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 leverkreft 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 påpekte: "Disse dataene viser i utgangspunktet forholdet mellom TLL1 / Tll1-ekspresjon og aktivering av hepatisk stellatcelle eller hepatisk fibroseprogresjon hos dyr eller in vitro og hos mennesker (modellen er ikke-alkoholisk steatohepatitt-relatert leverkreft). Det kan være i stand til å avklare en ny mekanisme for leverfibrose eller kreft. Etter at pasienten mottok radikal behandling for hepatitt C-virus og oppnådde SVR, kan TLL1 SNP-relaterte eksperimenter brukes til å identifisere personer med risiko for leverkreft. Hvis TLL1 SNP sammenlignes med Kombinasjonen av alder, grad av fibrose, høyt alfa-fetoproteinnivå og andre signifikante risikofaktorer kan hjelpe klinisk å forutsi risikoen for leverkreft etter SVR. Ingen oral behandlingsplan for interferon kombinert med direktevirkende antiviral medikamentterapi, er i ferd med å bli standard anti-hepatitt C-virusbehandling i utviklede land. Det er imidlertid fortsatt behov for ytterligere forskning for å vurdere om TLL1-mutasjoner er relatert til forekomsten av leverkreft etter behandling med interferonfri SVR.
