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 aknu vēzis 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 norādīja: "Šie dati sākotnēji parāda saistību starp TLL1 / Tll1 ekspresiju un aknu zvaigžņu šūnu aktivāciju vai aknu fibrozes progresēšanu dzīvniekiem vai in vitro un cilvēkiem (modelis ir bezalkoholisks ar steatohepatītu saistīts aknu vēzis). Tas var precizēt jaunu aknu fibrozes vai vēža mehānismu. Pēc tam, kad pacients saņēma C hepatīta vīrusa radikālu ārstēšanu un ieguva SVR, ar TLL1 SNP saistītus eksperimentus var izmantot, lai identificētu cilvēkus, kuriem ir aknu vēža risks. Ja TLL1 SNP salīdzina ar Vecuma, fibrozes pakāpes, augsta alfa-fetoproteīna līmeņa un citu nozīmīgu riska faktoru kombinācija var palīdzēt klīniski prognozēt aknu vēža risku pēc SVR. Nav interferona perorālas ārstēšanas plāna, kas apvienots ar tiešas darbības pretvīrusu zāļu terapiju. Tā kļūst par standarta C hepatīta vīrusa terapiju attīstītajās valstīs. Tomēr joprojām ir nepieciešami turpmāki pētījumi, lai novērtētu, vai TLL1 mutācijas ir saistītas ar aknu vēža rašanos pēc ārstēšanas ar interferonu nesaturošu SVR.
