## 6 Microbiota Alterations in HCV Patients  
HCV infection has been extensively associated with significant alterations in gut microbiota composition, a phenomenon referred to as dysbiosis. This disruption in microbial equilibrium has been implicated in various pathological processes, including immune dysregulation, systemic inflammation, and the progression of liver disease. The gut-liver axis, a bidirectional communication system between the gut microbiota and the liver, plays a critical role in maintaining homeostasis. However, HCV-induced dysbiosis can compromise this balance, leading to adverse health outcomes. A study conducted by [PERSON] et al. (2016) [39] provided compelling evidence of a marked decrease in microbial diversity among cirrhotic patients infected with HCV compared to healthy individuals. This decline in microbial richness is particularly concerning, as microbial diversity is a key determinant of gut ecosystem stability. Reduced diversity has been linked to compromised gut barrier integrity, increased intestinal permeability, and translocation of bacterial endotoxins into the systemic circulation. Such events exacerbate liver inflammation, promote hepatic fibrogenesis, and contribute to the progression of chronic liver disease [39]. These findings underscore the notion that gut dysbiosis is not merely a secondary consequence of liver dysfunction but may actively drive disease pathogenesis. Further supporting this concept, conducted a large-scale study involving 212 patients diagnosed with HCV at varying stages of disease progression. Their findings revealed that gut microbiota alterations were evident even in asymptomatic patients, suggesting that dysbiosis may develop at an early stage of HCV infection. Moreover, the severity of microbial dysbiosis exhibited a direct correlation with disease progression, reinforcing the potential utility of microbiota composition as a biomarker for monitoring liver disease severity and predicting clinical outcomes [41]. The persistence of gut dysbiosis following antiviral therapy has also been explored. [PERSON] et al. (2021) [42] investigated longitudinal changes in the gut microbiome of HCV-infected individuals before and after undergoing direct-acting antiviral (DAA) therapy. Their analysis identified significant alterations in specific bacterial taxa, highlighting the impact of both HCV infection and antiviral treatment on the gut microbiota. However, despite achieving sustained virological response (SVR), the overall microbial composition did not revert to a pre-infection state. This finding suggests that while viral clearance mitigates some aspects of dysbiosis, it does not fully restore microbial homeostasis, possibly due to long-term liver damage, immune alterations, or residual inflammatory processes [43]. The intricate interplay between the gut microbiota and the immune system plays a pivotal role in shaping the host's response to HCV infection. The immune system exerts selective pressure on microbial populations, influencing their composition and function. Conversely, microbial metabolites and structural components, such as lipopolysaccharidesaccharides (LPSs) and short-chain fatty acids (SCFAs), modulate immune responses, thereby impacting viral pathogenesis. In individuals with HCV who have achieved sustained virologic response (SVR), a correlation was observed between the extent of liver fibrosis and the dysbiosis of mucosa-associated SCFA-producing bacterial genera, which may influence the integrity of the intestinal barrier and the synthesis of bile acids in the ascending colon. In the context of HCV infection, dysbiosis has been associated with an impaired antiviral immune response, which may facilitate viral persistence and increase the likelihood of chronic infection. Furthermore, specific microbial metabolites can modulate the expression of key immunoregulatory molecules, including interferons and pro-inflammatory cytokines, further influencing the host's ability to mount an effective response against HCV [44].