- Open Access
Sofosbuvir-based regimen is safe and effective for hepatitis C infected patients with stage 4–5 chronic kidney disease: a systematic review and meta-analysis
Virology Journal volume 16, Article number: 34 (2019)
Whether sofosbuvir is suitable for hepatitis C virus (HCV) infected patients with severe renal impairment is inconclusive. This systematic review aims to evaluate the safety and effectiveness of SOF-based regimen in the setting of stage 4 and 5 chronic kidney disease (CKD).
We conducted a systematic literature search in PubMed, Web of Science, EMBASE and Google Scholar with searching strategy: (sofosbuvir OR Sovaldi OR Harvoni OR Epclusa OR Vosevi) AND (severe kidney impairment OR severe renal impairment OR end-stage renal disease OR dialysis OR renal failure OR ESRD OR renal insufficiency OR hepatorenal syndrome OR HRS). Sustained virological response (SVR12/24) rate and serious adverse event (SAE) rate with 95% confidence intervals were aggregated. Subgroup analysis was implemented to evaluate the impact of treatment strategy and patient characteristics.
Twenty-one studies met inclusion criteria, totaling 717 HCV infected patients with CKD stage 4 or 5 (58.4% on dialysis). Pooled SVR12/24 was 97.1% (95% CI 93.9–99.3%), and SAE rate was 4.8% (95% CI 2.1–10.3%). There was no significant difference at SVR12/24 (97.1% vs 96.2%, p = 0.72) or SAE rate (8.8% vs 2.9%, p = 0.13) between subgroups applying full or decreased dose of sofosbuvir. Cirrhotic and non-cirrhotic patients achieved comparable sustained virological response (RR 0.93, 95% CI 0.85–1.02). Four studies reported eGFR/serum creatinine pre- and post- treatment, with no significant modification.
Our study suggests SOF-based regimen might be used safely and effectively in patients living with HCV infection/stage 4–5 CKD, with normal and reduced dose of sofosbuvir. Prospective and well-controlled trials are needed to confirm these findings.
Hepatitis C virus (HCV) infection and chronic kidney disease (CKD) are epidemically correlated and clinically challenging.
It’s estimated that 71 million people were chronically infected with HCV globally, and around 10% of them live with CKD [1, 2]. For patients with CKD, particularly patients receiving hemodialysis, the incidence of HCV is much higher than general population, ranging from 3 to 50% . HCV infection significantly elevates renal disease progression, and clearing HCV has proved to reduce liver related mortality/complications as well as risk of HCV transmission, therefore, HCV cure is of great importance to the patients with dual burden [4,5,6].
Sofosbuvir, a nonstructural NS5B polymerase inhibitor, was approved in 2013 and has revolutionized HCV treatment, enhancing the cure bar to above 90% [7,8,9]. Sofosbuvir is mainly eliminated through renal pathway, and its use in patients with stage 4 and 5 CKD, defined according to KDIGO guidelines (GFR < 30 mL/min/1.73 m2), is not indicated in label [10, 11]. EASL Recommendations on Treatment of Hepatitis C 2018 suggested that sofosbuvir should be used with caution in patients with an eGFR< 30 ml/min/1. 73m2 or with end-stage renal disease, only if alternative treatment is not available . AASLD Guidance: Recommendations for testing, managing and treating hepatitis C mentioned the safe and effective dose of sofosbuvir in persons with an eGFR< 30 ml/min have not been established. However, there is accumulating evidence on use of sofosbuvir-based regimen in those with an eGFR< 30 ml/min . Therefore, we performed a systematic review and meta-analysis to evaluate the safety and effectiveness of SOF-containing therapy for this group of patients.
Literature search strategy
We followed PRISMA (Preferred reporting items for systematic review and meta-analyses) statement guidelines to conduct this study . Systematic literature search in PubMed, EMBASE, Web of science, and Google Scholar was performed by two reviewers independently, without publishing date or language limitation. The searching strategy used was: (sofosbuvir OR Sovaldi OR Harvoni OR Epclusa OR Vosevi) AND (severe kidney impairment OR severe renal impairment OR end-stage renal disease OR dialysis OR renal failure OR ESRD OR renal insufficiency OR hepatorenal syndrome OR HRS). References listed in these literatures were also reviewed. Literature search was lastly updated on August 2018.
