Abstract
Background
Patients with hepatitis C virus (HCV) undergoing primary elective total joint arthroplasty (TJA) are at increased risk of postoperative complications. Patients with chronic liver disease and cirrhosis, specifically Child-Pugh Class B and C, who are undergoing general surgery have high 2-year mortality risks, approaching 60% to 80%. However, the role of Child-Pugh and Model for End-Stage Liver Disease classifications of liver status in predicting survivorship among patients with HCV undergoing elective arthroplasty has not been elucidated.
Question/purpose
What factors are independently associated with early mortality (< 2 years) in patients with HCV undergoing arthroplasty?
Methods
We performed a retrospective study at three tertiary academic medical centers and identified patients with HCV undergoing primary elective TJA between January 2005 and December 2019. Patients who underwent revision TJA and simultaneous primary TJA were excluded. A total of 226 patients were eligible for inclusion in the study. A further 25% (57) were excluded because they were lost to follow-up before the minimum study requirement of 2 years of follow-up or had incomplete datasets. After the inclusion and exclusion criteria were applied, the final cohort consisted of 75% (169 of 226) of the initial patient population eligible for analysis. The mean follow-up duration was 53 ± 29 months. We compared confounding variables for mortality between patients with early mortality (16 patients) and surviving patients (153 patients), including comorbidities, HCV and liver characteristics, HCV treatment, and postoperative medical and surgical complications. Patients with early postoperative mortality were more likely to have an associated advanced Child-Pugh classification and comorbidities including peripheral vascular disease, end-stage renal disease, heart failure, and chronic obstructive pulmonary disease. However, both groups had similar 90-day and 1-year medical complication risks including myocardial infarction, stroke, pulmonary embolism, and reoperations for periprosthetic joint infection and mechanical failure. A multivariable regression analysis was performed to identify independent factors associated with early mortality, incorporating all significant variables with p < 0.05 present in the univariate analysis.
Results
After accounting for significant variables in the univariate analysis such as peripheral vascular disease, end-stage renal disease, heart failure, chronic obstructive pulmonary disease, and liver fibrosis staging, Child-Pugh Class B or C classification was found to be the sole factor independently associated with increased odds of early (within 2 years) mortality in patients with HCV undergoing elective TJA (adjusted odds ratio 29 [95% confidence interval 5 to 174]; p < 0.001). The risk of early mortality in patients with Child-Pugh Class B or C was 64% (seven of 11) compared with 6% (nine of 158) in patients with Child-Pugh Class A (p < 0.001).
Conclusion
Patients with HCV and a Child-Pugh Class B or C at the time of elective TJA had substantially increased odds of death, regardless of liver function, cirrhosis, age, Model for End-Stage Liver Disease level, HCV treatment, and viral load status. This is similar to the risk of early mortality observed in patients with chronic liver disease undergoing abdominal and cardiac surgery. Surgeons should avoid these major elective procedures in patients with Child-Pugh Class B or C whenever possible. For patients who feel their arthritic symptoms and pain are unbearable, surgeons need to be clear that the risk of death is considerably elevated.
Level of Evidence
Level III, therapeutic study.
Introduction
A recent meta-analysis of patients with hepatitis C virus (HCV) undergoing THA or TKA noted that these patients have a higher medical and mechanical revision complication risk with an extended length of stay than controls without HCV [30]. Great empahsis has been placed on treating these patients for HCV before elective total joint arthroplasty (TJA), irrespective of therapy modality, to minimize medical and surgical complications, including periprosthetic joint infection (PJI) [4]. Further research has confirmed the necessity of achieving a sustained negative viral load with treatment before TJA to mitigate the extended length of stay and greater mechanical complications and PJI in these patients than in those with a detectable viral load [7, 8, 20], as well as to achieve a similar risk of complications at 2 years postoperatively to controls without HCV [25, 26]. Achieving a sustained virologic response in nonsurgical patients with HCV has correlated well with a long-term decrease in all-cause mortality, liver-related mortality, and nonliver-related mortality, especially in patients with a history of decompensated liver cirrhosis [21]. This may explain why the overall mortality of patients with HCV and cirrhosis declined from 2010 to 2019 according to the Global Burden of Diseases, Injuries, and Risk Factors Study database, although the incidence of cirrhosis increased by 5.6% during this timeframe [29]. Postoperative mortality in patients with HCV undergoing general surgery has been thoroughly studied and correlates well with the severity of liver disease, which is represented by the Child-Pugh classification or the Model for End-Stage Liver Disease (MELD) score, and it can reach up to 82% in patients with Child-Pugh Class C [19]. The overall mortality risk after elective TJA in the general population is less than 0.6% at 90 days, mostly related to cardiovascular-related conditions [3], with peripheral vascular disease, elevated postoperative glucose, abnormal postoperative cardiac studies, and an advanced Charlson comorbidity index also contributing to this statistic [2].
