HEPATITIS C VIRUS AND LEUKEMIA PATIENTS: PREVALENCE AND RISK FACTORS ASSOCIATED WITH INFECTION AMONG LEUKEMIA PATIENTS WHO ACHIEVE LONG-TERM REMISSION AFTER CHEMOTHERAPY 

Monya Abdullah Yahya El-Zine1image, Yusra Ahmed Saleh Dawood2image, Maged Ali Amer Ali5image, Khaled Abdulkarim Al-Moyed2,4image, Eshrak Adulmalik Al-gunaid8image, Hassan Abdulwahab Al-Shamahy2,3image,  Ahmed Mohammed Al-Haddad6image, Azhar Azher Mohammed Al-Ankoshy7image

1Department of Histopathology, Faculty of Medicine and Health Sciences, Sana’a University, Republic of Yemen.

2Medical Microbiology department, Faculty of Medicine and Health Sciences, Sana’a University, Republic of Yemen.

3Department of Basic Sciences, Faculty of Dentistry, Sana’a University, Republic of Yemen.

4University of 21 September for Medical and Applied Sciences, Sana’a, Yemen.

5Department of Neurosurgery, Faculty of Medicine and Health Sciences, Sana’a University, Republic of Yemen.

6Department of Medical Laboratories, College of Medicine and Health Sciences, Hadhramout University, Al-Mukalla, Republic of Yemen. 7Jabir Ibn Hayyan Medical University, Faculty of Medicine, Department of Physiology, An-Najaf, Iraq.

8The National Center of Public Health Laboratories (NCPHL), Sana'a, Yemen.

 

Abstract

Aim and objective: Leukemia patients are at elevated risk of hepatitis C virus infections, with anti-HCV prevalence ranging from 4.3% to 70% post-chemotherapy remission. Long-term leukemia survivors' natural histories are unclear. We measured anti-HCV antibodies to investigate the frequency of HCV infections and the associated odds factors of contracting HCV among leukemia patients who achieved long-term remissions after chemotherapy. 

Methods: This study is a cross-sectional study, comprising leukemia patients at the oncology center at Kuwait Hospital in Sana'a, Yemen. It included people with leukemia of different ages and genders. Data was collected through a standard questionnaire prepared for this study, which includes clinical symptoms, risk factors, demographic data, and the results of diagnostic tests. Antibody tests for the hepatitis C virus (HCV) were done by ELISA.

Results: The majority of patients with HCV are male, with a mean age of 12.8 years. The prevalence is 5.5%, with males having a higher prevalence. Most patients receive blood transfusions more than twice, with major blood banks, Al-Kuwait hospitals, and private hospitals being the primary sources. AML and ALL are the two most common leukemias. Male patients have a higher risk, and those over 15 years old have a higher risk. 

Conclusions: This study is the first in Yemen to investigate the prevalence of HCV infections in patients with leukemia. According to our research, leukemia patients had a greater prevalence of HCV than the general population's national prevalence. However, health care workers (HCWs) and patients receiving maintenance hemodialysis (HD) patients have prevalence's of HCV that are comparable. 

Keywords: Anti-HCV antibodies, associated odds factors, chemotherapy, HCV infections, leukemia, long-term remissions.

 

INTRODUCTION

 

In a 2021 report, the WHO predicted that, as of 2019, 58 million people worldwide have chronic hepatitis C. An anticipated 290,000 individuals die every year from hepatitis C- associated illnesses, primarily cirrhosis and liver cancer, and an estimated 1.5 million people become infected each year1. In Yemen, thousands of people are affected by the serious public health issue of hepatitis virus-related liver illness. HAV, HBV, HCV, HEV, HDV, and recently discovered hepatitis viruses, for instance hepatitis G virus, combine to generate a unique combination of liver illness2-11. In Yemen, all of these viruses have been linked to high rates of illness and mortality2,3. Hepatitis virus prevalence in Yemen has been predicted to be significant2-11, yet specific data regarding the current state of infection among cancer patients in Yemen caused by hepatitis viruses is still lacking. Despite the availability of efficient treatments to eradicate HCV infection, the majority of afflicted persons remain unaware of their infection12. Patients with cancer present particular difficulties in managing and treating chronic HCV. There is no established standard of care to determine the best course of action for treating patients in this patient population, who also have a higher risk of developing occult HCV infection, developing liver disease, and experiencing viral reactivation. Studies on HCV infection in cancer patients are scarce, despite the fact that chronic HCV infection is widespread in this population. As a result, little is known about the natural course of HCV infection and the effectiveness of infection therapy in cancer patients. There is a dearth of information regarding HCV infection in cancer patients.

