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Total Joint Arthroplasty in Patients with Hepatitis C
Aidin Eslam Pour, MD1; Wadih Y. Matar, MD, MSc, FRCSC1; S. Mehdi Jafari, MD1; James J. Purtill, MD1; Matthew S. Austin, MD1; Javad Parvizi, MD, FRCS1
1 Department of Orthopaedic Surgery, Rothman Institute, Thomas Jefferson University Hospital, 925 Chestnut Street, 5th Floor, Philadelphia, PA 19107. E-mail address for J. Parvizi: Parvj@aol.com
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Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. One or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

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Investigation performed at Rothman Institute of Orthopaedics at Thomas Jefferson University, Philadelphia, Pennsylvania

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Aug 03;93(15):1448-1454. doi: 10.2106/JBJS.J.00219
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Hepatitis C is present worldwide. Little is known about the outcome of joint arthroplasty in asymptomatic patients with hepatitis C. We evaluated the surgical complications following hip and knee arthroplasty in patients who were seropositive for hepatitis C in a matched study.


Seventy-one patients with hepatitis C underwent forty total hip arthroplasties and thirty-two total knee arthroplasties from 1995 to 2006. The patients had normal preoperative liver function tests. Patients with human immunodeficiency virus infection, hepatitis B, and hemophilia were excluded. A control group was matched in a 2:1 ratio with the hepatitis-C group for age, body-mass index, sex, year of surgery, and medical comorbidities, including diabetes, rheumatoid arthritis, and immunosuppressive conditions.


In the group of patients with hepatitis C who were managed with total hip arthroplasty, six patients (15%) had wound complications requiring oral antibiotics or wound irrigation and debridement and four hips (10%) had mechanical complications, including implant loosening or dislocation. In the control group, three patients (3.8%) had wound complications requiring oral antibiotics or irrigation and debridement and three patients (3.8%) had mechanical complications, including dislocation, periprosthetic femoral fracture, and implant failure. In the group of patients with hepatitis C who underwent total knee arthroplasty, three patients (9.4%) had mechanical complications, including loosening and periprosthetic fracture requiring revision. In the control group, three patients (4.7%) had wound complications, one (1.6%) had a deep infection requiring two-stage revision, and one (1.6%) underwent revision because of a mechanical problem. The combined hepatitis-C group had significantly longer hospital stays and higher rates of surgical and mechanical complications, reoperation, and revision.


Patients with hepatitis C undergoing joint arthroplasty had a higher rate of surgical complications and a longer hospital stay. The reason for the higher rate of complications in this group of patients is unknown, and further investigation is needed. Patients with hepatitis C should be counseled about the potential for a higher incidence of postoperative complications prior to undergoing joint arthroplasty.

Level of Evidence: 

Prognostic Level III. See Instructions to Authors for a complete description of levels of evidence.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Aidin Eslam Pour, MD; Mitchell Matenlfort, PHD; Wadih Y. Matar, MD, MSc, FRCSC; S. Mehdi Jafari, MD; James J. Purtill, MD; Matthew S. Austin, MD; Javad Parvizi, MD, FRCS
    Posted on March 07, 2012
    Confidence Intervals, P-values, and Statistical Significance
    Rothman Institute of Orthopaedics at Thomas Jefferson University Hospital

    We would like to thank Dr. Paryavi and Sterling, Sung-Yen, Chin-Li, Chung-Feng, Wu-Cheng and Chia-Yen for their comments regarding our paper. We have read their comments carefully. We are in full agreement with them in that confidence intervals are more meaningful than p-values. However, the attraction of a p-value is that it boils the difference between groups, the variance within the groups, and the sample size down into one number. This is a false economy as it loses so much information. In addition, while a significant p-value is informative, it is difficult to discern whether a non-significant p-value truly means no effect, or if an effect might be detectable with more data or confounding variables accounted for. Somehow when this paper was being prepared, the p-values in Table IV were “rubber-stamped” with p < 0.05. We have no explanation for this, as the actual p-values were in Tables II and III. There’s a way to approximate what the true p-values should have been from the confidence intervals. Take log(H/L)/(2*1.96) where H and L are the higher and lower bounds of the confidence interval, which gives you the standard error. Divide that into the log of the estimated Odds Ratio and you have a t-statistic. For example, with “Any postoperative complication” that approach gives us a t-statistic of 1.72 and the resulting p-value is 0.0866, which is one of those annoying borderline values where you might have a significant result if you had more data. Despite the mislabeling of p-values and the question of statistical significance, Table IV is still informative. While individual complication rates may not be statistically significant, the consistent trend is for complication rates to increase with Hepatitis C, congruent with the results in Table III. Table IV can also inform the design of adequately powered studies to estimate the effect of Hepatitis C on specific complications. After gathering the results and finding difference between the 2 groups, considering that this was the first study on this patient population, we decided to publish the results and included the confidence intervals in the table for the readers. The problem of conducting a study on this patient population is the sample size. In most centers around the United States, there are not enough patients in this population for comparison and conducting a prospective study is very time consuming and unpractical. For this reason, a retrospective study design, despite all of its shortcomings, does tell a story that may resonate with clinicians taking care of these challenging cases. Despite the retrospective design of the study, rather small sample size and lack of more complex statistical analysis, we believe that the message of the paper is still valid and patients with asymptomatic hepatitis C can be at higher risk of developing perioperative complications after total joint arthroplasty. The statement we had placed in the Discussion points out the need for a study on a larger cohort in order to determine the influence of seropositive, but clinically asymptomatic hepatitis C disease, on the outcome of total joint arthroplasty.

