A study reported by Yasuhito Tanaka of the Nagoya City University Medical Department in Japan showed that the single nucleotide polymorphism (SNP) in the TLL1 gene is related to the occurrence and development of hepatocellular carcinoma after radical cure of hepatitis C virus infection. (Gastroenterology. 2017, 152: 1383-1394.) The researchers established different models by combining TLL1 gene mutation with other significant risk factors to predict the risk of liver cancer in patients with different degrees of liver fibrosis. TLL1 gene variants can be used to predict the risk of leverkræft in patients who have achieved a sustained virological response (SVR) in clinical practice. The study included Japanese patients who still suffered from liver cancer after interferon eradication of hepatitis C virus, and used genome-wide association analysis to identify which genes were mutated. The results showed that the TNP1 gene SNP rs17047200 on chromosome 4 is closely related to the occurrence of liver cancer after eradication of hepatitis C virus. There is no obvious linkage disequilibrium between other SNPs and rs17047200, and no more promising SNPs have been found in the exons and promoter regions of TLL1. Tanaka commented: “The mutant genes of liver cancer caused by hepatitis C virus include MICA and DEPDC5, which is very different from our test results.” In a multivariate analysis, the AT / TT base pairing of rs17047200 may lead to a 78% increased risk of liver cancer (P = 0.008). In the group of patients with mild fibrosis, older age is an independent risk factor for liver cancer; in the group of severe fibrosis, postoperative alpha-fetoprotein level and low albumin level are also risk factors. In two groups of liver fibrosis rat models, the mRNA level of TLL1 has increased, but only one group of models of TLL1 mRNA level is consistent with the progress of liver fibrosis. The level of TLL1 mRNA in patients with chronic hepatitis C also increases as liver fibrosis worsens.
Tananka påpegede: "Disse data viser oprindeligt forholdet mellem TLL1 / Tll1-ekspression og aktivering af hepatisk stellatcelle eller hepatisk fibroseprogression hos dyr eller in vitro og hos mennesker (modellen er ikke-alkoholisk steatohepatitis-relateret leverkræft). Det kan muligvis afklare en ny mekanisme for leverfibrose eller kræft. Efter at patienten modtog radikal behandling for hepatitis C-virus og opnåede SVR, kan TLL1 SNP-relaterede eksperimenter bruges til at identificere personer med risiko for leverkræft. Hvis TLL1 SNP sammenlignes med Kombinationen af alder, grad af fibrose, højt alfa-føtoprotein niveau og andre væsentlige risikofaktorer kan hjælpe med klinisk at forudsige risikoen for leverkræft efter SVR. Ingen interferon oral behandlingsplan kombineret med direktevirkende antiviral lægemiddelbehandling, er ved at blive standardbehandlingen mod hepatitis C-virus i udviklede lande. Der er dog stadig behov for yderligere forskning for at vurdere, om TLL1-mutationer er relateret til forekomsten af leverkræft efter behandling med interferonfri SVR.
