我父亲丙肝失代偿期还可以使用干扰素吗？

mdjcwc

我父亲丙肝8年，今年2月出现腹水住院至今，住院时白蛋白27，胆碱脂酶1710，住院10天后开始使用白蛋白，隔日一支，中间停止使用一周后又出现腹水（3月25、4月4号），继续使用，再没有出现。因为费用太高，一月前开始使用血浆至今。目前我知道的几项指标是（4月24日化验）：谷丙75，谷草100，胆碱脂酶3055，前白蛋白86，白蛋白33，总胆红素37.8，病毒1.5×10的5次方。总的来看指标都有一定好转，但是我认为是打白蛋白的原因，自身肝功能还是不行，现在医院的医生对目前是否使用干扰素的意见也不同，反对的认为有风险(观点是营养支持），主张的认为可以小剂量使用，这样才是治本，我倾向后者。想咨询大家的观点，同时请问，有抗丙肝的口服干扰素或类似的药品吗？ 恩替卡伟可以吗？

liver411

应该在调整身体状况后，比如，去掉维持没有腹水，LF恢复，评估那个基因型的HCV（对药物效益不同，联合用药不同）。 在此基础上，小剂量，定期检查LF前提下，治疗根本才是。有文献说失代偿干扰治疗有效益但是会有副作用的~可能牵扯到药物减量/暂停治疗等。

有两种口服药物目前一期临床试药效果不错，不过国内可能没有试药点，不能参与试验。

liver411

Promising Early Results from the First Clinical Trial of a Combination Regimen of 2 Oral Antiviral Agents for Chronic Hepatitis C

Combination therapy consisting of pegylated interferon (Pegasys or PegIntron) plus ribavirin is the current standard of care for chronic hepatitis C virus (HCV) infection, but there is an urgent need for anti-HCV therapies that are more potent, less toxic, and more convenient. To this end, researchers are studying several oral agents that directly target various steps of the HCV lifecycle, an approach referred to as "STAT-C."

In a late-breaker session at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) last week in Copenhagen, Denmark, researchers reported early promising results from a study of an all-oral, direct-acting combination antiviral regimen consisting of the experimental nucleoside analog polymerase inhibitor R7128 and the experimental HCV protease inhibitor R7227 (also known as ITMN-191).

The study, called INFORM-1, is the first to test 2 direct-acting oral antiviral agents, without interferon or ribavirin, in hepatitis C patients. Combining 2 potent agents targeting 2 distinct viral enzymes may offer advantages over single-agent therapy by enhancing potency, reducing the emergence of drug resistance, and possibly eliminating the need for pegylated interferon and/or ribavirin, the researchers noted as background.

This randomized, double-blind, ascending-dose Phase I trial included 57 treatment-naive adults with genotype 1 chronic hepatitis C. Participants received R7128 plus R7227 oral combination therapy for up to 14 days.

Groups A and B received low dose monotherapy with either 500 mg R7128 every 12 hours (group A, n=8) or 100 mg low-dose R7227 every 8 hours (group B, n=9) on days 1-3. Both groups then received a combination of R7128 plus R7227 on days 4-7.

Groups C through F (8 active/2 placebo) received R7128 every 12 hours plus R7227 every 8 hours for 14 days at the following doses: 500 mg/100 mg, 1000 mg/100 mg, 500 mg/200 mg, and 1000 mg/200 mg.

The investigators evaluated safety, viral kinetics, resistance, and pharmacokinetics of R7128 plus R7227 in all groups. None of the participants received pegylated interferon or ribavirin.

Results

    Groups A through C (n = 27) completed the study with no treatment-related serious adverse events (SAEs), dose modifications, or discontinuations.

    Pharmacokinetic analysis confirmed no drug-drug interactions between R7128 and R7227.

    The mean decrease in HCV RNA from baseline was similar in Groups A and B at day 7.

    Overall, the mean change in HCV RNA from baseline ranged from -4.8 to -5.2 log10 IU/mL using the highest doses tested.

    The combination of R7128 plus R7227 provided greater than additive antiviral activity.

    No viral rebound (sustained viral load increase > 0.5 log10) was observed.

    Approximately 63% of patients experienced a decrease in HCV RNA to below the quantification limit of the diagnostic assay.

    25% of patients in the highest dose groups had undetectable HCV in their blood after 14 days.

These findings led the investigators to conclude, "The orally administered combination of low dose R7128 and R7227 provided significant antiviral potency, suppressed viral rebound, and appears safe and well-tolerated for 14 days."

"These results confirm for the first time that a protease and nucleoside polymerase inhibitor can be combined in vivo, and remain a promising combination for future treatment," they added

A press release from Roche announced that Roche, InterMune, and Pharmasset -- the 3 companies collaborating on development of this combination regimen -- are now exploring twice-daily dosing of R7227 and higher total daily doses (600 mg twice-daily and 900 mg twice-daily) than those used in the INFORM-1 study.

In addition to clinical trials of combination direct-acting antiviral regimens such as those studied in INFORM-1, R7227 and R7128 are each "proceeding rapidly in development" in combination with Roche's pegylated interferon alfa-2a (Pegasys) plus ribavirin (Copegus), the announcement stated. A Phase 2b study with R7128 is now underway, while a Phase 2b study with R7227 is slated to begin this summer.

Auckland Clinical Studies, Auckland, New Zealand; Alfred Hospital, Melbourne, Victoria, Australia; Christchurch Clinical Studies, Christchurch, New Zealand; Austin Hospital, Heidelberg, Victoria, Australia; Royal Adelaide Hospital, Adelaide, Australia; Roche Palo Alto LLC, Palo Alto, CA; Pharmasset, Inc., Princeton, NJ; Intermune, Inc., Brisbane, CA.

4/28/09

Reference
EJ Gane, SK Roberts, C Stedman, and others. First-In-Man Demonstration of Potent Antiviral Activity with a Nucleoside Polymerase (R7128) and Protease (R7227/ITMN-191) Inhibitor Combination in HCV: Safety, Pharmacokinetics, and Virologic Results from INFORM-1. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009. Late-breaker Abstract 1046.

Other Source
Roche Laboratories. Ground-breaking Combination of All-oral Agents Demonstrates Potential as Hepatitis C Treatment Regimen. Press Release. April 25, 2009.

mdjcwc

411老师，不好意思，LF和HCV是什么意思呀？