The Journal of Arthroplasty xxx (2018) 1e4
Contents lists available at ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Treatment for Chronic Hepatitis C Prior to Total Hip Arthroplasty Significantly Reduces Periprosthetic Joint Infection Hany S. Bedair, MD a, b, *, Brian M. Schurko, MD a, Maureen K. Dwyer, PhD a, b, David Novikov c, Afshin A. Anoushiravani, MD c, Ran Schwarzkopf, MD, MSc c a b c
Department of Orthopaedics, Massachusetts General Hospital, Boston, MA Kaplan Joint Center, Department of Orthopedics, Newton-Wellesley Hospital, Newton, MA Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, NY
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 August 2018 Received in revised form 7 September 2018 Accepted 10 September 2018 Available online xxx
Background: Patients with chronic hepatitis C (HCV) have had extremely high complication rates after total hip arthroplasty (THA). We sought to compare perioperative complication rates between untreated and treated HCV in THA patients and to compare these rates between patients treated with 2 different therapies (interferon vs direct antiviral agents). Methods: A multicenter retrospective database query was used to identify patients diagnosed with HCV who underwent THA between 2006 and 2016. All patients (n ¼ 105) identified were included and divided into 2 groups: untreated (n ¼ 63) and treated (n ¼ 42) HCV; treated patients were further subdivided into those receiving interferon (n ¼ 16) or direct antiviral agent therapies (n ¼ 26). Comparisons between the treated and untreated groups were made with respect to demographic data, comorbidities, preoperative viral load, Model for End-Stage Liver Disease score, and all surgical and medical complications; a subgroup analysis of the treated patients was also performed. Separate independent t-tests or Mann-Whitney U tests were conducted for continuous variables. Categorical variables were compared using the chi-squared test of independence. Results: A greater number of untreated patients were human immunodeficiency virus infected (P ¼ .01), while a reduced number of treated patients were either former or current smokers (P ¼ .004). The untreated group had greater surgical complication rates (25.4% vs 4.8%; P ¼ .007), with a higher rate of periprosthetic joint infection (14.3% vs 0%, P ¼ .01). For treated patients, no differences were observed between treatment types for postsurgical complications. Conclusion: Treatment for HCV prior to THA appears to be associated to fewer postoperative complications, primarily periprosthetic joint infection. Although further investigation is warranted, strong consideration should be given to treating patients for HCV prior to elective THA. © 2018 Elsevier Inc. All rights reserved.
Keywords: hepatitis C periprosthetic joint infection joint arthroplasty complications direct antiviral agents
Preoperative medical optimization and comorbidity management is recognized as a critical element in perioperative orthopedic care with a central role in avoiding complications for patients undergoing elective total hip or total knee arthroplasty [1]. Although there are many known risk factors that may lead to suboptimal outcomes after total joint arthroplasty (TJA) (eg, renal disease,
One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2018.09.036. * Reprint requests: Hany Bedair, MD, Department of Orthopaedics, Massachusetts General Hospital, 55 Fruit Street, Yawkey Building, Boston, MA 02114. https://doi.org/10.1016/j.arth.2018.09.036 0883-5403/© 2018 Elsevier Inc. All rights reserved.
