|Year : 2016 | Volume
| Issue : 2 | Page : 215-221
A study on how patients catch hepatitis C virus
Reda S Badr, Tarek E Korah, Ahmad R Tawfeek, Kamal A Mohamed
Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||11-Dec-2014|
|Date of Acceptance||17-Mar-2015|
|Date of Web Publication||18-Oct-2016|
Kamal A Mohamed
Biala-AbdEl-Monem Riad Street, Kafr El-Sheikh Governorate, 33634
Source of Support: None, Conflict of Interest: None
The aim of this study was to evaluate the prevalence of hepatitis C virus (HCV) and its mode of transmission in Kafr El-Sheikh governorate.
The overall prevalence of antibody to HCV in the general population is around 15–20%. Knowledge of the risk factors and clinical outcome of hepatitis C will provide important information regarding treatment and public health guidelines.
Patients and methods:
Data were collected on patients exposed to risk factors for HCV transmission or have clinical manifestation of liver cell failure from among outpatients and inpatients at the Liver Institute, Kafr El-Sheikh governorate. Two hundred patients who were HCV positive and 60 patients who were HCV negative, determined according to the one-step test device by ACON Laboratories, were included as cases and controls, respectively. Patients recently exposed to sources of risk factors (at least 6 weeks) were excluded from the study. All the study participants were subjected to history taking and complete physical examination.
The study showed that 200 of the studied samples were seropositive (cases), and 60 were seronegative (control). With regard to the risk factors to which the patients were exposed, there were highly significant differences in patients than in controls in relation to blood transfusion, family history, antischistosomal drug (tartar emetic), and surgery. The most significant cause of HCV transmission was intrafamilial exposure [odds ratio (OR) = 8.522, 95% confidence interval (CI) 3.704–19.605], followed by antischistosomal drug injection (OR = 3.905, 95% CI 1.605–9.503) and blood transfusion (OR = 0.2, 95% CI 0.099–0.743).
There are several modes of transmission. The most significant cause of HCV transmission was intrafamilial exposure, followed by antischistosomal drug injection and blood transfusion. There should be focus on preventing HCV by reducing its transmission, particularly among those at risk of acquiring the virus. Screening of all family members of HCV-infected patients should be made mandatory.
Keywords: hepatitis C virus, hepatitis C virus prevalence, risk factors for hepatitis C virus transmission
|How to cite this article:|
Badr RS, Korah TE, Tawfeek AR, Mohamed KA. A study on how patients catch hepatitis C virus. Menoufia Med J 2016;29:215-21
| Introduction|| |
Viral hepatitis is defined as a systemic viral infection in which hepatic cell necrosis and hepatic inflammation lead to characteristic clinical, biochemical, immune serological, and morphological changes. Viral hepatitis is the main cause of liver disease in Egypt , with a high prevalence (6–28%) , and the Hepatitis C virus (HCV) is the main causative factor. Risk factors associated with acquiring HCV infection include transfusion of blood and blood products, transplantation of solid organs from infected donors, illegal injections, unsafe therapeutic injections, occupational exposure to blood primarily through a contaminated needle, and sexual transmission . Knowledge of the clinical outcome of hepatitis C will provide important information regarding treatment and public health guidelines. Heterogeneity of the disease process and lack of prospective longitudinal studies beyond 20 years led to compromised data regarding the natural history of this viral infection. Disease progression is believed to be a function of both host-related (age at exposure, coexistent alcoholism, and immune status) and virus-related (genotype and possibly viral load) factors. The sequential progression from infection to cirrhosis and hepatocellular carcinoma has been described after transfusion-associated hepatitis . Blood-borne transmission of HCV is undisputed and reflected in the prevalence of HCV among intravenous drug abusers and patients exposed to contaminated blood products before 1990 . It is estimated that intravenous drug use accounts for ∼60% of HCV transmissions in the USA and France. Other known exposures (occupational, hemodialysis, household, perinatal, and sexual) taken together explain ∼10% of infections. No recognized source of infection could be identified for the remaining 20–40%, although the HCV incidence rate appears to have reduced in recent years .
| Aim|| |
This aim of this study was to evaluate the risk factors for HCV transmission.
| Patients and Methods|| |
This was a cross-sectional casecontrol study on patients exposed to risk factors for HCV transmission or had clinical manifestation of liver cell failure from among outpatients and inpatients of the Liver Institute, Kafr El-Sheikh governorate, from May 2013 to March 2014. Two hundred patients with HCV positive and 60 patients with HCV negative were included as cases and controls, respectively.
