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 kanser hati 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 menegaskan: "Data ini pada mulanya menunjukkan hubungan antara ekspresi TLL1 / Tll1 dan pengaktifan sel stellate hepatik atau perkembangan fibrosis hepatik dalam haiwan atau in vitro dan pada manusia (modelnya adalah kanser hati yang berkaitan dengan steatohepatitis bukan alkohol). Ia mungkin dapat menjelaskan mekanisme baru fibrosis hati atau kanser. Selepas pesakit menerima rawatan radikal untuk virus hepatitis C dan memperoleh SVR, eksperimen berkaitan TLL1 SNP boleh digunakan untuk mengenal pasti orang yang berisiko menghidap kanser hati. Jika TLL1 SNP dibandingkan dengan Gabungan umur, tahap fibrosis, tahap alfa-fetoprotein yang tinggi dan faktor risiko penting lain boleh membantu secara klinikal meramalkan risiko kanser hati selepas SVR. Tiada pelan rawatan oral interferon digabungkan dengan terapi ubat antivirus bertindak langsung , Menjadi terapi virus anti-hepatitis C standard di negara maju. Walau bagaimanapun, kajian lanjut masih diperlukan untuk menilai sama ada mutasi TLL1 berkaitan dengan kejadian kanser hati selepas rawatan dengan SVR bebas interferon.