    Ebrahim Paryavi, MD, MPH, RObert Sterling, MD
    Posted on February 26, 2012
    Confidence Intervals, P-values, and Statistical Significance
    University of Maryland School of Medicine

    We commend the authors of the paper titled “Total Joint Arthroplasty in Patients with Hepatitis C,” in the 3-August-2011 issue of the journal for presenting data on a large series of patients with HCV with regards to post-operative complications (1). We believe that this work can be extremely helpful for surgeons planning for arthroplasty in this complex patient population; however, we also believe that analysis of the statistics presented in Table 4 brings the significance of some the conclusions from this data into question Table 4 is a presentation of logistic regression results which yield odds ratios, 95% confidence intervals (CI), and p-values. Odds ratios are always positive and can be less than 1 (lower odds or likelihood of having the outcome) or greater than 1 (higher odds of having the outcome) for the comparison group compared to the baseline group. In this context, an odds ratio tells us that the likelihood, or relative odds of having an outcome is higher or lower for people with the risk factor (in this example, HCV) than those without that risk factor. For statistical ratios (odds ratios, relative risks, risk ratio, incidence rate ratio), confidence intervals are always positive. A significant confidence interval should be either greater than 1 or less than 1 but not include 1. If the 95% confidence interval includes 1, this would mean that a finding of no difference in the groups is just as likely as any other ratio in that 95% CI range. Therefore, while the p-values listed in table 4 are almost all significant at a level less than alpha of 0.05, many of the confidence intervals for the odds ratios include 1. This by definition means that the p-values cannot be less than 0.05 meaning that these outcomes are in fact not significantly different between patients with HCV and those without. If we missed this important point in the CIs and just looked at p-values we would be misled.This is an important point as many authors have advocated for the transition from p-values to confidence intervals alone in the presentation of results in scientific publications (2-5). This idea has been met with resistance by the readership, particularly physicians. This may be due to a fundamental lack of understanding of the underlying statistical concepts (6). It behooves us to learn these fundamentals if we expect to critically read and appraise our literature.References:1) 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 Aug 3;93(15):1448-54.2) Gardner, M. J. and Altman, D. G. (1986) Confidence intervals rather than p-values: estimation rather than hypothesis testing. British Medical Journal, 283, 600–602.3) Bulpitt, C. J. (1987) Confidence intervals. Lancet, i, 494–497.4) Simon, R. (1986) Confidence intervals for reporting of results of clinical trials. Annals of Internal Medicine, 105, 429–435.5) Yates, F. (1951) The influence of statistical methods for research workers on the development of the science of statistics. Journal of the American Statistical Association, 46, 19–34.6) Mathews, D. R. and McPherson K. (1987) Doctors' ignorance of statistics. British Medical Journal, 294, 856–857.

    Sung-Yen Lin1, Chin-Li Wu2, Chung-Feng Huang3,4,5, Wu-Cheng Chen5, Chia-Yen Dai2,3
    Posted on October 31, 2011
    Commentary on an article by Pour, A. E., MD, et al.: “Total Joint Arthroplasty in Patients with Hepatitis C. ”
    1 Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 2Department of Preventive Medicine, Kaohsiung Medical University Hospital,

