EXPLOSION OF HEPATITIS B AND C VIRUSES AMONG HEMODIALYSIS PATIENTS AS A RESULT OF HEMODIALYSIS CRISIS IN YEMEN

Omar Ayedh Abdullah Amran1, Hassan A. Al-Shamahy1, Ahmed Mohamed Al Hadad2,

Bushra Mohammed Jaadan3

1Medical Microbiology and Clinical Immunology Department, Faculty of Medicine and Health Sciences, Sana’a University, Republic of Yemen.

2Medicinal Chemistry, Faculty of Pharmacy, Sana’a University, Republic of Yemen.

3Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Hadhramout University, Republic of Yemen.

DOI: https://doi.org/10.22270/ujpr.v4i5.311

ABSTRACT

The United Nations considers the situation in Yemen to be the worst humanitarian crisis in the world. In the midst of this, the fastest-spreading viral infection among HD patients was recorded. Therefore, this cohort study based in HD unit was conducted in Dhamar Hospital to estimate the outbreak of hepatitis B and C viruses among dialysis patients during the dialysis crisis in Yemen. All the patients who continuous go through hemodialysis from January 2018 to December 2018 and they were free from HBV/HCV infections at the start of the study (January 2018) were included. Patients who were discontinued from dialysis before the end of the year due to death or relocation were excluded from the study. Patients were tested for anti-HCV antibodies and hepatitis B surface antigen (HBsAg) at study start (January 2018) then at the end of the follow up (December 2018). The individual’s data were collected in a pre-designed questionnaire including; demographic data of HD frequency, and laboratory results. The study included 202 patients, 20 (9.9%), 18 (8.9%) and 6 (2.97%) were found to be infected with HCV, HBV and Co-HBV/HCV infection respectively. There was significant association between rise of HCV rate and younger patient age, and high frequency of dialysis.  In conclusion, the prevalence of HBV and HCV infection and HBV / HCV infection in hemodialysis patients in our surroundings one year after HD was extremely common and lead to disaster for HD patients. This catastrophe is due to the lack or limited availability of materials and tools for dialysis and laboratory materials for virus tests due to the unfair siege on Yemen from Saudi Arabia and the United Arab Emirates and the closure of Sana'a airport, which is the only entrance to medicines.

Keywords: Dhamar, haemodialysis (HD), hepatitis B virus (HBV), hepatitis C virus (HCV), Yemen.

INTRODUCTION

Viral infections of hepatitis B (HBV) and hepatitis C (HCV) are major causes of morbidity and mortality in dialysis patients and pose problems in the management of these patients in renal dialysis units1.  An estimated 400 million people are living with HBV around the world; 75% of them reside in Asia and the Western Pacific, and an estimated 170 million people worldwide are living with hepatitis B virus2.  The prevalence and incidence of hepatitis C infection in dialysis patients varies from country to country and ranges from 1 to 84.6%3.  Due to the common transmission methods, infection with HBV/HCV is not common in severely infested areas and among people at high risk of parenteral transmission. Patients with dual HBV/HCV infection have a higher risk of progressing to cirrhosis4, as well as an increased risk of hepatocellular carcinoma (HCC)5.

Long-term exposure to blood vessels and multiple blood transfusions increase the risk of these blood-borne diseases in dialysis patients. Contaminated devices, equipment and supplies, environmental surfaces and staff involved may play an important role in the transmission of this infection6.  Infections of hepatitis viruses in dialysis patients are enhanced by a significant dysfunction of the immune state that develops due to irreversible renal settlement6.  HBV infection is less prevalent than HCV in dialysis units due to the introduction of HBV vaccine, isolation of HBV-positive patients, use of dedicated dialysis machines and regular monitoring of HBV infection have significantly reduced HBV prevalence in this situation7.