Studies were included when following criteria was met:
Subject: HCV patients with stage 4 or 5 chronic kidney disease.
Intervention: SOF-based regimen.
Publication: articles, abstracts or letters.
Patients with normal kidney function or early stage (1–3) CKD.
Number of enrolled patients or number of patients 12 weeks after treatment completion less than 10.
Insufficient data on SVR12/24, which is defined as undetectable HCV RNA 12 weeks (SVR12) or 24 weeks (SVR24) after treatment completion .
Insufficient HCV treatment combination information.
Two authors independently extracted data of study design, patients demographics and characteristics, treatment strategy, SVR12/24, renal function, SAE, discontinuation due to AE. Disagreement was resolved by consensus.
Newcastle-Ottawa scale (NOS) was applied to evaluate the quality and risk of bias of each study by two authors . Studies were judged on three aspects, namely selection of study groups, the comparability of the groups and the exposure or outcome of participants. A score system was used for quality assessment in which a cumulative 7–9 score indicates high quality, 4–6 as fair quality.
SVR12/24 rate, SAE rate were combined and assessed by fixed effect model/random effect model via R software. Heterogeneity among studies was evaluated by I2 index, with value > 50 implying substantial heterogeneity . Fixed effect model was applied in the absence or minor heterogeneity, and random effect model was adopted for significant heterogeneity . Comparison was made in subgroup analysis between studies that adopted full dose and decreased dose of sofosbuvir, RBV-containing and RBV-free regimen, studies that enrolled dialysis-dependent and dialysis-independent patients, as well as studies of different geographic origin. The relative risk (RR) with 95% CI was used to examine the impact of cirrhosis status to sustained virological response. We conducted sensitivity analysis to examine the robustness of primary findings. Publication bias was assessed by the Egger test for funnel plots asymmetry.
A total of 496 literatures were identified after preliminary search. Four hundred forty-two were excluded for duplication or irrelevancy. After further judgement by inclusion/exclusion criteria, final 21 studies were included for our review and meta-analysis, and IRB approval information were reported in 12 studies. Figure 1 shows the process of literature review and selection.
Studies and patients’ characteristics
Twenty-one studies included manuscripts (n = 13), abstracts (n = 6) and letters (n = 2). All of them were prospective or retrospective cohort studies, with NOS score ranging 4–5 (two literatures scored 3). The absence of high quality is mainly due to absence of control arm. All of the studies met the inclusion criteria while one study enrolled patients with eGFR< 35 mL/min/1.73 m2 .
In total 717 patients were enrolled, including 419 (58.4%) hemodialysis or peritoneal dialysis recipients. Patients’ characteristics were shown in Table 1. Mean/median age ranged from 35 to 62 among studies. Eighteen studies provided genotype information, overall GT 1 was predominant genotype (67%), followed by GT 3 (20%) and GT2 (8%). Cirrhotic patient was eligible for most studies, and 4 studies included patients with decompensated cirrhosis. SOF-based regimen included: SOF + SMV ± RBV, SOF + PR, SOF + RBV, SOF + DCV ± RBV and SOF/LDV ± RBV, with varied administration of sofosbuvir: 400 mg daily (QD), 200 mg QD, 400 mg/48 h, 400 mg three times a week (TIW). Dose of sofosbuvir during treatment was rarely adjusted, except 2 patients increased from 200 mg QD to 400 mg QD after 4–6 weeks, and 3 reduced dosing due to sepsis, digestive discomfort or headache.
Sustained virological response
Per protocol (PP) analysis set was applied for sustained virological response analysis. The pooled SVR12/24 rate was 97.1% with random effect model (95% CI 93.9–99.3%, I2 = 61%) (Fig. 2). By aggregating dialysis-dependent patients (n = 306) and the others who were not on dialysis (n = 88) based on data available, we found significant difference of SVR12/24 between these two groups (95.1% vs 100%, p = 0.019). (Additional file 1: Figure S1).