cardiac disease, obesity, diabetes mellitus, malnutrition, and immunosuppressed states), only some are modifiable, such as diabetes mellitus, and few are reversible [2]. Chronic hepatitis C (HCV) infection is a risk factor for arthroplasty candidates that can lead to unacceptably high complication rates, including devastating periprosthetic joint infection (PJI) [3e7]. It is unknown whether chronic hepatitis C (HCV) is a reversible or modifiable risk factor for perioperative complications. Traditional treatment for chronic HCV has been interferon (IFN)based regimens which have had variable success in controlling this infection [8e10]. In addition to its inconsistent therapeutic effect, the high rate of unacceptable side effects has limited its use. In 2014, the US Food and Drug Administration approved for clinical use a group of oral medications termed direct antiviral agents
2
H.S. Bedair et al. / The Journal of Arthroplasty xxx (2018) 1e4
(DAA) [11]. The molecular target of this class of medications is the HCV replication life cycle. By disrupting viral replication, these pharmacologic agents have successfully provided a well-tolerated cure for hepatitis C at an exceptionally high rate. These medications typically consist of combination therapies such as ledipasvir/ sofosbuvir (Harvoni) or singular formulations such as sofosbuvir (Sovaldi) and are administered orally for approximately 12-24 weeks depending on the clinical situation [12]. One of the limiting factors preventing widespread use is its high cost, with a typical treatment course costing approximately more than $60,000 USD [13,14]. Currently, not all patients with HCV receive treatment for their disease. Although DAAs appear to be safe and effective, the high cost of treatment may limit access for many patients [15]. IFN treatments cost substantially less, but are often poorly tolerated and either abandoned prior to completion or never initiated due to the potential for adverse events. Complicating matters, there are no accepted standards for the treatment of HCV prior to elective surgery. There currently exists a large cohort of patients with chronic HCV who are aging into the sixth and seventh decade of life with failing hips who are seeking total hip arthroplasty (THA) [3,16]. Many will seek THA treatment without addressing their HCV infection, increasing their risk for perioperative complications [17,18]. The purpose of this multicenter retrospective cohort study is to investigate the following: (1) if patients treated for chronic HCV prior to primary THA experience lower overall perioperative complication rates compared to untreated patients undergoing the same procedure and (2) if there exists a difference in outcomes between patients treated with IFN or DAA-based therapies. Methods This study is a multicenter retrospective cohort study approved by the respective institutions. The institutional databases of each center were queried for patients with the diagnosis of HCV who underwent primary unilateral THA from January 2006 through December 2016. Each patient chart was manually reviewed by a trained member of each institution’s research team. All patients with chronic HCV were included (n ¼ 105); those patients who were exposed to the virus but did not become chronically infected were not included in our analysis. HCV THA recipients were divided into 2 cohorts: (1) untreated HCV at the time of THA (“Untreated HCV,” n ¼ 63) and (2) those who completed treatment prior to THA (“Treated HCV,” n ¼ 42). Patients who did not tolerate a complete treatment course were included in the Untreated HCV cohort (n ¼ 2). Those who had completed treatment and continued to have a detectable viral load (typically those treated with IFN) were included in the Treated HCV group. Patients in the Treated HCV group were then further categorized based on their treatment regimen (IFN or DAA). The variables of interest included basic demographic information including age, gender, and body mass index. Preoperative medical comorbidity data were also collected for all patients including diabetes status, human immunodeficiency virus (HIV) status, hypertension, hyperlipidemia, coronary artery disease, chronic renal disease, peripheral vascular disease, presence of hepatic fibrosis, and smoking status (current, former, or never). In addition, the most recent laboratory values (alanine aminotransferase, aspartate aminotransferase, bilirubin, international normalized ratio, albumin, creatinine, and serum sodium) prior to surgery were used to calculate a preoperative MELD (Model for End-Stage Liver Disease) score for each patient. Each patient’s preoperative viral load was also recorded. The primary outcome measures were perioperative complications. These were divided into surgical and medical complications.
