丙肝治疗新进展

丙肝治疗新进展

时间:2008-3-18 17:06:56 来源：国际肝病点击次数:54

HEPATOLOGY DIGEST：In your clinic practice, how do you determine treatment duration of peg-interferon plus ribavirin?

《国际肝病》：在临床实践中，您是怎样决定长效干扰素和利巴韦林联合治疗的疗程的？

Prof. Maddrey：We are very interested in using the labeled virus at 4 weeks and 12 weeks to make our decisions. If patients have no detectable virus at 4 weeks, those patients generally regardless of suggested time can be treated for 6 months or less. If the patient is positive at 4 weeks and become negative at 12 weeks for genotype 1, we treat them for one year. For genotype 2 or 3, we generally treat them for 6 months.

Maddrey教授：我们主要是通过检测4周和12 周的病毒载量来决定治疗疗程。如果患者在第4周检测不出病毒，我们通常认为这些患者可以治疗6个月或更短的时间。如果患者在第4周阳性而在12周阴性，对于基因1型患者我们通常将治疗疗程延至1年；而对于基因2型和3型患者我们通常治疗6个月。

HEPATOLOGY DIGEST：Are there any differences in genotype 1, 2 and 3 patients with HCV on treatment?

《国际肝病》：关于基因1型、2型和3型丙型肝炎患者在治疗上有哪些不同之处呢？

Prof. Maddrey：Yes, the differences are considerable. Genotype 2 responds to treatment in 6 month or less. Eighty to eighty-five percent of the time with sustained getting off virus. But for genotype 1 ,it is 45 to 50 percent patient clear completely in the one year. In genotype 3 , we get about 75 percent clearance in 6 month. So there are differences based on the genotype but very important.

Maddrey教授：是的，他们之间的差别是非常显著的。基因2型患者通常在6个月或更短的时间内对治疗产生应答。80%～85%的时间他们具有持续的病毒清除能力。但对基因1型，只有45%～50%的患者在1年以内能彻底清除病毒。而在基因3型，我们发现约75%的患者可以在6个月时清除病毒。所以不同基因型之间是有差别的，而且这种差别很重要。

HEPATOLOGY DIGEST：How do you think the new advance in this AASLD?

《国际肝病》：您是怎样看待今年的美国肝病学会年会的新进展的？

Prof. Maddrey ：I think the major advances this year and next year all will be the introduction of small molecules that inhibit the proteinase of hepatitis virus. I think that will be the next great advance. What other people think will be the polymerase which are small molecules in the fusion replications of viruses by setting polymerase. Since I hope within 5 years, there are 3 or more proteases we can start to choose and pick based on the patient’s needs.

Maddrey教授：我认为今年乃至明年的主要进展都将是——能抑制肝炎病毒的小分子蛋白酶的发现。这可能是下一个巨大的进展。也有人认为是聚合酶，他们是通过释放聚合酶影响病毒融合复制过程的小分子蛋白酶。因此我希望在未来5年的时间内，能有3个甚至更多的小分子蛋白酶让我们依据患者的需要进行选择。

丙型肝炎患者合并胰岛素抵抗及脂肪肝时的管理HEPATOLOGY DIGEST：Please talk about the management of insulin resistance

and fatty liver disease in hepatitis C.

《国际肝病》：请您谈谈丙型肝炎患者合并胰岛素低抗及脂肪肝时的管理。

Prof. Jensen: We currently have no good therapies for fatty liver disease except with genotype 3 hepatitis C virus infection. Genotype 3 HCV is different from the other hepatitis c genotypes in terms of fatty liver disease. In genotype 3, fatty liver disease has been shown to be related to virus replication. If we successfully treat and eradicate the virus, the fatty liver also goes away. For other hepatitis C viruses, specifically genotype 1, treating the virus is more difficult if fat is present. Second, when the virus is successfully treated, fat may still be present in the liver: it doesn’t go away with successful treatment. It may decrease slightly during therapy, but it doesn’t go away. Fatty liver may be related to the metabolic syndrome. The cornerstone of treatment is to change life style, so the patient is able to lose weight through diet and exercise. Maybe before they start therapy, they can control the body weight. There is evidence that if they can decrease the fatty liver disease, they also decrease the fibrosis. So perhaps improving metabolic syndrome might be associated with a better response to the interferon. We just don’t know that for certain yet, it has not been studied prospectively. But this is something that needs to be done.

Jensen教授：目前对非基因型3型的慢性丙型肝炎合并脂肪肝的患者还没有特别满意的治疗方案。合并脂肪肝的HCV患者，基因3型与其他类型不同，其脂肪肝与病毒复制相关。如果经过治疗彻底清除病毒，那么脂肪肝也随之消失。但是，对其他基因型特别是基因1型的HCV患者，当脂肪肝存在时清除病毒就十分困难，即使抗病毒治疗成功，脂肪肝也可能不会消失。脂肪肝和代谢综合征存在一定相关性，所以首要的治疗就是改变生活方式，通过饮食控制和锻炼来控制体重。患者最好在开始药物治疗之前已经将体重控制在正常范围。有证据显示，脂肪肝减轻的同时肝纤维化也会有所减轻。另外，改善代谢综合征后患者对干扰素治疗的应答也会提高。但目前还没有这样前瞻性的研究在进行。

HEPATOLOGY DIGEST：What is the relationship between nonalcoholic fatty liver and metabolic syndrome ?

《国际肝病》:非酒精性脂肪肝（NAFL）与代谢综合征（MS）的有什么关系？

Prof. Jensen: Patients can have fatty liver from a number of causes. One of them is the metabolic syndrome. In many people, fatty liver can be associated with obesity or alcohol: they may have fatty liver, but not metabolic syndrome. They do not necessarily have insulin resistance. When we talk about the metabolic syndrome, we are really speaking about those patients who have insulin resistance. In simple terms, insulin resistance means that a higher level of insulin is required to do the things that it is normally required to perform in the body. As a feed back mechanism, the fatty liver itself can be associated with some insulin resistance. In addition, primary changes in certain inflammatory cytokines may also be associated with the insulin resistance. Many of NAFLD patients do have metabolic syndrome，but not all of them.

Jensen教授：脂肪肝的原因有很多，代谢综合征只是其中的一个。脂肪肝与肥胖症和酒精有关，很多人可能患有脂肪肝，但不一定会有胰岛素抵抗和代谢综合征。当我们谈到胰岛素抵抗时，往往也会谈到代谢综合征。简单的说，胰岛素抵抗是指患者体内存在着高水平的胰岛素，而且需要高水平的胰岛素才能够行使正常的生理功能。所以理论上，脂肪肝与胰岛素抵抗有关。另外还有一些炎性细胞因子与胰岛素抵抗的发生有关。很多非酒精性脂肪肝的患者存在着代谢综合征，但不是所有的患者。