## 3 HCV Infection  
HCV is a major global health concern, contributing significantly to the burden of viral-hepatitis-related morbidity and mortality. Epidemiological data indicate that HCV accounts for approximately 17.5% of acute hepatitis cases, with studies suggesting that around 65% of individuals who contract an acute HCV infection fail to achieve spontaneous viral clearance and subsequently progress to chronic infection [18]. Chronic hepatitis C (CHC)is a persistent, long-term condition that can lead to progressive liver damage, ultimately culminating in severe hepatic complications if left untreated. According to the World Health Organization (WHO), an estimated 170 million individuals worldwide are currently living with HCV infection, underscoring its substantial prevalence and public health significance. The natural course of CHC varies among individuals; however, a considerable proportion of those infected remain asymptomatic for years, during which ongoing hepatic inflammation contributes to progressive fibrosis and liver dysfunction. Over time, persistent HCV infection poses a significant risk for the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), which together constitute the most severe complications associated with chronic HCV infection [19; 20; 21]. Cirrhosis, characterized by extensive hepatic fibrosis and architectural distortion, is a critical turning point in disease progression, as it significantly increases the likelihood of liver failure and the need for liver transplantation. Additionally, hepatocellular carcinoma, the most common primary malignancy of the liver, represents a major cause of cancer-related mortality in individuals with chronic HCV infection, particularly in cases of advanced fibrosis or cirrhosis. Beyond its direct hepatic manifestations, HCV infection is also associated with a range of extrahepatic complications, which further contribute to its complex clinical presentation. A growing body of research has established a link between chronic HCV infection and several metabolic, immunological, and renal disorders. Notably, HCV has been implicated in the pathogenesis of type 2 diabetes mellitus and insulin resistance, conditions that are believed to arise due to viral-induced disruptions in glucose metabolism and inflammatory signaling pathways. The association between HCV and metabolic dysfunction suggests a broader impact of the virus beyond the liver, reinforcing its role as a systemic disease rather than a strictly hepatotropic infection [22; 23; 24; 25]. Virus molecular evolution is a critical factor influencing HCV transmission, the progression of the disease, and the outcomes of therapeutic interventions. The significant genetic diversity inherent to HCV serves as a fundamental aspect that enables the rapid adaptation of the viral population within a host to various selective pressures, such as immune responses and antiviral treatments. The molecular evolution of HCV is influenced by several mechanisms, including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal fluctuations, and compartmentalization. These evolutionary dynamics continuously modify the composition of the HCV population within the host in a staged manner. Recent advancements in understanding the molecular mechanisms governing HCV replication have led to the development of numerous direct-acting antiviral agents, resulting in enhanced sustained viral response rates [26]. Additionally, emerging evidence suggests a correlation between chronic HCV infection and deteriorating oral health, with studies reporting an increased prevalence of periodontal disease, dental caries, and salivary gland dysfunction among affected individuals. The underlying mechanisms of these associations remain an area of active investigation, though they are hypothesized to involve chronic inflammation, immune dysregulation, and alterations in oral microbiota composition.