In clinical work, we often encounter the situation of chronic hepatitis C combined with fatty liver. The following is a brief discussion of this common concern. The etiology and pathogenesis of hepatic steatosis in patients with chronic hepatitis C (CHC) Studies have shown that the incidence of hepatic steatosis in patients with CHC is about 2.5 times higher than in the general population, and hepatocellular steatosis exists in about 50% of patients, and both the virus and the host (the patient itself) are involved in its development. First, the patient’s own metabolic factors can lead to the development of hepatic steatosis, and there are many etiologies that cause hepatic steatosis. The common clinical ones are drugs, heavy alcohol consumption, obesity, and diabetes mellitus. Risk factors associated with nonalcoholic fatty liver disease (NAFLD) such as insulin resistance (IR) and its related syndromes may also be involved in the development of hepatic steatosis in CHC patients. Studies of liver biopsy specimens from CHC patients have found that about 5-10% of patients have combined non-alcoholic steatohepatitis (NASH). The mechanism of hepatic steatosis formation in NAFLD is currently thought to be related to IR and secondary hyperinsulinemia, which leads to a weakening of hormone-sensitive lipase inhibition and a large mobilization of adipose tissue. In addition, the virus itself may play a significant role in the formation of hepatocellular steatosis in CHC patients. The reason for the significantly higher incidence of steatosis in HCV genotype 3a-infected patients than in other types is unclear. HCV is directly involved in the formation of hepatic steatosis. In a recent antiviral clinical study, HCV genotype 3a-infected patients showed a reduction in steatosis with virus clearance and a reappearance of steatosis with virus reinfection. The mechanism by which HCV directly promotes the development and progression of hepatocellular steatosis is poorly understood. It is currently thought that the HCV core protein may be involved. The presence of progressive hepatic steatosis was found in both transgenic murine models expressing the core protein and in transfected cells. The core protein may act through the following mechanisms: (1) The core protein alters the lipid bilayer structure of the mitochondrial membrane, thereby disrupting lipid β-oxidation and causing lipid accumulation. (2) Core proteins act on triglyceride transport protein (MTP) in microsomes to reduce its activity and prevent hepatic apoB secretion and VLDL assembly, resulting in hepatocyte steatosis. A clinical study found that in CHC patients with significant steatosis, blood apoB levels were extremely low. Hepatocellular steatosis consistent with this can occur in the presence of hyper-R lipoproteinemia due to mutations in the MTP gene. Microsomal triglyceride transfer protein (MTP) is a rate-limiting enzyme with an important role in the assembly and secretion of very low density lipoprotein (VLDL), and its inactivation may directly contribute to the deposition of non-secreted triglycerides, leading to steatosis.MTP exists as a heterodimer on the endoplasmic reticulum and consists of a 97 kDa subunit and a 58 kDa subunit protein disulfide bond isomerase (PDI), an endoplasmic reticulum chaperone protein involved in translocation of MTP into the endoplasmic reticulum lumen and folding of MTP. In vitro, MTI transports lipids from different locations providing lipid droplets to receptor sites. In vivo, MTP is important for the transport of apolipoprotein B (ApoB) to the endoplasmic reticulum and its localization in lipids, preventing the degradation of ApoB, an apolipoprotein necessary for the synthesis and secretion of triglyceride-rich (TG) VLDL by the liver, and a structural protein of VLDL involved in VLDL synthesis, assembly and secretion of VLDL. In this way, precursor particles are formed and VLDL is formed by the addition of large amounts of TG.(3) The core protein binds directly to apoA II through its C-terminus, thus affecting lipid metabolism. One study found that core proteins were detectable in 90.4% of patients with HCV combined with fatty liver and 36.4% of those without fatty liver, so viral core proteins are indeed an independent factor in the increased development of fatty liver in patients with hepatitis C. Second, what is the impact of CHC combined with hepatic steatosis on the progression of the disease and the efficacy of antiviral therapy (a) Hepatic steatosis aggravates hepatic fibrosis in CHC patients: liver biopsy studies have found that the degree of hepatocellular steatosis in CHC patients correlates with the severity of hepatic fibrosis, and severe hepatic steatosis (grade 3-4) is also associated with an increased rate of progression of hepatic fibrosis. hepatic steatosis or liver The mechanism by which