Highlights
- ●An increased risk of acquiring hepatitis B and C following exposure to invasive procedures was observed
- ●Compared with hepatitis A (controls), the risk was twice as high for HBV and over five times higher for HCV
- ●Most of the procedures (surgical specialties) evaluated were associated with the risk of acquiring HBV or HCV
- ●Minor surgeries, biopsies, and endoscopies showed a strong association with both HCV and HBV infection
- ●Observance of universal precautions in healthcare settings is crucial
Abstract
Background & Aims
Surgical interventions and invasive diagnostic/therapeutic procedures are known routes of transmission of viral hepatitis. Using data from the Italian surveillance system for acute viral hepatitis (SEIEVA), the aim of the study was to investigate the association between specific types of invasive procedures and the risk of acute HBV and HCV infections.
Methods
Data from SEIEVA surveillance (period 2000-2021) were used. The association between acute HBV and HCV infection and potential risk factors, i.e. surgical interventions and diagnostic/therapeutic procedures, (given according to the ICD-9-CM classification), was investigated in comparison to age-matched hepatitis A cases, used as controls, by conditional multiple logistic regression analysis.
Results
8,176 cases with acute HBV, 2,179 with acute HCV, and the respective age-matched controls with acute HAV infection were selected for the main analysis. Most of the procedures evaluated were associated with the risk of acquiring HBV or HCV. The strongest associations for HBV infection were: gynaecological surgery (OR=5.19; 95%CI=1.12-24.05), otorhinolaryngological surgery (OR=3.78; 95%CI=1.76-8.09), and cardiac/thoracic surgery (OR = 3.52; 95%CI = 1.34-9.23). For HCV infection, neurosurgery (OR=11.88; 95%CI=2.40-58.85), otorhinolaryngological surgery (OR=11.54; 95%CI=2.55-52.24), and vascular surgery (OR=9.52; 95%CI=3.25-27.87). A high association was also found for ophthalmological surgery (OR=8.32; 95%CI=2.24-30.92). Biopsy and/or endoscopic procedures were significantly associated with both HCV (OR=3.84; 95%CI=2.47-5.95) and, to a lesser extent, HBV infection (OR=1.48; 95%CI=1.16-1.90).
Conclusions
Despite the progress made in recent years, invasive procedures still represent a significant risk factor for acquiring parenterally transmitted hepatitis viruses, thus explaining the still numerous and unexpected cases diagnosed among the elderly population in Italy. Our results underline the importance of observing universal precautions to control the iatrogenic transmission of hepatitis viruses.
Impact and implications
Cases of parenterally transmitted acute viral hepatitis in the elderly population, that are difficult to explain by the most recognized risk factors, continue to bde diagnosed in Italy. Based on the Italian SEIEVA surveillance of acute viral hepatitis data, the study highlights an increased risk of acquiring hepatitis B and C following exposure to invasive procedures, which might explain the cases in elderly individuals. Furthermore, this finding emphasises the need to observe universal precautions strictly, in healthcare settings, also in case of minor surgery procedures.
Graphical abstract
Graphical Abstract
Keywords
Conflict of interest
The authors have no conflict of interest to declare in relation to this manuscript.
Financial support
no funding
Authors contribution
MET developed the concept for the study and its design; SiC, GI and the SEIEVA Collaborating Group collected the data; SuC, AM, LF, VA, and MET analysed and interpreted the data; SuC, AM, VA, and MET drafted the manuscript; SuC, AM, LF, VA, SiC, GI, MS and MET critically revised the manuscript to ensure its intellectual content: MET and LF performed the statistical analyses; all authors had access to the study data and reviewed and approved the final manuscript.
