Figures released from Saudi epidemiology studies consistently identify HAV as the most prevalent form of hepatitis among the three most common viral types. The anti-HAV prevalence rate in the KSA was recently estimated at 18.6%, a considerable reduction from the 90-100% rates reported only two decades ago in the adult population .[55
] The rate of HAV infection among children aged 1-12 years has also reduced dramatically from 52% in 1989 to 25% in 1997 according to community-based studies.[58
] A comparative study that monitored the prevalence of HAV infection in a single cohort of children from 1989 to 2008 and spread over three regions of Saudi Arabia found a significant linear decline from 53% in 1989 to 25% in 1997, and finally to 18.6% in 2008.[55
] Likewise, data from a school-based seroprevalence study of 2399 Saudi children attending the National Guard schools in 2005 showed 28.9% seropositivity for anti-HAV-IgG among 4-18-year olds.[60
Changing patterns of hepatitis A prevalence within the Saudi population over 18 years
Data regarding the incidence of HAV in Saudi Arabia have also emerged. An evaluation of 14,224 cases of viral hepatitis documented between 2000 and 2007 at King Abdulaziz Medical City-NGHA in Riyadh demonstrated a significantly lower annual incidence of seropositivity for HAV (13.6) compared with HCV (78.4) or HBV (104.6) per 100,000 served population.[27
] Moreover, the incidence of HAV seropositive cases among children followed a clear seasonal cyclical pattern, with peaks in March and September, likely as a result of more children being exposed during the mid-year and summer vacations.[27
] Similar to HBV, gender is also an important risk factor for HAV infection in Saudi Arabia.[10
] The study by Memish et al
., found a higher prevalence of HAV infection in males vs. females HAV (14.7 vs. 12.4; P
= 0.008) per 100,000 served compared with HCV. Other reports demonstrated either no gender biases in anti-HAV prevalence or higher positivity in Saudi males.[59
] Culinary habits and preferences coupled with social practices that differ among Saudi males and females may explain the higher incidence of HAV infections seen in Saudi males.[55
The prevalence of HAV differs according to the socioeconomic status of a population and may vary within a country depending on hygienic conditions.[62
] Studies conducted since 2008 have revealed continued variations in anti-HAV-IgG prevalence among different regions of Saudi Arabia despite marked decreases in overall infection rates. Monitoring of patterns of HAV endemicity among children and adolescents in Saudi Arabia over 20 years has shown persistent and significant differences in HAV seroprevalences between three regions when classified according to socioeconomic status. In 2008, the prevalence of HAV stratified by class showed a 36.8% seropositivity among the lowest class compared with 9.6-16.6% and 5.9% for middle- and high-class adolescents aged 16-18 years, respectively.[55
] A cross-sectional, sero-epidemiological investigation of HAV among children aged 1-6 years in the province of Northern borders between 2006 and 2007 revealed a 33.8% HAV-IgG prevalence overall.[64
] The most significant independent predictors of infection included rural residence, non-Saudi nationality, and availability of safe municipal water. The nationality factor suggests a more rapid decline in HAV endemicity in the local population, which has a higher per capita income compared to other Middle Eastern countries.
Changes in the epidemiology of HAV infection are likely to be largely due to improvements in living conditions leading to fewer infected children.[10
] During the period 1974-2003, the Saudi government's real-estate bank funded the building of 851,000 housing units bringing many Bedouins and rural citizens into urban areas with better sewage disposal and water sanitation systems.[55
] The country also witnessed increases in GDP per capita from 1145 USD in 1970 to 10,853 USD in 2002. Mounting life expectancies from birth that climbed 17 years between 1970 and 2000 (53.9-70.9 years of age) further demonstrates improved socioeconomics within the country's borders.[55
] The average age of HAV infection in the KSA has been increasing with time mainly due to these improvements in living conditions, consequently leading to more cases of symptomatic adults being diagnosed. According to recent data from a surveillance system monitoring trends in viral hepatitis incidence among NGHA-served regions from 2000 to 2007, HAV seropositivity rose by 61% during this period for those 15 years or older whereas rates in the <15 year-old cohort declined by 42%.[27
The shift in the HAV epidemiologic status of KSA from a classic high to a moderate/low endemic country prompted the country's MOH to add the HAV vaccine to the list of infant/childhood immunizations in 2008.[60
] Long-term follow-up of this strategy among different communities remains an important goal toward understanding the impact of HAV immunization in the KSA.