Studies with full sofosbuvir dose (400 mg QD) or decreased dose were compared for subgroup analysis. The difference between full dose (97.1, 95% CI: 92.1–99.9%) and decreased dose (96.2, 95%CI: 88.3–100%) was not significant (p = 0.72) (Additional file 2: Figure S2). Studies that applied single therapy of decreased-dose of sofosbuvir (i.e. 200 mg QD or 400 mg/48 h or 400 mg TIW) were further selected and compared, concluding that 200 mg QD and 400 mg/48 h demonstrated similar treatment effect on total population (100% vs 97.7%, p = 0.30) (Additional file 3: Figure S3) [19,20,21,22,23,24,25]. For patients on dialysis, SVR12/24 was also comparable among varied doses of sofosbuvir (p = 0.25) (Additional file 4: Figure S4) [19,20,21,22, 24,25,26,27,28,29,30]. Ten studies adopted RBV-free regimen (SOF/LDV, SOF + DCV, SOF + SMV) with pooled SVR12/24 99.1% (95% CI: 96.2–100%), higher than that of studies using RBV-containing therapy (94.0%,95 CI: 87.5–98.6%) (p = 0.035). Seven studies provided sufficient data for comparison between patients with or without cirrhosis [21,22,23, 29, 31,32,33]. Non-cirrhotic patients trended to have higher sustained virological response, while there was no significant difference between these two subgroups (RR 0.93, 95% CI 0.85–1.02, I2 = 33%) (Fig. 3).
Most of the studies in this analysis originated from Asia and Norther America, and the pooled SVR12/24 was comparable among different regions (p = 0.15) (Additional file 5: Figure S5).
Serious adverse event
Information of SAE rate was provided in 16 studies, of which the pooled incidence was 4.8% (95% CI 2.1–10.3%, I2 = 60.0%) (Fig. 4). SAE occurred in 5 studies, and 4 provided case description (Table 2). Subgroup analysis was conducted for studies with full dose and decreased-dose sofosbuvir, resulting no significant difference (8.8% vs 2.9%, P = 0.13).
Change in renal function
Four studies reported the dynamic of kidney function [18, 22, 34, 35], with detailed data before and after treatment (Table 3). Generally, eGFR was stable during treatment, and 2 cases reported discontinuation from hemodialysis due to eGFR improvement .
SVR12/24 of 13 manuscripts (PP analysis set) was aggregated, with pooled result of 97.0% (95% CI: 92.4–99.7%, I2 = 66%). 90.3% SVR12/24 (95% CI: 83.4–95.6%, I2 = 84%) was resulted in intention to treat (ITT) analysis set for 21 studies. Not reaching SVR12 time point and lost follow-up were two major reasons for relative lower result in ITT analysis set.
P value of Egger test for funnel plots asymmetry was not significant for ITT analysis set (0.537), and bordered significance level for PP analysis set (0.0498).
Patients living with HCV infection and end-stage renal disease (ESRD) are special population for HCV treatment. Although current guidelines recommend the first-line therapies as elbasvir/grazoprevir, glecaprevir/pibrentasvir, paritaprevir/ ritonavir/ombitasvir/dasabuvir (PrOD) [12, 13], unmet medical needs still exist at some cases (e.g. comorbidity of advanced liver disease, non-GT1 genotype) and when other therapies are not available. In these circumstances, sofosbuvir might be applied after weighing risk and benefit. In vivo, sofosbuvir undergoes intra-hepatic metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which eventually results in ultimate metabolite GS-331007 via dephosphorylation . Sofosbuvir and GS331007 are mainly eliminated through kidney. Compared with subjects of normal renal function, area under the curve (AUC0-inf) of sofosbuvir and GS-331007 is 171 and 451% higher for patients with eGFR< 30 ml/min (not receiving hemodialysis) . Desnoyer examined plasma concentrations of sofosbuvir (full dose) and GS331007 on hemodialysis patients and concluded they did not accumulate throughout the treatment course and between hemodialysis sessions . Whether sofosbuvir and its metabolite accumulate in ESRD patients who are not on dialysis needs to be answered by further study.
