Economic Burden of Hepatitis B Virus-Related Diseases: Evidence From Iran


avatar Khosro Keshavarz 1 , 2 , avatar Abbas Kebriaeezadeh 1 , avatar Seyed Moayed Alavian 3 , avatar Ali Akbari Sari 1 , 4 , avatar Farid Abedin Dorkoosh 1 , avatar Maryam Keshvari 5 , avatar Seyed Ali Malekhosseini 6 , avatar Saman Nikeghbalian 6 , avatar Shekoufeh Nikfar ORCID 1 , *

Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IR Iran
Health Human Resource Research Center, School of Management and Information Sciences, Shiraz University of Medical Sciences, Shiraz, IR Iran
Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
Department of Health Management and Economics, Tehran University of Medical Sciences, Tehran, IR Iran
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization, Tehran, IR Iran
Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran

how to cite: Keshavarz K, Kebriaeezadeh A, Alavian S M, Akbari Sari A, Abedin Dorkoosh F, et al. Economic Burden of Hepatitis B Virus-Related Diseases: Evidence From Iran. Hepat Mon. 2015;15(4):e58832. doi: 10.5812/hepatmon.15(4)2015.25854.



Hepatitis B infection is still the main cause of chronic liver disease in Iran, which is associated with significant economic and social costs.


This study aimed to estimate the financial burden caused by CHB infection and its complications in Iran.

Patients and Methods:

Prevalence-based and bottom-up approaches were used to collect the data. Data on direct medical costs were extracted from outpatient medical records in a referral gastroenterology and hepatology research center, inpatient medical records in several major hospitals in Tehran and Shiraz in 2013, and the self-reports of specialists. Data on direct non-medical and indirect costs were collected based on the patients’ self-reports through face-to-face interviews performed in the mentioned centers. To calculate the indirect costs, friction cost approach was used. To calculate the total cost-of-illness in Iran, the total cost per patient at each stage of the disease was estimated and multiplied by the total number of patients.


The total annual cost for the activate population of CHB patients and for those receiving treatment at various disease stages were respectively 450 million and 226 million dollars, with 64% and 70% of which allocated to direct costs respectively, and 36% and 30% to indirect costs respectively. The total direct costs alone for each group were respectively 1.17% and 0.6% of the total health expenditure. Furthermore, the cost spent on drugs encompasses the largest proportion of the direct medical cost for all stages of the disease.


According to the perspectives of payers, patients, and community, CHB infection can be considered as one of the diseases with a substantial economic burden; the disease, specifically in extreme cases, can be too expensive and costly for patients. Therefore, patients should be protected against more severe stages of the disease through proper treatment and early diagnosis.

1. Background

In recent decades, health expenditure has increased considerably worldwide. In addition, because of the skyrocketing costs of health related services, the health system of in Iran has faced significant challenges (1). These costs may be generated directly by medical diagnostic services or indirectly by the loss of productivity and quality of life (1). Hepatitis B virus (HBV) is now considered a serious problem for health all over the world (2) so that it is the most common and most important type of viral hepatitis and liver disease worldwide. It is subject to costly risks, high mortality, and morbidity, particularly in developing countries (3). Despite the availability of effective vaccines for HBV since the 1980s (4), it is estimated that still about 350 million people are suffering from chronic HBV infection (CHB) worldwide, which results in annually 500000 to 1.2 million deaths, of which 75% are Asian (5, 6). Hepatitis B infection is the tenth leading cause of death in the world (7). The main cause of death from hepatitis B is various related conditions such as cirrhosis and hepatocellular carcinoma (HCC), which impose very high costs to patient and health system (5, 8, 9). Thus, HBV infection is a serious health problem (10); for example, in the United States more than one billion united states dollars (USD) each year is spent due to hospitalization costs of patients with hepatitis B infection. Therefore, enormous economic and social costs are associated with this infection (11). As to the prevalence of this disease, with a prevalence of about 2%, Iran is among the countries with moderate prevalence and fortunately, the country has approached those with lower prevalence rates (1.5%) in recent years. Currently, about 1.2 million people in our country are infected with the virus (12), and if left untreated, about 15% to 40% of them are at risk of developing cirrhosis or HCC (12-14). As a result, it is estimated that 180000 to 480000 people are facing serious problems associated with HBV infection and require immediate attention (12). In Iran, there is no published study on the costs of CHB with comprehensive and simultaneous assessment of the direct and indirect costs of disease among patients with different states of the disease including compensated cirrhosis (CC), decompensated cirrhosis (DC), HCC, and liver transplantation (LT). However, in two studies, it has been shown that the economic burden of hepatitis can be significant for the community (15, 16). The economic burden of CHB on communities and individuals in the country is unknown because of insufficient evidence. The provision of accurate data on the economic burden of HBV infection can help healthcare policymakers to make appropriate decisions about the prevention and treatment of this disease (17). Considering the significance of the burden of HBV infection in the world and Iran on one hand, and the lack of a comprehensive economic analysis of the disease in the country on the other hand, doubled the need for conducting this study.