    TO THE EDITOR: We read the report with great interest in the article published in a recent issue of Journal of Bone and Joint Surgery-American volume. Pour AE et al. retrospectively reviewed the clinical and radiographic records of asymptomatic hepatitis C virus (HCV) carriers who received joint arthroplasty in their institution, and concluded that patients with HCV infection have a higher incidence of postoperative complications in joint arthroplasty(1). Replication of HCV in tissues and extrahepatic organs may have direct cytopathic effects leading to a wide spectrum of extrahepatic manifestations, such as thyroid dysfunction, lipid disorders, glucose abnormalities, mixed cryoglobulinemia, and autoimmunity(2). Because of the systemic associations, patients with chronic hepatitis C (CHC) may result in more complications in surgery. Though the authors take the lead in reporting the inferior results in total joint arthroplasty in patients with CHC, two potential selection biases in the HCV group should be clarified before the conclusive statement could be made.First, the author did not clearly mention about how CHC patients were defined, which should be not only seropositive for HCV antibodies but also detectable HCV RNA by polymerase chain reaction for more than 6 months. The percentage of spontaneous clearance of HCV infection after acute infection ranged from 10-50%(3-)5. Micallef JM. et al. made a systemic review of 31 longitudinal studies and concluded a 26% spontaneous viral clearance rate after HCV infection(6). We have also confirmed the finding by conducting a large scale community-based study in Taiwan where HCV infection are widely endemic, which demonstrated that only 74.5% anti-HCV positive subjects are in state of viraemia (7). Therefore, in this study it is estimated that approximately one quarter of patients in the case group might be free of HCV infection despite of anti-HCV seropositivity. And this will cause major impact on the results of this study if HCV RNA data were unavailable. Secondly, although liver cirrhosis is one of the exclusion criteria, it is difficult to completely exclude the patients with liver cirrhosis from this study. The diagnosis of liver cirrhosis is basically dependent on live biopsy or from liver sonography if histological data are not available. The authors selected patients with normal enzyme in the current study. However, liver enzyme is not an reliable marker of disease severity in chronic hepatitis C infection(8-10). Approximately 20%-46% of CHC patients have persistent normal serum alanine transaminase levels (PNALT)(10-12). It is noteworthy that a proportion of patients with PNALT actually have advanced liver fibrosis and liver cirrhosis(10,12). Because of having normal liver function test biochemically, patients with PNALT might not undergo regular surveillances for the liver disease severity such as sonography. Thus it is hard to know if there is ongoing liver cirrhosis in these patients before surgery. Substantially lower platelet counts with borderline significance in the case group might be surrogate markers for existing advanced liver disease. Liver cirrhosis is proven to be a factor contributing to inferior results in arthroplasty(13). If the authors cannot strictly exclude the patients with advanced liver disease and liver cirrhosis from the study, the results of this study will be greatly affected. In summary, Pour AE et al. presented an inferior outcome in patients with chronic hepatitis C undergoing joint arthroplasty, but this conclusion should be viewed cautiously. Because only a small number of chronic hepatitis C patients receive joint arthroplasty, any error in case selection may change the conclusions. Thus we suggested that the diagnosis of chronic hepatitis C infection and the detection of liver cirrhosis should be more accurately assessed to prevent the possible biases in this study. REFERENCES: (1) 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;93:1448-54. (2) Jacobson IM, Cacoub P, Dal Maso L, Harrison SA, Younossi ZM. Manifestations of chronic hepatitis C virus infection beyond the liver. Clin Gastroenterol Hepatol 2010;8:1017-29. (3) Sheu JC, Lee SH, Wang JT, Shih LN, Wang TH, Chen DS. Prevalence of anti-HCV and HCV viremia in hemodialysis patients in Taiwan. J Med Virol 1992;37:108-12. (4) Gretch D, Lee W, Corey L. Use of aminotransferase, hepatitis C antibody, and hepatitis C polymerase chain reaction RNA assays to establish the diagnosis of hepatitis C virus infection in a diagnostic virology laboratory. J Clin Microbiol 1992;30:2145-9. (5) Zhang YY, Hansson BG, Widell A, Nordenfelt E. Hepatitis C virus antibodies and hepatitis C virus RNA in Chinese blood donors determined by ELISA, recombinant immunoblot assay and polymerase chain reaction. APMIS 1992;100:851-5. (6) Micallef JM, Kaldor JM, Dore GJ. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J Viral Hepat 2006;13:34-41. (7) Dai CY, Chuang WL, Ho CK, et al. Associations between hepatitis C viremia and low serum triglyceride and cholesterol levels: a community-based study. J Hepatol 2008;49:9-16. (8) Sanai FM, Benmousa A, Al-Hussaini H, et al. Is serum alanine transaminase level a reliable marker of histological disease in chronic hepatitis C infection? Liver Int 2008;28:1011-8. (9) Shiffman ML, Stewart CA, Hofmann CM, et al. Chronic infection with hepatitis C virus in patients with elevated or persistently normal serum alanine aminotransferase levels: comparison of hepatic histology and response to interferon therapy. J Infect Dis 2000;182:1595-601. (10) Lawson A. Hepatitis C virus-infected patients with a persistently normal alanine aminotransferase: do they exist and is this really a group with mild disease? J Viral Hepat 2010;17:51-8. (11) Bacon BR. Treatment of patients with hepatitis C and normal serum aminotransferase levels. Hepatology 2002;36:S179-84.(12) Alberti A, Noventa F, Benvegnu L, Boccato S, Gatta A. Prevalence of liver disease in a population of asymptomatic persons with hepatitis C virus infection. Ann Intern Med 2002;137:961-4. (13) Shih LY, Cheng CY, Chang CH, Hsu KY, Hsu RW, Shih HN. Total knee arthroplasty in patients with liver cirrhosis. J Bone Joint Surg Am 2004;86-A:335-41.

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