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 leverkanker 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 merkte op: “Deze gegevens laten in eerste instantie de relatie zien tussen TLL1/Tll1-expressie en hepatische stellaatcelactivatie of progressie van leverfibrose bij dieren of in vitro en bij mensen (het model is niet-alcoholische steatohepatitis-gerelateerde leverkanker). Het kan mogelijk een nieuw mechanisme van leverfibrose of kanker ophelderen. Nadat de patiënt een radicale behandeling voor het hepatitis C-virus heeft ondergaan en SVR heeft verkregen, kunnen TLL1 SNP-gerelateerde experimenten worden gebruikt om mensen te identificeren die risico lopen op leverkanker. Als TLL1 SNP wordt vergeleken met de combinatie van leeftijd, mate van fibrose, hoog alfa-foetoproteïneniveau en andere significante risicofactoren kan het risico op leverkanker na SVR klinisch worden voorspeld. Geen oraal behandelplan met interferon in combinatie met direct werkende antivirale medicamenteuze therapie wordt de standaard anti-hepatitis C-virustherapie in ontwikkelde landen. Er is echter nog steeds verder onderzoek nodig om te beoordelen of TLL1-mutaties gerelateerd zijn aan het optreden van leverkanker na behandeling met interferonvrije SVR.