However, there is a paucity of information related to the mortality of patients with HCV after elective TJA beyond one large study, which included a heterogenous population of various surgical procedures in patients with cirrhosis (orthopaedics, cardiovascular, and digestive) [28]. The orthopaedic subpopulation in this study was only 14% of the total cohort (107 patients) and consisted of a variety of elective and trauma-related major surgeries in the upper and lower extremities. That study generated heterogeneity and the findings cannot be generalized to patients undergoing elective TJA. Orthopaedic studies recently conducted on patients with HCV undergoing elective TJA have focused either on early postoperative outcomes including in-hospital complications and readmissions for mechanical or infectious etiologies in matched case-control studies [23] or the outcomes of treating HCV with antiviral medications to achieve a negative viral load compared with untreated patients, with limited emphasis on early mortality and its risk factors [8, 25]. Other investigations have used large-registry databases either on the state or national level to assess the impact of HCV on early postoperative complication risks within 90 days and 1 year of surgery, with a specific emphasis on reoperation for PJI, which is the most morbid complication sustained postoperatively [12, 15, 27]. However, these large registries, including the Medicare or Nationwide Inpatient Sample database, lack granularity and detailed information specifically about liver-related variables, characteristics, treatments used, and viral loads that are confounding and necessary when investigating early mortality after TJA in patients with HCV.
We conducted a large multicenter study with granular patient-specific details and HCV variables that are necessary in analyzing early mortality after elective TJA in patients with HCV. Therefore, we asked: What factors are independently associated with early mortality (< 2 years) in patients with HCV undergoing arthroplasty?
Patients and Methods
Study Design and Setting
This retrospective multicenter study involved three academic tertiary care centers in the United States with specialized clinics dedicated to treating patients with HCV. Mortality within 2 years of surgery was our primary endpoint, with a requirement of 2-year postoperative follow-up for inclusion and analysis. Patient mortality was confirmed through a detailed review of medical records and online searches of obituaries.
Participants
All patients with a diagnosis of HCV who underwent primary elective TJA between January 2005 and December 2019 at the three participating institutions were included, while patients who underwent revision TJA and simultaneous primary TJA were excluded. Patients with prior liver transplantation were included in our study. Patients who underwent multiple primary TJAs during the study period were included, and each arthroplasty admission was registered as a separate case in the analysis. We identified 226 patients who underwent 270 TJAs during this time period who met our eligibility criteria for analysis. Only patients with available HCV characteristics including viral load and liver disease variables before primary TJA were included. A further 25% (57 of 226) were excluded because they were lost to follow-up before the minimum study requirement of 2 years of follow-up or had incomplete datasets, especially variables related to liver function and status. After the inclusion and exclusion criteria were applied, the final cohort consisted of 75% (169 of 226) of the initial patient population eligible for analysis, 9.5% of whom (16 patients) died within 2 years of surgery.
Study Variables
We collected patient demographics, comorbidities including the presence of HIV and cirrhosis, HCV and liver characteristics, perioperative variables, and in-hospital outcomes or complications through a thorough medical record review. Patients either selected their race from a survey questionnaire or self-reported this information. HCV characteristics included viral load (IU/mL), virus genotype, treatment medication (interferon and direct-acting antivirals), liver function tests, MELD score [14, 17], Child-Pugh classification [6, 24], liver fibrosis staging, and activity. The MELD score is derived from a scoring system based on metabolic laboratory test results that can range from 6 to 40, with higher scores indicating decompensating liver status [14, 17]. The MELD level was defined by mortality risk levels as MELD Level 1 (score 6 to 9), Level 2 (score 10 to 19), Level 3 (score 20 to 29), Level 4 (score 30 to 39), or Level 5 (score > 39). Similarly, the Child-Pugh classification is based on scoring of metabolic laboratory test results in which Class A (5 or 6) is considered well-compensated disease, Class B (7 to 9) indicates significant functional compromise, and Class C (10 to 15) represents decompensated disease. The Child-Pugh classification is widely used to predict overall mortality in patients with cirrhosis [16]. Patients who were unable to achieve a sustained virologic response, defined as an undetectable viral load for at least 12 weeks after completion of treatment [13], were considered as not responding to the treatment. Postoperative outcomes including complications at 90 days, 1 year, and at any time during the patients’ follow-up were collected. PJI was defined according to the Musculoskeletal Infection Society criteria [22].