 Saudi-Emirati aggression in Yemen has destroyed the country's infrastructure, resulting in disasters such as the modern HD crisis. But the damage to Yemen's healthcare sector is so great that individuals with chronic illnesses do not have access to life-saving treatment. Of the 32 dialysis centers in Yemen before the war, four were closed. The others are struggling to provide services, with broken machines, lack of basic supplies and unpaid staff8.  Patients usually need three sessions of four hours per week. In Yemen, the fragile situation has forced patients to reduce two cycles. The United Nations considers the situation in Yemen to be the worst humanitarian crisis in the world. In the midst of this, the fastest-spreading viral infection among HD patients was recorded. Therefore, this cohort study based in HD unit was conducted in Dhamar Hospital, Dhamar City, Yemen to estimate the outbreak of hepatitis B and C viruses among dialysis patients during the dialysis crisis in Yemen.

 SUBJECTS AND METHODS

This cohort, single study centered was conducted in the HD unit at Dhamar Hospital, Dhamar City, Yemen. All patients consistently undergoing dialysis from January 2018 to December 2018 and were free of HBV / HCV infection at the beginning of the study (January 2018). Patients who stopped dialysis before the end of the year due to death or transfer were excluded from the study.  Patients were tested for anti-HCV antibodies hepatitis B surface antigen (HBsAg) at study start (January 2018) then at the end of the follow up (December 2018).

Specimen Collection and Laboratory Investigation After obtaining informed consent, 5 ml of venous blood was withdrawn under sterile conditions from 202 HD patients. Serums were then screened for hepatitis B surface antigen (HBsAg) and an hepatitis C virus (anti-HCV) antibody using the fourth generation of the enzyme-linked immunosorbent assay (ELISA) (Boehlinger, Germany).

 Results greater than or equal to the cut off value and the percent neutralization is>50%, the sample is considered confirmed positive for both HBsAg and HCV and results less than the cut off value are considered negative for both.

Data collection

 Individual data were collected in a pre-designed questionnaire including; HD frequency, demographic data, HD duration, risk factors for hepatitis B and hepatitis C virus infection, and laboratory results.

Statistical analysis

To relate possible risk factors for HBV and HCV infection, the data were examined in a case-control study format. For HBV or HCV, persons with evidence of previous or current infection with HBV or HCV positive were matched up with those who were HBV or HCV negative.  The chi square was used to see the association Odds ratios (OR) and their 95% confidence intervals (CI). Values (OR, CI, χ2) were estimated using 2x2 tables to identify possible odds ratio on occurrence of HBV and HCV and their significance. The result at p-value 0.05 or less was considered as statistically significant.

 ETHICAL CONSIDERATION

Ethical authorization for the study was obtained from the Research Review Committee of the Faculty of Medicine and Health Sciences. Informed consent was taken from HD patients before sampling.

 

RESULTS

Table 1 shows the prevalence of different types of viral infections hepatitis among HD patients one year after dialysis. The prevalence rate of single hepatitis B virus was 8.9%, the rate of single hepatitis C virus infection was 9.9%, and 2.97% of HD patients found to have Co-HBV / HCV infection.

Table 2 shows the effects of sex and age groups on HBV infection among HD patients. The HBV rate among female patients was 15% higher than 9.8% of male patients. There was an increase in the HBV rate in the age group 30-39 years where the rate was 18.8% with OR equal to 1.8 and there was a lower rate of HBV in the age group less than 30 years (5.6%) but the differences between the rates in all age groups were not statistically significant. Table 3 shows the effects of sex and age on hepatitis C virus infection among HD patients. The hepatitis C virus rate among female patients was 15% higher than 11.5% of male patients. There was an increase in the HCV rate in the age group below 30 years where the rate was 27.8% with OR equal to 3.0, CI=1.0-9.2, and P=0.04; followed by 20.3% with OR equal to 2.5, CI =1.1-5.6, and P=0.03 in the age group 50-59 years; while there was a decrease in the rate of hepatitis C infection in the age group ≥60 years (4.5%) but differences between rates in the sexual groups and most age groups were not statistically significant. Table 4 shows the effect of hemodialysis frequency on contraction HBV infection among HD patients. There was an increase in HBV rate in dialysis frequency 7 times where the rate was 16.7% with OR equal to 1.5, followed by 12.3% with OR equal to 1.1for 8 times; but differences between rates in the dialysis frequency groups were not statistically significant. Table 5 shows the effect of dialysis frequency on hepatitis C virus infection among HD patients. There was an increase in HCV rate in dialysis frequency 8 times where the rate was 15.7% with OR equal to 1.9, while lower rates occurred in other frequency groups; however, differences between rates in dialysis frequency groups were not statistically significant.