The sample size was calculated according to the following equation:
N = (Z a) 2 × PQ/D2,
where N is the sample size, Z a is the value of standard normal distribution for type 1 error probability for the sided test and equals 1.96, P is the prevalence of HCV in Egypt about 14.7-%Q = 1−P, and D 2 is that accuracy of estimate (=0.01).
Therefore, according to the calculations the sample size is ∼200 patients.
A written letter explaining the purpose of the study was given to each volunteer in this study, explaining the importance of gathering information about a serious infection such as HCV, especially in our governorate. The local ethics committee approved the study protocol. Formal consents were obtained from the patients or their relatives. Data were collected, tabulated (virus, alcoholic, etc.), and statistically analyzed.
The following patients were excluded from the study: patients recently exposed to sources of risk factors (at least 6 weeks) and patients with liver disease other than HCV (e.g. coinfection with hepatitis B).
Selection of patients
The study group was subjected to the following:
- History taking: complete history was taken from all participants of the study group with special emphasis on symptoms and its duration (e.g. abdominal pain, enlarged abdomen, lower limb edema, fatigue, loss of weight, jaundice), and with special reference to risk factors of HCV exposure in surgical wards, blood transfusion, dental therapy, needle-stick injuries, parenteral anti-schistosomiasis therapy, tattooing, positive cases, and the family habits of the patients such as shaving and circumcision.
- Complete physical examination was carried out with special emphasis on signs of liver cell failure (e.g. jaundice, pallor, ascites, hepatomegaly, splenomegaly, and lower limb edema).
- Laboratory investigation included evaluation of HCV antibody using a one-step test device (ACON Laboratories, San Diego, California USA).
Sampling and methods
Blood sample was collected from the patients by vacuum venipuncture using a dry 5-ml tube. The serum was separated, centrifuged, and stored at −20°C. HCV antibody was detected using one-step test device (ACON Laboratories). The HCV one-step test device (serum/plasma) is a rapid qualitative test that detects the presence of antibody to HCV in serum or plasma specimen. The test utilizes a combination of protein A-coated particles and recombinant HCV proteins (encoded by the genes for both structural/nucleocapsid and nonstructural proteins) to selectively detect antibody to HCV.
Selection of control
Controls were selected from among those exposed to risk factors or having manifestation of liver cell failure with HCV antibody test negative on condition of exposure to risk factors exceeding 6 months.
Instruments of data collection
Using a questionnaire, the data were collected from the study participants where a verbal witness or written consent from each studied participant was taken.
To avoid bias, the collected data were considered highly confidential and analyzed anonymously.
Two types of statistics were calculated: descriptive statistics in the form of mean (X) and SD.
Qualitative data were expressed in number and percentage and analyzed using the χ2-test to study the statistical relation between different variables. Logistic regression was used to predict the outcome in exposed individuals. Quantitative data were expressed to measure the central tendency of data and diversion around the mean.
P value more than 0.05 was considered statistically nonsignificant, P value less than 0.05 was considered statistically significant, and P value less than 0.001 was considered statistically highly significant.
| Results|| |
In this study, 260 individuals were included from inpatient and outpatient clinics of Liver Institute, Kafr El-Sheikh governorate.
[Table 1] indicates that 200 of the studied sample were seropositive (cases) and 60 were seronegative (control). It demonstrates the relation between HCV test results and the sociodemographic data of the studied group in relation to cases and controls. With regard to seropositive cases, this table shows that 60% of the cases were male and 40% were female. Nearly 65% of the positive cases were farmers and 46.5% were illiterates. Nearly half (48.5%) of the patients were of low socioeconomic level. About 70% of the cases were from rural areas. There are significant differences between the cases and controls with regard to socioeconomic level, occupation, education, and residence (P < 0.001), as shown in [Table 1] and [Table 2] that summarize the risk factors for HCV transmission. It was found that 15.5% of the patients were diabetic and nearly half (45.5%) of the patients had a history of surgical operation. Nearly three-quarters (71%) of the patients with family history of HCV were positive, whereas 35.5% of those subjected to a used needle were positive. Of the patients who had received parenteral antischistosomal treatment, 70% were positive. There was no statistically significant difference related to sexual relations.
In contrast, 15% of the patients exposed to HCV had undergone upper gastrointestinal endoscopy, and 20% were mucosally exposed to HCV.
With regard to patients and controls in relation to risk factors exposed, there were higher differences among patients than among controls with regard to blood transfusion, family history, antischistosomal drug (tartar emetic), and surgery.
