Tmu Naveen, Kumar Ashish, Sharma Praveen, Singla Vikas, Bansal Naresh, Arora Anil
Institute of Liver, Gastroenterology, & Panceatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India.
J Clin Exp Hepatol. 2019 Jan-Feb;9(1):4-12. doi: 10.1016/j.jceh.2018.02.009. Epub 2018 Mar 6.
Sofosbuvir (SOF), a direct acting antiviral, has revolutionized the treatment of chronic Hepatitis C Virus (HCV) infection. However, data is scarce about efficacy of SOF plus Ribavarin (RBV) in Indian patients with decompensated cirrhosis. We evaluated the efficacy of SOF plus RBV in decompensated cirrhosis, and compared the outcome with compensated cirrhosis and non-cirrhotics.
Consecutive decompensated cirrhotic patients of chronic HCV with detectable HCV RNA were treated with 24-week course of SOF (400 mg) plus weight based RBV. Sustained Virological Response (SVR), Child Turcotte Pugh (CTP) and Model for Endstage Liver Disease (MELD) scores were assessed at 36 weeks (i.e. 12 weeks after completion of therapy). Non-cirrhotic chronic hepatitis C patients and patients with compensated cirrhosis treated with SOF plus RBV during the same period were used as controls. During the period of this study ledipasvir and daclatasvir were not available in India.
A total of 47 patients [median age 50 (29-82) years, 64% males] with decompensated cirrhosis were included as 'cases' in the study; while, 27 patients with compensated cirrhosis and 29 patients with chronic hepatitis were included as 'controls'. Age, gender, HCV RNA levels, and genotype distribution were similar in cases and controls. The median CTP and MELD scores of cases were 8 (7-12) and 13 (6-25), respectively. Among cases 39 (83%) could complete the therapy, while 1 (2%) was intolerant and 7 (15%) died before completion of therapy. End of Treatment Response (ETR) was achieved in 37/39 (95%) cases. Of these, another 3 died before SVR, and 7 failed to achieve SVR, thus 27/34 (79%) could achieve SVR. Thus according to intention-to-treat analysis, only 27/47 (57%) cases could achieve SVR. In comparison, 24/28 (86%) compensated cirrhotics and 27/28 (96%) of chronic hepatitis achieved SVR. There was a significant improvement in mean CTP score in cases who achieved SVR ( < 0.01) compared to those who did not achieve SVR/ETR. On multivariate analysis the only independent factor influencing successful outcome patients was a serum albumin >3.5 g/dL.
A 24-week course of SOF plus ribavirin in decompensated HCV cirrhosis could lead to SVR in only 57% of patients. The failure of therapy in 43% patients was either due to non-response, intolerance, or death. A serum albumin of more than 3.5 is associated with success of antiviral therapy. Thus an early initiation of antiviral therapy is recommended before decompensation sets in as it precludes successful outcome.
索磷布韦（SOF）是一种直接作用抗病毒药物，它彻底改变了慢性丙型肝炎病毒（HCV）感染的治疗方式。然而，关于索磷布韦联合利巴韦林（RBV）治疗印度失代偿期肝硬化患者的疗效数据却很匮乏。我们评估了索磷布韦联合利巴韦林治疗失代偿期肝硬化的疗效，并将结果与代偿期肝硬化患者和非肝硬化患者进行了比较。
连续纳入慢性HCV感染且HCV RNA可检测到的失代偿期肝硬化患者，接受为期24周的索磷布韦（400mg）联合基于体重的利巴韦林治疗。在治疗36周时（即治疗结束后12周）评估持续病毒学应答（SVR）、Child Turcotte Pugh（CTP）评分和终末期肝病模型（MELD）评分。同期接受索磷布韦联合利巴韦林治疗的非肝硬化慢性丙型肝炎患者和代偿期肝硬化患者作为对照。在本研究期间，来迪派韦和达卡他韦在印度无法获得。
共有47例失代偿期肝硬化患者[中位年龄50（29 - 82）岁，64%为男性]被纳入研究作为“病例组”；同时，27例代偿期肝硬化患者和29例慢性肝炎患者被纳入作为“对照组”。病例组和对照组在年龄、性别、HCV RNA水平和基因型分布方面相似。病例组的中位CTP评分和MELD评分分别为8（7 - 12）和13（6 - 25）。病例组中39例（83%）能够完成治疗，1例（2%）不耐受，7例（15%）在治疗结束前死亡。39例中的37例（95%）实现了治疗结束时应答（ETR）。其中，另外3例在获得SVR前死亡，7例未实现SVR，因此27/34（79%）能够实现SVR。因此，根据意向性分析，仅27/47（57%）的病例能够实现SVR。相比之下，24/28（86%）的代偿期肝硬化患者和27/28（96%）的慢性肝炎患者实现了SVR。与未实现SVR/ETR的患者相比，实现SVR的患者平均CTP评分有显著改善（P<0.01）。多因素分析显示，影响患者成功治疗结局的唯一独立因素是血清白蛋白>3.5g/dL。
索磷布韦联合利巴韦林治疗24周的失代偿期HCV肝硬化患者中，仅57%的患者可实现SVR。43%的患者治疗失败要么是由于无应答、不耐受，要么是死亡。血清白蛋白超过3.5与抗病毒治疗成功相关。因此，建议在失代偿发生前尽早开始抗病毒治疗，因为这可提高成功治疗结局的可能性。