The incidence of HCV infection in cancer patients is predictable to be among 1.5% and 32%13,16. HCV antibody-based serological testing may produce false-negative results for cancer patients, especially those with hematologic malignancies. PCR testing for HCV RNA quantification in blood is necessary for the identification of patients with concealed infections in some of these critically immunocompromised individuals, as routine finding of anti-HCV antibodies may not be sufficient for diagnosis17-20. Furthermore, HCV reactivation may occur following chemo-therapy21. Hematopoietic stem cell (HSCT) recipients with the virus have a higher chance of developing early cirrhosis and a faster pace of fibrosis advancement compared to HCV-infected individuals who do not receive this transplant. For example, it was found that patients who had HSCT and had a persistent HCV infection had an estimated median period to cirrhosis development of 18 years, while patients in the control group who had the same infection but did not receive HSCT had an expected median time to development of 40 years. Therefore, regardless of the genotype of the virus, doctors should think about doing a liver biopsy before to starting conditioning therapy if they have a medical suspicion of cirrhosis or severe fibrosis brought on by a persistent viral infection, including HCV infection18.

In conclusion, the treatment decisions for cancer patients, especially those with leukemia, are made more difficult by the presence of the HCV. The lack of average of care recommendations for the management of HCV-infected cancer patients exacerbates this. Not only can HCV infection cause non-Hodgkin lymphoma and hepatocellular cancer, but it can also impact how antineoplastic chemotherapy treats cancer when HCV infection is present in cancer patients. Patients with cancer may experience worsening side effects from HCV therapy as a result of comorbidities and underlying cytopenias. Compared to the general non-cancer population, cancer patients respond to treatment less well when they are treated for HCV infection22. The current study aims to study the prevalence of HCV infections by measuring anti-HCV antibodies and the associated odds factors of contracting HCV among leukemia patients who completed long-term remissions after chemotherapy.

 

METHODS

 

Study design: This research was a case-control study.

Subjects and study area: This study included individuals with acute leukemia who have achieved remission after chemotherapy at the Oncology Center in Al-Kuwait Hospital in Sana’a City, Yemen.

Sample size: 

The population to estimate is 999–999. If the prevalence of hepatitis C among the risk group is 5%10, with a margin of error of 2.9%, at least 217 patients would need to be within 95% confidence.

Data collection: Each case was given a thorough history, which was then entered into a pre-made questionnaire containing demographic, private, and medical information.

Specimen collection: Each patient had five milliliters of whole blood drawn aseptically via venous puncture, and the serum was separated by centrifugation following coagulation. Samples were put in an Eppendorf tube, and sera were kept until testing at -20 °C.

Laboratory tests: Samples were evaluated using a commercially available kit (abia HCV Ab) in a closed-system Enzyme-Linked Immunosorbent Assay (ELISA). The “sandwich” form of direct immunoenzymatic approach, known as bio-ELISA anti-IgG immunoglobulin, involves incubating the samples to be evaluated in microplate wells covered with highly pure IgG antigens.

Ethical approval: The Institutional Ethical Committee of the Sana'a University Faculty of Medicine and Health Sciences approved the current study. Written informed permission was obtained from each subject prior to recruitment and research initiation. 

Statistical analysis: The statistical program's software was used to do the statistical analyses, which were then shown as percentages, tabulations, or graphical representations. Risks' odds ratio and significance as determined by logistic regression, geometric means, 95% confidence interval, and chi-square test calculations. If there were significant differences, the p-value was less than 0.05. The Statistical Package for Epi-Info version 7 was used for all statistical analyses. 