[Table 3] shows that the most significant cause of HCV transmission was intrafamilial exposure [odds ratio (OR) = 8.522, 95% confidence interval (CI) 3.704–19.605], followed by antischistosomal drug injection (OR = 3.905, 95% CI 1.605–9.503) and blood transfusion (OR = 0.2, 95% CI 0.099–0.743).
|Table 3: Logistic regression of causes for hepatitis C virus transmission|
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[Table 4] shows significant differences with regard to age in relation to needle prick, disposable use for HCV patients, anti-bilharzial drug injection, and surgery (P < 0.001).
|Table 4: Comparison between hepatitis C virus patients above and below 45 years|
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[Table 5] shows significant differences with regard to sex in relation to needle prick, disposable use for HCV patients, and anti-bilharzial drug injection value (P < 0.001).
|Table 5: Comparison between male and female hepatitis C virus patients with regard to causes of hepatitis C virus transmission|
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| Discussion|| |
Chronic hepatitis C is a leading cause of end-stage liver disease, with worldwide prevalence of up to 3%. However, the number of new cases of chronic hepatitis C has decreased substantially over the last decade, with well-established risk factors for transmission of HCV .
The Egyptian Demographic Health Survey (EDHS), a cross-sectional survey including HCV biomarkers, was conducted in 2008 on a large nationally representative sample. It estimated HCV prevalence among the 15–59 years age group to be 14.7% . Accordingly, Egypt has the highest HCV prevalence in the world ,.
In our study, prevalence is higher among patients residing in rural versus urban areas (70 vs. 30%). In another study carried out on 1000 participants more than half (57.1%) of the farmers were positive .
In our study, the intrafamilial exposure was a significant factor in HCV transmission as the prevalence of HCV positive patients was 71% among patients with positive family history. In another cohort study in Egypt, the strongest predictor of incident HCV infection was having an anti-HCV-positive family member. Among those who did, incidence was 5.8/1000 per year compared with 1.0/1000 per year (P < 0.01) among those with no positive family members. The highest incidence rate (14.1/1000 per year) was in children younger than 10 years who were living in households with an anti-HCV-positive parent. The study did not determine the factors responsible for this association . Most recent study provided evidence that there is a greater probability of intrafamilial transmission of HCV infection, especially from wife to husband rather than from husband to wife in Egypt. The data also support the plausible hypothesis that the probability of transmission is greater if the spouse is positive for HCV-RNA .
Mostafa et al.  recommended screening of families of infected HCV individuals as an essential part of case management for early detection and further management.
In our study, 45.5% of patients with a history of surgical operations had anti-HCV-positive results, and this was less than that found by Awadalla et al.  who reported that nearly 43.3% of the controls who had undergone surgical treatment were negative. Possible source of such transmission, besides poor blood and donor screening, could be ineffective sterilization methods, overcrowding hospital, and lack of maintenance of safety standards ,.
In our study, nearly half (45.5%) of the patients with a history of blood transfusion were positive. Results of the study by Awadalla et al.  showed a higher number [nearly three-quarters (72%)] of positive participants with a history of blood transfusion. Studies carried out in the 1970s suggested that about 7% of transfusion recipients developed non-B hepatitis, and that up to 1% of blood units might contain causation virus. The introduction of anti-HCV screening has obviously reduced the transmission .
The frequency of HCV infection (0.004–0.0004% per unit transfused) reported to be attributed to blood transfusion is low because of the nondetection of infectious donors by currently available antibody screening tests. Before the availability of a screening test, the risk of contracting the virus was one in 200 U transfused . However, we have found that blood transfusion recently reported to account for only 7% of HCV infections in the USA . Of our patients, 45.5% received transfusions. Many of these patients were identified in HCV-screening campaigns that focused on recipients of transfusions before 1992, before the introduction of more sensitive HCV testing. In our population, the older age of recipients of blood products compared with injecting drug users likely reflects a cohort effect owing to the relatively higher risk of acquiring HCV from blood transfusion in the more distant past.
Besides blood transfusions, several other routes appear to be responsible for the spread of HCV infection. These include the use of unscreened blood, blood products, tissues and organs, medical and dental care with contaminated or inadequately sterilized needles, syringes and equipment, sharing needles among drug users, sexual transmission, perinatal transmission, and sharing of other personal things such as razor, blades, or tooth brushes . The results of this study demonstrated that 35.5% of those subjected to a used needle were positive. Frank et al.  found that primary modes of HCV transmission included unsafe injections; this agreed with our study results, which found that nearly one-fifth (21%) of the exposed participants were positive and more than one-half (53.6%) of the positive cases were exposed to parenteral antischistosomal therapy. Of even greater importance in the spread of HCV are unsafe therapeutic injections administered by both professionals and nonprofessionals. It has been estimated that approximately two million HCV infections are acquired annually from contaminated healthcare injections and may account for up to 40% of all HCV infections worldwide . This was in accordance with the study by Klenerman et al.  who showed that a past injection treatment remains likely to be responsible for the high prevalence of HCV morbidity. In our study, diabetes was observed in 15.5% of patients with HCV infection. This result was concordant with most recent result that concluded that frequency of prediabetes among nondiabetic chronic HCV patients was 64%, which denotes that HCV infection could be a significant risk factor for the development of type 2 diabetes mellitus . Although it remains to be determined whether HCV infection leads to diabetes mellitus or vice versa, based on the current available evidence, it seems that this is the HCV infection that causes diabetes mellitus. On the contrary, most recent research by Ruhl et al.  in the US population was unable to demonstrate an association of HCV infection with diabetes or with insulin resistance. Elevated liver enzyme activities were associated with both diabetes and insulin resistance.
