## 4 Discussion  
Hepatocyte damage due to HBV infection and pathogenesis of liver disease are not directly associated with HBV; however, they are caused by immune-mediated host HBV interactions [41]. The complex mechanisms that cause HBV-mediated liver disease are not fully understood due to the involvement of complex protein-protein interactions with multiple host factors [42]. However, the utilization of already existing single drug molecules against a cluster of HBV-mediated liver disease pathways may cause adverse drug effects by disrupting the host tissue mechanisms. The utilization of chemotherapeutic agents during HCC may alter hepatic metabolism, reduce efficacy, or may cause liver toxicity by the disposition of the drug in liver tissue [43]. Further, physicians utilize palliative treatments such as systemic chemotherapy, interferon, transarterial chemo-embolization, and hormone therapy against HCC when there are no curative treatment options. However, the utilization of these therapies for HCC patients is challenging because HCC is highly resistant to systemic therapies [44]. In the current study, we elucidated the molecular mechanisms and probable safe use of traditionally used herbs of Western Ghats, Karnataka against jaundice, fever, inflammation, and viral infections via cluster and enrichment analysis of potential HBV disease protein targets that participate in the progression of immune processes and inflammatory responses. The results obtained from the current study predict that flavonoids and triterpenoids from _A. paniculata_ and flavonoids from _T. populnea_ could potentially prevent disease progression and could be effective therapeutics against chronic HBV-induced HCC. Identification of potent candidates from herbal medicines is not only the key focus of new drug discovery against HBV-induced HCC, but drug safety is also a key concern. This means that ensuring that the drugs have a positive benefit-risk balance is the goal [45]. Hepatotoxicity induced by herbs is one of the most important factors limiting treatment. The issue has often been responsible for post-marketing warnings and withdrawal [46]. Figure 11: EGFR–Gössypetin complex sustained intermolecular interactions and percentage interaction fraction throughout 100 ns production run. Many researchers have well documented adverse hepatic reactions and idiosyncratic liver damage caused by herbs. The major hepatotoxic herbs reported thus far are _Teucrium chameadrys_, _Larrea tridentate_, _Cimicifuga racemosa_, _Scutellaria lateriflora_, and _Scutellaria bacialensis_[47]. In the current study, we screened 274 phytocompounds from 16 herbs for their druggable characteristics using the Lipinski rule of five, and we selected only compounds with positive drug-like properties. Further, these compounds were screened for major adverse drug reactions and side effects, i.e., hepatotoxicity, cardiac toxicity, nephrotoxicity, and potential to cause myocardial infarction using the ADVERpred online prediction. To minimize the toxicity, compounds with a probable toxic activity (Pa) with a \(p\) value \(\leq\) 0.5 were considered. Further, compounds were also predicted for their probable affinity toward potential drug targets using BindingDB (\(p\) value \(\geq\) 0.7), and they segregated the target associated with HBV infection and HCC with the aid of published literature, KEGG pathway, and Therapeutic Target Database (TTD). STRING database was also utilized to identify the molecular functions, biological processes, and pathways regulated by the predicted targets, wherein the targets were meticulously chosen solely based on potential molecular functions, processes, and pathways with higher significance (\(p\)\(\leq\) 0.05) and those that are only associated with HBV-induced HCC. Based on the results obtained from STRING, we constructed a compound-protein pathway network building to understand the relations between compounds, target proteins, and pathways.