Baseline Descriptive Data
Patients who died within 2 years after TJA were more likely to be men and have associated comorbidities including peripheral vascular disease, end-stage renal disease, heart failure, and chronic obstructive pulmonary disease (Table 1). Patients who died had similar rates of cirrhosis (44% [seven of 16] versus 19% [29 of 153]; p = 0.1) and history of hepatocellular carcinoma (13% [two of 16] versus 4% [six of 153]; p = 0.12) to their counterparts. The aspartate transaminase level was higher (46.9 versus 37.4 U/L ; p = 0.02) in the mortality group than in those who survived. When analyzing the liver status, the Child-Pugh classification and liver fibrosis staging were more advanced in the mortality group than in the survival group, while the MELD level and liver fibrosis activity were similar between the groups (Table 2). Patients who died within 2 years of surgery were more likely to have undergone THA (75% [12 of 16] versus 47% [72 of 153]; p = 0.04). However, there were no differences in operative duration, intraoperative blood loss, transfusion rates, use of tranexamic acid, or type of anesthesia (Table 3). Although patients in the mortality group were more likely to be discharged to a skilled nursing facility or inpatient rehabilitation and have an extended length of stay than those who survived, the groups had similar risks of in-hospital complications including myocardial infarction, stroke, anemia, and postoperative blood transfusion (Table 4).
Table 1.
Patient demographics and comorbid conditions of patients who had HCV with 2-year mortality compared with those without
| Characteristic | Mortality (n = 16) | No mortality (n = 153) | p value |
| Male sex | 88 (14) | 58 (88) | 0.03 |
| Racea | |||
| White | 56 (9) | 56 (86) | 0.89 |
| Black | 31 (5) | 35 (53) | |
| Other | 13 (2) | 9 (14) | |
| Age in years | 57 ± 14 | 56 ± 10 | 0.53 |
| BMI in kg/m2 | 25.7 ± 2.7 | 28.8 ± 6.3 | 0.06 |
| Comorbid conditions | |||
| Obesity | 0 (0) | 31 (48) | 0.007 |
| Hemophilia | 6 (1) | 7 (10) | 0.96 |
| Prior liver transplant | 19 (3) | 7 (10) | 0.08 |
| Cirrhosis (any) | 44 (7) | 19 (29) | 0.10 |
| Compensated | 86 (6) | 86 (25) | > 0.99 |
| Decompensated | 14 (1) | 14 (4) | > 0.99 |
| Hepatocellular carcinoma history | 13 (2) | 4 (6) | 0.12 |
| Diabetes mellitus | 13 (2) | 20 (31) | 0.74 |
| Tobacco use | 25 (4) | 49 (75) | 0.11 |
| Hypertension | 75 (12) | 62 (95) | 0.42 |
| Hypothyroid | 13 (2) | 8 (13) | 0.64 |
| Peripheral vascular disease | 31 (5) | 7 (11) | 0.009 |
| End-stage renal disease | 44 (7) | 16 (24) | 0.01 |
| Iron-deficiency anemia | 19 (3) | 9 (14) | 0.21 |
| Cerebrovascular accident or stroke | 19 (3) | 5 (8) | 0.07 |
| HIV | 0 (0) | 13 (20) | 0.22 |
| Coronary artery disease | 25 (4) | 8 (12) | 0.05 |
| Heart failure | 38 (6) | 7 (11) | 0.002 |
| Chronic obstructive pulmonary disease | 38 (6) | 9 (14) | 0.005 |
| Depression | 44 (7) | 31 (47) | 0.40 |
Data are presented as % (n) or mean ± SD.
aEleven patients were missing race information.
Table 2.
