Chronic Hepatitis Delta: The Enigma of Disproportionate Prevalence in Sindh Pakistan

Vol. 30, Issue 1 (March 2025)

Nazish Butt, MBBS, FCPS
Associate Professor
Head of Gastroenterology Department
Jinnah Postgraduate Medical Centre
Karachi, Pakistan
 

Muhammad Ali Khan, MBBS, FCPS
Consultant Gastroenterologist
Sindh Government Hospital, Liaquatabad
Karachi, Pakistan

 

Hepatitis Delta Virus (HDV) is an incomplete, single-stranded RNA virus that cannot replicate nor infect human cells in vivo and requires simultaneous infection with Hepatitis B Virus (HBV) to cause these effects. It is transmitted via contaminated body fluids and blood, quite like HBV. HDV-HBV co-infection can result in a variety of liver-related outcomes, including acute infection, chronic infection, liver fibrosis, cirrhosis, development of hepatocellular carcinoma, and eventually end-stage liver disease with its ensuing complications such as variceal bleeding, hepatic encephalopathy, and ascites. HDV active disease patients are more likely to develop cirrhosis and its complications than patients infected with HBV alone.¹

Global prevalence of chronic HDV infection among HBV carriers is between 13% and 17%.2, 3 However, some regions, notably Mongolia, the Republic of Moldova, and some Western and Middle African nations, have disproportionately high rates; the highest prevalence rate of any region in the world for chronic HDV is found in the province of Sindh, with reports indicating a prevalence rate
in excess of 50%.^2-5 Not only is this rate inordinately high when compared to neighboring regions of Iran, India, and China, but even within Pakistan. The ubiquity of chronic HDV in Sindh is shockingly uneven when compared to the provinces of Khyber Pakhtunkhwa and Punjab.^4-7 The adjoining areas of Baluchistan (to Sindh) have also demonstrated similar rates, while Karachi, the largest and most populated city of the state, has relatively lower prevalence rates, as does the adjoining province of India, Rajasthan.⁸ This suggests that this is a very regional problem.

Factors such as vertical transmission, use of contaminated surgical and dental tools, sharing of needles, reuse of equipment at barbershops without disinfection, unhygienic practices of piercing and tattooing, lack of check on transfusions of blood products, and sexual contact, contribute to the spread of the HDV-HBV coinfection, yet none of these practices are unique or perennial to Sindh and cannot account for the disparity of prevalence of HDV. There needs to be a concerted effort undertaken by all branches and personnel of the healthcare system to identify variables that contribute to this problem; the existing literature on chronic HDV is sparse and fails to identify variables for this discrepancy.

As of writing, new trials are being conducted for HBV-HDV co-infection, but a cure remains elusive.^{9, 10} With such a high burden of the disease in Sindh, it is unlikely that a quick fix solution will be found anytime soon. The existing number of chronic HDV patients in Sindh is quite large, and without a cure in sight, they not only represent a massive healthcare challenge but also constitute an ever increasing probability of propagating and potentiating the disease even further. On a personal level, the patient faces the inevitability of disease progression and eventual organ failure as treatment options are limited, ineffective, and not easily accessible. No doubt, a harrowing experience.

Urgent insights are required into the variance of HDV prevalence in Pakistan, especially Sindh. As long as a cure is unavailable, measures to halt disease spread will have to do; these must address all of the aforementioned elements. Only then can future generations be spared from the devastating effects of chronic HDV. As for the patients already infected with HDV, the overall picture remains bleak; hopefully future trials and endeavors will provide some relief for them.

References

1. Papatheodoridi M, Papatheodoridis GV. Current status of hepatitis delta. Curr Opin Pharmacol. 2021 Jun;58:62-67. doi: 10.1016/j.coph.2021.03.008.
2. Stockdale AJ, Kreuels B, Henrion MYR, Giorgi E, Kyomuhangi I, de Martel C, Hutin Y, Geretti AM. The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis. J Hepatol. 2020 Sep;73(3):523-532. doi: 10.1016/j.jhep.2020.04.008.
3. Miao Z, Zhang S, Ou X, Li S, Ma Z, Wang W, Peppelenbosch MP, Liu J, Pan Q. Estimating the Global Prevalence, Disease Progression, and Clinical Outcome of Hepatitis Delta Virus Infection. J Infect Dis. 2020 Apr 27;221(10):1677-1687. doi: 10.1093/infdis/jiz633.
4. Khan, A.U., Waqar, M., Akram, M. et al. True prevalence of twin HDV-HBV infection in Pakistan: a molecular approach. Virol J 8, 420 (2011). https://doi.org/10.1186/1743-422X-8-420.
5. Seetlani, N. K., Abbas, Z., Raza, S., Yakoob, J., Jafri, W. (2009). Prevalence of Hepatitis D in HBsAg positive patients visiting liver clinics. Journal of Pakistan Medical Association, 59(7), 434-437.
6. Polaris Observatory Collaborators. Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories. J Hepatol. 2024 Feb;80(2):232-242. doi: 10.1016/j.jhep.2023.10.043.
7. Wang Y, Shen G, Lu R, Liu J, Zhang F, Wang H, Cai W, Zhang F. The prevalence of HDV among HBsAg-positive populations with and without HIV-1 in China. Int J Infect Dis. 2024 Mar;140:70-77. doi: 10.1016/j.ijid.2023.12.014.
8. Jat SL, Gupta N, Kumar T, Mishra S, S A, Yadav V, Goel A, Aggarwal R. Prevalence of hepatitis D virus infection among hepatitis B virus-infected individuals in India. Indian J Gastroenterol. 2015 Mar;34(2):164-8. doi: 10.1007/s12664-015-0555-6.
9. Ghany MG, Buti M, Lampertico P, Lee HM; 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference Faculty. Guidance on treatment endpoints and study design for clinical trials aiming to achieve cure in chronic hepatitis B and D: Report from the 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference. J Hepatol. 2023 Nov;79(5):1254-1269. doi: 10.1016/j.jhep.2023.06.002.
10. Krause A, Haberkorn U, Mier W. Strategies for the treatment of HBV/HDV. Eur J Pharmacol. 2018 Aug 15;833:379-391. doi: 10.1016/j.ejphar.2018.06.030.