An estimation of the overall disease burden
According to data compiled in 2011 by the Central Department for Statistics and Information in Saudi Arabia ( www.cdsi.gov.sa
), the number of Saudis is just below 20 million. Taking into consideration the information presented in this review, and classifying 60% of the Saudi population as being under 25 years of age, we can estimate that at least 60% of the Saudi population has been vaccinated for HBV either at birth or at school entry. As such, this segment of the population would have a negligible prevalence of infection (less than 0.1%). The remaining 40% (about 8 million) of the population may show varying trends in HBV prevalence depending on age and geographical area of birth and residence. Taking into account data from studies conducted on children in the late 80s (who now represent part of the adult population) and from blood donor screening studies, we can approximate HBV prevalence in the 3-6% range for older populations. This is commensurate with an overall HBV prevalence of about 2-4% in the general population (both younger vaccinated and older not vaccinated groups). Therefore, although the cycle of horizontal and childhood transmission of HBV has probably been broken and has significantly compromised the HBV epidemiological sequence, we estimate that we are still confronted with an estimated number of 240,000 Saudis who are chronically infected with the virus, many of whom may still be undiagnosed.
Although most studies indicate that the risk of developing significant liver disease in individuals infected with HBV lies somewhere between 20% and 40%, we must consider the possibility of a somewhat different natural history of HBV manifesting in the KSA. Disease progression unique to Saudi Arabia may arise due to a different average age for onset of spontaneous viral clearance among infected persons in this region. Several studies from Italy, where genotype-D also dominates, indicate that HBsAg-positive patients sero-convert mostly before the age of 20 years in contrast to Chinese patients, who convert mostly by the age of 40 years.[67
] Furthermore, Chen et al
] have demonstrated in a recent longitudinal study that patients with HBeAg sero-conversion before 30 years of age have a very low cumulative risk of developing cirrhosis and HCC. Our baseline study in 1991[13
] and studies in young Saudi populations like pregnant women have shown that the majority of HBeAg-positive patients sero-convert before the age of 20 years. In addition, unpublished data from an HBV database, which has enrolled more than 1000 patients so far from three centers in Saudi Arabia, indicate that the majority (more than 70%) of patients have HBV DNA levels less than 10,000 IU/ml. Given that it is now well understood that HBV DNA level is strongly predictive of the risk of future cirrhosis and HCC,[72
] it is likely that progression rates in Saudi Arabia will be less than what has been described in regions such as South-East Asia.
Unlike HBV, the prevalence of HCV in Saudi Arabia is much more difficult to quantify due to a veritable lack of recent literature. Given the available data discussed in this review, one can reasonably estimate an overall prevalence of HCV in the Saudi population to be 1-3%, but given that the majority of the population are in the younger age group (with a lower prevalence rate), an overall general prevalence of about 1% maybe more realistic, giving us an estimated number of patients of about 200,000, many of whom may still be undiagnosed.
Recognizing the limitations of the reported studies and the speculative nature of these assumptions, we can reasonably estimate that 20% of all chronic viral hepatitis patients will eventually develop cirrhosis in the next 20 years (240,000 hepatitis B patients and 200,000 hepatitis C patients), leading the Saudi healthcare system to confront an imposing burden of about 88,000 cirrhotic patients facing advanced and costly medical care. Given an estimated 10% annual risk of de-compensation (without treatment), we can further anticipate approximately 8800 decompensated cirrhotic patients per year becoming potential candidates for liver transplantation. Moreover, the likelihood of developing hepatocellular carcinoma (HCC) at an estimated 1-4% annual incidence in cirrhotic patients translates to around 1500 new cases of HCC per year. These patients need a multidisciplinary approach to care, intensive interventions, and costly treatments, which further inflates the burden on the kingdom's healthcare system.
It must be strenuously emphasized that this disease burden estimation does not take into account cirrhosis secondary to non-viral etiology that would likely impose a further strain related to liver disease alone on the healthcare system. Nonetheless, viral hepatitis remains the only transmissible but preventable cause of cirrhosis and HCC in Saudi Arabia. Collection and documentation of accurate epidemiological data therefore represent a critical step in the prevention and control of viral hepatitis in the KSA.