Our meta-analysis included 21 studies, with a total of 717 patients. Pooled SVR12/24 was satisfying (97.1%), similar or higher than that of non-SOF-based therapies [37,38,39]. Patients who were on dialysis also achieved a SVR12/24 as high as 95.1%. Although it was lower than that of patients without dialysis, we assume it might not necessarily be the case given limited number of dialysis-free patients in our sub-analysis. Further well-designed RCT are needed to conclude whether effect of sofosbuvir is influenced by dialysis. Aggregated SAE rate was 4.8%, slightly higher than that in HCV infected patients with normal renal function [8, 9], which is reasonable since the patients involved in our meta-analysis had quite a few safety risk factors: old age, severe renal dysfunction, liver/renal transplant recipient, and advanced liver fibrosis. In another meta-analysis, SAE rate was 12.1% for direct-acting antivirals-based antiviral therapies in HCV/Stage 4–5 CKD patients . Common SAEs included renal failure, cirrhosis complications, indicating special attention is needed on renal and liver function during treatment (Table 2).
Treatment strategy of SOF-containing therapy has been under broad discussion. Many physicians explored unconventional dose of sofosbuvir for safety concern, although there is no established pharmacokinetics profile for administration at 200 mg QD, 400 mg/48 h or 400 mg three times a week. Our subgroup analysis suggests that regimen with full and decreased dose of sofosbuvir might be both considerable at acceptable SAE rate (8.8% vs 2.9%) and high SVR12/24 (97.1% vs 96.2%). We assume that sofosbuvir could be alternatively applied at a lower dose as half as normal or at a frequency extended to once every 2 days without compromising its efficacy significantly. While administering three times a week might not be optimal, given that median terminal half-lives of sofosbuvir and its metabolite GS331007 were 0.4 and 27 h (healthy subjects), and possible low SVR12/24 (60% reported in very small sample size) . Ribavirin should be used with caution, considering higher risk of anemia for RBV-containing regimen than RBV-free treatment. Anemia was the most frequently reported AE (6 to 43.7%) in studies of our review, and RBV was included in almost all of these studies (8/9). Manoj reported that 65.4% (17/26) patients in SOF + RBV group developed anemia, and 30% had to discontinue ribavirin . What is worth mentioning is that we found RBV-containing regimen reached lower SVR12/24. One of the reasons is likely to be tolerability issue of ribavirin, another reason might be potent combination drug with sofosbuvir in most RBV-free regimen, 9 studies applied SOF/LDV or SOF + DCV, and 7 achieved 100% SVR12/24.
Kidney function deterioration is a concern for sofosbuvir usage. On one hand, there are few case reports proposed the correlation of nephrotoxicity and SOF-based therapy [41, 42], on the other hand, several large retrospective cohorts conclude SOF-based regimen does not introduce higher acute kidney injury for HCV patients compared to SOF-free treatment [43, 44]. Studies that reported renal function in our review had generally stable eGFR and serum creatinine during treatment. Two SAE cases of AKI and acute renal failure were considered not related to study drug.
There are some limitations to our study. First, we could not perform subgroup analysis according to HCV genotype, CKD stage for lack of enough information. Second, geographical origin of studies enrolled is mainly USA and India, and that limits the representativeness of our analysis. Third, all of the studies were observational studies without control group, and most studies were of medium quality. Heterogeneity was substantial which might attribute to varied sample size and treatment therapy. Furthermore, some newly approved SOF-based therapy (e.g. SOF/VEL) was not included in this analysis for lack of evidence and analysis time frame. The factors above compromise the quality of this review. Prospective and well-controlled studies are expected in near future to provide more robust evidence.
This systematic review and meta-analysis evaluated SOF-based therapy for HCV infected patients with comorbidity of stage 4–5 CKD. Data from this study suggests satisfying sustained virological response and tolerance. For treatment strategy, both full and decreased dose of sofosbuvir could be appropriate. Caution is still needed at clinical practice.
Acute kidney injury
Chronic kidney disease
End-stage renal disease
Glomerular filtration rate
Hepatitis C virus
Intention to treat
Kidney Disease Improving Global Outcomes
Model for end-stage liver disease
Preferred reporting items for systematic reviews and meta-analyses
Serious adverse event
Sustained virological response
Three times a week
Kasuno K, Ono T, Matsumori A, Nogaki F, Kusano H, Watanabe H, Yodoi J, Muso E. Hepatitis C virus-associated tubulointerstitial injury. Am J Kidney Dis. 2003;41(4):767–75.