 

RESULTS

 

The age and sex distribution of 218 leukemia patients who had HCV testing is displayed in Table 1. There are 44.9% females and 55.1% males. In terms of ages, 12.8 ±12.3 years was the mean. The age range of the majority of patients was 6-10 years (32.1%), then 1-5 years (24.8%), 11-15 years (22.9%), and older than 15 years (20.2%). Table 2 displays the frequency of HCV in 218 leukemia patients by age and sex. The crude prevalence of HCV was 5.5%, with a 6.7% greater prevalence in males than in females (4.1%). When it came to age groups, the group older than 15 had the highest percentage (13.6%). The frequency of residency, blood transfusion frequency, and blood source information for leukemia patients tested for HCV is displayed in Table 3. The majority of patients (64.2%) live in cities, while 35.8% do so in rural areas. 

When it came to blood transfusions, 89.9% of the patients received them more than twice, while 3.7% received them just once. The major blood bank (15.6%), Al-Kuwait hospital (15.6%), Al-Thorah hospital (7.3%), Al-Sabian hospital (32.6%), Al-Jumhori hospital (11.9%), and private hospital (33.5%) were the sources of the blood. The kind of leukemia among leukemia patients with HCV testing is displayed in Table 4. Acute myelogenous leukemia (AML or myeloblastic) counts 2.8%, acute lymphoblastic leukemia (ALL) counts 78.9%, chronic lymphocytic leukemia (CLL) counts 14.3%, chronic myelogenous leukemia (CML) counts 4.1%. When examining the related factors of HCV, a male patient's associated odds ratio of 1.7 was found, compared to a female patient's OR of 0.6. However, the results were not statistically significant (p=0.4). When age groups were taken into account, the age >15 years showed a high associated odds ratio of 4.4, with a confidence interval ranging from 1.4 to 14.5 and a significant p-value of 0.008. Al-Jumhori Hospital exhibited a high associated odds ratio of 9.3, with a confidence interval ranging from 2.7 to 31, and a significant p-value of less than 0.0001, when blood sources were taken into account as a risk factor for HCV infection. A family history of HBV linked odds ratio of 25.3 with a confidence range spanning from 5.4 to 119 and a significant p-value of <0.0001 was found when looking at the related factors of HCV.

Additionally, a significant p-value of less than 0.0001 was found for the related odds ratio of 19.6 with a confidence range spanning from 5.2 to 71.7 and a family history of jaundice as a risk factor for HCV infection. Additionally, the history of dental visits was found to be a risk factor for HCV infection; the related odds ratio for this factor was 4.9, with a significant p-value of 0.0008 and a confidence interval that ranged from 1.4 to 17.8. The risk factors for HCV linked with each form of leukemia are listed in Table 7. A linked risk factor for HCV infection was discovered to be Chronic Lymphocytic Leukemia (CLL); the related odds ratio for this factor was 3.3, with a significant p-value of 0.05 and a confidence interval spanning from 1.1 to 11.7.

 

DISCUSSION

 

The chronic HCV infection prevalence in the Sana'a, Yemen, among leukemia survivors was 5.5%, approximately 10 times greater than the 0.5% national prevalence23,24. Additionally, past international studies have documented a noteworthy prevalence of HCV infection acquired through transfusion in children who have survived cancer25,28. The geography, time period, and cancers included in the study all affect the prevalence. The incidence of 5.5% chronic HCV infection was found in the HCV tested cohort of leukemia survivors in Sana'a city, which is equivalent to HCV risk groups such as dental workers 5.5%7,10, albeit being lower than the 11.5% of public health center workers in Yemen10. The greater than anticipated percentage of HCV infections among our leukemia patients, given that nearly all of them need blood transfusions while undergoing therapy29,30.

The higher incidence of HCV in environments with insufficient resources is recognized to be caused by several variables. Among these problems are under diagnosis, inadequate preventive measures, contact tracking, and inadequate treatment for those who are affected. Low community awareness of infection and transmission, treatment accessibility and cost concerns, and occasionally healthcare providers' ignorance of current treatment guidelines are further contributing factors.

