Prevalence and Determinants of Hepatic Steatosis in Chronic Hepatitis B Virus Infection

By Abere, S, Oyan, B; Amachree, E; Amadi, U; Chukwu, Chika; Amadi, Blessing (2024).

Greener Journal of Medical Sciences

Vol. 14(1), pp. 1-7, 2024

ISSN: 2276-7797

https://gjournals.org/GJMS

Click on Play button...

Prevalence and Determinants of Hepatic Steatosis in Chronic Hepatitis B Virus Infection

Abere Sarah¹, Oyan Boma¹, Amachree Enohor¹, Amadi Uzoaku¹, Chukwu Chika¹,Amadi Blessing¹

1. Department of internal medicine, Rivers State University Teaching Hospital (RSUTH).

ARTICLE INFO

ABSTRACT

Article No.: 121823161

Type: Research

Full Text: PDF, PHP, HTML, EPUB, MP3

Background and aim: Globally, viral hepatitis B and C are the leading causes of chronic liver disease. Viral hepatitis is highly prevalent in Sub-Saharan Africa with a 5-20% carrier rate in the general population and a high mortality of up to 10.8/100,000 in some regions. Patients with chronic Hepatitis B (CHB) are also affected by lifestyle related challenges of obesity, alcoholic liver disease, metabolic associated fatty liver disease affecting the larger populace thus we set out to determine the prevalence and risk factors for hepatic steatosis in CHB patients.

Methodology: This was a cross-sectional retrospective study of 114 CHB patients. All study participants were screened for baseline parameter and abdominal sonography was performed by an expert radiologist to detect the presence of hepatic steatosis.

CHB patients attending the Gastroenterology outpatient clinic of the Rivers State University Teaching Hospital (RSUTH) between November 2022-April 2023 were included in the study.

Data was collected through review of hepatitis B register and patients’ interview. Data was analyzed using the statistical software package SPSS version 22. Bivariate logistic regression analysis was used to identify variables influencing Hepatic steatosis and p-values <0.05 were considered statistically significant. Hepatic steatosis was defined as fat accumulation of >5% in the hepatocytes on abdominal ultrasound scan.

Results: The prevalence of Hepatic steatosis was 29.8% and BMI, older age, raised blood glucose (r=0.553, p=0.000, r=0.295 p=0.026, r=0.457 p=0.000 respectively), including HBeAg negativity (χ2=15.774, p=0.000) were significant determinants of its occurrence. There was no significant relationship between HBV DNA levels and Hepatic steatosis.

Conclusion: Hepatic steatosis is common in CHB patients and both metabolic and virological factors play a role in its occurrence.

Accepted: 26/12/2023

Published: 06/01/2024

*Corresponding Author

Abere Sarah

E-mail: tamsabere@ yahoo.com

Phone: +234-8068803398

Keywords: viral hepatitis B, Hepatic steatosis, CHB, HBV DNA

Abbreviations: chronic Hepatitis B(CHB), HBV DNA (Hepatitis B virus DNA).

INTRODUCTION

Fatty liver or hepatic steatosis is the accumulation of triglycerides in the hepatocytes which occurs when intrahepatic fat is greater than or equal 5% of Liver weight. (1)

Hepatitis B(HBV) is a global health challenge which affects over 2 billion people and results in over 600,000 annual deaths. (2)

Globally, viral hepatitis B and C are leading causes of chronic liver disease(3) though there has been a predictable decline in recent years due to the availability of ‘cure’ for hepatitis C, and an increased global preventative strategy for HBV. Furthermore, the availability of newer and better treatment options, well placed control and preventative measures has resulted in a decline in CLD- related age adjusted mortalities from 21 deaths/100,000 persons to 16 deaths/100,000 persons from 1990-2017. (4)