Characteristics of patients with HCV with 2-year mortality compared with those without after undergoing primary elective TJA
| Variable | Mortality (n = 16) | No mortality (n = 153) | p value |
| Viral load positive | 44 (7) | 61 (93) | 0.20 |
| Viral load, IU/mL | 0.8x106 ± 2.3x106 | 1.7x106 ± 3.6x106 | 0.16 |
| HCV QL10, LogIU/mLa | 2.6 ± 3.0 | 3.6 ± 3.0 | 0.17 |
| Genotype | |||
| 1a | 31 (5) | 48 (74) | 0.30 |
| 1b | 13 (2) | 12 (18) | |
| 2b | 25 (4) | 14 (21) | |
| 3a | 6 (1) | 5 (8) | |
| 4 | 6 (1) | 5 (8) | |
| Indeterminate | 19 (3) | 16 (24) | |
| Treatment group | |||
| Untreated | 44 (7) | 59 (91) | 0.68 |
| Interferon | 44 (7) | 21 (32) | |
| Direct-acting antivirals | 13 (2) | 20 (30) | |
| Failed viral therapy | 13 (2) | 12 (19) | > 0.99 |
| Time from 0 VL to surgery in months | 83 ± 71 | 50 ± 45 | 0.08 |
| Aspartate transaminase | 47 ± 25 | 37 ± 36 | 0.02 |
| Alanine transaminase | 39 ± 20 | 39 ± 31 | 0.56 |
| MELD levelb | |||
| 1 | 75 (12) | 82 (125) | 0.95 |
| 2 | 25 (4) | 12 (19) | |
| 3 | 0 (0) | 6 (9) | |
| Child-Pugh classc | |||
| A | 56 (9) | 97 (149) | < 0.001 |
| B | 38 (6) | 3 (4) | |
| C | 6 (1) | 0 (0) | |
| Liver fibrosis staged | |||
| F0 | 0 (0) | 17 (26) | 0.046 |
| F1 | 6 (1) | 13 (20) | |
| F2 | 6 (1) | 9 (14) | |
| F3 | 13 (2) | 14 (21) | |
| F4 | 44 (7) | 17 (26) | |
| Not obtained | 31 (5) | 30 (46) | |
| Liver fibrosis activitye | |||
| A0 | 25 (4) | 24 (36) | 0.83 |
| A1 | 38 (6) | 31 (48) | |
| A2 | 6 (1) | 13 (20) | |
| A3 | 0 (0) | 2 (3) | |
| Not obtained | 31 (5) | 30 (46) |
Data presented as % (n) or mean ± SD.
aQL10 = quantitative log 10.
bMELD level: Level 1 (score 6 to 9), Level 2 (score 10 to 19), Level 3 (score 20 to 29).
cChild-Pugh class: A (well compensated disease), B (significant liver function compromise), C (decompensated disease).
dLiver fibrosis stage: F0: no fibrosis, F1: minimal fibrosis, F2: significant fibrosis, F3: severe fibrosis, F4: cirrhosis.
eLiver fibrosis activity: A0: no activity, A1: mild activity, A2: moderate activity, A3: severe activity.
Table 3.
Perioperative characteristics of patients with HCV with 2-year mortality compared with those without after undergoing primary elective TJA
| Variable | Mortality (n = 16) | No mortality (n = 153) | p value |
| TJA type | |||
| THA | 75 (12) | 47 (72) | 0.04 |
| TKA | 25 (4) | 53 (81) | |
| Operative duration in minutes | 91 ± 34 | 102 ± 35 | 0.15 |
| Blood loss in mL | 200 ± 12 | 200 ± 17 | 0.72 |
| Implant details | |||
| Cemented | 38 (6) | 55 (84) | 0.29 |
| Antibiotic cement (in cemented cases) | 33 (2) | 56 (47) | 0.41 |
| ASA score | 0.16 | ||
| 1 | 0 (0) | 1 (1) | |
| 2 | 13 (2) | 18 (28) | |
| 3 | 75 (12) | 78 (120) | |
| 4 | 12 (2) | 3 (4) | |
| Tranexamic acid use | 44 (7) | 33 (51) | 0.40 |
| General anesthesia | 88 (14) | 78 (119) | 0.53 |
| Intraoperative blood transfusion | 0 (0) | 1 (1) | > 0.99 |
| Intraoperative blood transfusion volume in units pRBCs | 0 (NA) | 2 (NA) | > 0.99 |
| Hemovac drain | 50 (8) | 73 (111) | 0.08 |
Data presented as % (n) or mean ± SD. ASA = American Society of Anesthesiologists; pRBCs = packed red blood cells.
Table 4.
Acute postoperative outcomes of patients with HCV with 2-year mortality compared with those without after undergoing primary elective TJA
| Outcome | Mortality (n = 16) | No mortality (n = 153) | p value |
| Altered mental status or delirium | 6 (1) | 3 (4) | 0.40 |
| Acute renal failure | 6 (1) | 1 (1) | 0.18 |
| Deep vein thrombosis | 13 (2) | 0 (0) | 0.01 |
| Pulmonary embolism | 6 (1) | 1 (1) | 0.18 |
| Myocardial infarction | 6 (1) | 0 (0) | 0.09 |
| Acute respiratory distress syndrome | 6 (1) | 1 (1) | 0.18 |
| Acute cerebrovascular accident or stroke | 6 (1) | 0 (0) | 0.09 |
| Pneumonia | 6 (1) | 0 (0) | 0.09 |
| Sepsis | 0 (0) | 1 (1) | > 0.99 |
| Postoperative anemia resulting in blood transfusion | 31 (5) | 18 (27) | 0.19 |
| Total hospital blood transfusion, units pRBCs | 2.4 ± 2.0 | 2.0 ± 1.8 | 0.42 |
| ICU stay | 13 (2) | 4 (6) | 0.17 |
| ICU LOS in days | 8 ± 6 | 3 ± 2 | 0.17 |
| LOS in days | 5 ± 3 | 4 ± 2 | 0.02 |
| Discharge disposition | |||
| Home | 50 (8) | 82 (125) | 0.01 |
| Skilled nursing facility or inpatient rehabilitation | 50 (8) | 18 (28) | |
| Intraoperative fracture | 6 (1) | 1 (1) | 0.18 |
Data presented as % (n) or mean ± SD. pRBCs = packed red blood cells; ICU = intensive care unit; LOS = length of stay.