Rising rates of both internal and external migration, administrative and organizational issues that obstruct the national health organization's commitment to resource mobilization, inadequate coordination with international partners or their departure from Yemen due to the conflict, and a lack of sense of duty on the part of some state employees towards the community members' health are other factors that contribute to the spread of this disease31,36. The most frequent cancer in the group of HCV-positive was ALL, as virtually all of these patients needed blood transfusions while undergoing therapy37,38.  Current study found that the HCV sero-prevalence in men was 5.5% and higher (6.7%), but the HCV rate in the age group under 15 was 13.6%. These results are in line with the general reports of HCV seropositive rates in African nations39,42. Patients with CLL, where the prevalence of HCV was 12.9%, showed variations in HCV prevalence. This stands in contrast to studies that discovered higher HCV virus prevalence among AML patients in Korea43,44. This could be connected to differences in the onset age of HCV infection and leukemia43,44. According to previous reports, people with leukemia are more likely to get transfusion-associated hepatitis C virus (HCV) infections.The current investigation found that the frequency of HCV in leukemia patients in Yemen was higher than that of the community population in general45. The prevalence of anti-HCV in matures with acute leukemia who are in remission following treatment ranges from 4.3 to 70%46-48. Similarly, the anti-HCV prevalence in recipients of bone marrow transplants (BMT) ranges from 3.3 to 70%49-51. Studies limited to children with leukemia have found a somewhat lower frequency of 1 to 49%52-54. Since the induction of subsequent generation assessment in 1992 and anti-HCV screening for blood donors in 1990, the rate of infection has declined46. There is a paucity of information on how immunosuppression affects the severity of liver disease and viral load in long-term anti-HCV positive leukemia survivors. Nonetheless, a number of researchers have noted that people who are co-infected with HIV and anti-HCV positive have far greater viral levels than people who are anti-HIV negative55. According to certain findings55,56, HCV RNA levels rise as the immune deficit worsens, but not according to other reports57,58.

Additionally, it has been demonstrated that co-infection with HIV raises the risk of liver failure and cirrhosis59-61. Similar outcomes have been reported in patients with primary hypogammaglobulinemia62. In contrast, leukemia patients who achieved remission following chemotherapy had only a little increase in liver disease-related mortality, according to long-term follow-up of immunocompetent individuals63.

Limitation of the study

The current study has some limitations that should be discussed. First, there was a lack of information about prior antiviral therapies for HCV. If leukemia patients had received effective treatment for HCV infections, however, this would not have had a substantial effect on the identification of antibodies linked to the virus. Secondly, results of imaging studies of the hepatobiliary system or tests for abnormalities of liver enzymes were not included in the patient database. Fourth, the detection tests had a number of limitations that could have led to an overestimation or underestimation of the frequency of occult HCV in this population. Finally, the lack of liver tissue makes it impossible to draw firm conclusions on the incidence of occult HCV infections in leukemia patients, given that HCV infection can exist even in cases where tests on sera and peripheral blood lymphocytes come out negative. Furthermore, we cannot be positive that the prevalence of viral infections is the same as it is in the general population because we did not include a control population of non-leukemic patients; nonetheless, these findings are in line with earlier systematic reviews of numerous population-based studies conducted globally.

 

CONCLUSIONS

 

This study is the first in Yemen to investigate the prevalence of viral infections in patients with leukemia. According to our research, leukemia patients had a greater prevalence of HCV than the general population's national prevalence. However, HCWs and patients receiving maintenance (HD patients) have a prevalence of HCV that is comparable. Screening patients for HCV infections is strongly encouraged by clinicians, as these individuals are susceptible to complications connected to chemotherapy.

 

ACKNOWLEDGEMENT 

 

The authors are appreciative to Sana'a University in Sana'a, Yemen, for funding this effort. 

 

AUTHOR’S CONTRIBUTIONS 

 

The author of the original draft, method, and investigation is Monya Abdullah Yahya El-Zine. Formal analysis, data organizing, and visualization by Yusra Ahmed Saleh Dawood. Khaled Abdul-Karim Al-Moyed: technique; writing, reviewing, and editing. Formal analysis, data organization, and visualization were handled by Hassan Abdel-Wahab Al-Shamahy, while the remaining authors reviewed and edited the piece.

 

DATA AVAILABILITY

 

Anyone can seek access to the data by contacting the respective author.

 

CONFLICT OF INTEREST 

 

There is no conflict of interest around this work.