2. Objectives

The aim of this study was to estimate direct and indirect costs of various states of CHB in the country.

4. Results

In this study, 280 patients at different stages of the disease (130 patients with CHB, 56 with CC, 71 with DC, and 23 with HCC) were enrolled. Table 1 briefly presents the descriptive results, classified by the stages of the disease based on sex, education, occupational status, and the mean age of the patients. According to Table 1, the mean age of the entire sample in all states of the disease was 47 years (range, 43.45 - 54.7 years) and 70% of the patients were male.

Table 1. Socio-Demographic Characteristics of Patients With Chronic Hepatitis B Infection in Different Disease Stages in Iran a
VariableStage of Disease
Total number of patients130567123280
Non Academic98111116135
The mean age43.454850.554.747

4.1. Direct Medical and Non-Medical Costs

Based on data extracted from the mentioned centers, 80% of the patients were from other cities and 20% lived in Tehran and Shiraz. This point was considered in the estimation of direct non-medical costs. Table 2 presents the annual costs of utilization of treatment and diagnostic services (direct medical costs) and the costs of other services required to receive healthcare services (direct non-medical costs) for CHB per patient for each stage of the disease. As shown, the minimum cost (about 866 USD) was observed in patients with CHB and the maximum cost (11494 USD) in patients with HCC. Table 2 also shows that the annual direct medical costs of treatment increased with disease progression. In all cases, except for patients with CHB, the costs of medicine accounted for the greatest share of healthcare costs so that 46%, 37%, and 44% of direct health care costs were spent on drugs required for CC, DC, and HCC stages, respectively. It covered 28% of the costs in patients with CHB. The cost of the test, which is 52%, has the greatest share of healthcare costs in patients with CHB.

Table 2. Average Annual Direct Medical and Non-Medical Costs Per Patient With Chronic Hepatitis B Infection Based on Various Stages of the Disease, 2013 a,b
Type of ServiceCHB, USDPercentageCC, USDPercentageDC, USDPercentageHCC, USDPercentage
Direct medical costs
Visits to the doctor49 ± 7.23849 ± 7.23599 ± 37.092391 ± 96.424
Tests342 ± 13.8152354 ± 9.2536403 ± 9.610536 ± 30.435
Diagnostic services82 ± 24.1712124 ± 31.41131060 ± 171.66252,195 ± 198.3922
Drug188 ± 141.0728455 ± 286.21461554 ± 915374,418 ± 79744
Hoteling----1063 ± 580.42261,417 ± 601.1214
Other health services------1,116 ± 470.5011
Direct non-medical costs
Transportation96 ± 39.524796 ± 39.5247288 ± 73.8820288 ± 73.8820
Meals36 ± 16.231836 ± 16.2318378 ± 101.2827378 ± 101.2827
Accommodation72 ± 33.883572 ± 33.8835756± 192.0753756 ± 192.0753
Total costs8661186-5600-11494-

Non-direct medical costs: Because many patients come from neighboring provinces, and their travel time is often a full working day or more, the costs of travelling, meals, especially accommodation, increases with progression of the disease to more severe stages (Table 2). Table 3 presents the estimated costs of medical and diagnostic services (direct medical costs) as well as the costs of other services needed to receive medical care (direct non-medical costs) and to undergo liver transplantation in patients with cirrhosis and liver cancer caused by HBV per patient; it is estimated to cost more than 36994 USD.