Introduction
Hepatitis B and C are viral infections that can cause acute and chronic diseases, ranging in severity from mild illnesses to severe, lifelong diseases leading to liver cirrhosis and cancer. As blood-borne viruses, most infections occur through exposure to blood and fluid from infected individuals by injection drug use, unprotected sexual practices, or unsafe injection practices. Hepatitis B Virus (HBV) and, to a much less extent, Hepatitis C Virus (HCV) are also transmitted from mother to child during pregnancy and delivery. They represent significant public health problems: according to 2019 World Health Organization (WHO) estimates, about 350 million people worldwide are chronically infected
1
, WHO - World Health Organization. Hepatitis B. Key facts. WHO, Geneve; 2021 [Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b].
2
. In Italy, infections due to HBV and HCV represent a major public health problem and a heavy burden on the Italian Healthcare System WHO - World Health Organization. Hepatitis C. Key facts. WHO, Geneve; 2021 [Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c].
3
, being responsible for a large proportion of chronic liver diseases, cirrhosis, and hepatocellular carcinomas 4
, 5
, 6
, 7
. In particular, Italy is recognised as having the highest HCV prevalence in Western Europe, with a peak prevalence observed in elderly individuals and in the southern regions 8
, 9
. However, the estimated epidemiological data, especially for HCV, are often based on outdated or non-representative figures as the studies were conducted in limited geographical areas 9
, 10
, 11
, 12
. Other estimations, based on mathematical models, suggest a prevalence of viraemic HCV infection in 2019-2020, for Italy, ranging from 0.68% (0.64-0.71) to 1.0% (0.4 -1.4) 13
, 14
. In order to detect undiagnosed hepatitis C virus infections and improve the possibility of early diagnosis and treatment to avoid complications of advanced liver disease, in 2020 a free national screening for HCV infection was introduced for the birth cohort 1969-1989, for people who inject drugs or were in custody 15
.Although the incidence of both infections in Italy has decreased over the past decades
10
, 16
, 17
, 18
, also thanks to the introduction of compulsory HBV vaccination in 1991 19
, 20
, 21
and to the development of treatment options for HCV, largely available in the country since 2017 22
, 23
, 24
, new infections still occur.The Italian National Hepatitis Surveillance System (SEIEVA) has shown that there are cases of parenterally transmitted acute viral hepatitis in the elderly population that are difficult to explain by the most recognized risk factors.
Surgery and diagnostic or therapeutic invasive procedures are known to be important transmission routes for HBV and HCV infections
25
, 26
, 27
. However, we found no recent studies in the literature investigating the risk of transmission of HBV infection through such practices. On the other hand, a recently published meta-analysis has investigated the risk of contracting HCV for various hospital-based invasive procedures, including surgery 28
.In Italy, data is limited and the last paper dates back to 20 years ago, when a study conducted by the same research group was published
29
.Using SEIEVA data, the aim of our study is to investigate the association between specific types of surgery or other invasive procedures, including biopsy and endoscopy, and the risk of acute HBV and HCV infections, in order to update, with the same methodology, the results found by Mele et al. in 2001
29
.Methods
SEIEVA surveillance
The present study was performed with data from the SEIEVA surveillance, collected from a network of Local Health Units (LHUs) located throughout Italy and now covering more than 83% of the population (coverage has increased over time, compared to 30% in 1990 and 59% in 2000). SEIEVA is a routine surveillance system active in Italy, established in 1985
30
and coordinated by the Istituto Superiore di Sanità (National Institute of Health, Italy). Individuals diagnosed with acute viral hepatitis are interviewed through a standardised questionnaire collecting information on the sociodemographic characteristics, exposure to parenteral risk factors within 6 months of disease onset, and exposure to faecal/oral risk factors within 6 weeks of onset. Since 1994, information has been collected on the type of surgery and other medical invasive procedures, including biopsy and endoscopy. SEIEVA’s detailed methods are described elsewhere 30
.Information on the surgical procedure performed was classified in accordance with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
31
and then categoriszed according to the surgical specialty.National Center for Health Statistics (U.S), Council on Clinical Classifications. Commission on Professional and Hospital Activities & World Health Organization. (1978). The International classification of diseases, 9th revision, clinical modification: ICD. 9. CM. Ann Arbor, Mich: Commission on Professional and Hospital Activities.
