Background and Objectives: Chronic hepatitis C virus (HCV) infection is intricately linked with dysregulation of lipid metabolism. In particular, cholesterol plays a crucial role in HCV replication. Direct-acting antiviral agents (DAAs) therapy has revolutionized the hepatitis C treatment landscape, achieving high rates of sustained virological response (SVR). However, viral clearance comes with some alterations in lipid-related markers. This prospective study aimed to evaluate the impact of HCV clearance on lipid homeostasis and non-invasive liver fibrosis markers in hepatitis C patients treated with DAAs. Material and Methods: Fifty-two patients with varying degrees of fibrosis treated with DAAs therapy were evaluated at baseline and 24 weeks post-SVR. Lipid profiles and non-invasive liver fibrosis markers were assessed. Results: Our findings revealed an increase in total cholesterol, triglyceride, and LDLc (low-density lipoprotein cholesterol) levels at 24 weeks post-SVR, alongside an improvement in serum liver enzymes. Although improvements in liver stiffness were observed in non-invasive tests, there was an increase in lipid-related markers post-SVR. Conclusions: This suggests a potential increased cardiovascular risk despite improvements in liver function and fibrosis, highlighting the necessity for statin therapy in some cases and extended follow-ups for these patients. These findings underscore the importance of closely monitoring lipid profiles in chronic hepatitis C patients post-SVR, as well as the potential need for statin therapy to mitigate cardiovascular risk. Additionally, extended follow-up is essential to assess long-term outcomes and ensure the optimal management of these patients.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC.
METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events.
RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001).
CONCLUSIONS: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

BACKGROUND: Chronic HC leads to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The treatment of chronic HC with DAAs reduces mortality from LC and HCC. The study aimed to investigate the serological markers specific to HCC (PIVKA-II and AFP) in patients with chronic HC before and after DAA treatment.
METHODS: The study involved 35 HCV patients (mean age: 56.23 ± 1.45) divided into two groups. Group 1 included 15 HCV + HCC patients and Group 2 included 20 HCV non-HCC patients.
RESULTS: At the end of treatment all the patients were HCV RNA negative. Three months after the end of antiviral treatment, HCV RNA was undetectable in all patients, while a complete biochemical and virological response was observed in 66.7% of HCV + HCC patients and 85.0% of HCV non-HCC patients. PIVKA-II levels before the initiation of antiviral treatment were high in all patients. At the end of the treatment, in the HCV non-HCC group, normalization of PIVKA-II levels was observed only in 20.0% cases, and in 60.0% of cases 3 months after the treatment. Meanwhile, in patients with HCC and chronic HCV, PIVKA-II levels were within the normal range 3 months after treatment in only 13.3% of patients.
CONCLUSIONS: It is necessary to monitor HCV patients with cirrhosis (F4) and severe fibrosis (F3) without HCC, who have high PIVKA-II and AFP levels and/or ALT activity despite obtaining sustained virologic response 3 months after treatment with DAAs.

BACKGROUND: Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters.
METHODS: PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively.
RESULTS: Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment.
CONCLUSIONS: Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment.
BACKGROUND: PROSPERO CRD42020180793.

Chronic hepatitis C is a kind of viral hepatitis caused by hepatitis C virus infection, which can further progress to cirrhosis, liver failure, hepatocellular carcinoma, and even death. Presently, there is no preventive vaccine yet. Therefore, preventing infection and safe and effective drug treatment are currently the most effective strategies for dealing with hepatitis C virus infection. Since 2014, the clinical application of direct-acting antiviral drugs has brought revolutionary changes to the treatment of chronic hepatitis C. Direct-acting antiviral drugs have an excellent hepatitis C virus clearance effect, are well tolerated, have a good safety profile, and can significantly improve liver function, metabolic disorders, immune dysfunction, etc. However, some studies have pointed out that even if the hepatitis C virus is cleared during the treatment of chronic hepatitis C-related cirrhosis with direct-acting antiviral drugs, a considerable proportion of patients still have severe liver failure, hepatocellular carcinoma, and even liver disease-related death, so there are still some problems in the treatment of chronic hepatitis C- related cirrhosis with direct-acting antiviral drugs that need to be further explored. This article reviews the research progress of direct-acting antiviral drugs so as to provide meaningful references for the treatment of patients with chronic hepatitis C-related cirrhosis.
慢性丙型肝炎是由丙型肝炎病毒感染引起的一种病毒性肝炎，可进一步进展为肝硬化、肝衰竭、肝细胞癌，甚至死亡。目前尚未有预防性的疫苗，因此，预防感染及安全有效的药物治疗是目前应对丙型肝炎病毒感染最有效的应对策略。自2014年以来，直接抗病毒药物的临床应用对慢性丙型肝炎的治疗带来了革命性的变化。直接抗病毒药物具有极佳的清除丙型肝炎病毒效果，且耐受性、安全性良好，可显著改善肝功能、代谢障碍及免疫功能障碍等。然而有研究指出，直接抗病毒药物在治疗慢性丙型肝炎肝硬化时即使清除了丙型肝炎病毒，仍有相当比例的患者出现严重肝衰竭、肝细胞癌甚至肝病相关死亡，所以直接抗病毒药物治疗慢性丙型肝炎肝硬化仍有些问题需要进一步探讨。现综述直接抗病毒药物对慢性丙型肝炎肝硬化患者的研究进展，为慢性丙型肝炎肝硬化患者的治疗提供有意义的参考。.

Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC.
the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy.
A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome.
Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET.
according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.

There is no established rescue therapy for hepatitis C patients with decompensated cirrhosis who experience treatment failure on 12-week sofosbuvir (SOF)/velpatasvir (VEL) therapy that is the only approved regimen for decompensated cirrhosis in Japan. We experienced a patient with decompensated cirrhosis who showed virologic relapse at post-treatment week 7 following 12-week SOF/VEL therapy. She had resistance-associated substitutions (RASs) against VEL before therapy but did not achieve new RASs against VEL or SOF after therapy. We considered rescue therapy following strong demand from her and her family. The drug adherence of therapy was 100%, and the treatment was well tolerated. Because we prioritized the safety and drug adherence of the regimen, we performed prolonged 24-week SOF/VEL therapy without ribavirin at her own expense with the approval of the ethics board in the hospital where the first author belongs. Fortunately, a sustained virologic response 24 was achieved without any adverse events. Hepatocellular carcinoma that had developed after 12-week SOF/VEL therapy recurred and was treated near the end of rescue therapy, but hepatic functional reserve improved. Although this was a single case report and was assumed to be very rare, the same regimen might be effective for treatment failure with 12-week SOF/VEL therapy.

Using organs from donors with treatable infections is a strategy to increase the quality and number of organs for transplantation. For HIV, pilot studies of kidney and liver transplantation from donors with HIV to recipients with HIV demonstrate excellent early outcomes. However, the number of donors and transplants per year remains lower than projected due to several barriers. For HCV, the use of organs from donors with HCV has expanded to recipients without HCV due to safe, effective direct-acting antivirals for HCV, which are well-tolerated in transplant recipients. Studies across organ types demonstrate good outcomes and shorter wait times.

Hepatitis C virus (HCV) infection contributes significantly to liver cirrhosis and hepatocellular carcinoma (HCC), often requiring liver transplantation. Introducing direct-acting antiviral agents (DAAs) has radically changed HCV treatment. DAAs achieve high rates of sustained virological response (>98%). Even then, resistant-associated substitution and HCC during or after treatment have become prominent clinical concerns. Further, several clinically significant issues remain unresolved after successful HCV eradication by DAAs, including treating patients with chronic kidney disease or decompensated liver cirrhosis. Extensive and large-scale screening and treatment implementation programs are needed to make DAA therapies effective at the population level.

Renal transplantation is the most beneficial treatment in patients with chronic kidney disease (CKD), increasing life expectancy and improving quality of life. A better understanding of organ and tissue functions, the development of surgical techniques, and new and effective immunosuppressive and antimicrobial drugs increase the success of transplantation. However, the number of renal transplantations from living and cadaveric donors is not at the desired frequency. Among the leading causes of the restrictions for transplantation are both the recipients\' and donors\' chronic diseases. While hepatitis B and C infections are a significant problem affecting the number and success of renal transplantations, the innovation of hepatitis C virus treatments has improved outcomes. Thus, the recipient and donor hepatitis B and C virus infections are no longer considered as relative contraindications for renal transplantation. This review discusses the management of patients and donors with hepatitis B and hepatitis C in renal transplantation.