Table 3. Average Direct Costs of Liver Transplantation Per Patients With Cirrhosis and Liver Cancer Caused Due to Hepatitis B Virus in Iran, 2013
Type of CostCost, USD
Before surgery
Preoperative counseling and examinations1803
Diagnostic and laboratory services2697
Total costs of the examinations before admission4500
Operating room costs
Cost of surgery & anesthesia9375
Costs of anesthesia drugs and materials2904
Costs of operating room consumable materials2705
The total cost of the operating room14984
Hospitalization costs
Hospitalization costs associated transplant ICU hoteling and services3360
Costs associated transplant ward hoteling and services3023
Cost of the drugs consumed in the ward4406
Cost of the consumable materials in the ward3221
Cost of tests during admission1678
Total costs of hospitalization15688
Cost of post-discharge follow-up
Examinations, counseling, and actions after patient discharge686
Accommodation expenses for one month after discharge
Assuming 85% of people as non-resident574
Meals and travelling costs during operation and after discharge for one month
Assuming 85% of people as non-resident562
Total costs36994

4.2. Indirect Costs

In our cost survey, none of the participants with CHB and CC had to lose their own job to receive care for disease complications. As the results of the study showed, it seems that these elements had negligible effect on indirect costs for this group of patients. As it is shown, like the rest of the costs, indirect annual treatment costs increases with the progression of the disease, and indirect costs for LT patients have the greatest share of health care costs, which is about 3223 USD (Table 4).

Table 4. Estimated Average Direct Medical and Non-Medical Costs, Indirect Costs, Total Costs, and the Ratio of Direct to Indirect Costs of Chronic Hepatitis B Infection Per Patient Based on Various Stages of the Disease in Iran, 2013 a,b
1DMC662 (44)982 (55)4179 (57)10072 (76)35858 (86)
2DNMC204 (13)204 (11)1422 (19)1422 (11)2647 (6)
3IC c649 (43)607 (34)1765 (24)1721 (13)3223 (8)
4DC to IC Ratio1.3:12:13.2:17.6: 112:1
Total Cost1515 (100)1793 (100)7366 (100)13215 (100)41728 (10)

4.3. Financial Burden of Direct Medical and Non-Medical Costs and Indirect Costs for Chronic Hepatitis B Infection in Iran

Based on estimated prevalence, the active and inactive population of patients, the numbers of people receiving treatment in a year, and direct medical costs for different stages of CHB were calculated via the aforementioned methods and the results are presented in Table 5. Since 20% of chronic carriers are the active population of the country, direct medical costs for different stages of disease among active hepatitis population was estimated at about 224444906 USD (Table 5). Finally, to estimate actual medical costs occurred in a year due to HBV for different stages of disease, the share of patients receiving treatment from the active population with HBV infection was determined to be 126529148 USD (Table 5). The total direct non-medical costs for different stages of disease among active hepatitis population and patients receiving treatment were approximately estimated at 62090907 and 31917471 USD, respectively (Table 5). The total indirect costs of different stages of disease for active population with HBV infection and in patients receiving treatment were estimated at 163386610 and 67393669 USD, respectively (Table 5).

Table 5. Estimated Average Direct medical and Non-Medical Costs, Indirect Costs, Total Costs and the Ratio of Direct to Indirect Costs of Chronic Active Hepatitis B patients in Iran, 2013 a
Disease CategoryNumber of PatientsPatient’s ConditionDMC, USDDNMC, USDIC, USDCOI, USDDC to IC Ratio
CHB1.33: 1
184,886Total number of CHB patients12239453237716744119991014280102290
36977Under treatment2447877475433082399807356020155
CC37440Under treatment36766080763776022726080671299201.95: 1
DC9360Under treatment391154401330992016520400689457603.17: 1
HCC2203Under treatment2218861631326663791363291126456.68: 1
LT111Under treatment3980238293817357753463180812.00: 1
86091Under treatment12652914831917471673936692258402882.35: 1
234000Considering all active patients224444906620909071633866104499224231.75: 1

4.4. Estimated Total Cost of Illness for Chronic Hepatitis B Infection in Iran

Figure 1Table 4 present a summary of the direct medical costs, direct non-medical costs, and the ratio of indirect costs to direct costs per patient and for different stages of disease in Iran. The total cost of CHB for different stages of the disease among the active hepatitis B population and patients receiving treatment in the country were calculated as 449922423 and 225840288 USD, respectively. In addition, the ratio of direct to indirect costs increases with the progress of the disease (Table 5). The results showed that the direct medical costs are the main component of the total cost of treating patients with HBV infection and encompasses about 64% and 70% of the costs for active hepatitis B population and patients receiving treatment, respectively.