The data analysed in this paper refer to the two decades from 2000 to 2021. During this period, no changes were made to the notification system.
In regards to the ethical aspects, the SEIEVA surveillance was approved since its foundation (1985), and it is now monitored by the Data Protection Officer of the Italian National Institute of Health. Hence, for the analysis and publication of aggregated data from the surveillance, specific approval of the ethics committee is not requested.
Case-control study
To evaluate the strength of associations between parenterally transmitted viral hepatitis and different types of surgery or invasive procedures, individuals with acute HBV or HCV infection were individually matched with acute HAV cases, identified by the same surveillance system in the same period, using a matched case-control study. Hepatitis A cases were chosen as controls because they belonged to the same population as hepatitis B and C cases, as they came from the same surveillance system and, therefore, may have undergone the same selection processes. Given that HAV has different modes of transmission from HBV and HCV, hepatitis A cases can be considered similar to the general population in terms of the likelihood of undergoing surgery. Matching was performed by age (± 5 years). One control was randomly selected for each case whose age, at the time of their presentation, was within 5 years of that of the case. Two different control groups were selected for hepatitis B and hepatitis C cases, respectively. Age-matched analysis was chosen because the age distribution of hepatitis A cases is very different from B and C cases, and the age adjustment could have resulted in residual confounding.
Individuals under 15 years of age were excluded from the analysis because few were exposed to invasive procedures; cases with missing information on age were also excluded because of age matching. In the primary analysis, cases with missing data on undergoing invasive procedures were also excluded; in a secondary sensitivity analysis, these cases were included once, as if they had all undergone surgery, and once as if none had undergone surgery.
Statistical Analysis
To evaluate the statistical significance of the differences observed between hepatitis types regarding socio-demographic characteristics, the chi-squared test was used.
A p-value < 0.05 was considered to be significant.
A conditional multiple logistic regression model was used to estimate the adjusted odds ratios (OR) and their 95% confidence intervals (CI). Possible confounding to be adjusted for in the models were selected among sex, educational level, area of residence, intravenous drug use, blood transfusion, household HBV/HCV positivity, other parenteral exposures (ear piercing, tattooing, acupuncture, attendance at a chiropodist or manicurist) and intercourse with multiple sexual partners. Factors significantly associated (by chi-squared test) with both the outcome and the exposure of interest (to undergo an invasive procedure) were included in the models. Statistical analysis was performed with STATA version 16 (StataCorp 2019).
Results
In the timeframe 2000-2021, 27,936 cases of acute HAV, HBV, and HCV infection were notified to SEIEVA. A total of 3,270 individuals were excluded from the analysis because they were less than 15 years of age or without information on age. For the main analysis, other 2,090 cases without information on surgical intervention and/or endoscopy were excluded. After the described selections, 8,176 acute hepatitis B cases (and their age-matched hepatitis A controls) and 2,179 acute hepatitis C cases (and their age-matched hepatitis A controls) were included in the primary analysis.
The individual age-matching made the hepatitis B and C cases comparable with their respective controls. Table 1 shows the other demographic features of the study population by type of hepatitis infection. Statistically significant differences between cases, hepatitis B and C cases, and their respective controls (hepatitis A cases) were observed regarding gender (only hepatitis B), educational level, and area of diagnosis. In particular, there was a lower percentage of HBV cases notified by the Southern regions.
Table 1Study population by demographic features. SEIEVA 2000-2021, Italy.
