## 5 HCV and Microbiota  
Despite growing interest in this field, the precise nature of the interactions between HCV and the microbiota is still inadequately explored. A deeper understanding of these interactions is essential, as emerging evidence suggests that the gut microbiota may play a critical role in modulating both viral pathogenesis and the progression of HCV-associated liver disease. A recent clinical study involving 95 patients diagnosed with chronic HCV infection, with and without cirrhosis, provided significant insights into the alterations of intestinal microbiota associated with disease progression. The findings revealed substantial differences in the composition of gut microbiota between individuals with cirrhosis and those without. Notably, the study highlighted a marked reduction in alpha diversity--a measure of microbial richness and evenness--in patients with more advanced liver disease. This decline in microbial diversity is hypothesized to be driven by either a direct interaction between HCV and host-associated bacterial communities or an indirect consequence mediated by immune system dysfunction [32]. These observations underscore the potential role of microbiota in influencing both viral persistence and the progression of hepatic fibrosis. Furthermore, the inverse correlation between microbial diversity and the severity of cirrhosis complications suggests that microbiota composition may serve as a biomarker for disease progression. Alterations in gut microbiota have been reported across various stages of HCV-related liver disease, including chronic hepatitis C (CHC), cirrhosis, and HCC. Studies have demonstrated that patients with CHC exhibit significant dysbiosis, characterized by an increase in the relative abundance of Proteobacteria and a concomitant decrease in the phyla Bacteroidetes and Firmicutes. This microbial imbalance is even more pronounced in individuals with cirrhosis and HCC, suggesting a progressive deterioration of microbial homeostasis as liver disease advances [33]. The expansion of Proteobacteria, a phylum that includes numerous pathogenic bacteria, has been implicated in inflammatory processes and gut permeability dysfunction, potentially exacerbating hepatic damage through systemic endotoxemia and immune activation. Consequently, these findings suggest that the gut microbiota may not only reflect the severity of HCV-induced liver disease but also contribute to its pathophysiology. In this context, the disruption of gut microbial communities in HCV-infected individuals highlights the potential for microbiota-targeted therapeutic strategies to mitigate disease progression. Several studies have proposed that interventions aimed at restoring microbial balance--such as the administration of prebiotics, probiotics, or fecal microbiota transplantation (FMT)--could offer therapeutic benefits by modulating gut-liver axis interactions. FMT is widely regarded as a safe and well-tolerated procedure, even among high-risk patient populations. The majority of short-term risks are mild and are linked to the methods of administration. Currently, long-term adverse effects have not been definitively identified, and no evidence of harm has been observed thus far. Nevertheless, it is essential to establish causality for various diseases associated with the microbiome [34]. Similarly, probiotic bacteria, upon colonizing the small intestine, have the capacity to deconjugate and dehydroxylate bile salts, which may lead to diarrhea and intestinal damage. Probiotic strains are known to produce bile salt hydrolase (BSH), resulting in the accumulation of deconjugated bile salts. Subsequently, these bile salts can be transformed into potentially harmful secondary bile acids by the intestinal microbiota. The presence of these cytotoxic substances in the enterohepatic circulation may elevate the risk of cholestasis and colorectal cancer [35]. Septic complications are common contributors to morbidity associated with liver diseases and subsequent hepatic surgeries.