Direct Medical Costs, Direct Non-medical Costs, and Indirect Costs as a Percentage of Total Cost for Each Group of Patients

4.5. Financial Burden of Illness Survey

A total of 280 patients with a mean age of 47 years (range, 43 - 55 years) with different stages of disease participated in the study among which 70% were male. Moreover, 94 persons had DC and HCC; when this group of patients with liver disease were asked “Whether they have had to spend their own or their family members saving or loans to provide their medical cost in the last one year?” almost all of the participants (approximately 96%) expressed their concerns about the high cost of the disease, especially in drugs and tests. Due to the high financial burden of the disease (range, 7500-75000 USD), many of the patients were obliged to borrow from relatives, sell their assets, or get a loan, and consequently, their treatment had greatly influenced their household income. Of all participants with CHB and CC (186 patients), about 30% were forced to get a loan or spend their savings; however, it was more common among patients with CC. Most patients with CHB (80%) had not been forced to borrow money due to the disease expenses. It should be noted that the effect of the disease on the psychologic aspects of the patient and all family members, especially in severe cases of disease, is considerable; almost all the participants with severe stages of the disease (over 90%) expressed this concern.

4.6. Sensitivity Analysis

Table 6 presents the results of one-way sensitivity analysis for direct medical costs, direct non-medical costs, indirect and total costs of CHB for different stages of the disease (where the number of patients is variable and cost components are fixed). The results also showed that direct to indirect cost ratio is fixed by changing the number of patients. It indicates the robustness of the results.

Table 6. Sensitivity Analysis for Direct Medical and Non-Medical Costs, Indirect Costs and Total Costs of Chronic Hepatitis B Infection in Iran, 2013 a
Disease CategoryEstimated Number of Patients, RangeDMC (One-Way Sensitivity Analysis),USDDNMC (One-Way Sensitivity Analysis), USDIC (One-Way Sensitivity Analysis), USDCOI (One-Way Sensitivity Analysis), USDDC to IC Ratio
160416 - 471301106195392 - 31200126232724864 - 96145404104109984 - 305874349243030240 - 7140210151.33:1
32083 - 9426021239078 - 624002526544973 - 1922908120821997 - 6117487048606048 - 142804203
CC32448 - 9484831863936 - 931407366619392 - 1934899219695936 - 5757273658179264 - 1700624641.95:1
DC8112 - 2371233900048 - 9909244811535264 - 3371846414317680 - 4185168059752992 - 1746625923.17:1
HCC1728 - 265817404416 - 267713762457216 - 37796762973888 - 457441822835520 - 351254706.68:1
LT96 - 2813442368 - 10076098254112 - 743807309408 - 9056634005888 - 1172556812:1
74467 - 215759107849846 - 29148091027410957 - 7682002058118909 - 166079367193379712 - 5317459222.26:1
202800 - 592800192806160 - 54108192053590848 - 153736343141406896 - 410778846387803904 - 11055971091.72:1