Ethical Approval
Ethical approval for this study was obtained from the University of Alabama at Birmingham (IRB-300001997 and IRB-300001997-013).
Statistical Analysis
We used chi-square tests to compare categorical variables, and we used two-tailed t-tests to compare continuous variables between the patients who died within 2 years of surgery and those who were still alive at the latest follow-up. We compared all patient-related variables, liver characteristics, surgical variables, and outcomes noted above between the two groups. Significant preoperative variables with p < 0.05 were then enrolled into a multivariable logistic regression analysis to identify the independent risk factors for mortality. We considered p values < 0.05 to be statistically significant.
Results
Factors Independently Associated With Death After Arthroplasty
After accounting for the variables present in the univariate analysis including male sex, aspartate transaminase level, peripheral vascular disease, heart failure, end-stage renal disease, chronic obstructive pulmonary disease, and surgery type, Child-Pugh Class B or C was found to be the only independent factor associated with increased odds of early (within 2 years) mortality in patients with HCV undergoing elective TJA (adjusted odds ratio 29 [95% confidence interval 5 to 174]; p < 0.001) (Table 5). Seven of the 11 patients with Child-Pugh Class B or C died after TJA within 2 years after elective TJA compared with 6% (nine of 158) with Child-Pugh Class A (p < 0.001).
Table 5.
Multivariable analysis of risk factors for 2-year mortality in patients with HCV undergoing elective TJA
| Variable | OR (95% CI) | p value |
| Men (compared to women) | 1.1 (0.2 to 7) | 0.95 |
| Aspartate transaminase | 1.01 (0.99 to 1.02) | 0.28 |
| Child-Pugh class (B or C compared with A) | 29 (5 to 174) | < 0.001 |
| Peripheral vascular disease | 3 (0.5 to 20) | 0.21 |
| End-stage renal disease | 2 (0.3 to 8) | 0.59 |
| Heart failure | 5 (0.8 to 30) | 0.08 |
| Chronic obstructive pulmonary disease | 3 (0.5 to 15) | 0.26 |
| TJA type (THA or TKA) | 2 (0.5 to 10) | 0.29 |
Postoperative DVT, LOS, and discharge disposition were excluded from model because it was meant to include preoperative variables to better assist physicians counseling patients with HCV before elective surgery.
Other Findings
Readmissions within 90 days and 1 year for mechanical etiologies and PJI were similar between the mortality group and patients who were alive at the 2-year follow-up interval (Table 6). The mortality group and survival group had similar risks of hematoma (0% [0 of 16] versus 3% [five of 153]; p > 0.99) and cellulitis (0% [0 of 16] versus 3% [five of 153]; p > 0.99) postoperatively.
Table 6.
Postoperative outcomes at 90 days and 1 year in patients with HCV with 2-year mortality compared with those without after undergoing primary elective TJA
| Outcome | Mortality (n = 16) | No mortality (n = 153) | p value |
| 90-day complications | |||
| Dislocation | 0 (0) | 1 (2) | > 0.99 |
| Periprosthetic joint infection | 6 (1) | 4 (6) | 0.51 |
| Periprosthetic fracture | 0 (0) | 1 (1) | > 0.99 |
| Mechanical revision | 0 (0) | 3 (4) | > 0.99 |
| 1-year complications | |||
| Dislocation | 0 (0) | 1 (2) | > 0.99 |
| Periprosthetic joint infection | 6 (1) | 6 (9) | > 0.99 |
| Periprosthetic fracture | 0 (0) | 1 (2) | > 0.99 |
| Mechanical revision | 0 (0) | 7 (10) | 0.89 |
| Complications at any time | |||
| Periprosthetic joint infection | 6 (1) | 10 (15) | > 0.99 |
| Mechanical revision | 0 (0) | 11 (17) | 0.37 |
| Cellulitis or wound dehiscence | 0 (0) | 3 (4) | > 0.99 |
| Hematoma | 0 (0) | 3 (5) | > 0.99 |
Data presented as % (n) or mean ± SD.