 DISCUSSION

Since dialysis requires access to the circulatory system, patients undergoing dialysis may expose the microbial circulatory system, which may lead to bacteremia, or viral infections as HBV, HCV, HIV. The risk of infection varies depending on the type of access used. Bleeding may also occur, again the risk varies depending on the type of access used. Infection can be minimized by strict adherence to best infection control practices9.  The results of the current study showed that the prevalence of HBV and HCV infection in HD patients is 8.9% and 9.9%, respectively, with the combined infection rate of HBV-HCV equal to 2.97% and the overall infection rate was 21.8%.

This finding confirmed that 21.8% of our patients were converted to positive viral hepatitis within a year, and this suggests that within the next four years of HD all HD patients who participated in this study will acquire viral hepatitis.The results indicated that spread of HBV and HCV may be of greater importance in HD units through contamination HD equipments.  Infection for our HD patients may be from a reuse analyzer or transfusion. As is known, dialysis apparatus can be disused after each treatment or reused. Reuse requires extensive and high-level disinfection and there has been a preliminary debate on whether the reuse of dialysis machines has exacerbated patient outcomes.10  Today's consensus is that the reuse of dialysis machines, if done carefully and correctly, leads to results similar to the single use of dialysis machine, but due to situations arising from the war in Yemen, dialysis machines are reused, not carefully and properly done, and the bad results as HBV, HCV infections to reuse of dialyzers is the consequence. The second source of HBV and HCV infection in the participated HD patients may be through blood transfusion and this important relationship of HD with HBV and HCV, reflects poor measures in screening blood donors for hepatitis C and B using insufficient materials, and instruments in most hospitals in Yemen due to the Saudi/UAE aggression and the closure of Sana'a Airport, which is the only entrance to medical materials.11

The prevalence of HBV and HCV infection in HD patients in the current study is lower than the rates reported from old previous various studies in developing countries where the prevalence of HBV and HCV in dialysis patients ranged from 15-40%7,12-15.  The prevalence of HBV and HCV infection in dialysis patients in current study is lower than previously reported in Yemen among HD patients where the prevalence of HBV and HCV infection in dialysis patients was 17.9% and 22.5%, respectively.16   Because these two viruses share a common method of transmission, we searched for co-infection with HBV and HCV among patients, and were seen in 6 patients, male (2/122=1.6%) and four females (4/80 = 5%). Studies on the prevalence of HCV and HBV infection in HD are rare; Kara et al.17 in Turkey reported a dual incidence of three out of 67 paralysis patients. Hong et al.18 in China reported a common infection of 30.4% and was higher than dialysis patients who had only 3.8%. Reddy et al.14 in India found a prevalence of 3.7% of dual infections in HD patients.