 

REFERENCES

 

  1. Global progress report on HIV, viral hepatitis and sexually transmitted infections 2021. Global report 2021. https://www.who.int/publications/i/item/9789240027077. Retrieved 2024-06-19
  2. Al-Shami HZ, Al-Mutawakal ZAM, Al-Kholani AIM, et al. Prevalence of Hepatitis A virus, Hepatitis B virus, and Hepatitis C virus, among patients with hepatic jaundice in Sana’a city, Yemen: A hospital based study. Universal J Pharm Res 2021; 6(6):12-17.https://doi.org/10.22270/ujpr.v6i6.693
  1. Al-Shawkany EM, AlShawkany AARM, Bahaj SS, et al. Prevalence of different Hepatitis B virus genotypes and risk factors associated among selected Yemeni patients with chronic hepatitis B infection. Universal J Pharm Res 2021; 6(3):24-29. https://doi.org/10.22270/ujpr.v6i3.603
  2. Edrees WH, Al-Ofairi BA, Alrahabi LM, et al. Seroprevalence of the viral markers of hepatitis B, hepatitis C, and HIV among medical waste handers in some hospitals in Sana'a city-Yemen. Universal J Pharm Res 2022; 7(3):12-19.https://doi.org/10.22270/ujpr.v7i3.774
  1. Al Makdad ASM, Al-Haifi AY, Al-Mutaa NAM, Al-Shamahy, HA. Immunological status of hepatitis B virus infection among freshmen university students in Yemen. Universal J Pharm Res 2023; 8(1):55-60.https://doi.org/10.22270/ujpr.v8i1.900
  1. Amran OAA, Al-Shamahy HA, Al-Haddad AM, Jaadan, BM. Explosion of Hepatitis B and C viruses among hemodialysis patients as a result of hemodialysis crisis in Yemen. Universal J Pharm Res 2019, 4(5):13-17. https://doi.org/10.22270/ujpr.v4i5.311
  2. Al-Kebsi AM., Othman AM, Abbas AKMA, et al. Sero-prevalence of hepatitis C virus among dental clinic workers in Sana’a city-Yemen and the risk factors contributing for its infection. Universal J Pharm Res 2017; 2(5):24-29. https://doi.org/10.22270/ujpr.v2i5.R6
  3. 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.https://doi.org/10.22270/ujpr.v4i2.251
  1. Al-kadassy AM, Al-Ashiry AFS, Al-Shamahy HA. Sero-epidemiological study of hepatitis B, C, HIV, and Treponema pallidum among blood donors in Hodeida city-Yemen. Universal J Pharm Res 2019, 4(2):38-42.https://doi.org/10.22270/ujpr.v4i2.256
  1. AL-Marrani WHM, Al-Shamahy HA. Prevalence of HBV and HCV; and their associated risk factors among public health center cleaners at selected public health centers in Sana'a city-Yemen. Universal J Pharm Res 2019, 3(5):58-62. https://doi.org/10.22270/ujpr.v4i5.204
  2. Al-Dabis EM, Al-Shamahy HA, Al-Hadad MMS, Al-Shamahi EH. Prevalence of hepatitis G virus among patients with chronic liver disease and healthy individuals, Sana'a city-Yemen. Universal J Pharm Res 2019, 3(6):1-5.https://doi.org/10.22270/ujpr.v3i6.216
  1. Manns, M.P., Maasoumy, B. Breakthroughs in hepatitis C research: From discovery to cure. Nat Rev Gastroenterol Hepatol 2022; 19, 533–550.https://doi.org/10.1038/s41575-022-00608-8
  1. Lam JO, Hurley LB, Lai JB, et al. Cancer in people with and without hepatitis C virus infection: Comparison of risk before and after introduction of direct-acting antivirals. Cancer Epidemiol Biomarkers Prev 2021; 30(12):2188-2196. https://doi.org/10.1158/1055-9965.EPI-21-0742
  2. Darvishian M, Tang T, Wong S, et al. Chronic hepatitis C infection is associated with higher incidence of extrahepatic cancers in a Canadian population based cohort. Front Oncol. 2022 Oct 13;12:983238.https://doi.org/10.3389/fonc.2022.983238
  1. Chen YJ, Huang JY, Baskaran R, et al. Long-term survival and cancer risk in the Hepatitis C virus-infected patients after antiviral treatment: A nationwide cohort study. J Cancer 2024; 15(1):113-125.https://doi.org/10.7150/jca.87259