Chronic hepatitis B (CHB) infection is highly prevalent in Sub-Saharan Africa with a 5-20% carrier rate in the general population and a high mortality of up to 10.8/100,000 in some regions.(5) Lazano et al (6) reported an increasing trend in cirrhosis related mortality of up to 31% within a 20 year period (1990-2010) with viral hepatitis related cirrhosis as a major etiology. Arguably, chronic viral hepatitis related cirrhosis and Hepatocellular carcinoma could rank among the top ten causes of mortality worldwide. (7)

In a 2017 report from 193 countries by the global, regional and national collaboration on the burden of cirrhosis(8), hepatitis B was reported to account for 31.5% and 24% of cirrhosis-related deaths in men and women respectively. In the same report, hepatic steatosis was reported as the cause of death in 7.7% and 11.3% of men and women respectively. (8)

Patients with CHB are also affected by lifestyle related challenges of obesity, alcoholic liver disease (ALD), Metabolic associated liver disease (MALD) or Non-alcoholic fatty liver disease (NAFLD) affecting the larger populace. Thus, there is a global trend towards increased alcohol consumption (9) accounting for 30-50% of cirrhosis related death (10,11) and a disproportionate chronic liver disease and cirrhosis- related mortality in young people less than 45years of age (12,13) which is the same age bracket most affected by CHB- related liver diseases in Sub-Saharan Africa. (14)

With the increasing burden of alcohol and metabolic fatty liver disease in Africa owing to the adoption of western lifestyle, obesity, diabetes mellitus, HIV and much more added to the already existing high prevalence and incidence of viral hepatitis occasioned by poor screening, inadequate disease surveillance and poor access to healthcare, CHB- related liver diseases especially NAFLD may soon be a major cause of morbidity and mortality in Africa identical to that of HIV and malaria.

METHODOLOGY

Study site and Participants: This was a cross-sectional study of 114 chronic viral hepatitis B patients attending the Gastroenterology outpatient clinic of the Rivers State University Teaching Hospital (RSUTH) in southern Nigeria between November 2022-April 2023. Data was collected through review of hepatitis B register and patients’ interview. Ethical approval was obtained from the hospital ethical committee with approval number RSUTH/REC/2022213.

Inclusion criteria: eligible adult patients who are 18years and above with HbeAg positivity for > 6months who gave an informed consent were included in the study.

Exclusion criteria: Patients <18years of age, with a self-reported history of significant alcohol consumption >14 units/day and/or pregnant females were excluded. Also, patients who are known diabetic, and those who are positive for HCV antibody and/or HIV were excluded from the study.

Materials and method: All study participants were screened for baseline parameters including HCV-Ab, HIV, Fasting blood sugar (FBS), total cholesterol (CHOL), low density cholesterol (LDL), high density cholesterol (HDL), triglyceride (TG), ammonium aminotransferase (ALT) and aspartate aminotransferase (AST) were measured with enzymatic photometry on blood samples. Height and weight were evaluated and Body mass index (BMI) was calculated with weight (in kilograms) over height squared (in meters). Persons with BMI 18.5 to 24.9 was considered normal Persons, with BMI of more than 25-29.99 were considered overweight, and more than 30 obese.

Abdominal sonography was performed by an expert radiologist to detect the presence of hepatic steatosis. Hepatic steatosis which is fat accumulation of >5% in the hepatocytes was graded into mild, moderate and severe (15): -

Mild Hepatic steatosis: diagnosed when there was raised hepatic echogenicity in contrast to the kidney cortex.

Moderate Hepatic steatosis: in addition to raised echogenicity there is blurring of the vessels.

Severe Hepatic steatosis: Severe form of fatty liver was diagnosed based on disappearance of diaphragm in addition to the features of the mild and moderate form.

Data was analyzed using the statistical software package SPSS version 22. Bivariate logistic regression analysis was used to identify variables influencing Hepatic steatosis and p-values <0.05 were considered statistically significant.

RESULTS

Socio-Demography of the Study Population

This was a cross-sectional study of 114 chronic hepatitis B infected patients with a mean age of 36.04 ± 7.238years (range 18-44years). (figures 1 & 2). Chronic HBV patients with a significant history of alcohol consumption were excluded from the study.