| Hepatitis B (8,176 cases/controls) | Hepatitis C (2,179 cases/controls) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Cases | Controls | p-value | Cases | Controls | p-value | |||||
| n | % | n | % | n | % | n | % | |||
| Gender | ||||||||||
| Male | 6,157 | 75.6 | 5,799 | 71.2 | <0.001 | 1,363 | 62.7 | 1,405 | 65.0 | 0.116 |
| Female | 1,984 | 24.4 | 2,345 | 28.8 | 810 | 37.3 | 756 | 35.0 | ||
| Educational level | ||||||||||
| ≥ 9 years | 2,605 | 52.1 | 1,914 | 38.1 | <0.001 | 820 | 62.5 | 686 | 46.5 | <0.001 |
| ≤ 8 years | 2,399 | 47.9 | 3,105 | 61.9 | 493 | 37.5 | 790 | 53.5 | ||
| North | 4,360 | 53.3 | 4,109 | 50.3 | <0.001 | 1,100 | 50.5 | 951 | 43.6 | <0.001 |
| Centre | 2,974 | 36.4 | 2,293 | 28.0 | 657 | 30.1 | 635 | 29.1 | ||
| South - Islands | 842 | 10.3 | 1,774 | 21.7 | 422 | 19.4 | 593 | 27.2 | ||
∗ Subjects < 15 were excluded from the analysis
∗∗ SEIEVA: national hepatitis surveillance system
† chi squared test
Tables 2 and 3 show the percentage of patients who had undergone an invasive procedure. Overall, 15.2% of the individuals with acute HBV infection (and 8.0% of their controls) and 31.2% with acute HCV infection (and 8.7% of the respective controls) reported that they had undergone at least one invasive procedure in the 6 months before the onset of the disease. The differences between cases and controls were highly statistically significant (p<0.001) for both HBV and HCV. The adjusted association (OR) between undergoing an invasive procedure and hepatitis risk was 1.99 (95%CI = 1.78-2.22) for B (Table 2), and 4.28 (95%CI = 3.50-5.23) for C (Table 3). A sensitivity analysis performed attributing an invasive procedure to all the patients with missing information gave the following results: OR = 1.82 (95%CI = 1.64-2.03) for hepatitis B and OR = 4.26 (95%CI = 3.44-5.29) for hepatitis C. When attributing “No intervention” to all the patients with missing information, OR was 1.80 (95%CI = 1.60-2.02) for hepatitis B and 4.01 (95%CI = 3.28-4.89) for hepatitis C (data not shown).
Table 2Adjusted odds ratio (OR) and 95% confidence interval (CI) for different types of invasive procedure among hepatitis B cases. SEIEVA 2000-2021, Italy.
| Hepatitis B | adjusted OR (95% CI) | ||||
|---|---|---|---|---|---|
| Cases | Controls | ||||
| n | % | n | % | ||
| Invasive procedure | |||||
| No | 6,934 | 84,8 | 7,521 | 92.0 | 1.00 |
| Yes | 1,242 | 15.2 | 655 | 8.0 | 1.99 (1.78-2.22) |
| Intervention type | |||||
| Cardiac/thoracic surgery | 17 | 0.2 | 7 | 0.1 | 3.52 (1.34-9.23) |
| General Surgery | 255 | 3.2 | 120 | 1.5 | 2.2 (1.74-2.80) |
| Oral/maxillofacial surgery | 230 | 2.9 | 102 | 1.3 | 2.18 (1.68-2.82) |
| Vascular surgery | 23 | 0.3 | 10 | 0.1 | 2.79 (1.27-6.11) |
| Biopsy/endoscopy | 269 | 3.4 | 185 | 2.3 | 1.58 (1.28-1.95) |
| Gynaecological surgery | 46 | 2.4 | 27 | 1.2 | 5.19 (1.12-24.05) |
| Neurosurgery | 19 | 0.2 | 10 | 0.1 | 2.42 (1.04-5.64) |
| Ophthalmological surgery | 19 | 0.2 | 9 | 0.1 | 2.61 (1.04-6.59) |
| Orthopaedic surgery | 85 | 1.1 | 56 | 0.7 | 1.52 (1.05-2.19) |
| Otolaryngological surgery | 33 | 0.4 | 9 | 0.1 | 3.78 (1.76-8.09) |
| Urological surgery | 31 | 0.4 | 15 | 0.2 | 1.89 (0.98-3.65) |
| Other intervention | 31 | 0.4 | 12 | 0.1 | 2.12 (1.03-4.37) |
∗ Subjects < 15 were excluded from the analysis
† Adjusted for factors associated to both outcome and surgery intervention: area of residence, intravenous drug use and beauty treatments (tattoo, piercing, barber's shave, manicure) in multiple conditional logistic regression analysis
‡ SEIEVA: national hepatitis surveillance system
§ For females
∗∗ Some patients report a surgical intervention but without specifying the type
Table 3Adjusted odds ratio (OR) and 95% confidence interval (CI) for different types of invasive procedure among hepatitis C cases. SEIEVA 2000-2021, Italy.
