Familial clustering of hepatitis C virus in a Pakistani population
Abstract
Pakistan has the second-highest burden of hepatitis C patients in the world. A total of 683 individuals, who visited the Liver Clinic during the study period, were screened for the presence of hepatitis C virus (HCV) infection. A total of 534 individuals who showed positive HCV infection were grouped into the case group and 149 individuals with HCV negative status were grouped into the control group. A detailed questionnaire was used to collect demographic, clinical, HCV risk factor, and familial clustering data. HCV familial clustering was found in 30.1% in the case group compared with 17.4% in the control group. We also found 17% of patients had spouses who were also infected with HCV compared to 4% spouse infection in the control group. Only 3.7% of patients had HCV positive mothers. These results were further expanded by regression analysis that showed that family history and sexual history are independent risk factors for transmission of hepatitis C infection and mother's history has no significance as a risk factor for transmission. The major risk factor for getting HCV infection are dental procedures, unsafe injections, surgery, and blood transfusions. There is a strong need to increase awareness about HCV transmission routes among positive patients to reduce the chances of HCV familial clustering.
Highlights
Pakistan has second highest burden of HCV in the world.
There is joint family system in Pakistan and the number of people living in a house is very high as compared with Western countries.
Our study shows 30.1 of HCV familial clustering.
The major risk factor for HCV transmission in Pakistan are dental procedures, unsafe injection, surgery, and blood transfusion.
There is strong need to increase awareness about HCV transmission routes among positive patients to reduce the chances of HCV familial clustering.
1 INTRODUCTION
Hepatitis C virus (HCV) infection is a worldwide health problem. Approximately, 1.4 million deaths occur from viral hepatitis each year, out of which 48% deaths are from HCV.1 Almost, 70 million people have HCV globally and 10% (7.1 million) of them are living in Pakistan.2
The World Health Organization (WHO) has developed a policy to control hepatitis by 2030. The major targets of the strategy are to reduce hepatitis incidence from 6 to 10 million cases per year to 0.9 million cases per year and to reduce annual hepatitis deaths from 1.4 million cases to 500 000 cases per year.1 The WHO is also working with different countries to develop control programs against hepatitis. So far, 84 countries have developed programs to eliminate hepatitis by 2030, out of which only 9 countries are on track to eradicate hepatitis by 2030. Pakistan is among those countries who are working toward the targets to accomplish HCV elimination by 2030.3, 4
Pakistan is a developing country with low health standards. According to the latest study on health access and quality of life, Pakistan is ranked 159th out of 195 countries of the world.5 The major sources of HCV transmission in Pakistan are infected blood and blood products, barber's shaving, contaminated needles and syringes, and infected dental and surgical instruments.4 There are different reports of familial clustering of HCV from different countries, but no such data is reported from Pakistan.
Although there is no vaccine available against HCV, very effective drugs are available for the treatment of HCV.6 After the clearance of HCV infection, the immune system of the person may not be able to clear a subsequent infection completely. Having a household contact with an HCV positive patient is also a risk factor. Reinfection may occur in household settings especially if other family members are unaware of transmission routes of HCV and the infection status of households.7 In addition to HCV treatment, there is also a need to increase awareness about transmission routes of HCV infection in family members of HCV patients so that lifestyles can be modified to avoid reinfection from household settings.
In some studies, it is reported that HCV can be transmitted in family members if the patient has high HCV RNA levels, long-term contacts, advanced age, shares personal hygiene items, and has an HCV positive spouse. HCV transmission among siblings and offspring are also reported in a few studies.7
In Pakistan, there is a joint family system and the number of people living in a house is very high as compared with Western countries. The sharing of personal hygiene items like nail clippers, shaving razors, beard-trimming machine, etc is very common. There are high chances of familial clustering of HCV infection. Our study is the first study of familial clustering of HCV in Pakistan; no such data is reported to date from Pakistan. The primary aim of this study is to find whether familial clustering of HCV infection occurs or not in our general population. The other risk factors are also studied as the secondary aim of this study.
2 MATERIALS AND METHODS
A cross-sectional study was conducted at the Medical Department of Fauji Foundation Hospital, Rawalpindi, Pakistan from October 2017 to April 2018.
2.1 Study cohort
Before conducting the study, ethical approval was taken from the ethical board of the hospital. Six hundred and eighty-three patients visiting the Liver Clinic of the hospital during the study period were screened for the presence of antibodies against hepatitis C infection. The patients who had antibodies to HCV were taken as the case group, whereas the individuals with absent antibodies against hepatitis C infection were considered the control group. The study cohort was informed about the study and their consent was taken. All individuals who were willing to give information were included in this study. Patients infected by dual viruses, HIV, or hepatitis B were not counted in this study.