Discussion
In the past two decades, orthopaedic research of patients with HCV undergoing elective TJA has centered around identifying short-term risk factors for unplanned readmission and reoperations for surgical complication, specifically PJI, to prevent them [7, 8, 12, 15, 27]. However, little is known about early mortality and, more importantly, its risk factors in this complex patient population after TJA. Patients with HCV are often affected by major comorbidities that can influence mortality risks after emergency or elective orthopaedic and nonorthopaedic procedures, especially liver function and status [5, 10]. The mortality risks of patients with HCV undergoing general, cardiothoracic, and trauma surgery have been thoroughly investigated, and the MELD score was strongly correlated with postoperative mortality while the Child-Pugh classification is predictive of overall mortality [16, 19]. However, the various arthroplasty studies conducted on patients with HCV could not address mortality after TJA because they either lacked granular data about liver status, liver function, and treatment variables or were designed to determine the effects of antiviral medication treatment on postoperative outcomes including PJI [7, 12, 15, 27]. Hence, the goal of our study was to identify variables associated with early mortality within 2 years of elective TJA. We concluded from our multicenter study that Child-Pugh Class B or C in patients with HCV is independently associated with increased overall early mortality after TJA, as was observed in other general surgical specialties. Patient education and a thorough discussion with them highlighting these elevated risks of mortality within 2 years of elective TJA is paramount in the decision-making process.
Limitations
First, we lost approximately 25% (57 of 226) of our initial population because of loss to follow-up; we were unable to contact the patients to determine their living status, and some patients had incomplete medical records for inclusion in our analysis. This attrition of patients can generate transfer bias in which patients lost to follow-up possibly had a greater risk of complications, including mortality within the first 2 years, and this could have impacted our analysis. Although our study included three large-volume academic centers, our analysis was underpowered, especially when reporting on complications, with a low number of endpoints in addition to mortality. This limits our ability to make strong recommendations regarding these outcome variables. The three participating institutions have diverse patient populations based on their geographic location and the region they serve, in addition to variable practice methods, HCV treatments, and postoperative protocols, which generates inherent variability in the data and analysis. The heterogeneity is reflected, to a large degree, in the complex patients with Child-Pugh Class B who vary considerably in terms of liver function and comorbidities. We believe having three participating centers helped us to capture some of that diversity, and therefore our results can be generalized to large academic centers across different geographic areas of the United States. However, our findings cannot be generalized to community centers or hospitals that are not equipped with dedicated HCV clinics to optimize patients preoperatively or follow them postoperatively. Furthermore, we were unable to characterize the cause of death and whether it was related to the surgical procedure or caused by comorbidities, further liver deterioration, or other kinds of complications; hence, we reported the overall mortality risk, which encompasses all causes of death. In addition, we used a follow-up period of 2 years to accrue enough events to analyze, which limits us from generalizing our results to early (such as 30-day or 90-day) postoperative mortality, for which the associated risk factors for mortality may differ.
Discussion of Key Findings
Patients with HCV and major functional compromise or decompensation of their liver (Child-Pugh Class B or C) have substantially higher risks of death within 2 years of elective TJA than those with well-compensated disease (Child-Pugh Class A). The Child-Pugh score has been shown to be predictive of mortality in extrahepatic surgeries in which patients with Class B had a 30% risk of death after abdominal surgery; the risk was up to 82% for those with Class C [11, 18]. The postoperative mortality risks of patients with Child-Pugh classes A, B, and C were 6%, 67%, and 100%, respectively, after open heart surgery, which is similar to our findings in elective TJA [1]. A recent long-term natural history study of patients with HCV cirrhosis treated with direct-acting agents revealed that those with Child-Pugh Class A have similar all-cause mortality risks to the general population when adjusting for age and comorbidities at 5 years of follow-up (5% [95% CI 3% to 7%]) [9]. However, patients with Child-Pugh Class B had a much higher risk of death at 5 years (25% [95% CI 13% to 37%]) than the general population after a standardized mortality ratio was generated using the Human Mortality Database [9]. In our study, we noted a 2-year mortality risk of greater than 60% for patients with Child-Pugh Class B or C after elective TJA. Clearly, the surgical procedure is an impactful event and compounds the mortality risk, which is not a consequence of the natural history of the disease.
Comorbidities including chronic obstructive pulmonary disease, heart failure, peripheral vascular disease, and end-stage renal disease were much more frequent in our study among patients who died within 2 years of TJA, but none of these factors were independently associated with early mortality in our multivariable model. This is in stark contrast to what has been published on elective TJA in the general population, in whom cardiovascular disease, peripheral vascular disease, and advanced Charlson comorbidity index score were associated with 90-day early mortality [2, 3]. Our findings highlight the singular important role liver status plays in patients with HCV undergoing elective TJA. In addition, the surgical procedures, especially more extensive procedures including cardiovascular, trauma, and pancreatic, have higher mortality risks in patients with HCV than less morbid procedures such as inguinal hernia repairs [10]. Although we noted a disparity in the mortality risks between patients undergoing THA and those with TKA, the procedure type (THA versus TKA) was not independently associated with early mortality.