There was a predominance of males in the study population compared to females (68, 59.6%: 46, 40.4%), and a larger proportion of the study population were civil servants and unemployed persons (38[33.3%], 14[12.3%]). figure 3. The study participants were fairly educated (table 1) with a strong urban residency (112, 91.2%).

Figure 1: age distribution of the study population.

PRESENTING COMPLAINTS AT FIRST VISIT

There were varied presenting complaints by the participants at their first presentation to the clinic as shown in table 4, the most common of which was fatigue (18.2%). Others were abdominal swelling (10.2%), early satiety (3.4%), abdominal pain (3.4%), and leg swelling (4.5%). Notably, non-gastrointestinal related complaints comprised a significant proportion (19.3%) of patients’ complaints at first visit. Furthermore, 2.3% of our study population was diagnosed of hepatitis B during compulsory pre-employment screening.

Table 4: frequency of presenting complaint of the study population

Complaint Frequency Percentage

None 64 36.4

Early Satiety 6 3.4

Fatigue 32 18.2

Abdominal Pain 6 3.4

Abdominal Swelling 18 10.2

Anorexia 4 2.3

Leg Swelling 8 4.5

Others 34 19.3

Pre-Employment 4 2.3

Total 176

DISCUSSION

This retrospective study of 114 chronic HBV patients sought to examine the association between Hepatic steatosis and possible risk factors in a Nigerian cohort.

Globally, studies on Hepatic steatosis, especially on the NAFLD/MAFLD subset has gained preeminence in recent years including studies on Hepatic steatosis in viral hepatitis B. There is however a dearth of information on the burden and spectrum of NAFLD in African populations, both from population-based and clinical studies (16). The paltry clinic- based studies available are mostly in Type 2 Diabetes mellitus and HIV and the reported prevalence of sonographically detected NAFLD in Nigeria varies from 9.5% to 68.8%.(17–20) Our reported prevalence of 29.8% is also in consonance with these reported figures and is similar to the prevalence trends obtained in Asia (21) and the western world. (22)

Our observation of a higher number of males with Hepatic steatosis compared with females (χ2 = 5.696, p = 0.017) is similar to a finding in a South African study that reported a lower Hepatic fat content in African women. (23)

Consistent with findings from other studies (24,25), we observed that older age( r = 0.295, p = 0.026) and hyperglycemia (r = 0.457, p < 0.001) were significantly associated with the incident of Hepatic steatosis. Also in accordant with other studies (26–28), our study showed that there is an increased risk for Hepatic steatosis in patients with raised ALT levels (r = 0.292, p = 0.002). Moreover, our finding that obesity is an independent risk factor for Hepatic steatosis in chronic HBV subjects (r = 0.553, p < 0.001) was consistent with other studies and is similar with the general population. (29,30)

The spectra of presenting complaints of the patients in our study (table 4) divulge that most of our patients present late when symptoms of Liver disease have developed. It is a well-known fact that HBV infection is mostly asymptomatic and symptoms only develop when there is some degree of hepatic impairment. This then underlines the exigency for a comprehensive national screening program for viral hepatitis in countries with high endemicity such as Nigeria.

Lastly, in our retrospective cohort, we explored the relationship between viral parameters namely the level of HBV DNA and HbeAg status and the presence of Hepatic steatosis. contradictory to other studies (31,32) we observed no cogent relationship between HBV DNA viral load and the risk of Hepatic steatosis (r = -0.088, p = 0.354). Our study also demonstrated that the presence of steatosis correlated positively with HbeAg (χ2 = 15.774, p < 0.001) negativity converse to the finding by Huang et al. (33)

Study limitation: our study is limited by the non-availability of histological data to further stage Hepatic steatosis in our patients as well as the absence of data parameters on factors such as dyslipidemia. Moreover, the retrospective nature of our study is also a limitation and a well-designed prospective study will be needed to thoroughly investigate the interplay between Hepatic steatosis and CHB.