  1. Lau G, Yu ML, Wong G, et al. APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy. Hepatol Int 2021; 15, 1031–1048. https://doi.org/10.1007/s12072-021-10239-x
  2. Torres HA, Boeckh M, Chemaly RF. Viral infections. In: Yeung SJ, Escalante C, Gagel RF, editors. Internal medicine care of cancer patient. 1st Shelton, CT: BC Decker Inc., 2009:151-161.
  3. Sahu KK. Infectious disease in hematopoietic stem cell transplantation. Ther Adv Infect Dis 2021;8.https://doi.org/10.1177/20499361211005600
  1. Sharma V, Ramachandran VG, Mogha NS, Bharadwaj M. Hepatitis B and Hepatitis C virus infection in HIV seropositive individuals and their association with risk factors: A hospital-based study. Indian J Med Res 2018 Jun; 147(6):588-593.https://doi.org/10.4103/ijmr.IJMR_1151_16
  1. Woo J, Choi Y. Biomarkers in detection of Hepatitis C virus infection. Pathogens 2024; 13:331.https://doi.org/10.3390/pathogens13040331
  1. Torres HA, Davila M. Reactivation of hepatitis B virus and hepatitis C virus in patients with cancer. Nat Rev Clin Oncol 2012; 9(3):156-166. PMID: 22271089. https://doi.org/10.1038/nrclinonc.2012.1
  2. Ran Wang, Xinyu Wang, Linlin Zhang, et al. The epidemiology and disease burden of children hospitalized for viral infections within the family Flaviviridae in China: A national cross-sectional study. PLOS Neglected Trop Dis 2022;16:7, e0010562.
  3. Al-Nabehi BAH, Al-Shamahy H, Saeed WSE, Musa AM, El Hassan AM, Khalil EAG. Sero-molecular epidemiology and risk factors of viral hepatitis in urban Yemen. Int J Virol 2015; 11(3):133-138.https://doi.org/10.3923/ijv.2015.133.138
  1. Al-Shamahy HA, Abdu SSA. Genotyping of Hepatitis C Virus (HCV) in infected patients from Yemen. Eur J Basic Med Sci 2014; 3 (4):78-82.https://doi.org/10.15197/sabad.2.3.15
  1. Jakhar N, Gera A, Mittal R, Mehndiratta S, Shalimar, Singh A. Treatment of Hepatitis C in a case of pediatric B-cell acute leukemia. J Glob Infect Dis 2021 Aug 3;14(1):35-37.https://doi.org/10.4103/jgid.jgid_1_21
  1. Amin A, Mookerjee RP. Acute-on-chronic liver failure: Definition, prognosis and management. Frontline Gastroenterol 2019; 11(6):458-467.https://doi.org/10.1136/flgastro-2018-101103
  1. Castellino S, Lensing S, Riely C, et al. The epidemiology of chronic hepatitis C infection in survivors of childhood cancer: An update of the St Jude Children’s Research Hospital hepatitis C seropositive cohort. Blood 2004; 103(7):2460-2466.https://doi.org/10.1182/blood-2003-07-2565
  1. Psaros Einberg A, Ekman AT, Söderhäll S, et al. Prevalence of chronic Hepatitis C virus infection among childhood cancer survivors in Stockholm, Sweden. Acta Oncologica 2019;, 58(7), 997–1002.https://doi.org/10.1080/0284186X.2019.1574105
  1. Lieberman L, Liu Y, Portwine C, Barty RL, Heddle An epidemiologic cohort study reviewing the practice of blood product transfusions among a population of pediatric oncology patients. Transfusion 2014; 54(10 Pt 2):2736-2744. https://doi.org/10.1111/trf.12677
  2. Martinez-Torres V, Torres N, Davis JA, Corrales-Medina FF. Anemia and associated risk factors in pediatric patients. Pediatric Health Med Ther 2023;14:267-280.https://doi.org/10.2147/PHMT.S389105
  1. Bane A, Patil A, Khatib M. Healthcare cost and access to care for viral hepatitis in Ethiopia. Int J Innov Appl Stud 2014; 9(4):1718-1723.
  2. Sheena BS, Hiebert L, Han H, et al. Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the global burden of Disease Study 2019. Lancet Gastroenterol Hepatol 2022; 7(9):796–829.https://doi.org/10.1016/S2468-1253(22)00124-8