Conclusion
Patients with HCV and decompensated liver function (Child-Pugh Class B or C) undergoing elective TJA have a high risk of mortality of more than 60% within 2 years of surgery. This exceptionally high early death risk is similar to what was observed in other extensive surgical procedures including cardiac and pancreatic surgery. With the understanding that severe arthritis pain that is resistant to nonoperative measures may create desperation among patients, surgeons should be wary of these sobering statistics and cognizant that TJA would decrease patients’ life expectancy. Future studies should focus on incorporating novel pain control methods in a multimodal manner, including long-acting injectables, frequent nerve blocks, nerve cryotherapy, and medical marijuana, to keep the patients comfortable, given that this complex patient population is susceptible to high mortality risks with any type of surgical intervention.
Footnotes
One of the authors (AFC) certifies having received or may receive payments or benefits, during the study period, in an amount of less than USD 10,000 from Slack Inc; in an amount of less than USD 10,000 from Joint Purification Systems; in an amount of USD 10,000 to USD 100,000 from Stryker; in an amount of less than USD 10,000 from bOne; in an amount of less than USD 10,000 from Graftworx; in an amount of less than USD 10,000 from Pfizer; in an amount of USD 10,000 to USD 100,000 from Avanos; in an amount of less than USD 10,000 from IrriMax; in an amount of less than USD 10,000 from Convatec; in an amount of less than USD 10,000 from 3M; in an amount of less than USD 10,000 from Recro; in an amount of less than USD 10,000 from Heraeus; in an amount of less than USD 10,000 from Hyalex; in an amount of less than USD 10,000 from Ethicon; and in an amount of less than USD 10,000 from UpToDate. One of the authors (ENH) certifies receipt of personal payments or benefits, during the study period, in an amount of USD 10,000 to USD 100,000 from Corin Ltd.
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.
Ethical approval for this study was obtained from the University of Alabama at Birmingham Office of the Institutional Review Board for Human Use (IRB-300001997 and IRB-300001997-013).
This work was performed at the University of Alabama, Birmingham, AL, USA.
Contributor Information
Kyle H. Cichos, Email: kcichos@uab.edu.
Eric Jordan, Email: EJORDAN6@bwh.harvard.edu.
Kian Niknam, Email: Kian.Niknam@ucsf.edu.
Antonia F. Chen, Email: afchen@bwh.harvard.edu.
Erik N. Hansen, Email: Erik.Hansen@ucsf.edu.
Gerald McGwin, Jr, Email: gmcwin@uabmc.edu.
References
- 1.An Y, Xiao YB, Zhong QJ. Open-heart surgery in patients with liver cirrhosis: indications, risk factors, and clinical outcomes. Eur Surg Res. 2007;39:67-74. [DOI] [PubMed] [Google Scholar]
- 2.Aynardi M, Jacovides CL, Huang R, Mortazavi SM, Parvizi J. Risk factors for early mortality following modern total hip arthroplasty. J Arthroplasty. 2013;28:517-520. [DOI] [PubMed] [Google Scholar]
- 3.Aynardi M, Pulido L, Parvizi J, Sharkey PF, Rothman RH. Early mortality after modern total hip arthroplasty. Clin Orthop Relat Res. 2009;467:213-218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Bedair HS, Schurko BM, Dwyer MK, Novikov D, Anoushiravani AA, Schwarzkopf R. Treatment for chronic hepatitis C prior to total hip arthroplasty significantly reduces periprosthetic joint infection. J Arthroplasty. 2019;34:132-135. [DOI] [PubMed] [Google Scholar]
- 5.Carbonell AM, Wolfe LG, DeMaria EJ. Poor outcomes in cirrhosis-associated hernia repair: a nationwide cohort study of 32,033 patients. Hernia. 2005;9:353-357. [DOI] [PubMed] [Google Scholar]
- 6.Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1-85. [PubMed] [Google Scholar]
- 7.Cichos KH, Jordan E, Niknam K, et al. Total joint arthroplasty should not be delayed in hepatitis C patients after successful treatment achieving a sustained viral load. Arthroplast Today. 2022;17:107-113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Cornell E, Novikov D, Niu R, Staatz K, Schwarzkopf R, Smith EL. Hepatitis C antiviral treatment decreases all-cause complications after total joint arthroplasty regardless of the presence of fibrosis. J Arthroplasty. 2021;36:1551-1555. [DOI] [PubMed] [Google Scholar]