2.2 Study method
A structured questionnaire was used to evaluate the individual's demographic profile, including age, gender, marital status, number of children, and the presence of comorbidities. This questionnaire was filled by the house officer or postgraduate trainees of the medicine department after communicating with patients, keeping in view the language barrier and low education status in society. The family members and spouses were also involved during history taking. Previous medical records of patients were also analyzed where needed.
2.3 Clinical parameters
For biochemical characteristics, the blood complete picture, prothrombin time, liver function tests, thyroid-stimulating hormone (TSH), and blood glucose random were analyzed. A complete blood picture was obtained by an automated hematology analyzer after taking 2 mL of blood in EDTA tubes (Automated Hematology Analyzer XT-2000i of Sysmex Corporation of Japan). Prothrombin time was analyzed by a blood coagulation analyzer after taking 3 mL of blood in 3.2% Na-citrate tubes (CA-500 Coagulation Analyzer; Sysmex of Siemens Healthcare Diagnostics of Japan). A chemistry analyzer was used to carry out all serum chemistry tests of patients (Max Chemistry Analyzer; Dimensions RxL of Siemens Healthineers Laboratories of USA). Antibodies against hepatitis C infection were detected by third-generation enzyme-linked immunosorbent assay (ELISA; Architect i1000SR of Abbott Laboratories of USA). The weight of every individual was measured by weighing scale and expressed in kilograms.
2.4 Risk factors evaluation
The possible risk factors for hepatitis C infection were assessed in detail. The history of dental procedures, surgeries, blood transfusion, sexual exposure to infection, and the mother's history of hepatitis C infection were taken. The history of intravenous or intramuscular injections was significant if the individual had greater than 5 injections per year by a formal or informal healthcare provider. The number of children was also studied as a risk factor of hepatitis C infection by dividing the cohort into two groups based on the number of children (<2 or >2).
2.5 Familial clustering
The term familial clustering was used when one or more than one of the family members of the study cohort had hepatitis C infection. Medical tests or records referring to the infection of hepatitis C infection were necessary in the case of first-degree relatives or spouses. However, in the case of other family members, we relied on the history given by the individual.
2.6 Statistical analysis
Statistical analysis was done on SPSS version 21. Frequency and percentages were used for qualitative variables while quantitative variables were expressed as means and ranges. Quantitative and qualitative variables for cases and controls were equated by χ2 tests and Students' t tests depending on the type of variables to be compared. The risk factors of both groups were evaluated by the χ2 test. Finally, univariate and multinomial regression analysis was done to find the predictors of hepatitis C infection in both groups.
3 RESULTS
Antibodies against hepatitis C infection were present in 78.2% (n = 534) patients. This group was assigned as the case group. However, 21.8% (n = 149) individuals were negative for hepatitis C infection and they were marked as the control group.
3.1 Basic characteristics
The age of the study cohort was 51.71 ± 13.08 years (9-88 years). The gender distribution among the group was 96.6% (n = 660) females and 3.4% (n = 23) males.
The basic characteristic features of both groups are shown in Table 1.
Variables | Cases (n = 534) | Controls (n = 149) | OR | 95% CI | P-value |
---|---|---|---|---|---|
Age | 51.06 ± 10.89 | 54.09 ± 18.90 | 1.07 | 1.03-1.26 | .01 |
Gender | |||||
Male | 3 (0.6%) | 20 (13.4%) | 0.37 | 0.01-0.12 | .00 |
Female | 530 (99.3%) | 129 (86.6%) | |||
Marital status | |||||
Married | 474 (88.8%) | 126 (84.6%) | 1.49 | 0.88-2.51 | .13 |
Single | 58 (10.9%) | 23 (15.4%) | |||
Number of children | |||||
Mean | 4.6 ± 1.7 | 3.9 ± 1.7 | 0.50 | 0.37-0.69 | .00 |
<2 children | 50 (9.4%) | 29 (19.5%) | 0.38 | 0.22-0.63 | .00 |
>2 children | 417 (78.1%) | 92 (61.7%) | |||
Comorbids | |||||
None | 375 (70.2%) | 47 (31.5%) | .00 | ||
Diabetes mellitus | 34 (6.4%) | 22 (14.8%) | |||
Hypertension | 77 (14.2%) | 38 (25.5%) | |||
Both | 35 (6.5%) | 42 (28.2%) | |||
Thalassemia | 2 (0.4%) | 0 | |||
Weight (kg) | |||||
Mean | 59.39 ± 13.90 | 62.34 ± 12.76 | 1.05 | 1.01-1.09 | .02 |
<55 kg | 186 (34.8%) | 43 (28.9%) | 1.69 | 1.13-2.55 | .01 |
>55 kg | 247 (46.2%) | 97 (65.1%) |
- Abbreviations: CI, confidence interval; kg, kilograms; n, number of patients; OR, odds ratio.
