Evaluation of Five International HBV Treatment Guidelines: Recommendation for Resource-Limited Developing Countries Based on the National Study in Nepal

Abstract

Hepatitis B virus (HBV) infects the liver, causing cirrhosis and cancer. In developed countries, five international guidelines have been used to make a decision for the management of patients with chronic HBV infection. In this review, since the guidelines were established by clinical and epidemiological data of developed countries, we aimed to evaluate whether (1) HBV patient profiles of developing countries are similar to developed countries, and (2) which guideline can be applicable to resource-limited developing countries. First, as an example of the most recent data of HBV infections among developing countries, we evaluated the national HBV viral load study in Nepal, which were compared with the data from other developing countries. In Nepal, the highest number of patients had viral loads of 20-2000 IU/mL (36.7%) and belonged to the age group of 21-30 years; HBV epidemiology in Nepal, based on the viral loads, gender, and age groups was similar to those of not only other developing countries but also developed countries. Next, we reviewed five international HBV treatment guidelines of the World Health Organization (WHO), American Association for the Study of Liver Diseases (AASLD), National Institute for Health and Care Excellence (NICE), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). All guidelines require the viral load and alanine aminotransferase (ALT) levels for decision making. Although four guidelines recommend elastography to assess liver cirrhosis, the WHO guideline alternatively recommends using the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), which is inexpensive and conducted routinely in most hospitals. Therefore, in resource-limited developing countries like Nepal, we recommend the WHO guideline for HBV treatment based on the viral load, ALT, and APRI information.

Keywords: DNA viruses; Hepadnaviridiae; chronic human hepatitis; elastography; viral diseases.

Figure 1

(A) Levels of hepatitis B virus (HBV) DNA in plasma among the hepatitis B surface antigen (HbsAg)-positive patients. Each column represents the number (left y axis) and percentage (right y axis) of HBV patients (open, male; shaded, female) at each range of viral loads. The percentage of the HBV patients was calculated as follows: % = (Male + Female patient number at each viral load range) X100/ 300 (=total patient number of HBV samples). The highest number of patients was in the viral load range of 20–2000 IU/mL. Among 300 patients tested for the viral loads, 244 patients (81.3%) were male and 56 patients (18.7%) were female. (B) Percentage of HBV patients at each viral load range in each gender (open, male; shaded, female). The percentage of patients with viral loads of 20–2000 IU/mL was highest in both males and females, and significantly higher in females (48.2%) than in males (34.0%) (* p < 0.05, χ² test). The percentage of the HBV patients in each gender was calculated as follows: % = (Patient number at each viral load range in males or females) X100/ [244 samples (males) or 56 samples (females)]. HBV DNA was quantified by real-time polymerase chain reaction (PCR) using the COBAS^® AmpliPrep/COBAS^® TaqMan^® System (Roche Diagnostic, Pleasanton, NJ, USA). The linear range of the standard curve was 20–1.7 × 10⁸ IU/mL; the HBV DNA levels less than 20 IU/mL were described as <20 IU/mL. When HBV DNA was undetectable, it was described as the target not detected (TND).

Figure 2

(A) HBV patient distribution at different age ranges. Each column represents the number of HBV patients (open, male; shaded, female) at each age range. The highest number of patients was the age range 21–30 years old, followed by 31–40 years old. (B) HBV patient percentages in different viral load ranges at two age-groups. The patients were categorized into two age-groups; 139 patients were 30 years old or below (filled bar), and 161 patients were above 30 years old (hatched bar). The percentages in two age-groups had no significant difference in any viral load ranges. p values were calculated by the χ² test. The HBV patient percentages in each age-group were calculated as follows: % = (Number of patients <30 years-old or patients >30 years-old at each viral load range) X100/[139 samples (<30 years-old) or 161 samples (>30 years-old)].

Figure 3

Proposed algorithm for treatment of chronic hepatitis B virus (HBV) infection for resource-limited countries based on the viral loads. First, clinicians conduct laboratory tests of the HbsAg in blood, diagnose HBV infection, and test the viral loads, alanine aminotransferase (ALT), complete blood counts (CBC), and the aspartate aminotransferase-to-platelet ratio index (APRI) as well as elastography, if it is available. Since the World Health Organization (WHO) guideline recommends the use of the APRI to assess the presence of cirrhosis (APRI > 2) in resource-limited settings, we propose the use of the APRI, ALT levels, and viral load information to determine treatment of HBV infection.