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 câncer de fígado 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 destacou: “Esses dados mostram inicialmente a relação entre a expressão de TLL1/Tll1 e a ativação de células estreladas hepáticas ou progressão da fibrose hepática em animais ou in vitro e em humanos (o modelo é câncer de fígado relacionado à esteatohepatite não alcoólica). Pode ser capaz de esclarecer um novo mecanismo de fibrose ou câncer hepático. Depois que o paciente recebeu tratamento radical para o vírus da hepatite C e obteve RVS, experimentos relacionados ao SNP TLL1 podem ser usados para identificar pessoas com risco de câncer de fígado. Se o SNP TLL1 for comparado com A combinação de idade, grau de fibrose, alto nível de alfa-fetoproteína e outros fatores de risco significativos pode ajudar a prever clinicamente o risco de câncer de fígado após RVS. Nenhum plano de tratamento oral com interferon combinado com terapia medicamentosa antiviral de ação direta está se tornando a terapia padrão contra o vírus da hepatite C nos países desenvolvidos. No entanto, ainda são necessárias mais pesquisas para avaliar se as mutações do TLL1 estão relacionadas com a ocorrência de câncer de fígado após tratamento com RVS sem interferon.
