The risk of fatty liver progression to liver cancer is as high as 23%! The sub-issue of "Nature" takes stock of 3 major developments

Focus on research progress

First, artificial intelligence can quantitatively evaluate liver fibrosis
after anti-NAFLD treatment through second harmonic (SHG)/two-photon excitation fluorescence (TPEF) microscopic imaging technology.

Second, the weight loss effect of the double agonist tisipatide (Tirzepatide) is comparable to surgery, and it shows a strong anti-lipogenic effect
.

Third, the protein secretion group composed of 133 gene markers and 4 proteins can accurately predict the risk of hepatocellular carcinoma in patients with NAFLD, and has a high negative predictive value
.

Evaluation of NAFLD-related liver fibrosis

Patients with NAFLD have a poor prognosis and low survival
.
Liver histologic features, particularly liver fibrosis, have been shown to be associated
with a long-term poor prognosis in patients with NAFLD.
Early diagnosis of NAFLD-associated liver fibrosis is key to
improving patient outcomes.
The traditional light microscope evaluation method belongs to semi-quantitative classification, personal subjectivity is strong, the results are difficult to guarantee, and therefore there is a lack of unified standards to evaluate liver fibrosis schemes, how to accurate, clear and non-invasive imaging of intrahepatic collagen fibers is the bottleneck
of liver fibrosis research.

A study using SHG/TPEF microscopy to show the position and three-dimensional morphology of collagen in organ tissues, and then using computer modeling for automated evaluation, proved that tropifexor can help reverse liver fibrosis
.

Advances in NAFLD treatment

The most effective way to treat NAFLD is to lose weight
.
When patients lose more than 10% of their body weight, steatosis can be improved in almost all patients and liver fibrosis in 80% of patients
.
However, only 10% of patients can achieve their weight loss goals
through lifestyle changes.

A 2022 SURPASS-3 clinical trial was published, which compared the effects of tisiparatide and deguline on liver fat content (LFC) and found that at doses of at least 10 mg/week tisiparatide, LFC can be reduced by 8%, mainly due to weight loss, visceral and abdominal fat loss
.
The results of the SYNERGY-NASH trial, which will be published in November 2023, are expected to clarify whether tisiparatide can help reverse liver fibrosis
.

Prediction of liver cancer risk in patients with NAFLD

NAFLD can eventually progress to hepatocellular carcinoma (HCC), with an annual progression rate of about 1.
5%~3.
8
%.
About 15% of HCC patients are NAFLD patients, of which 20%~50% occur before
cirrhosis.
Therefore, improving the screening and diagnosis ability of NAFLD-related HCC is one of the
current research hotspots.

At present, the known joint diagnostic models include GALAD model, ASAP model, etc
.
One study proposed a PLS-NAFLD model
based on 133 genetic markers.
The results showed that the incidence of HCC at 15 years in high-risk patients in the PLS-NAFLD model was 23%, while the incidence of HCC in low-risk patients was 0%.

The researchers then developed PLSec-NAFLD based on a protein secretion group composed of four proteins of PLS-NAFLD, which can stratify
high- and low-risk patients.
This means that the risk screening of patients with NAFLD with HCC may usher in new developments
.