In the population studied, there was a higher prevalence in males, with a higher proportion in the immunoactive chronic hepatitis B group. This observation is not yet fully elucidated, however, in the Western Amazon, there are reports of predominance in men, a pattern applicable to most endemic areas in the world [14, 15]. Other clinical studies also report a prevalence of men classified as having advanced liver disease [16–19].
When analyzing the biochemical markers in the study samples, alterations in the laboratory components (AST, ALT and albumin) possibly indicate a direct correlation in terms of progression, which is related to higher mortality in patients with chronic liver disease [19]. Bilirubin levels were found to be elevated to a greater extent in co-infected patients with detectable HDV-RNA and, as a result, this marker was a differential in HDV infection compared to HBV monoinfection in this population. This marker consists of a functional reserve of the liver parenchyma and has important prognostic value [20].
Our findings showed elevated ALT and AST levels with a higher proportion among individuals with immunoactive chronic hepatitis B and those with detectable HDV viral load. ALT levels correlate with inflammatory activity and also serve as a marker for assessing response to treatment [2, 21]. This profile is expected in individuals with chronic immunoactive hepatitis B, since in this phase the immune response is crucial not only for viral elimination and inhibition of replication, but also for hepatocyte apoptosis through a response mainly from CD8 T cells, which leads to the release of transaminases into the circulation [22].
In this study, hypoalbuminemia was found predominantly in individuals with detectable HDV-RNA. This profile is strongly associated with inflammation and is directly related to liver function disorders [23]. In the group analyzed, this marker was very similar to the results observed for ALT and AST. On the other hand, in a study of cirrhotic individuals with HBV, it was observed that changes in albumin levels were not significantly related to ALT levels, but rather to a reduction in viral replication, thus associating the improvement in hypoalbuminemia with the treatment applied to carriers [24].
HBV viral load levels in monoinfected individuals correlated with higher AST and ALT levels in this study. This association between viral load and high transaminase values has already been observed in previous studies; A study has already reported the relationship between HBV-DNA values and high ALT levels in 110 chronic HBeAg-negative individuals, however the same was not observed for AST [25]. An evaluation of 91 patients observed a greater sensitivity of AST for the detection of liver damage, which may suggest that AST dosage would be more indicated as a screening test for evaluation in these cases [26]. In a study by researchers in China with 11,738 treatment-naïve adult patients, fifty-five percent of patients with HBV-DNA ≥ 20,000 IU/mL had abnormal ALT and/or AST values, which was significantly higher than in patients with HBV-DNA levels below 20,000 IU/mL[25].
On the other hand, the mechanisms involved in HDV pathogenesis are not fully elucidated due to multifactorial mechanisms in addition to the complex dynamics of HBV/HDV interaction [27]. However, HDV is not commonly considered cytopathic, since viremia may not be directly related to liver damage, and pathogenesis is generally associated with immune system mediation [28]. However, our results showed significant changes in biochemical markers in individuals with HDV viremia, which suggests that replication may be influencing the poor prognosis of infected individuals. In agreement with this finding, longitudinal multicenter studies have shown that individuals who had persistent detectable viremia had a worse prognosis of the disease over the years [29, 30].
It was observed that the majority of patients in both groups had low HBV viral load values (< 2,000 IU/mL), possibly influenced by the recommended antiviral therapy. A study of monoinfected individuals showed that, regardless of the low viral load, there is still a high chance of developing liver cirrhosis [31]. On the other hand, the course of HBV/HDV infection can be very dynamic, since fluctuating viral load profiles can be observed for both viruses throughout the infection; however, some studies have shown that HDV tends to suppress HBV replication [32–35].
Our results showed a significant prevalence of individuals with advanced fibrosis, including cirrhosis, among the group of delta hepatitis carriers compared to those with conical hepatitis B. Co-infection caused by HDV is commonly associated with more severe conditions and the appearance of complications such as hepatic decompensation and cirrhosis [9], which directly corroborates the data we found regarding signs and symptoms among those infected, with a higher percentage of hepatomegaly and splenomegaly for co-infected individuals. Research also carried out in a population in the west of the Amazon showed that the progression to fibrosis in patients with Delta hepatitis is rapid, taking less than 5 years to develop [9, 36]. It is worth noting that the presence of liver cirrhosis possibly represents an indirect risk for the development of hepatocarcinoma, with a higher risk in co-infected individuals compared to HBV infected individuals [37].