Surgical complications recorded within the first year postoperatively were further subdivided into PJI, hematoma, persistent wound drainage, intraoperative fracture, postoperative fracture, aseptic implant loosening, and dislocation. The medical complications recorded within a 90-day perioperative period included pneumonia, urinary tract infection, sepsis, blood transfusions, deep vein thrombosis, pulmonary embolism, myocardial infarction, acute renal failure, gastrointestinal bleed, and death. Statistical comparisons were made between Untreated and Treated HCV THA recipients. Separate independent t-tests were conducted for dependent variables that were normally distributed, and Mann-Whitney U tests were conducted for variables which were not normally distributed. Categorical variables were compared using the chi-squared test of independence. Among treated patients, the different types of disease treatment (IFN vs DAA) were comparatively evaluated for the same outcome measures. All statistical analyses were performed using IBM SPSS v.23.0 (IBM Corporation, Armonk, NY). The level of statistical significance was set at P < .05. Results Of the 105 patients included in this analysis, 40% (42/105) were treated for HCV prior to THA, with 62% (26/42) of treated patients completing a DAA treatment course. The demographic data and medical comorbidities of the untreated and treated groups are reported in Table 1. The untreated cohort had more patients who were coinfected with HIV (19.0% vs 2.4%, P ¼ .01), but fewer patients who were never smokers (12.7% vs 40.5%, P ¼ .004) compared to the treated group. There was no difference between the prevalence of patients who were former or current smokers between groups (P ¼ .63). THA recipients in the treated cohort had a lower preoperative viral load (P < .001). There were otherwise no differences between the groups with respect to demographics, comorbidities, hepatic fibrosis, or MELD scores. Patients in the untreated group had a significantly higher rate of all surgical complications (25.4% vs 4.8%, P ¼ .007) (Table 2). There were no infections among the 42 treated patients, while the untreated cohort had a periprosthetic infection rate of 14.3% (9/63, P ¼ .01). There were no differences with respect to 90-day medical complications (Table 3). In comparing patients who were treated with IFN to those treated with DAA, there were more patients in the IFN group with hyperlipidemia (37.5% vs 3.8%, P ¼ .008), but fewer patients with hepatic fibrosis (13.3% vs 56.0%, P ¼ .01) (Table 4). In the DAA Table 1 Demographics and Select Comorbidities. Variable
Untreated (n ¼ 63)
Treated (n ¼ 42)
P-Value
Age (y) Female gender Diabetes mellitus HIV status (yes) Hypertension Hyperlipidemia Coronary artery disease Obesity (BMI >30) Peripheral vascular disease Smoking (never) Fibrosis Preoperative MELD score Viral load (IU/L)
58.8 ± 9.0 31.7% (20) 22.2% (14) 19.0% (12) 52.4% (33) 15.9% (10) 14.3% (9) 23.8% (15) 3.2% (2) 12.7% (8) 29.6% (16) 7.5 ± 2.0 2,788,490.3 ± 8,492,548.8
61.8 ± 7.3 47.6% (20) 21.4% (9) 2.4% (1) 64.3% (27) 16.7% (7) 4.8% (2) 21.4% (9) 7.1% (3) 40.5% (17) 40.0% (16) 8.1 ± 3.6 106,690.9 ± 544,592.6a
.08 .11 1.00 .01a .31 1.00 .19 .82 .39 .004a .38 .78 <.001a
HIV, human immunodeficiency virus; BMI, body mass index; MELD, Model for EndStage Liver Disease. a Significant at the P < .05 level.
H.S. Bedair et al. / The Journal of Arthroplasty xxx (2018) 1e4 Table 2 Surgical Complications. Variable Infection Deep infection Superficial infection Wound hematoma Wound drain Intraoperative fracture Postoperative fracture Aseptic loosening Hip dislocation All surgical complications a
3
Table 4 Demographics and Select Comorbidities Treated Patients Only. Untreated (n ¼ 63)
Treated (n ¼ 42)
P-Value
14.3% 9.5% 4.8% 4.8% 0.0% 0.0% 1.6% 0.0% 4.8% 25.4%
0.0% 0.0% 0.0% 0.0% 2.4% (1) 0.0% 0.0% 2.4% (1) 0.0% 4.8% (2)
.01a .08 .27 .27 .40 e 1.00 .40 .27 .007a
(9) (6) (3) (3)
(1) (3) (16)
Significant at the P < .05 level.