| Hepatitis C | adjusted OR (95% CI) | ||||
|---|---|---|---|---|---|
| Cases | Controls | ||||
| n | % | n | % | ||
| Intervention | |||||
| No | 1,499 | 68.8 | 1,989 | 91.3 | 1.00 |
| Yes | 680 | 31.2 | 190 | 8.7 | 4.28 (3.50-5.23) |
| Intervention type | |||||
| Cardiac/thoracic surgery | 32 | 1.5 | 5 | 0.2 | 6.22 (2.31-16.78) |
| General Surgery | 153 | 7.3 | 31 | 1.4 | 6.84 (4.3-10.88) |
| Oral/maxillofacial surgery | 39 | 1.9 | 32 | 1.5 | 1.46 (0.87-2.44) |
| Vascular surgery | 31 | 1.5 | 6 | 0.3 | 9.52 (3.25-27.87) |
| Biopsy/endoscopy | 173 | 8.3 | 40 | 1.9 | 6.09 (4.04-9.17) |
| Gynaecological surgery | 31 | 4.0 | 8 | 1.1 | 2.49 (0.47-13.22) |
| Neurosurgery | 16 | 0.8 | 2 | 0.1 | 11.88 (2.4-58.85) |
| Ophthalmological surgery | 15 | 0.7 | 3 | 0.1 | 8.32 (2.24-30.92) |
| Orthopaedic surgery | 46 | 2.2 | 24 | 1.1 | 1.9 (1.07-3.39) |
| Otolaryngological surgery | 20 | 1.0 | 2 | 0.1 | 11.54 (2.55-52.24) |
| Urological surgery | 20 | 1.0 | 4 | 0.2 | 6.99 (2.17-22.55) |
| Other intervention | 7 | 0.3 | 2 | 0.1 | 4.5 (0.84-24.09) |
∗ Subjects < 15 were excluded from the analysis
† Adjusted for factors associated to both outcome and surgery intervention: area of residence and blood transfusion in multiple conditional logistic regression analysis
‡ SEIEVA: national hepatitis surveillance system
§ For females
∗∗ Some patients report a surgical intervention but without specifying the type
Tables 2 and 3 also show the distribution of surgical intervention by type and hepatitis infection, and the association of the different intervention types with hepatitis B or C. The most frequent invasive procedures for individuals with acute HBV infection were biopsy/endoscopy, general surgery, and oral/maxillo-facial surgery interventions. For those with acute HCV infection, the most frequently reported invasive procedures were biopsy/endoscopy, general surgery, and gynaecological interventions. Among individuals who had undergone biopsy/endoscopy in the previous 6 months, 57.9% of those with acute HBV infection and 59.7% of those with acute HCV infection had undergone gastrointestinal endoscopy, with no statistically significant difference from the control groups. Among individuals who had undergone an ophthalmological intervention, 57.9% of those with acute HBV infection (11/19) and 86.7% of those with acute HCV infection (13/15) had undergone this procedure for cataracts. Regarding oral/maxillo-facial surgery, almost all the interventions (96.5% for hepatitis B and 100% for hepatitis C) were oral surgery.