  1. Tordrup D, Hutin Y, Stenberg K, et al. Additional resource needs for viral hepatitis elimination through universal health coverage: projections in 67 low-income and middle-income countries, 2016-30. Lancet Glob Health 2019; 7(9):e1180-e8.https://doi.org/10.1016/S2214-109X(19)30272-4
  1. Easterbrook P, Johnson C, Figueroa C, Baggaley R. HIV and hepatitis testing: global progress, challenges, and future directions. AIDS Rev 2016; 18(1):3-14.
  2. Odimayo MS, Adebimpe WO, Jeff-Agboola YA, et al. Screening, vaccination, and referrals as viral Hepatitis elimination Triad among internally displaced persons in Edo state, Nigeria. Clin Liver Dis 2020; 16(5):218-22.https://doi.org/10.1002/cld.1063
  1. Shiferaw F, Letebo M, Bane A. Chronic viral hepatitis: Policy, regulation, and strategies for its control and elimination in Ethiopia. BMC Public Health 2016; 16(1):1-13. https://doi.org/1186/s12889-016-3459-1
  2. Busca A. Viral infections in patients with hematological malignancies. Leuk Suppl 2012; 1(Suppl2):24‑25. https://doi.org/1038/leusup.2012.15
  3. Biadgo B, Shiferaw E, Woldu B, Alene KA, Melku M. Transfusion-transmissible viral infections among blood donors at the north Gondar district blood bank, northwest Ethiopia: A three year retrospective study. PLoS One 2017; 12(7):e0180416.https://doi.org/10.1371/journal.pone.0180416
  1. Woldegiorgis AE, Erku W, Medhin G, Berhe N, Legesse M. Community-based sero-prevalence of hepatitis B and C infections in South Omo Zone, Southern Ethiopia. PLoS One 2019; 14(12):e0226890.https://doi.org/10.1371/journal.pone.0226890
  1. Kumalo A, Teklu T, Demisse T, Anjulo A. Undiagnosed seroprevalence of Hepatitis B and C Virus Infections in the community of Wolaita Zone, Southern Ethiopia. Hepat Med 2022; 14:111-22. PMID: 35971532.https://doi.org/10.2147/HMER.S374029
  1. Salomon I, Olivier S, Egide N. Advancing Hepatitis C Elimination in Africa: Insights from Egypt. Hepat Med. 2024; 16:37-44. doi: 10.2147/HMER.S470344.https://doi.org/10.2147/HMER.S470344
  1. Zenebe Y, Mulu W, Yimer M, Abera B. Sero-prevalence and risk factors of hepatitis C virus infection among pregnant women in Bahir Dar city, Northwest Ethiopia: cross sectional study. Pan Afr Med J 2015; 21(1):158. https://doi.org/11604/pamj.2015.21.158.6367
  2. Kang J, Cho JH, Suh CW, et al. High prevalence of hepatitis B and hepatitis C virus infections in Korean patients with hematopoietic malignancies. Ann Hematol 2011; 90(2):159-164. PMID: 20821327.https://doi.org/10.1007/s00277-010-1055-5
  1. Anderson LA, Pfeiffer R, Warren JL, et al. Hematopoietic malignancies associated with viral and alcoholic hepatitis. Cancer Epidemiol Biomarkers Prev 2008; 17(11):3069-3075. https://doi.org/1158/1055-9965.EPI-08-0408
  2. Hetherington ML, Buchanan GR. Elevated serum transaminase values during therapy for acute lymphoblastic leukemia correlated with prior blood transfusions. Cancer 1988; 62(8):1614-1618.https://doi.org/10.1046/j.1537-2995.1995.35495216080.x
  1. Li YR, Hu TH, Chen WC, Hsu PI, Chen HC. Screening and prevention of hepatitis C virus reactivation during chemotherapy. World J Gastroenterol 2021; 27(31):5181-5188. https://doi.org/10.3748/wjg.v27.i31.5181
  2. Henriot P, Castry M, Luong Nguyen LB, Shimakawa Y, Jean K, Temime L. Meta-analysis: risk of Hepatitis C virus infection associated with hospital-based invasive procedures. Aliment Pharmacol Ther 2022; 56(4):558-569. https://doi.org/10.1111/apt.17106