CONCLUSION

In our retrospective study multiple metabolic and virological factors were significant potential determinants of Hepatic steatosis in our cohort including male sex, older age, HbeAg positivity, raised ALT levels, elevated BMI or obesity and hyperglycemia. Concurrent Hepatic steatosis and CHB could potentiate the development of NASH and fibrosis in hepatitis B infected patients.

Acknowledgments: We appreciate all the interns and residents of gastroenterology team who painstakingly assisted in the data collection process.

Competing interest: the authors declare no conflict of interest.

REFERENCES

1. Nassir F, Rector RS, Hammoud GM, Ibdah JA. Pathogenesis and Prevention of Hepatic Steatosis. Gastroenterol Hepatol. 2015 Mar;11(3):167–75.

2. Rizzetto M, Ciancio A. Chronic HBV-related liver disease. Mol Aspects Med. 2008;29(1–2):72–84.

3. Cheemerla S, Balakrishnan M. Global Epidemiology of Chronic Liver Disease. Clin Liver Dis. 2021 Jun 4;17(5):365–70.

4. Waheed Y, Siddiq M, Jamil Z, Najmi MH. Hepatitis elimination by 2030: Progress and challenges. World J Gastroenterol. 2018 Nov 28;24(44):4959–61.

5. Kiire CF. The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa: a view from tropical and subtropical Africa. Gut. 1996;38(Suppl 2):S5-12.

6. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet Lond Engl. 2012 Dec 15;380(9859):2095–128.

7. Lemoine M, Eholié S, Lacombe K. Reducing the neglected burden of viral hepatitis in Africa: strategies for a global approach. J Hepatol. 2015 Feb;62(2):469–76.

8. GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020 Mar;5(3):245–66.

9. Cheemerla S, Balakrishnan M. Global Epidemiology of Chronic Liver Disease. Clin Liver Dis. 2021 Jun 4;17(5):365–70.

10. Moon AM, Singal AG, Tapper EB. Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2020 Nov;18(12):2650–66.

11. Stein E, Cruz-Lemini M, Altamirano J, Ndugga N, Couper D, Abraldes JG, et al. Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide. J Hepatol. 2016 Nov;65(5):998–1005.

12. Yoon Y, Chen C. Surveillance report #105liver cirrhosis mortality in the United States: national, state and regional trends, 2000–2013. technical report, National institute of alcohol abuse and alcoholism. Oct 2016

13. Kim D, Li AA, Gadiparthi C, Khan MA, Cholankeril G, Glenn JS, et al. Changing Trends in Etiology-Based Annual Mortality From Chronic Liver Disease, From 2007 Through 2016. Gastroenterology. 2018 Oct;155(4):1154-1163.e3.

14. Spearman CW, Afihene M, Ally R, Apica B, Awuku Y, Cunha L, et al. Hepatitis B in sub-Saharan Africa: strategies to achieve the 2030 elimination targets. Lancet Gastroenterol Hepatol. 2017 Dec 1;2(12):900–9.

15. Azarkar G, Zeinali T, Sharifzadeh G, Abedi F, Hajihosseini M, Ziaee M. Prevalence of Non-Alcoholic Fatty Liver and its Related Factors in Birjand, During Year 2015. Mod Care J [Internet]. 2016 [cited 2023 Jun 8];13(4). Available from: https://brieflands.com/articles/mcj-58829.html#abstract

16. Paruk IM, Pirie FJ, Motala AA. Non-alcoholic fatty liver disease in Africa: a hidden danger. Glob Health Epidemiol Genomics. 2019 Jan;4:e3.

17. Onyekwere C, Ogbera A, Balogun B. Non-alcoholic fatty liver disease and the metabolic syndrome in an urban hospital serving an African community. Annals of Hepatology; 2011:10(2):119-124.