5. Discussion

This study was the first comprehensive study on the cost of illness among hepatitis patients in Iran; it tried to estimate the direct and indirect costs of CHB and its related complications at the national level. The present study showed that CHB and its associated complications can impose a considerable financial burden on the country’s health system and community in general; in this regard, the present study is in line with the study of Kalantari et al. in which the researchers only calculated the direct costs of the mentioned disease (1). The total annual costs for the population of active CHB and patients receiving treatment were respectively 450 million USD (range, 387 million to 1103 million USD) and 226 (range, 192 million to 532 million USD); the obtained result was not consistent with the results of two previously studies in the country (1, 15), because they only calculated the prevalence among chronic carriers in the estimation of costs for patients with CHB; moreover, unlike the standards used in this study, they have made no distinction between the inactive population, active population, and those receiving treatment. Therefore, they overestimated the costs (1, 15). Of this amounts, respectively 64% and 70% have been assigned to the direct costs. The total direct cost alone was roughly equal to 1.17% (range, 1% - 2.83%) and 0.6% (range, 0.5% - 1.5%) of total health costs in 2013. The total health system cost in Iran in 2013 was 24471951402 billion USD, which was equal to 6.6% of gross domestic product (GDP) (28). Among the active population and patients receiving treatment at different stages of CHB, patients with CHB and cirrhosis, respectively, had caused the largest share of direct costs to the health system in Iran. Compared to patients with CHB, a patient with LT) or HCC impose respectively 31-times and 12-times higher burden of health costs to the community. It might be due to the higher number of patients with CHB and cirrhosis compared with patients with LT or patients with HCC. In view of the mentioned fact, this study is consistent with the study of Ong et al. (20), which was conducted in Singapore. In this study, the cost of medicines had the largest share among the direct medical costs for all stages of the disease, especially CC, DC, and HCC; it includes about half of the direct medical costs and is considered as a major problem for patients. In a study by Tu et al. which was conducted on a cost of illness among patients with CHB in Vietnam in 2012, medical costs were reported as the major item among direct medical costs (21). Thus, in general, our results were similar to the results reported from other countries, which showed the increase of direct cost is line with disease progression (29-32).

In addition, the indirect costs of active CHB and patients receiving treatment for CHB at different stages encompassed 36% and 30% of total costs, respectively. In other published studies, almost one-third of the costs were attributed to indirect costs and as the disease progresses; hence, the direct costs to indirect costs ratio was increased (15, 20). These results suggest that the indirect costs are an important cost component in the estimation of total costs caused by CHB. Because governmental supports provide only one-third of the financial burden of healthcare and the remaining two-thirds (55% - 65%) is provided by out of pocket payments in Iran (33), this can be very disturbing and important. Therefore, this study showed that CHB with a prevalence rate of 1.5% among chronic carriers (1.17 million people) in the absence of proper management of the disease can put 15% to40% (i.e., approximately 175500 to 468000 people) at risk of developing cirrhosis or HCC (12-14), It will impose the average cost of 982 million to2620 million USD on community and the health system, which will lead to four-times to 12-times higher costs than the current costs imposed on patients receiving treatment. Therefore, a considerable financial burden will be imposed on the health system and society, and stops or slows the effective treatment of liver disease.

Similar to other published studies (20, 21); this study demonstrated that severe disease states, including DC and HCC are very expensive for patients. When patients were asked whether they had to spend their own or their family members’ saving or loans, almost all participants with more severe stages of disease, including DC, HCC, and LT, said they were forced to get a loan or borrow from friends. They also said that the disease had imposed heavy financial burden on patients and their families, and most of them had many difficulties to cover the cost of treatment. The problem is more significant for services that are not covered by insurance, such as certain medications or receiving services from nongovernmental centers (34), and is considered as a catastrophic cost. Considering the abovementioned problems, it should be tried to prevent the progress of disease to more severe stages via proper and timely diagnosis and treatment. On the other hand, because only the overall prevalence rate of chronic carriers had been taken into account for calculating the costs in the two previous studies conducted in Iran (1, 15) , it had led to an overestimation of the disease costs. In this study, we tried to resolve this issue. In fact, the active and inactive population as well as patients receiving treatment was identified distinctively and their costs were estimated to calculate the actual current cost of the disease in the country. Because the Hepatology and Gastroenterology Research Center of Baqiyatallah University in Tehran and the Liver Transplantation Center of Nemazee Hospital in Shiraz are among the main referral centers in the country, the cost estimates in this study can provide a good estimate of the true cost in patients with CHB in Iran. Hence, the results can be used by health policymakers to plan and assign the resources more effectively.

One limitations of this study was the lack of documentary evidence about the exact number of patients with CHB receiving treatment in different stages as well as the prevalence of HCC in the Iran. As a result, in this study, we used the opinions of some of the best specialists in this field. In conclusion, due to the chronic nature of the disease, the management of patients with HBV infection is not only a therapeutic challenge, but also a method for the prevention of considerable economic burden of disease from the perspective of the payer, patient, and community. Therefore, patients should be protected against more severe stages of the disease through proper treatment and early diagnosis. This can be an important message for policymakers and administrators of healthcare system.



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