Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Vic., Australia.
J Viral Hepat. 2011 Jan;18(1):53-60. doi: 10.1111/j.1365-2893.2010.01283.x.
Hepatitis C virus (HCV) infection is frequently associated with hepatic steatosis, particularly in patients with HCV genotype-3 (HCVGT3). It has variously been hypothesized, largely from in-vitro studies, to be the result of increased synthesis, decreased metabolism and export of triglycerides. We measured by real-time PCR the expression of genes involved in lipid metabolism [acetyl-Coenzyme A carboxylase alpha, apolipoprotein B (APOB), diacylglycerol O-acyltransferase 2, fatty acid-binding protein 1, fatty acid synthase, microsomal triglyceride transfer protein (MTTP), peroxisome proliferator-activated receptor alpha (PPARA), peroxisome proliferator-activated receptor gamma (PPARG), protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) and sterol regulatory element-binding transcription factor 1 (SREBF1)] in liver biopsies from patients infected with HCV genotype-1 (HCVGT1), HCVGT3 and Hepatitis B (HBV) using β-glucuronidase (GUSB) and splicing factor arginine/serine-rich 4 (SFRS4) as housekeeping genes. Patients infected with HCVGT3 were younger than those infected with HCVGT1 (36.3 ± 2.5 vs 45.6 ± 1.5, P < 0.05, Mann-Whitney) and were more likely to have steatosis (69.2%vs 11.8%). No significant difference was found in the expression of genes involved in lipogenesis or transport in patients infected with HBV or HCV of either genotype. Contrary to expectation, given the greater degree of steatosis in HCVGT3-infected liver, expression of enzymes involved in lipogenesis was not elevated in HCVGT3 compared with HCVGT1 or HBV-infected liver. Significantly less mRNA for SREBF1 was found in HCVGT3-infected liver tissue compared with HCVGT1-infected liver (1.00 ± 0.06 vs 0.70 ± 0.15 P < 0.05). These results suggest that steatosis in patients infected with HCVGT3 is not the result of a sustained SREBF1 driven increase in expression of genes involved in lipogenesis. In addition, a significant genotype-independent correlation was found between the expression of APOB, MTTP, PRKAA1 and PPARA, indicating that these networks are functional in HCV-infected liver.
丙型肝炎病毒（HCV）感染常伴有肝脂肪变性，尤其是在 HCV 基因型 3（HCVGT3）患者中。从体外研究中提出了各种假设，认为这是由于甘油三酯的合成增加、代谢和输出减少所致。我们通过实时 PCR 测量了肝脏活检中参与脂质代谢的基因的表达[乙酰辅酶 A 羧化酶α、载脂蛋白 B（APOB）、二酰基甘油 O-酰基转移酶 2、脂肪酸结合蛋白 1、脂肪酸合酶、微粒体甘油三酯转移蛋白（MTTP）、过氧化物酶体增殖物激活受体α（PPARA）、过氧化物酶体增殖物激活受体γ（PPARG）、蛋白激酶 AMP 激活的α 1 催化亚基（PRKAA1）和固醇调节元件结合转录因子 1（SREBF1）]，这些患者感染了 HCV 基因型 1（HCVGT1）、HCVGT3 和乙型肝炎（HBV），使用β-葡糖醛酸酶（GUSB）和剪接因子精氨酸/丝氨酸丰富 4（SFRS4）作为管家基因。感染 HCVGT3 的患者比感染 HCVGT1 的患者年轻（36.3±2.5 岁比 45.6±1.5 岁，P<0.05，Mann-Whitney），且发生脂肪变性的可能性更高（69.2%比 11.8%）。感染 HBV 或任何基因型 HCV 的患者中，参与脂肪生成或转运的基因表达无显著差异。与预期相反，鉴于 HCVGT3 感染的肝脏中脂肪变性程度更大，与 HCVGT1 或 HBV 感染的肝脏相比，参与脂肪生成的酶的表达并未升高。与 HCVGT1 感染的肝脏组织相比，HCVGT3 感染的肝脏组织中 SREBF1 的 mRNA 明显减少（1.00±0.06 比 0.70±0.15，P<0.05）。这些结果表明，HCVGT3 感染患者的脂肪变性不是 SREBF1 持续驱动参与脂肪生成的基因表达增加的结果。此外，还发现 APOB、MTTP、PRKAA1 和 PPARA 的表达之间存在显著的基因型独立相关性，表明这些网络在 HCV 感染的肝脏中具有功能。
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