Our study tried to indicate the relationship between noninvasive markers of liver fibrosis among patients with HBV mono-infection versus those with HBV-HIV coinfection. Such assessments were not carried out previously in the Ethiopian setup and most studies were carried among treatment naïve groups in Africa.
Our study indicated that patients with HIV/HBV coinfection had a better platelet count compared to those with HBV mono-infection. This is counter to most published literature suggesting that patients with HIV infection are likely to have a low platelet count and hence likely to have elevated noninvasive markers(30). However, the thrombocytopenia in these patients was characterized when the results were compared to the general population and not with a condition known to cause low platelet count, like Hepatitis B. Furthermore, with an adequate duration of HAART therapy, thrombocytopenia has been shown to improve compared to ART naïve individuals(31). The lower platelet count in patients with HBV mono-infection could be attributed to an advanced liver disease even though platelet count is a crude indicator of advanced liver fibrosis. One explanation is that only those with lower platelet count and evidence of liver fibrosis are initiated on antivirals compared to the larger cohort of HBV-infected patients. This indicates that patients with HBV mono-infection might be at a disadvantage when starting antivirals as a significant amount of time is elapsed before the decision to initiate antivirals is made; by the time, patients are already developing more advanced fibrosis. However, the design of our current study is not geared towards such a conclusion, and further studies might be needed with a particular emphasis on the specific point. Among patients with HBV and HIV, previous studies conducted by Iroezindu et al, indicated that patients with HIV and HBV coinfection were likely to have a lower platelet count; however, the included patients were those without ART initiation.(32)
Similarly, Patients untreated for HIV and HBV were likely to have a higher APRI score on previous studies. Wandeler and colleagues tried to compare the APRI score of patients with HIV/HBV coinfection in Zambia and Switzerland(33). They showed that those with coinfection had a higher score but this study also used ART untreated patients as the study population. A Study using conducted among participants from the Multicenter AIDS Cohort Study (MACS) also showed a higher APRI score among coinfected individuals. However, the MACS study used both HBV and HCV-infected individuals, and the patients were grouped as Hepatitis Coinfected(34). In addition, the patients with HBV coinfection were not on TDF therapy, and effect of viral hepatitis treatment was not accounted for. A study conducted in Uganda showed that those with HIV/HBV coinfection had a 3 fold increased risk of elevated APRI score, and similarly, the included patients were evaluated before enrollment into the study(35).
A recent South African study by Maponga and colleagues has shown that patients with HIV and HBV coinfection are at an advantage over patients with HBV mono-infection as evidenced by lower HBV viral load, lower APRI score, higher platelet count, and more frequent evaluation by elastography(36). This study included similar patients to our participants and indicated that with adequate antiviral suppression of HBV, patients with HIV coinfection might actually have a better liver parameter than those with mono-infection.
The finding that our patients had a reasonable CD4 count and adequate ART duration might contribute to a better noninvasive assessment profile. Two studies from India indicated that those patients with low CD4 count and HBV coinfection were more likely to have worse liver parameters when compared with those with a higher CD4 count(37),(38). Both showed that patients were more likely to have higher liver enzymes and HBV viral loads if the CD4 count was low. Similarly, a study in China showed those patients with HBV coinfection were shown to have a lower CD4 count and higher liver enzymes prior to ART initiation(39).
Access to antiviral treatment is also a significant issue that might make patients with HBV mono-infection at a disadvantage compared to those with HIV coinfection. Current HIV treatment guidelines provide treatment access to those with HIV/HBV coinfection, and treatment is provided free of charge in Africa, whereas those with HBV mono-infection have to develop significant fibrosis or elevated liver enzymes to start antiviral treatment. In addition, patients have to pay for their treatment, and in some situations, access might be interrupted.
The strength of our study is that it is the first study from Ethiopia to characterize differences between HBV monoinfected and HIV/HBV coinfected patients in terms of noninvasive markers of liver fibrosis. The study included assessments using dual cutoffs to compensate for loss of sensitivity and specificity by the use of a single value. We also used both APRI and FIB4 markers and these are the most widely used clinical methods to measure liver fibrosis.
Our study also has different limitations. We did not include transient elastography measurements as the device is not widely available in the country, and it is currently expensive to acquire in most facilities. The inclusion of TE measurement would have helped further strengthen our findings; however, the machine is not available in the continent in most hospitals in Africa and has a limited clinical application. Hepatitis B viral load and e antigen status is not documented for most patients, and the inclusion of this data would have helped to reflect on the association of virologic suppression with liver fibrosis in both groups of patients. However, current guidelines from the WHO forgo a requirement of these tests on decision making to initiate antiviral therapy in resource-limited facilities if there is evidence for significant fibrosis and cirrhosis based on a noninvasive assessment of liver fibrosis.
Our study also relied on already diagnosed patients with HIV/HBV coinfection for inclusion in the study. A significant number of patients might have had the coinfection and not yet been diagnosed on followup. Ideally, all patients on followup at the ART clinic should have been tested for the presence of HBV coinfection; however, due to resource constraints, it was not possible. It is worth noting that the number of coinfected patients on followup is low compared to the estimated prevalence according to published African literature.