subgroup, there were no patients with a detectable viral load prior to THA. There were no differences in surgical or medical complications between THA recipients managed with IFN and DAA (Tables 5 and 6). Discussion Patients with hepatitis C undergoing elective THA have traditionally had unacceptably high perioperative complication rates [3,18]. It is unknown whether this risk factor for adverse outcome is modifiable [17]. Based on the data presented in this study, it appears that treatment for chronic HCV prior to THA reduces the risk of PJI. There does not appear to be a difference in outcomes based on the treatment regimen used to manage HCV. The main limitation to this retrospective cohort study is sample size. Although THA is a common procedure, the percent of patients with chronic HCV who undergo THA is less than 0.5% as reported by Best et al [18]. Even more uncommon are those patients who are treated for chronic HCV prior to THA. In North America, the treatment rates for HCV are only 18.7% as reported by Vutien et al [19]. If one assumes that treatment is uniformly distributed among all patients, the number of THAs in patients with HCV who are treated is approximately 0.009% of all THA patients. With an estimation of 250,000 THAs annually, this rate equates to 22 patients per year in the entire United States. This study reports on 42 treated patients or the rough equivalent of 2 years’ worth of patients in the United States undergoing THA who have been treated for chronic HCV. Although this study appears appropriately powered to detect the main outcome measure of the differences in the aggregate number of surgical complications between untreated and treated patients based on observed statistically significant differences, it may be underpowered to detect differences in specific complications, for example, dislocations or aseptic loosening. The observation that
Variable
DAA (n ¼ 26)
IFN (n ¼ 16)
P-Value
Age (y) Female gender Diabetes mellitus HIV status (yes) Hypertension Hyperlipidemia Coronary artery disease Obesity (BMI >30) Peripheral vascular disease Smoking (never) Fibrosis Preoperative MELD score Viral load (IU/L)
61.9 ± 6.9 53.8% (14) 26.9% (7) 3.8% (1) 65.4% (17) 3.8% (1) 3.8% (1) 19.2% (5) 3.8% (1) 26.9% (7) 56.0% (14) 8.6 ± 4.2 0.0 ± 0.0
61.6 ± 8.1 37.5% (6) 12.5% (2) 0.0% 62.5% (10) 37.5% (6) 6.3% (1) 25.0% (4) 12.5% (2) 62.5% (10)a 13.3% (2) 6.8 ± 1.2 303,658.6 ± 908,266.5
.93 .35 .44 1.00 1.00 .008a 1.00 .71 .55 .07 .01a .12 .46
DAA, direct antiviral agent; IFN, interferon; HIV, human immunodeficiency virus; BMI, body mass index; MELD, Model for End-Stage Liver Disease. a Significant at the P < .05 level.
there does appear to be a benefit in reducing the aggregate number of all surgical complications for those patients treated prior to THA should be recognized by clinicians and surgeons as both clinically significant and meaningful to patients. Ideally, a prospective randomized study could resolve some of the problems associated with retrospective studies; however, depending on the outcome measure of interest, the sample size would likely have to be quite large and patient eligibility numbers would be a significant barrier. Moreover, given the results reported, a follow-up prospective randomized study may raise ethical concerns as these patients may be at substantially greater risk for perioperative complications. There does appear to be an increased risk of perioperative complications after THA in patients coinfected with HIV and HCV [20]. In this analysis, there were a greater number of patients coinfected with HIV and HCV in the untreated group compared to the treated group which may be a confounding factor; however, none of the surgical complications observed occurred in any of the patients with HIV. With 42 patients in the treated group, no differences were detected within the treatment cohort based on the type of treatment (IFN vs DAA). This may be due to a type II error. This study did not account for cost, treatment access, treatment preference, completion of treatment regime, or downstream benefits of one treatment compared to the other. However, given the overwhelming success of DAA treatment and its implications beyond orthopedic ailments, it would be difficult to imagine a study designed to investigate IFN compared to DAA treatment prior to THA, perhaps relegating the treatment with IFN to one of historical interest only. Finally, in order to increase our sample size, we assessed patients who underwent surgery between 2006 and 2016. Given that DAAs were not approved for use in the treatment of HCV until 2014, there may have been a lower prevalence of patients
Table 3 Medical Complications. Variable
Control (n ¼ 63)
DAA Treated (n ¼ 42)
P-Value
Pneumonia UTI Sepsis Blood transfusion (yes) DVT Pulmonary embolism Myocardial infarction Acute renal failure GI bleed Death All medical complications
0.0% 0.0% 1.6% 6.3% 2.0% 0.0% 1.6% 1.6% 0.0% 4.8% 14.3%
0.0% 2.4% 0.0% 4.8% 0.0% 2.4% 0.0% 2.4% 0.0% 2.4% 9.5%
e .40 1.00 1.00 1.00 .40 1.00 1.00 e .65 .56
(1) (4) (1) (1) (1) (3) (9)
(1) (2) (1) (1) (1) (4)
DAA, direct antiviral agent; UTI, urinary tract infection; DVT, deep vein thrombosis; GI, gastrointestinal.
Table 5 Surgical Complications. Variable
DAA (n ¼ 26)
IFN (n ¼ 16)
P-Value
Infection Deep infection Superficial infection Wound hematoma Wound drain Intraoperative fracture Postoperative fracture Aseptic loosening Hip dislocation All surgical complications
0.0% 0.0% 0.0% 0.0% 3.8% (1) 0.0% 0.0% 0.0% 0.0% 3.8% (1)
0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 6.3% (1) 0.0% 6.3% (1)
e e e e 1.00 e e .38 e 1.00
DAA, direct antiviral agent; IFN, interferon.