In another study by Saravanan et al.15, out of 251 patients, 67 (26.7%) were positive for HCV, 112 (44.6%) were positive for HBV, 15 (5.9%) had a double infection, and 57 (22.7%) were non HBV/Non-HCV. Another study by Bhaumik and Debnath6 in India reported the prevalence of HBV, HCV and HBV/HCV co-infection by 7%, 46% and 37%; respectively.  What's more in another study by Jain et al.19 reported the prevalence of HBV, HCV and HBV/ HCV infection by 11%, 30% and 3%; respectively. Moreover, in another study by Alashek et al.20 in Libya reported that the prevalence of common infection HBV, HCV, and HBV / HCV is 2.6%, 31.1%, and 1.2%, respectively. There was a trend towards increased HB surface antigen levels with the third decade of age (age group 30-39 years) where the prevalence rate was 18.8%. This is similar to the findings of previous studies in Yemen among the general population and at-risk groups21-23.  There was a trend towards increasing HCV levels with the second and fifth decades of age (less than 30 years and 50-59 year groups) where the prevalence rate was 27.8% and 20.3%, respectively. This differs from the results of previous studies in developing and developed countries among dialysis patients24,25 which reported that the high prevalence of hepatitis C virus was in the sixth decade compared to the younger age groups of dialysis patients.  In the current study, there was an increase in the HCV rate in dialysis frequency 8 times where the rate was 15.7% with OR equal to 1.9, while lower rates occurred in other frequency groups; however, differences between rates in dialysis frequency groups were not statistical significance. These results differ from those of Saha and Agarwal1 and Bhaumik and Debnath6, where this former factor was a significant risk factor for hepatitis C virus infection in HD patients.

 CONCLUSION

In conclusion, the prevalence of HBV and HCV infection and HBV / HCV infection in hemodialysis patients in our surroundings one year after HD was extremely common and lead to disaster for HD patients. This catastrophe is due to the lack or limited availability of materials and tools for dialysis and laboratory materials for virus tests due to the unfair siege on Yemen from Saudi Arabia and the United Arab Emirates and the closure of Sana'a airport, which is the only entrance to medicines.

In addition, there is a high risk of developing the disease among chronic renal failure (CRF) patients due to frequent exposure to blood from transfusions and circulatory processes outside the body during dialysis. It was also found that the risk of co-infection is higher among patients with CRF due to the high frequency of blood transfusion / blood products and circulation outside the body during dialysis.

 ACKNOWLEDGMENTS

The authors would like to acknowledge Sana’a University, and the Microbiology Department of the National Center of Public Health Laboratories (NCPHL) Sana'a, Yemen which provided working space.

 CONFLICT OF INTEREST   

"No conflict of interest associated with this work”.

 AUTHOR’S CONTRIBUTION

This research work is part of a M.Sc. thesis. The candidate is the first author (OAA) who conducted the laboratory and field works; and wrote up the thesis. The corresponding author HAA, BMJ and MAH supervised the laboratory and field works, revised and edited the thesis draft and the manuscript.

 