3.2 Biochemical characteristics
The biochemical characteristics of both groups are shown in Table 2.
Variables | Cases (n = 534) | Controls (n = 149) | OR | 95% CI | P-value |
---|---|---|---|---|---|
Hb, g/dL | |||||
Mean | 12.97 ± 1.68 | 11.74 ± 2.05 | 0.84 | 0.66-1.08 | .00 |
<12 | 139 (20.3%) | 75 (10.9%) | 0.35 | 0.24-0.52 | .00 |
>12 | 384 (56.2%) | 74 (10.8%) | |||
WCC, ×103 cells/L | |||||
Mean | 7.50 ± 2.28 | 9.09 ± 4.17 | 1.27 | 1.06-1.53 | .00 |
<10 | 468 (68.5%) | 101 (14.7%) | 3.72 | 2.38-5.82 | .00 |
>10 | 56 (8.2%) | 45 (6.5%) | |||
Platelets, ×103 cells/L | |||||
Mean | 245.68 ± 102.77 | 257.87 ± 89.85 | 0.99 | 0.99-1.00 | .19 |
<350 | 84 (12.2%) | 17 (2.5%) | 1.50 | 0.86-2.62 | .09 |
>350 | 433 (63.3%) | 132 (19.3%) | |||
Bilirubin, μmol/L | |||||
Mean | 12.10 ± 7.61 | 11.47 ± 4.77 | 0.96 | 0.88-1.04 | .33 |
<17 | 442 (64.7%) | 134 (19.6%) | 0.75 | 0.41-1.35 | .21 |
>17 | 66 (9.6%) | 15 (2.1%) | |||
ALT, IU/L | |||||
Mean | 66.76 ± 39.33 | 40.79 ± 22.83 | 0.94 | 0.92-0.97 | .00 |
<40 | 95 (13.9%) | 107 (15.6%) | 0.09 | 0.06-0.14 | .00 |
>40 | 396 (57.9%) | 41 (6%) | |||
ALP, IU/L | |||||
Mean | 204.92 ± 83.09 | 190.86 ± 61.20 | 1.00 | 0.99-1.00 | .05 |
<110 | 10 (1.4%) | 4 (0.5%) | 0.72 | 0.22-2.34 | .39 |
>110 | 499 (73%) | 145 (21.2%) | |||
Albumin, g/L | |||||
Mean | 37.99 ± 4.07 | 34.96 ± 5.16 | 0.86 | 0.76-0.97 | .00 |
<40 | 337 (49.3%) | 137 (20%) | 0.19 | 0.10-0.36 | .00 |
>40 | 141 (20.6%) | 11 (1.6%) | |||
PT, s | |||||
Mean | 1.23 ± 1.06 | 1.48 ± 1.80 | 1.21 | 0.86-1.68 | .07 |
<1.2 | 268 (39.2%) | 121 (17.7%) | 1.74 | 1.00-3.04 | .03 |
>1.2 | 33 (4.8%) | 26 (3.8%) | |||
TSH, mIU/L | |||||
Mean | 2.40 ± 6.00 | 2.32 ± 2.61 | 1.00 | 0.95-1.06 | .87 |
<2.5 | 165 (24.1%) | 61 (8.9%) | 1.85 | 1.15-2.99 | .00 |
>2.5 | 67 (9.8%) | 46 (6.7%) | |||
BSR, mmol/L | |||||
Mean | 6.84 ± 3.99 | 6.86 ± 3.31 | 0.92 | 0.82-1.03 | .95 |
<8 | 224 (32.7%) | 49 (7.1%) | 0.97 | 0.57-1.65 | .51 |
>8 | 118 (17.2%) | 25 (3.6%) |
- Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; BSR, blood sugar random; CI, confidence interval; Hb, hemoglobin; OR, odds ratio; PT, prothrombin time; TSH, thyroid-stimulating hormone; WCC, white cell count.