- 9.D'Ambrosio R, Degasperi E, Anolli MP, et al. Incidence of liver- and non-liver-related outcomes in patients with HCV-cirrhosis after SVR. J Hepatol. 2022;76:302-310. [DOI] [PubMed] [Google Scholar]
- 10.de Goede B, Klitsie PJ, Lange JF, Metselaar HJ, Kazemier G. Morbidity and mortality related to non-hepatic surgery in patients with liver cirrhosis: a systematic review. Best Pract Res Clin Gastroenterol. 2012;26:47-59. [DOI] [PubMed] [Google Scholar]
- 11.Garrison RN, Cryer HM, Howard DA, Polk HC Jr. Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Ann Surg. 1984;199:648-655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.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;97:1952-1957 [DOI] [PubMed] [Google Scholar]
- 13.Jacobson IM, Lim JK, Fried MW. American Gastroenterological Association Institute clinical practice update-expert review: care of patients who have achieved a sustained virologic response after antiviral therapy for chronic hepatitis C infection. Gastroenterology. 2017;152:1578-1587. [DOI] [PubMed] [Google Scholar]
- 14.Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464-470. [DOI] [PubMed] [Google Scholar]
- 15.Kildow BJ, Politzer CS, DiLallo M, Bolognesi MP, Seyler TM. Short and long-term postoperative complications following total joint arthroplasty in patients with human immunodeficiency virus, hepatitis B, or hepatitis C . J Arthroplasty. 2018;33(7S):S86-S92.e1. [DOI] [PubMed] [Google Scholar]
- 16.Kim DH, Kim SH, Kim KS, et al. Predictors of mortality in cirrhotic patients undergoing extrahepatic surgery: comparison of Child-Turcotte-Pugh and model for end-stage liver disease-based indices. ANZ J Surg. 2014;84:832-836. [DOI] [PubMed] [Google Scholar]
- 17.Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PCJ. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000;31:864-871. [DOI] [PubMed] [Google Scholar]
- 18.Mansour A, Watson W, Shayani V, Pickleman J. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery. 1997;122:730-735. [DOI] [PubMed] [Google Scholar]
- 19.Nicoll A. Surgical risk in patients with cirrhosis. J Gastroenterol Hepatol. 2012;27:1569-1575. [DOI] [PubMed] [Google Scholar]
- 20.Novikov D, Feng JE, Anoushiravani AA, et al. Undetectable hepatitis C viral load is associated with improved outcomes following total joint arthroplasty. J Arthroplasty. 2019;34:2890-2897. [DOI] [PubMed] [Google Scholar]
- 21.Pageaux GP, Nzinga CL, Ganne N, et al. Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis. BMC Infect Dis. 2022;22:94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Parvizi J, Gehrke T; International Consensus Grouo on Periprosthetic Joint Infection. Definition of periprosthetic joint infection. J Arthroplasty. 2014;29:1331. [DOI] [PubMed] [Google Scholar]
- 23.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;93:1448-1454. [DOI] [PubMed] [Google Scholar]
- 24.Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646-649. [DOI] [PubMed] [Google Scholar]
- 25.Ross AJ, Ross BJ, Lee OC, Hood HW, Sanchez FL, Sherman WF. Does preoperative antiviral treatment for hepatitis C decrease risk of complications after total hip arthroplasty? A matched cohort study. J Arthroplasty. 2022;37:1326-1332.e3. [DOI] [PubMed] [Google Scholar]
- 26.Ross AJ, Ross BJ, Lee OC, Weldy JM, Sherman WF, Sanchez FL. A missed opportunity: the impact of hepatitis C treatment prior to total knee arthroplasty on postoperative complications. J Arthroplasty. 2022;37:709-713.e2. [DOI] [PubMed] [Google Scholar]
- 27.Salomon B, Krause PC, Dasa V, Shi L, Jones D, Chapple AG. The impact of hepatitis C and liver disease on risk of complications after total hip and knee arthroplasty: analysis of administrative data from Louisiana and Texas. Arthroplast Today. 2021;7:200-207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Teh SH, Nagorney DM, Stevens SR, et al. Risk factors for mortality after surgery in patients with cirrhosis. Gastroenterology. 2007;132:1261-1269. [DOI] [PubMed] [Google Scholar]
- 29.Veracruz N, Gish RG, Cheung R, Chitnis AS, Wong RJ. Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019. J Viral Hepat. 2022;29:352-365. [DOI] [PubMed] [Google Scholar]
- 30.Wei W, Liu T, Zhao J, Li B, Li S, Liu J. Does the hepatitis C virus affect the outcomes of total joint arthroplasty? A meta-analysis of ten studies. J Orthop Sci. 2019;24:822-829. [DOI] [PubMed] [Google Scholar]