomes

At this meeting, other experts also expressed their views on the early screening of MAFLD.

Ms. Donna Cryer of the Global Liver Institute in Washington, D.C., emphasized that to improve the rate of early detection and screening of MAFLD, there must be three basic elements: in addition to the first point of patient awareness of active testing, the second point of doctors need to be educated and involved, and the third point of providing accurate non-invasive testing methods, improve the compliance of testing is crucial.

Professor Gert Fricker of heidelberg University in Germany, Professor Chavdar Pavlov of Moscow State Medical University in Russia, and Professor Alexander V. Nersesov of the National Institute of Cardiology and Internal Medicine of Kazakhstan also unanimously affirmed the prognosis benefits of hepatic fibrosis in patients with MAFLD, as well as screening for the disease itself, through screening through acceptable, non-invasive means, early detection, early intervention. These include lifestyle changes and essential phospholipids (EPLs) to improve patient health.

brief summary

Noninvasive mafid screening, timely detection and intervention are of great significance for improving patient outcomes, but there has long been a dilemma in which non-invasive screening is not accurate enough and invasive screening is difficult to accept. The association between metabolic disorders and liver fibrosis provides new ideas to solve this puzzle. Noninvasive MetDis (decreased HDL-C and elevated FPG) are more sensitive, specific, and accurate for screening for advanced fibrosis, and the combination with FIB-4 further reduces the need for biopsy and may play an important role in mafld early screening.

Approval number: MAT-CN-2201218

Content Planner: Chen Jing

Content review: Ma Sen, Cui Xiaoxu

Title image source: Stand Cool Helo

bibliography

Xue Rui, Fan Jiangao. Introduction to the International Expert Consensus on the New Definition of Metabolism-Related Fatty Liver Disease[J]. Journal of Clinical Hepatobiliary Diseases, 2020, 36(6): 1224-1227.

Fatty liver and alcoholic liver disease group of Hepatology Branch of Chinese Medical Association, et al. Guidelines for the prevention and treatment of non-alcoholic fatty liver disease (updated edition 2018)[J]. Chinese Journal of Hepatology, 2018, 034(005):641-649.

[3]. Sumida Y, et al World J Gastroenterol 2014;20:475–85.

[4]. Jinjuvadia R, et al. J Clin Gastroenterol 2018;51(2):160-166.

[5]. Dulai PS, et al. Hepatol 2017;65(5):1557-1565.

[6]. Shi YW, et al. J Clin Transl Hepatol 2021; doi:10.14218/JCTH.2021.00058.