Most of the procedures considered were associated with the risk of acquiring acute HBV or HCV infection, even if, to a varying extent. After adjusting by conditional multiple logistic regression analysis, a statistically significant association was found to link acute HBV, in particular, with gynaecological surgery (OR = 5.19; 95%CI = 1.12-24.05), otorhinolaryngological surgery (OR = 3.78; 95%CI = 1.76-8.09), and cardiac/thoracic surgery (OR = 3.52; 95%CI = 1.34-9.23; table 2). Acute HCV infection resulted associated with several types of surgical intervention, the strongest associations being with neurosurgery (OR = 11.88; 95%CI = 2.40-58.85), otorhinolaryngological surgery (OR = 11.54; 95%CI = 2.55-52.24), and vascular surgery (OR = 9.52; 95%CI = 3.25-27.87). A high association was also found for ophthalmological surgery (OR = 8.32; 95%CI = 2.24-30.92; Table 3).
Bioptic and/or endoscopic procedures were significantly associated, above all, with HCV infection (OR = 3.84; 95%CI = 2.47-5.95), but a significant association also existed with HBV infection (OR = 1.48; 95%CI = 1.16-1.90).
Discussion
Parenteral hepatitis viruses (HBV and HCV) can be transmitted via invasive procedures and, therefore, have a high risk of iatrogenic transmission (i.e., resulting from the activity of a healthcare provider or institution)
32
. While this risk was more substantial in the past, it has gradually declined over time due to the rapid improvement of healthcare conditions in developed countries 33
, 34
. In particular, the blood donor selective recruitment and the introduction of NAT (Nucleic Acid Testing) screening has had a significant impact, making the risk posed by blood transfusion almost negligible 33
,35
, 36
, 37
. However, the iatrogenic epidemic of hepatitis is continuing to spread in developing countries, where the virus is still transmitted through unscreened blood transfusions and non-sterile injections - Velati C
- Romano L
- Piccinini V
- Marano G
- Catalano L
- Pupella S
- et al.
Prevalence, incidence and residual risk of transfusion-transmitted hepatitis C virus and human immunodeficiency virus after the implementation of nucleic acid testing in Italy: a 7-year (2009-2015) survey.
Blood Transfusion. 2018; 16: 422-432
33
. Moreover, outbreaks in healthcare settings can still occur due to breaches in infection control measures 34
,38
, and nosocomial transmission remains relevant also in the EU/EEA 32
and, particularly, in Italy 39
, 40
.Among the many possible routes of nosocomial transmission, diagnostic or therapeutic invasive procedures, including major and minor surgical interventions, still seem to be at significant risk
41
, 42
. Previous studies in Italy confirm this finding 25
,43
, including our previous study conducted in 2001 29
.Although a large number of studies in the scientific literature mainly address the occupational risks to the surgeon ,
45
, 46
, there is evidence of a significant risk of HBV and HCV infection to the patient undergoing the intervention, either from an infected healthcare worker (professional-to-patient transmission) 47
, 48
, 49
or from another infected patient (patient-to-patient transmission) 34
,50
, 51
. The transmission from infected healthcare providers to their patients, in particular, may be specifically associated with certain types of surgical procedures that may expose patients to the blood of healthcare workers 29
,32
. On the other hand, the patient-to-patient mode of viral transmission is mainly related to improperly sterilised medical instruments. Some healthcare environments are associated with extensive blood contamination, and, therefore, present a higher risk.In the present study, we have estimated the risk associated with each major type of surgery or invasive procedure in the Italian general population over a twenty-year period and have updated our earlier investigation
29
. Since previous studies showed that the risk of transmission also exists in the case of minor invasive procedures such as therapeutic/diagnostic endoscopy and biopsies 52
, 53
, although the evidence is controversial 28
,54
, 55
, 56
, these were included in our analysis. Hepatitis C cases report surgery more frequently than hepatitis B cases. This is a first indicator that surgery leads to an increased risk of hepatitis C. This finding is confirmed by the calculation of ORs in an age-matched case-control study in which individuals with acute HAV infection, which has different modes of transmission, were used as controls to estimate the strength of the association between acute HBV and HCV infection and various types of invasive procedures. All ORs for HCV are higher than those for HBV.The present results are consistent with the high risk of parenterally transmitted hepatitis associated with invasive procedures. Most invasive procedures were associated with HBV and/or HCV acute infection. The strongest associations were found with gynaecological surgery, otorhinolaryngology, and cardiac/thoracic surgery for HBV infection and with neurosurgery, otorhinolaryngology, and vascular surgery interventions for HCV infection, which showed the highest magnitude of the OR point estimates.