3.3 Characteristics of case group
The most common symptom for which patients sought medical advice was generalized body aches 25.3% (n = 173). The other symptoms were abdominal pain 17.8% (n = 122), fever 6.2% (n = 43), easy fatigability 5.7% (n = 39), whereas 0.7% patients came to the outdoor department for dark pigmentation of the skin. One hundred and fifty-one patients were asymptomatic.
On ultrasonography 13.9% (n = 95) patients had coarse liver, 1.1% (n = 8) patients had hepatomegaly, whereas the liver texture was normal in the rest of the case group. Forty-five patients had splenomegaly and eight patients had ascites.
3.4 Risk factor evaluation
A family history of hepatitis C was found in 30.1% (n = 161) patients in the case group as compared to the control group in which family history was significant only in 17.4% (n = 26). This variance was statistically significant (P < .05) showing familial clustering does play a role in acquiring hepatitis C infection.
The topmost risk factor for hepatitis C infection in our study group was dental procedures (50.7%). The other risk factors found were intravenous or intramuscular injections (48.8%), surgery (46.6%), blood transfusion (29.2%), and hepatitis C in spouses (17%). Hepatitis C in mothers was found only in 3.7% of patients in the study cohort.
Interesting results were found regarding the relation of hepatitis C with the number of children. Hepatitis C infection was more common in patients with more than 2 children. This difference was statistically significant (P < .05). The use of injections or blood transfusion during antenatal care and episiotomy done at the time of delivery might have contributed to these results.
The risk factors evaluation between the two groups is shown in Table 3.
Risk factors | Cases | Controls | OR | 95% CI | P-value |
---|---|---|---|---|---|
Dental procedures | |||||
Yes | 271 (50.7%) | 46 (30.9%) | 2.38 | 1.62-3.51 | .00 |
No | 254 (47.6%) | 103 (69.1%) | |||
IV or IM injections | |||||
Yes | 261 (48.8%) | 45 (30.2%) | 2.28 | 1.54-3.37 | .00 |
No | 264 (49.4%) | 104 (69.8%) | |||
Surgery | |||||
Yes | 249 (46.6%) | 44 (29.5%) | 2.15 | 1.45-3.18 | .00 |
No | 276 (51.7%) | 105 (70.5%) | |||
Blood transfusion | |||||
Yes | 156 (29.2%) | 41 (27.5%) | 1.11 | 0.74-1.67 | .68 |
No | 369 (69.1%) | 108 (72.5%) | |||
Family history of hepatitis C | |||||
Yes | 161 (30.1%) | 26 (17.4%) | 0.48 | 0.30-0.77 | .00 |
No | 370 (69.3%) | 123 (82.6%) | |||
Hepatitis C in spouses | |||||
Yes | 91 (17%) | 6 (4%) | 5.00 | 2.14-11.68 | .00 |
No | 433 (81.1%) | 143 (96%) | |||
Hepatitis C in mothers | |||||
Yes | 20 (3.7%) | 6 (4%) | 0.94 | 0.37-2.39 | .81 |
No | 505 (94.6%) | 143 (96%) | |||
Number of children | |||||
<2 | 50 (9.3%) | 29 (19.5%) | 0.38 | 0.22-0.63 | .00 |
>2 | 417 (78.1%) | 92 (61.8%) |
- Abbreviations: CI, confidence interval; IM, intramuscular; IV, intravenous; OR, odds ratio.
The risk factors contributing to acquiring hepatitis C infection were further evaluated by multivariate regression analysis. The model of analysis was statistically fit (χ2 = 55.29, P = .00). The model explained 14% (Nagelkerke R2) to 90% (Cox and Snell R2) of the variances and classified 78.8% of the cases. Dental procedures, surgeries, familial clustering, hepatitis C infection in sexual partners, and a greater number of children were found to be independent risk factors for hepatitis C infection; Table 4.
Univariate analysis | Multinomial analysis | ||||
---|---|---|---|---|---|
Variables | OR (95% CI) | P-value | χ2 value | OR (95% CI) | P-value |
Dental procedures | 0.58 (0.37-0.90) | .01 | 7.09 | .00 | |
IV or IM injections | 0.69 (0.44-1.09) | .11 | 2.74 | .09 | |
Surgery | 0.56 (0.34-0.93) | .02 | 6.81 | .00 | |
Blood transfusion | 1.62 (0.97-2.68) | .06 | 2.74 | .09 | |
Familial clustering of hepatitis C | 2.21 (1.25-3.91) | .00 | 8.25 | 1.26 (1.15-1.38) | .00 |
Hepatitis C in spouses | 0.29 (0.12-0.71) | .00 | 7.30 | .00 | |
Hepatitis C in mothers | 2.41 (0.77-7.55) | .12 | 1.90 | .16 | |
Number of children | 0.83 (0.74-0.94) | .00 | 29.34 | .00 |
- Abbreviations: CI, confidence interval; IM, intramuscular; IV, intravenous; OR, odds ratio.