4
H.S. Bedair et al. / The Journal of Arthroplasty xxx (2018) 1e4
Table 6 Medical Complications. Variable
DAA (n ¼ 26)
IFN (n ¼ 16)
P-Value
Pneumonia UTI Sepsis Blood transfusion (yes) DVT Pulmonary embolism Myocardial infarction Acute renal failure GI bleed Death All medical complications
0.0% 0.0% 0.0% 3.8% (1) 0.0% 0.0% 0.0% 0.0% 0.0% 3.8% (1) 3.8% (1)
0.0% 6.3% (1) 0.0% 6.3% (1) 6.3% (1) 6.3% (1) 0.0% 6.3% (1) 0.0% 0.0% 18.8% (3)
e .38 e 1.00 .38 .38 e .38 e 1.00 .15
DAA, direct antiviral agent; IFN, interferon; UTI, urinary tract infection; DVT, deep vein thrombosis; GI, gastrointestinal.
receiving treatment for HCV before this time point and this may have been a confounding variable for our study. The available peer-reviewed literature on the impact of hepatitis C on elective THA is surprisingly limited with a PubMed database search performed in February 2018 for published studies with the search terms “hepatitis c” AND “total hip arthroplasty” returning 19 results with only 7 reporting on postoperative medical and surgical complication rates. Issa et al [3] queried the Nationwide Inpatient Sample Database and reported that more patients with HCV were undergoing THA and total knee arthroplasty increasing from a rate of approximately 2/1000 to 6/1000 over a 12-year period. Of concern are the very high complication rates among these patients which approached 30%, similar to this study. Best et al [18] observed similar findings when examining the National Hospital Discharge survey with hepatitis C patients experiencing higher surgical and medical complications compared to control. The investigators also observed a nearly 9.5-fold increase in periprosthetic infections. In this study, we also observed exceptionally high periprosthetic infection rates (14.3%) in untreated patients with this disease undergoing elective surgery. The potential rates of reoperation and deep infection within this cohort are troubling high. Although Orozco et al observed increased rates of complication and HCV TJA candidates with liver fibrosis, Pour et al found that patients with HCV undergoing TJA had similarly high complication rates that were independent of liver function [4,17]. In patients with hepatitis C and normal liver function tests, the authors reported a nearly 24% overall complication rate and 15% reoperation rate. These authors postulated that this disease process may result in some type of unrecognized immunocompromised state which would lead to higher complication rates despite normally functioning livers. Although the baseline complication rate in untreated hepatitis C patients is unarguably high, it is interesting that even patients with no obvious sequela of liver dysfunction from chronic disease still have high perioperative complication rates. The data presented in this study maybe consistent with this theory, as there was no significant difference in MELD scores or hepatic fibrosis, but observed differences in postoperative outcomes. Despite the underlying reason as to why this may be the case, patients with hepatitis C should be treated prior to elective arthroplasty. Although the implications for treatment for hepatitis C are tremendous and have certainly reverberated through the medical community since the recent introduction of DAAs, to date there have been no studies examining the effect of treatment for HCV on outcomes for elective surgical procedures. We have observed that treating hepatitis C prior to THA may reduce the unacceptably high perioperative complication profile that has plagued this patient population. Although the clinical outcomes are clear, what is unclear is the ability of patients to gain access to newer more expensive