HCV has been found to play a role in many areas leading to insulin resistance: proteins on the virus play a role in the cascade of inflammation reactions through numerous pathways leading to an overall increase in interleukin-6, interleukin-8, tumor necrosis factor-a, and transforming growth factor-b, which lead to oxidative stress. HCV inhibits peroxisome proliferator-activated receptor (PPAR)g and PPARa, which are needed for proper metabolism of triglycerides and lipids causing an accumulation of hepatic lipids and an increase in insulin resistance. Decreased levels of adiponectin receptors are seen in HCV patients. As adiponectin has antiarthogenic and anti-inflammatory properties, decrease in its activity leads to insulin resistance. HCV plays a role in the downregulation of some insulin receptors, decreasing the effects of insulin in the body . Most recent study demonstrate that patients with chronic HCV infection had a high incidence of developing microalbuminuria (10%) and very high incidence of developing peripheral neuropathy (30%). Age, HCV-RNA level, and liver fibrosis are prominent risk factors for the occurrence of peripheral neuropathy in chronic HCV-infected patients .
In our study, according to our questionnaire, we did not find any patient with illegal sexual contact. Most experts believe that the risk of sexual transmission of HCV is low. A recently published study confirmed that sexual transmission is extremely rare among long-term monogamous couples .
Frequent sharing of razors and tooth brushes among persons who reported sexual exposure also belies the automatic assumption of sexual transmission between dually infected couples. The assessment of risk remains particularly difficult when comparing infrequent but high-risk contact (e.g. parenteral exposure) with more frequent but lower risk exposure such as sexual activity. Even with our relatively general definition of sexual exposure, we were unable to observe any individuals with sexual contact as a sole risk factor. Inability to test all current and/or past sexual partners of individuals reporting sexual exposure precluded definitive confirmation of partner HCV status. We were therefore unable to separate those who had at least one reported sexual contact with a person suspected of having HCV from those who had at least one sexual contact with a person known to have HCV.
Factors such as piercing and tattooing may need to be refined into different levels of risk depending upon the setting (e.g. service by an unskilled individual vs. a professional trained in proper hygiene).
Numerous risk factors promote HCV acquisition, and multiple risk factors may be present in a single individual. Infected persons cannot be dichotomized in 'injection drug users' and 'blood product recipients'; many in each group may have other risk factors as well. Investigators pursuing research on the origin or duration of HCV infection by sexual routes should consider multiplicity of exposure in designing studies in various settings. For example, blood contact from frequent sharing of razors could also result in HCV transmission.
The multiplicity of risk factors observed in our case series presents some important ramifications with respect to disease surveillance. Many of the disease surveillance networks use a hierarchical algorithm to determine routes for HCV acquisition when multiple risk factors are present in individuals. Although these hierarchies are based on the presumed likelihood of transmission per exposure, their use may potentially obscure the true contribution of 'lower risk' exposures.
Clearly, alternative methods of modeling risk factors should also be considered. Most importantly, attributing HCV acquisition to 'lower risk' behaviors such as sexual exposure should be done with caution, and only after exclusion of other risk factors, and in particular, those of 'higher risk', such as parenteral contact.
Detailed inquiry into risk factor exposure may also increase accuracy in the ascertainment of the time of HCV acquisition. Accurate estimates of the duration of infection have proved to be useful in interpreting data on factors that influence rate of disease progression .
If a high number of individuals have multiple risk factors, this may provide an inappropriate picture of the true distributions of risk factors and, consequently, routes of acquisition.
By comparing cases with control with regard to risk factors, we observed that most of the patients exposed to major risk factor, and most of them have multiple risk factors. On the contrary, even controls were exposed to major risk factors, although most of them were not exposed to multiple risk factors.
| Conclusion|| |
There are many modes of transmission. The most significant one of HCV transmission was intrafamilial exposure, followed by antischistosomal drug injection and blood transfusion. There should be considerations regarding the prevention of HCV for reduction in the transmission of HCV, particularly among those at risk of acquiring the virus. Screening of all family members of HCV-infected patients is mandatory.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]