4 DISCUSSION
Hepatitis C is a global health problem having multiple routes of transmission.1 As the WHO has aimed to eradicate hepatitis C by 2030, it is necessary to study the route of transmission of this virus; particularly the minor sources that also account for transmission of this virus.1 Familial clustering is also one of the minor sources that need to be extensively studied to meet the elimination aim of hepatitis C. Parenteral route of transmission through transfusing blood products, injections use, and dental or surgical procedures are well-known modes of transmission that are being appropriately studied and addressed.8
The prime aim of this study was to find out whether clustering of HCV occurs within the family or not. The other factors are also studied as an added aim of the study.
4.1 Familial clustering and hepatitis C infection
In our study, 30.1% patients with hepatitis C had a family history of hepatitis C in which one or more than one family member was affected by the same virus compared to the control group in which 17.4% individuals had a history of hepatitis C infection in the family. This variance was statistically significant between both groups (P < .05). Interesting data points were observed when we found that 17% patients had spouses who were also hepatitis C infected compared to 4% of the control group (P < .05). Only 3.7% of patients had mothers affected by hepatitis C infection (P > .05). These results were further expanded by regression analysis that showed family history (OR: 2.21, 95% CI: 1.25-3.91, P < .05) and sexual history (OR: 0.29, 95% CI: 0.12-0.71, P < .05) are independent risk factors for transmission of hepatitis C infection and mother's history (OR: 2.41, 95% CI: 0.77-7.55, P > .05) has no significance as risk factor for transmission.
Familial clustering of hepatitis C is an interesting risk factor, which is being highlighted in various studies in the last decade. We found that familial clustering does play a role in acquiring hepatitis C infection. Similar results were found by Omar et al9 who found nearly 30% of individuals had a family history of hepatitis C. Plancoulaine et al10 and Trickey et al11 also suggested a strong intrafamilial relationship of hepatitis C infection. However, in the literature, we came across studies that negate the hypothesis that familial clustering has a role in the transmission of this virus. Kim et al12 conducted a study on 250 family members and denied the possibility of intrafamilial spread of hepatitis C infection.
4.2 Factors resulting in familial clustering of hepatitis C
Luo et al7 conducted a study on 1000 members of the Chinese Han population to find the factors resulting in familial clustering of hepatitis C. The duration of relationship with positive cases (family members or spouses); advanced age; sharing razors, blades, and needles among household members were found to be resulting in intrafamily transmission of hepatitis C infection.7 Frosi et al13 studied a family with hepatitis C and followed them for 20 years for three generations and found that this virus got clustered among family members. They suggested the sharing of glass syringes for intramuscular therapies was a possible cause of this clustering. Interesting results were shown by Plancoulaine et al10 who proposed through their phylogenetic analysis that a similar hepatitis C strain was found between sibling-sibling, mother-offspring, and father-offspring suggesting a genetic predisposition also plays a role in familial clustering of hepatitis C.
4.3 Hepatitis C infection in spouses
A very elaborate analysis related to sexual transmission of hepatitis C was done by Dodge and Terrault14 who concluded that transmission of hepatitis C through sexual activity is a very rare event. Similar results were also found in many other studies.15, 16 Magder et al17 and Nijmeijer et al18 suggested that sexual transmission of this virus occurs only in cases of multiple partners, male homosexuals, and individuals having dual infection with HIV or hepatitis B virus. In contrast to these results, we found that spouses of hepatitis C infected individuals had a statistically significant prevalence of hepatitis (17% vs 4%, P < .05). Similarly Omar et al9 also found that approximately 30% of individuals had spouses who are seropositive for hepatitis C. Like other household contacts, spouses can also be infected with HCV infection by sharing of common domiciliary objects like razors, toothbrushes, and nail cutters.19 Those studies which suggest a high prevalence of seropositivity among spouses usually lack phylogenetic analysis to confirm that whether the HCV was acquired through sexual activity or other blood contaminated objects. Partners in whom other routes of transmission are excluded should undergo phylogenetic analysis to further confirm these results.