treatment regimens. Although the cost of a treatment course for HCV can exceed $60,000 USD [13,14], this expense pales in comparison to the enormous financial and personal burden of treating a PJI, which is estimated to be $300,000-$500,000 per case [21]. Conclusion Perioperative infection rates in THA patients with HCV previously treated with traditional and newer agents are lower than those patients who are not treated. Our analysis demonstrates that all THA candidates with an HCV infection should be considered for treatment prior to surgery. References [1] Edwards PK, Mears SC, Stambough JB, Foster SE, Barnes CL. Choices, compromises, and controversies in total knee and total hip arthroplasty modifiable risk factors: what you need to know. J Arthroplasty 2018;33:3101e6. https://doi.org/10.1016/j.arth.2018.02.066. [2] Tarabichi M, Shohat N, Kheir MM, Adelani M, Brigati D, Kearns SM, et al. Determining the threshold for HbA1c as a predictor for adverse outcomes after total joint arthroplasty: a multicenter, retrospective study. J Arthroplasty 2017;32:S263e267.e1. [3] Issa K, Boylan MR, Naziri Q, Perfetti DC, Maheshwari AV, Mont MA. The impact of hepatitis C on short-term outcomes of total joint arthroplasty. J Bone Joint Surg Am 2015;97:1952e7. [4] Orozco F, Post ZD, Baxi O, Miller A, Ong A. Fibrosis in hepatitis C patients predicts complications after elective total joint arthroplasty. J Arthroplasty 2014;29:7e10. [5] Kildow BJ, Politzer CS, DiLallo M, Bolognesi MP, Seyler TM. Short and longterm postoperative complications following total joint arthroplasty in patients with human immunodeficiency virus, hepatitis B, or hepatitis C. J Arthroplasty 2018;33:S86e92.e1. [6] Cancienne JM, Kandahari AM, Casp A, Novicoff W, Browne JA, Cui Q, et al. Complication rates after total hip and knee arthroplasty in patients with hepatitis C compared with matched control patients. J Am Acad Orthop Surg 2017;25:e275e81. [7] Chowdhury R, Chaudhary MA, Sturgeon DJ, Jiang W, Yau AL, Koehlmoos TP, et al. The impact of hepatitis C virus infection on 90-day outcomes following major orthopaedic surgery: a propensity-matched analysis. Arch Orthop Trauma Surg 2017;137:1181e6. [8] Puchades Renau L, Berenguer M. Introduction to hepatitis C virus infection: overview and history of hepatitis C virus therapies. Hemodial Int 2018;22(Suppl. 1):S8e21. [9] Maughan A, Ogbuagu O. Pegylated interferon alpha 2a for the treatment of hepatitis C virus infection. Expert Opin Drug Metab Toxicol 2018;14:219e27. [10] Enomoto H, Nishiguchi S. Factors associated with the response to interferonbased antiviral therapies for chronic hepatitis C. World J Hepatol 2015;7:2681e7. [11] Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB, Sulkowski MS. Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review. Ann Intern Med 2017;166:637e48. [12] Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014;370: 1889e98. [13] Bickerstaff C. The cost-effectiveness of novel direct acting antiviral agent therapies for the treatment of chronic hepatitis C. Expert Rev Pharmacoecon Outcomes Res 2015;15:787e800. [14] Iyengar S, Tay-Teo K, Vogler S, Beyer P, Wiktor S, de Joncheere K, et al. Prices, costs, and affordability of new medicines for hepatitis C in 30 countries: an economic analysis. PLoS Med 2016;13:e1002032. [15] Hayes CN, Chayama K. Why highly effective drugs are not enough: the need for an affordable solution to eliminating HCV. Expert Rev Clin Pharmacol 2017;10:583e94. [16] Rosenberg ES, Hall EW, Sullivan PS, Sanchez TH, Workowski KA, Ward JW, et al. Estimation of state-level prevalence of hepatitis C virus infection, US states and District of Columbia, 2010. Clin Infect Dis 2017;64:1573e81. [17] Pour AE, Matar WY, Jafari SM, Purtill JJ, Austin MS, Parvizi J. Total joint arthroplasty in patients with hepatitis C. J Bone Joint Surg Am 2011;93:1448e54. [18] Best MJ, Buller LT, Klika AK, Barsoum WK. Increase in perioperative complications following primary total hip and knee arthroplasty in patients with hepatitis C without cirrhosis. J Arthroplasty 2015;30:663e8. [19] Vutien P, Jin M, Le MH, Nguyen P, Trinh S, Huang JF, et al. Regional differences in treatment rates for patients with chronic hepatitis C infection: systematic review and meta-analysis. PLoS One 2017;12:e0183851. [20] Mahure SA, Bosco JA, Slover JD, Vigdorchik J, Iorio R, Schwarzkopf R. Risk of complications after THA increases among patients who are coinfected with HIV and hepatitis C. Clin Orthop 2018;476:356e69. [21] Parisi TJ, Konopka JF, Bedair HS. What is the long-term economic societal effect of periprosthetic infections after THA? A Markov analysis. Clin Orthop Relat Res 2017;475:1891e900.