18. Olusanya T, Lesi O, Adeyomoye A, Fasanmade O. Non-alcoholic fatty liver disease in a Nigerian population with type II diabetes mellitus. Pan African Medical Journal. 2016;24:20. [doi: 10.11604/pamj.2016.24.20.8181]

19. Afolabi BI, Ibitoye BO, Ikem RT, Omisore AD, Idowu BM, Soyoye DO. The Relationship Between Glycaemic Control and Non-Alcoholic Fatty Liver Disease in Nigerian Type 2 Diabetic Patients. J Natl Med Assoc. 2018 Jun;110(3):256–64.

20. Abere S, Orupabo B. Duration of HAART use: A key prognosticator for NAFLD in HAART experienced HIV patients. GSC Adv Res Rev. 2022;10(3):071–9.

21. Tong X, Song Y, Yin S, Wang J, Huang R, Wu C, et al. Clinical impact and mechanisms of hepatitis B virus infection concurrent with non-alcoholic fatty liver disease. Chin Med J (Engl). 2022 Jul 20;135(14):1653–63.

22. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatol Baltim Md. 2016 Jul;64(1):73–84.

23. Naran NH, Haagensen M, Crowther NJ. Steatosis in South African women: How much and why? PLoS One. 2018 Jan 19;13(1):e0191388. doi: 10.1371/journal.pone.0191388. PMID: 29351564; PMCID: PMC5774768.

24. Zhu L, Jiang J, Zhai X, Baecker A, Peng H, Qian J, et al. Hepatitis B virus infection and risk of non-alcoholic fatty liver disease: A population-based cohort study. Liver Int Off J Int Assoc Study Liver. 2019 Jan;39(1):70–80.

25. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatol Baltim Md. 2016 Jul;64(1):73–84.

26. Sanyal D, Mukherjee P, Raychaudhuri M, Ghosh S, Mukherjee S, Chowdhury S. Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes. Indian J Endocrinol Metab. 2015;19(5):597–601.

27. Hadizadeh F, Faghihimani E, Adibi P. Nonalcoholic fatty liver disease: Diagnostic biomarkers. World J Gastrointest Pathophysiol. 2017 May 15;8(2):11–26.

28. Kim SU, Jeon MY, Lim TS. Diagnostic Performance of Serum Asialo-α1-acid Glycoprotein for Advanced Liver Fibrosis or Cirrhosis in Patients with Chronic Hepatitis B or Nonalcoholic Fatty Liver Disease. Korean J Gastroenterol Taehan Sohwagi Hakhoe Chi. 2019 Dec 25;74(6):341–8.

29. Charatcharoenwitthaya P, Pongpaibul A, Kaosombatwattana U, Bhanthumkomol P, Bandidniyamanon W, Pausawasdi N, et al. The prevalence of steatohepatitis in chronic hepatitis B patients and its impact on disease severity and treatment response. Liver Int Off J Int Assoc Study Liver. 2017 Apr;37(4):542–51.

30. Lee JY, Kim KM, Lee SG, Yu E, Lim YS, Lee HC, et al. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: a review of 589 consecutive liver biopsies in a single center. J Hepatol. 2007 Aug;47(2):239–44.

31. Wang MM, Wang GS, Shen F, Chen GY, Pan Q, Fan JG. Hepatic steatosis is highly prevalent in hepatitis B patients and negatively associated with virological factors. Dig Dis Sci. 2014 Oct;59(10):2571–9.

32. Hui RWH, Seto WK, Cheung KS, Mak LY, Liu KSH, Fung J, et al. Inverse relationship between hepatic steatosis and hepatitis B viremia: Results of a large case-control study. J Viral Hepat. 2018 Jan;25(1):97–104.

33. Huang Y, Gan Q, Lai R, Wang W, Guo S, Sheng Z, et al. Application of Fatty Liver Inhibition of Progression Algorithm and Steatosis, Activity, and Fibrosis Score to Assess the Impact of Non-Alcoholic Fatty Liver on Untreated Chronic Hepatitis B Patients. Front Cell Infect Microbiol. 2022 Jan 17;11:733348.