Our data therefore confirm the importance of minor invasive procedures in the transmission of both HBV and HCV, such as oral surgery, minor surgery and biopsy/endoscopy. The different risk estimates associated with the various types of invasive procedures between HBV and HCV acute infections could be explained by the much higher prevalence rates of HCV infection in the general Italian population, particularly among the elderly
8
. In fact, admitting a person-to-person mode of viral transmission, the larger pool of subjects infected with HCV than with HBV in the general population causes a higher likelihood of exposure to hepatitis C. In fact, in Italy, surveillance of viral hepatitis in healthcare workers is in place, and the risk of professional-to-patient transmission should be limited. In addition, HBV vaccination could have played a role in the different risks compared to hepatitis C.In the literature, there is evidence of transmission of viral hepatitis, especially in gynaecological
57
, 58
and cardiothoracic 59
, 60
, 61
surgical settings. There are few studies, to our knowledge, that show an association between HCV or HBV infection and eye surgery, to compare with. In our study, within eye surgery, most interventions were performed for cataracts. During cataract surgery serious blood contamination usually does not occur. Nevertheless, the inadequate sterilisation of some instruments used, probably related to the fact that the surgery is often routinely performed in a day surgery setting with tight schedules and reduced staff attention to infection control, could likely favour patient-to-patient virus transmission, especially if the prevalence is high 62
, 63
. On the other hand, the risk during oral - maxillofacial surgery and dental procedures is highly reported 64
, 65
, 66
, and it is confirmed by our results, especially for oral surgery. It should be considered that dental tourism (the practice of travelling outside of one’s country to get dental care) is increasingly popular in Italy 67
. This practice is often chosen as it is cheaper. However, it may have health safety risks andfurther studies are needed to investigate its significance, if any, to hepatitis transmission.Moreover, we found that endoscopies do indeed pose a risk for hepatitis. In the scientific literature, the need for endoscope reprocessing practices for infection control is reported, and the importance of drying is emphasised
68
. In our study, most of the endoscopies reported by HBV and HCV cases were digestive endoscopies. However, they were also the most reported type in the HAV control group. Thus, there is no evidence that digestive endoscopies are at increased risk compared to others.Our previous study, conducted 20 years ago, found that the strongest associations were with abdominal, oral, and obstetric/gynaecological surgery for HBV infection and with obstetric/gynaecological, abdominal, and ophthalmological interventions for HCV infection
29
. Although the surgical disciplines most at risk have partially changed over time, the increased risk of encountering parenteral viral hepatitis for individuals who have undergone surgery in the last 6 months has remained constant in Italy, if we compare the present results with the previously published paper 29
.The fact that there has been no particular progress since a 20 years ago study shows that the problem is constant over time. This is, probably, due to failure to adopt adequate infection control practices and difficulties in controlling the transmission of bloodborne viruses in some medical settings, particularly during invasive procedures. However, it should be noted that the previous study excluded subjects who had undergone blood transfusions in the previous six months, whereas, in this study, we chose to include them to avoid the risk of excluding some surgeries from the analyses, given the almost complete safety of the practice nowadays
35
, 36
, 37
. A further difference with the previous study is the classification of invasive procedures now made using ICD-9-CM codes.- Velati C
- Romano L
- Piccinini V
- Marano G
- Catalano L
- Pupella S
- et al.
Prevalence, incidence and residual risk of transfusion-transmitted hepatitis C virus and human immunodeficiency virus after the implementation of nucleic acid testing in Italy: a 7-year (2009-2015) survey.