the exacerbation of steatosis is associated with fibrosis progression is now thought to be probably similar to that of liver fibrosis in patients with NAFLD. A recent study showed that the incidence of sinusoidal gap fibrosis and ballooning degeneration in patients with NASH was 16% and 19%, respectively, in patients with CHC, and that the severity of fibrosis correlated with age and the presence of type 2 diabetes.Clouston et al. also demonstrated that fibrosis in patients with CHC is similar to that formed in NAFLD. Recently, it is believed that hepatic steatosis, as a result of the initial strike, often requires a second strike to cause inflammation and fibrosis to develop in the liver. Although hepatic steatosis is more severe in patients with NAFLD, the rate of liver fibrosis tends to be higher in patients with CHC, suggesting that there may be other factors or “additional” second strikes in patients with CHC in addition to hepatocellular steatosis associated with its development. The immune inflammatory response of the body may also be involved in the development of hepatic fibrosis. The free radicals, pro-inflammatory and pro-fibrotic factors produced during this process are associated with the development of liver fibrosis. Studies have shown that the degree of sinusoidal gap fibrosis correlates with the severity of inflammation in the portal vein and lobules, and that hepatocytes with steatosis are more sensitive to damage such as inflammation. Studies in isolation or in vitro have also found that HCV core proteins can be involved in the formation of fibrosis by disrupting mitochondrial electron transport processes and directly inducing oxygen stress. (ii) Decreased sustained virologic response (SVR) due to hepatic steatosis: A number of studies have found that non-genotype 3 CHC patients with steatosis have a lower SVR after administration of standard antiviral therapy. The mechanisms related to the decrease in SVR due to hepatic steatosis may be related to altered immune system function, altered liver responsiveness to IFN and decreased bioavailability, and the development of hepatic fibrosis. 1, changes in immune system function: CHC patients with IR or BMI (Body Mass Index, BMI for short, is a number derived by dividing body weight in kilograms by height in meters squared, which is a standard commonly used internationally to measure the degree of fatness and thinness of the human body and whether it is healthy or not) may have lower SVR partly through this mechanism. This may be related to decreased immune function due to IR or obesity, a process that may be mediated through leptin. Interferon (IFN) initiates the body’s immune response process by upregulating Thl cell activity in the body to achieve HCV clearance. Leptin has the function of regulating T-cell activity and promoting its conversion to Thl. However, in patients with IR or high BMI, there is often leptin resistance and thus cellular immune dysfunction, resulting in reduced SVR. In those patients who do not respond to treatment there is often abnormal T-cell function as well as Thl/Th2 ratio. 2. Decreased liver responsiveness to IFN: Large fat deposits in hepatocytes can cause liver dysfunction, disrupting the normal structure of the liver and reducing the contact area between the drug and the virus-containing hepatocyte membrane, resulting in a decreased effective liver response to the drug. A recent study found that serum levels of 2′-5′-oligonucleotide synthase, which marks the intrinsic activity of IFN, decreased in CHC patients with combined severe steatosis after administration of standard IFN. 3.Decrease in bioavailability: When the dose is fixed, the drug distribution range of obese patients is wide but the effective blood concentration decreases, so it will definitely affect the SVR. SVR is reduced. 4, fibrosis: liver steatosis and fibrosis are closely related, and fibrosis is an independent predictor of SVR. The mechanism is generally believed to be the accumulation of many factors that resist the action of IFN during the long course of progression to cirrhosis, which may help explain the low response to IFN therapy in fibrotic patients. state. In conclusion, the high incidence of hepatic steatosis in CHC patients may be the result of both host and viral effects, and its presence leads to accelerated disease progression in CHC and reduced SVR of the organism to antiviral therapy.Further elucidation of the causes and mechanisms of hepatic steatosis in CHC patients would be helpful for clinical treatment of CHC and clearance of HCV.From the individual patient’s perspective, liver steatosis causing From the individual patient’s perspective, minimizing and avoiding the factors that cause hepatic steatosis and treating the developed steatosis accordingly will help to improve the clinical prognosis of CHC patients.