REFERENCES

  1. Saha D, Agarwal SK. Hepatitis and HIV infection during haemodialysis. J Indian Med Assoc 2001; 99:194–9; 203, 213.
  2. Bini EJ, Perumalswami PV. Hepatitis B virus infection among American patients with chronic Hepatitis C virus infection: Prevalence, racial/ethnic differences, and viral interactions. Hepatology 2010; 51:759–66. 
  3. Karoney MJ, Siika AM. Hepatitis C virus (HCV) infection in Africa: A review. Pan Afr Med J 2013; 14:44.
  4. Sagnelli E, Coppola N, Pisaturo M, Masiello A, Tonziello G, Sagnelli C, et al. HBV superinfection in HCV chronic carriers: A disease that is frequently severe but associated with the eradication of   Hepatology   2009; 49: 1090 –7.
  5. Shi J, Zhu L, Liu S, Xie WF. A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. Br J Cancer 2005; 92:607–12.
  6. Bhaumik P, Debnath K. Prevalence of hepatitis B and C among haemodialysis patients of Tripura, India. Euroasian J Hepato-Gastroenterol 2012; 2:10–3.
  7. Aghakhani A, Banifazl M, Eslamifar A, Ahmadi F, Ramezani A. Viral hepatitis and HIV infection in hemodialysis patients. Hepat Mon  2012;12:463–4. 
  8. ICRC 2019. Hidden cost of war: in Yemen. https://www.icrc.org/yemen- hidden-cost-war- thousands-kidney-dialysis-pa.
  1. Daugirdas JT, Black PG, Ing TS. In "Handbook of Dialysis". 4th Philadelphia, PA: Lippincott Williams & Wilkins, a Wolters  Kluwer  Business; 2007.
  2. Clinical Practice Guidelines for Hemodialysis Adequacy, 2006 Updates.
  3. Hemodiylasis crisis in Yemen. MHP report: 2018-03-11.
  4. Abumwais JQ, Idris OF. Prevalence of hepatitis C, hepatitis B, and HIV infection among haemodialysis patients in Jenin District (Palestine) Iran J Virol 2010; 4:38–44.
  5. Chowdhury A, Santra A, Chakravorty R, Banerji A, Pal S, Dhali GK, et al. Community-based epidemiology of hepatitis B virus infection in West Bengal, India: Prevalence of Hepatitis B e antigen-negative infection and associated viral variants. J Gastroenterol Hepatol 2005; 20:1712–20.
  6. Reddy GA, Dakshinamurthy KV, Neelaprasad P, Gangadhar T, Lakshmi V. Prevalence of HBV and HCV dual infection in patients on haemodialysis. Indian J Med Microbiol 2005; 23:41–3.
  7. Saravanan S, Velu V, Nandakumar S, Madhavan V, Shanmugasundaram U, Murugavel KG, et al. Hepatitis B virus and hepatitis C virus dual infection among patients with chronic liver disease. J Microbiol Immunol Infect 2009; 42:122–8. 
  8. Baghza Najla M. The Prevalence of Hepatitis C Virus among Hemodialysis Patients in Yemen. J Purity Utility Reaction Environ 2014; 3(4): 221-225.
  9. Kara IH, Yilmaz ME, Sari Y, Diizen S, Usul Y, Isikoglu B. Seroprevalence and risk factors of HCV in dialysis patients in a University Haemodialysis Center of southeast Anatolia, Turkey. Dial Transplant. 2001;30:748–55.
  10. Hung KY, Chen WY, Yang CS, Lee SH, Wu DJ. Hepatitis B and Hepatitis C in haemodialysis patients. Dial Transplant. 1995; 24:135–9.
  11. Jain P, Nijhawan S. Occult Hepatitis C virus infection is more common than hepatitis B infection in maintenance hemodialysis patients. World J Gastroenterol  2008; 14:2288–9. 
  12. Alashek WA, McIntyre CW, Taal MW. Hepatitis B and C infection in haemodialysis patients in Libya: Prevalence, incidence and risk factors. BMC Infect Dis 2012; 12:265.
  13. AL-Shamahy H. Prevalence of Hepatitis B surface antigen and Risk factors of HBV infection in a samples of healthy mothers and their infants in Sana’a, Yemen. Ann Saudi Medicine 2000; 20: 464-467.  
  14. Al-Shamahy HA, IA Rabbad, Al-Hababy A. Hepatitis B virus serum markers among pregnant women in Sana'a, Yemen. - Ann Saudi Med 2003; 23:87-89.
  15. Hanash SH, Al-Shamahy HA, Bamshmous MHS. Prevalence and genotyping of hepatitis C virus in hemodialysis patients and evaluation of HCV-core antigen test in screening patients for dialysis in Sana’a city, Yemen. Universal J Pharm Res 2019; 4(2): 14-18.
  16. Nelson, PK; Mathers BM; Cowie B; Hagan H; Des Jarlais D; Horyniak D; Degenhardt L. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet 2011; 378(9791): 571–83. 
  17. Zaltron S, Spinetti A, Biasi L, Baiguera, C; Castelli, F. "Chronic HCV infection: epidemiological and clinical relevance.". BMC infectious diseases 2012; 12 Suppl 2: S2

 

Table 1: The prevalence rate of different types of Hepatitis viral Infections among HD patients after 1 year of dialysis.

