HBV is one of the most common underlying causes of decompensated liver cirrhosis, especially in tertiary care hospitals where people often report to a healthcare facility only when the disease is in its advanced stage. Ascites is one of the most commonly encountered complications of cirrhosis. It might be proposed that after viral translocation, virus may enter the systemic bloodstream and access ascitic fluid.
In the present study, only a total of 21 patients fulfilling the eligibility criteria could be enrolled owing to COVID-19 pandemic, thus the present study reflects a pilot study to assess the issue in question. We enrolled patients with decompensated cirrhosis only. The mean age of patients was 45.43 years and mean BMI was 20.2 kg/m2. The study sample was predominantly male (85.7%) and was dominated by a lower socioeconomic class (85.7%) marked by high prevalence of uneducated patients (61.9%). HBV DNA was found to be positive in 4 (19.0%) ascitic fluid specimens only. Detection of HBV DNA in different body fluids in serum positive patients has been reported to vary substantially(6). Detection rates in different body fluids might be dependent on the interaction of these body fluids with the bloodstream. It would also be pertinent to mention here that in the present study, HBV DNA in serum was found in only 17 (81%) cases. Moreover, there were three cases having low serum HBV DNA expression (<2000 IU/L). It was also observed that one of the patients with undetectable serum HBV DNA had detectable HBV DNA in ascitic fluid. This finding indicates thst it is difficult to state that the detectability of HBV DNA is solely dependent on serum positivity. However further studies are needed to reach any definite conclusion. Although, some case reports like the one by Fagan and Coworkers et. al(11) who detected HBV DNA in the urine, semen and saliva of a HBV patient who failed to have detectable HBV DNA levels in serum. It is important to understand the reason for this discrepancy which might be dependent upon heterogeneity in the assay procedures used for detection of HBV DNA in different body fluids.
As far as replicability is concerned, there seems to be high inconsistencies among different studies(6–8,12–16). In the present study, we could detect HBV DNA in only 19% of ascitic fluid specimens in decompensated cirrhosis patients. The calculated 95% confidence intervals for the sample size used in the present study was in the range 5.45% to 41.91%, thus offering a vast range for replication of results. It must be seen that the previous studies have reported detection rates in different fluids to be highly diversified. Table 2 below shows the HBV DNA detection rates for different body fluids in different studies along with the calculated confidence intervals.
On the other hand van der Ejik et al(16) in their series of 27 chronic HBV patients, detected the HBV DNA in 23/27 (85%) of saliva specimens, thus showing a high detectability in saliva. However, there is a high chance of incidental findings as in a subsequent study the same authors failed to get replicable results and reported only 47% of saliva specimens to be positive for HBV DNA. In this study they also assessed HBV DNA in 32% of urine specimens(15).
Compared to the present study, van der Eijk(15,16) carried out their study in chronic hepatitis B patients but did not provide any information regarding the sociodemographic and anthropometric profile except for a male dominance (63%). The study of Heiberg et al.(13) conducted their study among children with chronic hepatitis B. Lin et al.(17) carried out their study in a study population consisting of adult hepatocellular carcinoma, hepatitis and cirrhosis patients. Jain et al.(14) carried out their study on 60 adult patients with a mean age 48.8 years with various chronic hepatitis B conditions including cirrhosis and HCC and a dominance of males (58.3%). The role of demographic profile becomes an important issue as detection of HBV DNA in different body fluids is considered to be transmitted from the bloodstream and thus the patient disease profile, nutritional and hygiene status and other sociodemographic factors are deemed to have a determining role.
A number of previous studies have tried to explore the predictive or prognostic role of detection of HBV DNA in body fluids(6). In the present study, we also assessed the relationship of HBV DNA detection in ascitic fluid with various clinico-demographic and outcome factors but failed to find a significant association except a significant difference in serum protein and HBV DNA levels. Serum protein levels of those with HBV DNA positivity in ascitic fluid were significantly higher as compared to those having undetectable HBV DNA in ascitic fluid.
Given the fewer number of cases with detectable HBV DNA in ascitic fluid (n=4/21), the statistical significance of any association needs to be viewed with caution. Most of the previous studies did not report an association of HBV DNA detection in different body fluids with clinico demographic profile or outcome.
Other internal body fluids like pleural fluid, crebrospinal fluid and pericardial fluids may be considered equivalent to ascitic fluid. One case report described presence of HBsAg in pleural fluid(18). However, no attempts have been made to look for presence of HBV DNA in them and their potential for infectivity may be explored in further studies.
Only raised serum protein and high serum HBV DNA level were positively associated with detection of HBV DNA in ascitic fluid. All other clinical and laboratory parameters were found not significantly associated. Further studies are needed to find the pathophysiological significance of this finding.
Detection of HBV DNA in ascitic fluid is comparable to detection of complete virion in it, as no good virus culuture is available. However, studies aimed to detect complete virion in body fluids including ascitic fluid may be planned to further substantiate the concept of body fluids as potential sources of horizontal transmission.
There were several limitations of the study. Smaller sample size, mostly descriptive data, absence of HBeAg and ascitic fluid parameters were few of them. However, the findings of the present study, within limitations, provide the first evidence of detectability of HBV DNA in ascitic fluid in patients with decompensated cirrhosis. Further studies with larger sample size are required to explore the replicability of these results and their clinical implications to establish the usefulness of such investigations in clinical or epidemiological context.