患有慢性乙型肝炎病毒感染的肾功能受损患者在低剂量TDF时

StephenW

Renally-Impaired Patients with Chronic Hepatitis B Virus Infection Find Success with Low Dose of TDF
DECEMBER 06, 2018
Danielle Mroz, MA
A low dose of tenofovir disoproxil fumarate (TDF) may help to preserve renal function and maintain viral suppression in patients with chronic hepatitis B virus infection, even those with advanced liver disease, according to new research.

TDF (Viread, Gilead) is currently approved for the treatment of chronic hepatitis B virus infection in adults and pediatric patients who are 12 years and older. Although the treatment is effective in inhibiting hepatitis B virus replication, it can cause renal impairment. To this end, investigators led by Dr. Kin Seng Liem from the Toronto Centre for Liver Disease and the University Health Network in Toronto, Ontario, Canada, studied renal function and viral breakthrough in a group of 739 patients from a North American hospital who were renally-impaired and treated with TDF. The investigators compared outcomes for those patients on a reduced dose of TDF (due to GFR [Cockcroft-Gault] <50mL/min/1.73m2 ± serum phosphate <0.8mmol/L) with outcomes for patients on a full dose.

A total of 67 patients (9%) were on a reduced dose of TDF and 672 (91%) were on the full dose. The mean age of the patients at baseline was 68 (standard deviation [SD] = 11 years) for those on a reduced dose of TDF versus those on the full dose (45; SD = 13 years). Furthermore, patients on the reduced dose were predominantly male (63%), and had a mean duration of 3 years (SD = 2 years) on TDF, versus the patients on the full dose who were 70% male and had a mean duration of 5 years (SD = 3 years on TDF.

Baseline hepatitis B virus DNA for the low-dose patients was 1.4log (71% undetectable). A total of 75% of patients received TDF doses of 300mg every 48 hours (range 75mg-300mg Q48hr). The mean Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) was 50ml (20ml), and 22% of the patients had hypophosphatemia. A total of 46% had chronic kidney disease stage G3b or worse and 14% had decompensated cirrhosis, according to the study abstract.

All patients across both study groups maintained viral suppression through a mean 3 years of follow-up (SD = 2 years), except for 1 patient who was on a full dose of TDF, who experienced viral breakthrough, but subsequently resolved naturally, and 1 patient who was on dialysis and taking TDF 300mg per week. That patient experienced viral breakthrough (HBV DNA peak 3.6 log) which resolved 4 months after the dosing was increased to Q72 hours without decompensation. Another patient on a reduced dose experienced a transient ALT increase (peak 2x ULN; however, they did not experience a rise in hepatitis B virus DNA, according to the study abstract.

The decline in CKD-EPI observed in patients on the full dose of TDF reversed in “the first year of lower dosing and remained stable thereafter (+2.0 (13) mL at EOF vs baseline; P = .28), with 50 (75%) patients reaching CKD-EPI>50mL and 11/15 (73%) patients normalizing serum phosphate,” study authors wrote.

Based on these results, the study investigators concluded that a lower dose of TDF could be used in patients with chronic hepatitis B virus infection who are renally-impaired, particularly those who are in resource-limited settings.

The study, “Low Dose Tenofovir Disoproxil Fumarate Improves Kidney Function and Sustains Virologic Suppression in Renally Compromised Chronic Hepatitis B Patients,” was presented at the 2018 American Association for the Study of Liver Diseases (AASLD) Liver Meeting, November 9-13, 2018, in San Francisco, California.

StephenW

患有慢性乙型肝炎病毒感染的肾功能受损患者在低剂量TDF时获得成功
2018年12月6日
Danielle Mroz，MA
根据一项新的研究，低剂量的替诺福韦地索普西富马酸盐（TDF）可能有助于保护慢性乙型肝炎病毒感染患者的肾功能和维持病毒抑制，即使患有晚期肝病的患者也是如此。

TDF（Viread，Gilead）目前被批准用于治疗12岁及以上成人和儿科患者的慢性乙型肝炎病毒感染。尽管该治疗有效抑制乙型肝炎病毒复制，但它可引起肾功能损害。为此，由多伦多肝病中心和加拿大安大略省多伦多大学健康网络的Kin Seng Liem博士领导的研究人员研究了一组来自北美医院的739名患者的肾功能和病毒突破。肾功能受损并接受TDF治疗。研究人员比较了减少剂量的TDF患者的结果（由于GFR [Cockcroft-Gault] <50mL / min / 1.73m2-血清磷酸盐<0.8mmol / L）与全剂量患者的结果。

共有67名患者（9％）接受TDF剂量减少，672名（91％）接受全剂量治疗。对于那些减少TDF剂量的患者，与基于完全剂量的患者（45; SD = 13年）相比，基线患者的平均年龄为68（标准差[SD] = 11年）。此外，减少剂量的患者主要是男性（63％），TDF平均持续时间为3年（SD = 2年），而全剂量患者为70％男性，平均持续时间为5年（SD = TDF 3年。

低剂量患者的基线乙型肝炎病毒DNA为1.4log（71％检测不到）。总共75％的患者每48小时接受300mg的TDF剂量（范围75mg-300mg Q48hr）。平均慢性肾病流行病学合作（CKD-EPI）为50ml（20ml），22％的患者患有低磷血症。根据研究摘要，共有46％患有慢性肾病G3b期或更严重，14％患有失代偿期肝硬化。

两个研究组的所有患者通过平均3年的随访（SD = 2年）维持病毒抑制，除了1名患有全剂量TDF的患者，其经历病毒突破，但随后自然消退，1接受透析并每周服用TDF 300mg的患者。该患者经历了病毒突破（HBV DNA峰值3.6log），其在给药后4个月消退，在没有失代偿的情况下增加至Q72小时。根据该研究摘要，另一名服用减量剂量的患者出现短暂的ALT升高（峰值2倍ULN;然而，他们没有经历乙型肝炎病毒DNA的升高。

在全剂量TDF患者中观察到的CKD-EPI下降在“低剂量给药的第一年逆转并且此后保持稳定（EOF +基线为+2.0（13）mL; P = .28），50（75）研究作者写道，患者达到CKD-EPI> 50mL，11/15（73％）患者血清磷酸盐正常化。

基于这些结果，研究调查人员得出结论，较低剂量的TDF可用于慢性乙型肝炎病毒感染的人，这些人患有肾功能受损，特别是那些资源有限的患者。

这项研究，“低剂量替诺福韦地索普西富马酸改善肾功能并维持肾功能不全的慢性乙型肝炎患者的病毒抑制”，于2018年11月9日至13日在2018年美国肝病研究协会（AASLD）肝病会议上发表。 ，在加利福尼亚州旧金山。