  3. Torres HA, Mahale P, Blechacz B, et al. Effect of Hepatitis C virus infection in patients with cancer: Addressing a neglected population. J Natl Compr Canc Netw 2015; 13 (1): 41-50.https://doi.org/10.6004/jnccn.2015.0007
  1. Torres HA, Chong PP, De Lima M, et al. Hepatitis C Virus infection among hematopoietic cell transplant donors and recipients: American society for blood and marrow transplantation task force recommendations. Biol Blood Marrow Transplant 2015; 21(11): 1870-1882.https://doi.org/10.1016/j.bbmt.2015.07.033
  1. Kyvernitakis A, Mahale P, Popat UR, et al. Hepatitis C virus infection in patients undergoing hematopoietic cell transplantation in the era of direct-acting antiviral agents. Biol Blood Marrow Transplant 2016; 22(4): 717-722. https://doi.org/10.1016/j.bbmt.2015.12.010
  2. Mallet V, van Bömmel F, Doerig C, et al. Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: Recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5). Lancet Infect Dis 2016; 16(5): 606-617.https://doi.org/10.1016/S1473-3099(16)00118-3
  1. Myers B, Irving W, Hollingsworth R, et al. Hepatitis C virus infection in multi-transfused children with haematological malignancy. Br J Haematol 1995; 91(2):480482.https://doi.org/10.1111/j.1365-2141.1995.tb05327.x
  1. Cesaro S, Petris MG, Rossetti F, et al. Chronic Hepatitis C virus infection after treatment for pediatric malignancy. Blood 1997; 90(3):1315-1320. PMID: 9242567
  2. Fink EM, S Höcker-Schultz S, Mohr W, et al. Association of hepatitis C infection with chronic liver disease in pediatric cancer patients. Eur J Pediatr 1993; 152:490. https://doi.org/1007/BF01955056
  3. Eyster ME, Fried M, Di Bisceglie A, Goedert JJ. Increasing HCV RNA levels in hemophiliacs: Relationship to HIV infection and liver disease. Multicenter Hemophilia Cohort Study. Blood 1994; 84(4):1020-1023.PMID: 8049420.
  1. Thomas DL, Shih JW, Alter HJ, et al. Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users. J Infect Dis 1996; 174(4):690-695. https://doi.org/1093/infdis/174.4.690
  2. Sherman KE, O’Brien J, Gufierrez AG, et al. Quantitative evaluation of hepatitis C virus RNA in patients with concurrent human immunodeficiency virus infections. J Clin Microbiol 1993; 31(10):2679-2682.https://doi.org/10.1128/jcm.31.10.2679-2682.1993
  1. Telfer PT, Brown D, Devereux H, Lee CA, DuSheiko GM. HCV RNA levels and HIV infection: Evidence for a viral interaction in haemophilic patients. Br J Haematol 1994; 88(2):397-399.https://doi.org/10.1111/j.1365-2141.1994.tb05038.x
  1. Soto B, Sanchez-Quijano A, Rodrigo L, et al. Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired Hepatitis C with an unusually rapid progression to cirrhosis. J Hepatol 1997; 26(1):1-5.https://doi.org/10.1016/s0168-8278(97)80001-3
  1. Eyster ME, Diamondstone LS, Lien JM, et al. Natural history of hepatitis C virus infection in multitransfused hemophiliacs: Effect of coinfection with human immunodeficiency virus. J Acquir Immune Defic Syndr 1993; 6(6):602-610. PMID: 8098752.
  2. Martin P, Di Bisceglie AM, Kassianides C, et al. Rapidly progressive non-A, non-B hepatitis in patients with human immunodeficiency virus infection. Gastroenterol 1989; 97(6):1559-1561.https://doi.org/10.1016/0016-5085(89)90405-8
  1. Bjoro K, Froland SS, Yun Z, Samdal H, Haaland T. Hepatitis C infection in patients with primary hypogammaglobulinemia after treatment with contaminated immune globulin. N Engl J Med 1994; 331(24):1607-1611. https://doi.org/1056/NEJM199412153312402
  2. Seeff L, Buskell-Bales Z, Wright E, et al. Long term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med 1992; 327(27):1906-1911. https://doi.org/10.1056/NEJM199212313272703