Types of Hepatitis viral Infections

Frequency

Number

%

HBV single infection

18

8.9

HCV single infection

20

9.9

HBV+HCV co-infections

6

2.97

Total infections

44

21.8

  

Table 2: The effects of  sex and age groups in HBV infections among  HD patients.

Characters

 

HBV positive cases (n = 24)

OR

CI

  χ 2

    p

 

No.           

%

 

 

 

 

Sex

Male (n= 122)

12

9.8

0.51

0.2-1.2

2.5

0.11

Female (n= 80)

12

15

1.36

0.59-3.1

2.5

0.11

Age groups

< 30 years (n=18)

1

5.6

0.37

0.04-2.5

0.9

0.33

30-39 years (n=48)

9

18.8

1.8

0.76-4.9

1.9

0.16

40- 49 years (n=50)

5

10

0.69

0.24-1.9

0.48

0.48

50- 59 years (n=64)

6

9.4

0.61

0.23-1.6

1.01

0.31

≥ 60 years   (n=22)

3

13.6

1.1

0.29-3.9

0.01

0.9

Total n=202

24

11.9

 

OR-Odds ratio = Relative risk, CI=Confidence intervals, χ2-Chi-square=3.9  or more significant,  p-Probability value = 0.05 or less  significant

  

Table 3:  The effects of sex and age groups in HCV infections among  HD patients.

Characters

 

HCV positive cases (n = 26)

OR

 

CI

 

  χ2

 

    P

 

 

No.           %

 

 

 

 

Sex

Male (n= 122)

14

11.5

0.7

0.32-1.6

0.53

0.46

Female (n= 80)

12

15

1.4

0.5-3.1

0.53

0.46

Age groups

< 30 years (n=18)

5

27.8

3.0

1.0-9.2

3.9

0.04

30-39 years (n=48)

3

6.3

0.37

0.1-1.3

2.5

0.1

40- 49 years (n=50)

4

8

0.51

0.16-1.57

1.4

0.23

50- 59 years (n=64)

13

20.3

2.5

1.1-5.6

4.6

0.03

≥ 60 years   (n=22)

1

4.5

0.29

0.03-2.29

1.5

0.21

Total n=202

26

12.9

 

OR-Odds ratio = Relative risk, CI=Confidence intervals, χ2-Chi-square=3.9 or more significant,  p-Probability value = 0.05 or less  significant

  

Table 4: The effect of dialysis frequency on HBV infections among  HD patients.

Frequency/months

HBV positive cases (n =24)

OR

CI

χ 2

P

 

No.

%

 

 

 

 

5or less times n=10

1

10

0.81

0.09-6.7

0.035

0.85

6 times n=58

6

10.3

0.80

0.3-2.1

0.18

0.66

7 times n=12

2

16.7

1.5

0.3-7.4

0.27

0.59

8 times n=122

15

12.3

1.1

0.45-2.7

0.05

0.82

OR-Odds ratio = Relative risk, CI=Confidence intervals, χ2-Chi-square=3.9 or more significant,  p-Probability value = 0.05 or less  significant 

Table 5: The effect of dialysis on HCV infections among HD patients.

Frequency/months

HBV positive cases (n =24)

OR

CI

χ 2

P

 

No.

 

 

 

 

 

5 or less times n=10

1

 

0.83

0.1-6.8

0.029

0.86

6 times n=58

5

 

0.61

0.2-1.7

0.88

0.34

7 times n=12

1

 

0.62

0.08-5.2

0.16

0.68

8 times n=122

19

 

1.9

0.76-4.8

2

0.15

OR-Odds ratio = Relative risk, CI=Confidence intervals, χ2-Chi-square=3.9 or more significant, p-Probability value = 0.05 or less significant