4.4 Hepatitis C infection in mothers
In our study, we had 3.7% (n = 20) individuals for whom mothers were also positive for HCV. Among them, two individuals were less than 10 years old. Their births were attended by informal birth handlers at home and the mothers were unaware of hepatitis C screening among these children. For vertical transmission it is necessary that mothers should be seropositive during delivery, and the infants acquire this virus intrauterine or at the time of delivery. We could not assess whether these were vertical or nonvertical exposures which resulted in hepatitis C infection among such children. So, we avoided the term vertical transmission in our study. A large meta-analysis conducted by Benova et al20 showed that mother to offspring transmission occurs in 5% of cases resulting in the primary source of transmission among children. Similarly a large study cohort was conducted with seropositive mothers and vertical transmission was found to be around 3%.20, 21 But in all these studies, the infants born to seropositive mothers were tested at the time of birth and then at regular intervals for polymerase chain reaction of HCV infection, which was lacking in our study.
4.5 Dental procedures and hepatitis C infection
Dental procedures are among the common routes of transmission of this infection. In this study, 50.7% patients with hepatitis C infection had undergone dental procedures (P < .05). Regression analysis also showed that dental procedures are a statistically significant risk factor for hepatitis C infection (OR: 0.58, 95% CI: 0.37-0.90, P = .01). Butt et al22 and Habib et al8 also found that nearly 40% of patients with hepatitis C infection had undergone dental procedures. Similar results were shown by Mahboobi et al23 in their study. Dental procedures are a clear route of transmitting hepatitis C infection. We need further evaluation regarding the type of dental procedures associated with increased transmission of this virus.
4.6 Injections and hepatitis C infection
Unsafe injecting practices among individuals and informal practitioners contribute substantially to hepatitis C infections globally.24 The number of injections in most of the third world countries are about 13 injections per year.25 Our results showed that injections use, whether intramuscular or intravenous, is the second common risk factor for getting HCV. Injection use was an independent risk factor for transmission of this virus (OR: 0.69, 95% CI: 0.44-1.09, P = .1). Habib et al8 also found that injection use, particularly from informal practitioners, increased the risk of hepatitis C infection.
4.7 Surgical procedures and hepatitis C infection
Surgical procedures are well-known risk factors for hepatitis C infection.8, 26, 27 Our results also showed that a significant proportion of patients had history of some surgical procedures.
4.8 Blood transfusion and hepatitis C infection
Transfusion-related infections are a huge problem for public health of the 20th century, but this problem has been tackled by appropriate screening methods. Our study showed that 29.2% individuals with hepatitis C infection had a history of blood or blood product transfusion, which was not statistically significant (P > .05). Regression analysis also failed to show this as an independent risk factor. Lopez-Menchero et al28 also suggested in their study that the transmission of hepatitis C transmission is almost negligible through transfusions due to appropriate screening methods.
4.9 Number of children and hepatitis C infection
Interesting results were obtained regarding the bond between the number of children and hepatitis C infection. Regression analysis showed the number of children is an independent risk factor for transmission of hepatitis C infection (OR: 0.83, 95% CI: 0.74-0.94, P = .00). Although many studies have revealed the incidence of hepatitis C during pregnancy and the risk of perinatal transmission, the relationship between the number of children and hepatitis C infection has not been studied previously. The possible reason for this risk factor is many of the deliveries are attended by informal birth attendants in our population due to low education level. Episiotomy and other procedures by unsterilized instruments during delivery predispose the women with more children to hepatitis C infection. Habib et al8 also proposed previous obstetric history as a risk factor for hepatitis C infection.
5 CONCLUSION
The rate of HCV familial clustering was found to be very high in a Pakistani population. There is a strong need to increase awareness about HCV transmission routes among positive individuals to decrease the rates of HCV familial clustering. The major risk factor for getting HCV infection are dental procedures, unsafe injections, surgery, and blood transfusions.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
AUTHOR CONTRIBUTIONS
ZJ and OA did the data extraction. YW and ZJ designed the study. ZJ, OA, YW, MHN, and HY did the data analysis and gave final approval for the study. ZJ and YW wrote the manuscript. YW and ZJ revised the manuscript. YW supervised the study.
ETHICAL APPROVAL
The study was approved by the Ethical Review Committee of Fauji Foundation Hospital, Rawalpindi, and the study was performed according to the Helsinki Declaration (1964).
CONSENT
Informed consent was taken from all the individuals for participating in the study and the identity of individuals was kept anonymous.