WHO. GUIDELINES FOR THE CARE AND TREATMENT OF PERSONS DIAGNOSED WITH CHRONIC HEPATITIS C VIRUS INFECTION. 2018.
Fissell RB, Bragg-Gresham JL, Woods JD, Jadoul M, Gillespie B, Hedderwick SA, Rayner HC, Greenwood RN, Akiba T, Young EW. Patterns of hepatitis C prevalence and seroconversion in hemodialysis units from three continents: the DOPPS. Kidney Int. 2004;65(6):2335–42.
Fabrizi F, Dixit V, Messa P. Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality? J Viral Hepat. 2012;19(9):601–7.
Fabrizi F, Takkouche B, Lunghi G, Dixit V, Messa P, Martin P. The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies. J Viral Hepat. 2007;14(10):697–703.
Lee JJ, Lin MY, Chang JS, Hung CC, Chang JM, Chen HC, Yu ML, Hwang SJ. Hepatitis C virus infection increases risk of developing end-stage renal disease using competing risk analysis. PLoS One. 2014;9(6):e100790.
Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889–98.
Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, et al. Sofosbuvir and Velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373(27):2599–607.
Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, Schultz M, Davis MN, Kayali Z, Reddy KR, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878–87.
Isakova T, Nickolas TL, Denburg M, Yarlagadda S, Weiner DE, Gutierrez OM, Bansal V, Rosas SE, Nigwekar S, Yee J, et al. KDOQI US commentary on the 2017 KDIGO clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Am J Kidney Dis. 2017;70(6):737–51.
Gilead. sovaldi_pi. 2017.
European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018;69(2):461–511.
AASLD, IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. 2018.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.
Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses; 2016.
Ryan R. Heterogeneity and subgroup analyses in Cochrane Consumers and Communication Review Group reviews: Planning the analysis at protocol stage; 2014.
Petitti DB. Approaches to heterogeneity in meta-analysis. Stat Med. 2001;20(23):3625–33.
Dumortier J, Bailly F, Pageaux GP, Vallet-Pichard A, Radenne S, Habersetzer F, Gagnieu MC, Grange JD, Minello A, Guillaud O, et al. Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure. Nephrol Dial Transplant. 2017;32(12):2065–71.
Aggarwal A, Yoo ER, Perumpail RB, Cholankeril G, Kumari R, Daugherty TJ, Lapasaran AS, Ahmed A. Sofosbuvir use in the setting of end-stage renal disease: a single center experience. J Clin Transl Hepatol. 2017;5(1):23–6.
Bera C, Das P, Pal S. Safety and efficacy of Sofosbuvir based regimen on patients with end stage renal disease—a single Centre experience. J Clin Exp Hepatol. 2017;7:S29. https://doi.org/10.1016/j.jceh.2017.05.061
Choudhary NS, Kumar A, Bodh V, Bansal SB, Sharma R, Jain M, Saigal S, Saraf N. Efficacy and safety of sofosbuvir-based regimens in chronic hepatitis C patients on dialysis. Indian J Gastroenterol. 2017;36(2):113–6.
Taneja S, Duseja A, De A, Mehta M, Ramachandran R, Kumar V, Kohli HS, Gupta KL, Dhiman RK, Chawla Y. Low-dose Sofosbuvir is safe and effective in treating chronic hepatitis C in patients with severe renal impairment or end-stage renal disease. Dig Dis Sci. 2018;63(5):1334–40.
Goel A, Bhadauria DS, Kaul A, Verma P, Mehrotra M, Gupta A, Sharma RK, Rai P, Aggarwal R. Daclatasvir and reduced-dose sofosbuvir: an effective and pangenotypic treatment for hepatitis C in patients with eGFR <30 ml/min. Nephrology (Carlton). 2019 Mar;24(3):316–21. https://doi.org/10.1111/nep.13222.
He Y, Chen T, Zhao Y. Safety, efficacy and tolerance of half-dose sofosbuvir plus daclatasvir in treatment of acute hepatitis C infection in patients with end-stage renal disease on hemodialysis: a prospective, single-center, open-label study. Hepatology. 2017;66:583A.