Blood Transfusion. 2018; 16: 422-432
It should be noted that in the last 2 years of our study, 2020-2021, in conjunction with the pandemic, the annual number of notifications received by SEIEVA decreased significantly. The containment measures taken to limit the spread of SARS-CoV-2 have, probably, partly contributed to reducing the risk of contracting other infectious diseases, including viral hepatitis. The increased interest in the ongoing pandemic may also have reduced attention to other diseases, including diagnosis and subsequent reporting. Assuming the results of this study are confirmed, the pandemic-related reduction in access to health services, which led to postposing some of the unnecessary interventions, may also have further decreased the risk of contracting hepatitis B and C.
One of the strengths of our study is that it focuses on patients with acute HBV and HCV infection for whom a limited period of previous exposure (6 months) was investigated. Thus, any potential recall bias has been minimised, also in light of the significance of the event to be remembered. Another strength lies in the comparability between cases and controls, as all individuals were identified through the same surveillance system and interviewed by the same interviewers, thus exposed to the same selective factors, if any. Even though hepatitis A patients cannot be considered the perfect controls since they can occasionally share the same risk factors as HBV and HCV, they may represent a valid and feasible choice in this study. In any case, using the age-matched multiple logistic regression analysis model, the confounding effects of variables, such as sex, educational level, other parenteral exposures, and intercourse with multiple sexual partners, are likely to have been removed, and there is no evidence of an association between undergoing an invasive procedure and the risk of acquiring hepatitis A. Finally, a major strength of the study is that it used surveillance data to analyse the risk of contracting infections with a long incubation time through common practices such as surgery, for which incidence studies would be complex and impractical.
However, this study has some limitations that should be considered. First, it might be difficult to distinguish the surgical risks from those incurred with anaesthesia, parenteral therapy, and other uses of needles. There are also methodological limitations peculiar to the case-control study, related to the retrospective collection of exposure history, including the social-desirability bias - especially considering that many questions in the SEIEVA questionnaire focus on sensitive topics such as sexuality and potentially stigmatising behaviours such as intravenous drug use. Some risk factors may, in fact, have been underreported.
On the other hand, there is no certainty that exposure preceded the disease, especially for long-induced diseases such as viral hepatitis. Among acute HCV cases, hepatitis exacerbations in HCV chronic carriers may have been included. However, since it is unlikely that HCV chronic carriers with acute exacerbations had a history of exposure different from that of the general population, this possible misclassification could have led to an underestimate of the actual risk.
Despite the reduction in notifications over the past 2 years, we expect this has not led to bias in association estimates.
Conclusion
Despite progress in recent years, surgery still appears to be a major risk factor for acquiring parenterally transmitted hepatitis viruses in Italy and could explain the unexpected new cases of parenteral hepatitis still diagnosed among the elderly population in the country. Considering the large proportion of the general population undergoing surgery or other invasive procedures, and considering the high preventability of this risk, the present results stress the importance of complying with infection control precautions and implementing efficient sterilisation and maintenance methods for medical instruments. Protocols and effective sterilisation procedures for dental therapy and biopsy/endoscopy need to be improved as well. More work needs to be done on staff training on the safety of surgical practices. The increasingly widespread HBV vaccination and the growing use of anti-HCV therapies will contribute to further reducing this risk also thanks to the introduction of free national screening for HCV infection among birth cohort 1969-1989, people who inject drugs or are in custody
15
.Data Availability Statement
The property of the data is of the participating Italian Regions and Local Health Units while Istituto Superiore di Sanità acts as coordinating centre for data management and analysis. Cumulative data are reported within the paper whereas individual patient data are not fully available and without restrictions for ethical reasons. Dr. ME Tosti ([email protected]) is in charge of data management and readers may contact her for specific data requests. She will provide the necessary ethical clearance for access to data.
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Article info
Publication history
Accepted:
March 3,
2023
Received in revised form:
March 1,
2023
Received:
August 5,
2022
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In Press Journal Pre-ProofIdentification
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© 2023 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
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