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 jigar saratoni 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 ta'kidladi: "Bu ma'lumotlar dastlab TLL1 / Tll1 ifodasi va hayvonlarda yoki in vitro va odamlarda jigar stellat hujayralari faollashuvi yoki jigar fibrozining rivojlanishi o'rtasidagi bog'liqlikni ko'rsatadi (model alkogolsiz steatohepatit bilan bog'liq jigar saratoni). Bu jigar fibrozi yoki saratonining yangi mexanizmini aniqlab berishi mumkin. Bemor gepatit C virusi uchun radikal davolashni olgach va SVR ni qo'lga kiritgandan so'ng, jigar saratoni xavfi bo'lgan odamlarni aniqlash uchun TLL1 SNP bilan bog'liq tajribalardan foydalanish mumkin. Agar TLL1 SNP bilan solishtirilsa, yosh, fibroz darajasi, yuqori alfa-fetoprotein darajasi va boshqa muhim xavf omillarining kombinatsiyasi SVRdan keyin jigar saratoni xavfini klinik jihatdan bashorat qilishga yordam beradi. To'g'ridan-to'g'ri ta'sir qiluvchi antiviral dori terapiyasi bilan birlashtirilgan interferon og'iz orqali davolash rejasi rivojlangan mamlakatlarda gepatit C virusiga qarshi standart terapiyaga aylanmoqda. Biroq, interferonsiz SVR bilan davolashdan keyin TLL1 mutatsiyalarining jigar saratoni paydo bo'lishi bilan bog'liqligini baholash uchun hali ham qo'shimcha tadqiqotlar talab etiladi.