Surendra M, Raju SB, Sridhar N, Vijay Kiran B, Rajesh G, Anvesh G, Raju N. Ledipasvir and Sofosbuvir for untreated HCV genotype 1 infection in end stage renal disease patients: a prospective observational study. Hemodial Int. 2018;22(2):217–21.
Akhil MS, Kirushnan B, Martin M, Arumugam K, Ganesh Prasad NK, Ravichandran R. Sofosbuvir-based treatment is safe and effective in Indian hepatitis C patients on maintenance haemodialysis: a retrospective study. Nephrology (Carlton). 2018;23(5):446–52.
Beinhardt S, Al Zoairy R, Ferenci P, Kozbial K, Freissmuth C, Stern R, Stattermayer AF, Stauber R, Strasser M, Zoller H, et al. DAA-based antiviral treatment of patients with chronic hepatitis C in the pre- and postkidney transplantation setting. Transpl Int. 2016;29(9):999–1007.
Manoj K, Nayak SL, Gupta E, Kataria A, Sarin SK. Generic sofosbuvir-based direct-acting antivirals in hepatitis C virus-infected patients with chronic kidney disease. Liver Int. 2018;38:2137–48.
Nazario HE, Modi AA, Ndungu M, Ramirez R, Tujague L, Weinstein JS. Excellent cure rates in largest ESRD patient cohort who completed treatment with full dose, daily sofosbuvir-based regimens. J Hepatol. 2017;66(1):S507. https://doi.org/10.1016/S0168-8278(17)31414-9
Saab S, AJ M, NB S, Choi G, Durazo FA, ME-K M, Han SB, Busuttil RW. Use of Sofosbuvir-based treatment of chronic hepatitis C in liver transplant recipients on hemodialysis. J Clin Gastroenterol. 2017;51(2):167–73.
Bhamidimarri KR, Czul F, Peyton A, Levy C, Hernandez M, Jeffers L, Roth D, Schiff E, O'Brien C, Martin P. Safety, efficacy and tolerability of half-dose sofosbuvir plus simeprevir in treatment of hepatitis C in patients with end stage renal disease. J Hepatol. 2015;63(3):763–5.
Desnoyer A, Pospai D, Le MP, Gervais A, Heurgue-Berlot A, Laradi A, Harent S, Pinto A, Salmon D, Hillaire S, et al. Pharmacokinetics, safety and efficacy of a full dose sofosbuvir-based regimen given daily in hemodialysis patients with chronic hepatitis C. J Hepatol. 2016;65(1):40–7.
Lawitz E, Landis CS, Maliakkal BJ, Bonacini M, Ortiz-Lasanta G, Zhang J, Mogalian E, De-Oertel S, Osinusi AO, Brainard DM, et al. Safety and Efficacy of Treatment with Once-Daily Ledipasvir/Sofosbuvir (90/400 mg) for 12 Weeks in Genotype 1 HCV-Infected Patients with Severe Renal Impairment. Hepatology. 2017;66-1(Suppl 1587):848A.
Gordon SC, Ahmed A, Saab S, Dieterich DT, Wong RJ, Kugelmas M, Brown KA, Younossi ZM. Health Outcomes Associated with Sofosbuvir-based Single-Tablet Regimens for Initial and Re-treatment of Chronic Hepatitis C in the US. Hepatology. 2017;66-1(Suppl 1181):635A.
Cox-North P, Hawkins KL, Rossiter ST, Hawley MN, Bhattacharya R, Landis CS. Sofosbuvir-based regimens for the treatment of chronic hepatitis C in severe renal dysfunction. Hepatol Commun. 2017;1(3):248–55.
McQuaid T, Savini C, Seyedkazemi S. Sofosbuvir, a significant paradigm change in HCV treatment. J Clin Transl Hepatol. 2015;3(1):27–35.
Miyazaki R, Miyagi K. Effect and safety of Daclatasvir-Asunaprevir combination therapy for chronic hepatitis C virus genotype 1b -infected patients on hemodialysis. Ther Apher Dial. 2016;20(5):462–7.
Pockros PJ, Reddy KR, Mantry PS, Cohen E, Bennett M, Sulkowski MS, Bernstein DE, Cohen DE, Shulman NS, Wang D, et al. Efficacy of direct-acting antiviral combination for patients with hepatitis C virus genotype 1 infection and severe renal impairment or end-stage renal disease. Gastroenterology. 2016;150(7):1590–8.
Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, Martin P, Pol S, Londono MC, Hassanein T, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015;386(10003):1537–45.
Li T, Qu Y, Guo Y, Wang Y, Wang L. Efficacy and safety of direct-acting antivirals-based antiviral therapies for hepatitis C virus patients with stage 4-5 chronic kidney disease: a meta-analysis. Liver Int. 2017;37(7):974–81.
Gadde S, Lee B, Kidd L, Zhang R. Antineutrophil cytoplasmic antibodies crescentic allograft glomerulonephritis after sofosbuvir therapy. World J Nephrol. 2016;5(6):547–50.
Wanchoo R, Thakkar J, Schwartz D, Jhaveri KD. Harvoni (Ledipasvir with Sofosbuvir)-induced renal injury. Am J Gastroenterol. 2016;111(1):148–9.
Durand F, Pianko S, Ni L, De-Oertel S, McNally J, Brainard DM, McHutchison JG, Schiff ER, Colombo M. Safety of Sofosbuvir-Based Regimens for the Treatment of Chronic HCV Infection in Patients with Mild or Moderate Renal Impairment. Hepatology. 2016;64-1(Suppl 867):428A.
Telep L, Brown A, Brainard DM, Chokkalingam AP. Assessment of risk of acute kidney injury associated with exposure to sofosbuvir-containing HCV treatment regimens and HCV infection. Hepatology. 2016;64-1(Suppl 770):380A.
Butt AA, Ren Y, Puenpatom A, Arduino JM, Kumar R, Abou-Samra AB. Effectiveness, treatment completion and safety of sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir + dasabuvir in patients with chronic kidney disease: an ERCHIVES study. Aliment Pharmacol Ther. 2018;48(1):35–43.
Mehta R, Desai K, Kabrawala M, Nandwani S, Shah J, Desai N, Parekh V. Preliminary experience with sofosbuvir-based treatment regimens for patients dependent on hemodialysis. Indian J Gastroenterol. 2018;37(1):72–3.
Saxena V, Koraishy FM, Sise M, Lim JK, Chung RT, Liapakis A, Nelson DR, Schmidt M, Fried MW, Terrault N. LP08 : Safety and efficacy of sofosbuvir-containing regimens in hepatitis C infected patients with reduced renal function: Real-world experience from HCV-target. J Hepatol. 2015;62:S267. https://doi.org/10.1016/S0168-8278(15)30162-8
We would like to thank Dr. Jia, Mr. Wong, Mr. Xia and Mr. Lu for helpful consultation and comments on this manuscript.
This study was not supported by any commercial company or grants. No Gilead funding supports it.
Availability of data and materials
The datasets supporting the conclusions of this article is included within the article and its additional files.
Ethics approval and consent to participate
Consent for publication
MSL works for Gilead while concurrently enrolled in Ph.D.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Figure S1. Forest plots showing the results of subgroup analysis result of SVR12/24 in dialysis-dependent patients and patients not receiving dialysis. (PDF 6 kb)
Figure S2. Forest plots showing the results of subgroup analysis result of SVR12/24 in studies applied full dose and decreased dose of sofosbuvir. (PDF 6 kb)
Figure S3. Forest plots showing the results of subgroup analysis result of SVR12/24 in studies applied 200 mg QD sofosbuvir or 400 mg/48 h sofosbuvir. (PDF 5 kb)
Figure S4. Forest plots showing the results of subgroup analysis result of SVR12/24 in dialysis-dependent patients applying different doses of sofosbuvir. (PDF 6 kb)
Figure S5. Forest plots showing the results of subgroup analysis result of SVR12/24 in patients originated from Asia, North America and Europe. (PDF 7 kb)
About this article
Cite this article
Li, M., Chen, J., Fang, Z. et al. Sofosbuvir-based regimen is safe and effective for hepatitis C infected patients with stage 4–5 chronic kidney disease: a systematic review and meta-analysis. Virol J 16, 34 (2019) doi:10.1186/s12985-019-1140-x
- HCV infection
- Stage 4–5 chronic kidney disease