Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents

We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 weeks], 11.7 ± 8.2 kPa [96 weeks], 10.09 ± 6.23 [144 weeks], all p < 0.001). With matched analysis, the decrease in LS value was significantly larger in DAA group than peg-IFN group at both 48 weeks (29% vs. 9%) and 96 weeks (39% vs. 17%). The incidence of HCC was not significantly different between DAA and peg-IFN groups (5.5% vs. 5.4%) at 144 weeks. HCV eradication with DAA can lead to improvement of liver stiffness over time. The regression of fibrosis was greater in the group with DAA than peg-IFN.Clinical trials registration: ClinicalTrials.gov (NCT02865369).

Evolutive Aspects Of Patients With Cirrhosis After Harvoni Therapy

Introduction: Cirrhosis, is a final pathway of chronic liver diseases. In recent years, Direct-Acting Antiviral Agents (DAAs) gained a leading role in the treatment of chronic hepatitis of viral etiology. Aim of the study: The proposed aims of this research are to estimate the virological response after 12 weeks after treatment completion and to evaluate the beneficial effects of the treatment on patients with decompensated cirrhosis. Patients and methods: The study was of a descriptive type, longitudinal and retrospective, conducted over a 15 months period, including patients with HCV-related cirrhosis patients. It was established the correlation between liver function, metabolic function, comorbidities and severity of cirrhosis and the level of HCV RNA before and after treatment. It was assessed also the neuroinflammatory activity from the results of Fibromas and the complication after therapy. Results: From January 2018 to April 2019, patients with liver cirrhosis were hospitalized. 48 HCV- related cirrhosis patients have fulfilled the eligibility criteria for antiviral treatment and they have constituted the study group. From all the HCV-infected patients with cirrhosis, 41.66% were women and 58.33% were men, most of them in the interval 60-70 years (37.5%) and 70-80 years (33,33%). 87.5% from the patients had compensated cirrhosis (Child-Pugh A class) and 12.5% had decompensated cirrhosis (Child-Pugh B and C class). 77.08% of the patients had severe neuroinflammatory activity – A3, 10.41% had moderate -A2 activity and 12.5% had lower neuroinflammatory activity-A1. The treatment with direct antiviral agents for the study group consisted in three treatment regimens.60% received a two-drug fixed-dose combination- sofosbuvir (SOF)/ledipasvir (LDV). 10% received SOF/LDV combination with Ribavirin. Only 1 patient with Child-Pugh C decompensated cirrhosis received SOF/LDV combination without Ribavirin. Also, a double combination received 10.48% of the patients- grazoprevir (GZR)/ elbasvir (EBR) 20.83% received quadruple combination ombitasvir (OBV)/ paritaprevir (PTV)/ritonavir(r) and dasabuvir (DSV). After 12 weeks from treatment completion, all the HCV-RNA’s level were undetectable. There were no side effects of the treatment. None of the patients didn’t stop the treatment during the period of treatment. There was a statistically significant difference between the ASAT and ALAT level before and after treatment (p<0.0001). 1 patient with Child-Pugh score C, died and another patient with Child-Pugh score B had an episode of variceal bleeding. Conclusion: Treatment with direct antiviral agents as Harvoni regimen, is a safe therapy and effective for HCV-infection and advanced liver disease. Despite the efficiency of the treatment on HCV-RNA, there were patients with complications due to the cirrhotic status of the subjects. The patients with existing decompensated cirrhosis remain at an elevated risk of numerous other complications.

Assessment of Doppler haemodynamic changes suggestive of portal hypertension in cirrhotic HCV patients after sustained virological response to direct antiviral agents

Background Egypt has the highest prevalence rate of HCV in the world. About 14.7% of the Egyptian people have HCV antibodies and 9.8% have an active infection. The death rate due to liver disease about 40,000 each year (near10% of all deaths). It is the second after the cardiac diseases. Aim of Work to assess Doppler haemodynamic changes suggestive of portal hypertension in cirrhotic HCV Egyptian patients after sustained virological response to direct antiviral agents, and their correlation with liver stiffness measurements by Fibroscan. Patients and Methods This prospective cohort study was conducted at Viral Hepatitis Unit at Ain Shams University Hospital and Al-Agouza Police Hospital during the period from May 2018 to July 2019. The study included 50 Egyptian treatment-naïve chronic hepatitis C patients with cirrhosis on Sofosbuvir, Daclatasvir for 12 weeks. Patients were subjected to history and full physical examination, radiology assessment (Abdominal Ultrasound and color Doppler), Upper GI endoscopy and Fibroscan before treatment and 6 months after treatment. Followed up with CBC, AST, ALT, Total bilirubin, Albumin, creatinine and Coagulation profile before and after 12 weeks of treatment And HCV RNA by PCR and HCV CORE Antigen before and then after 12 weeks of treatment. Results Treatment with sofosbuvir plus Daclatasvir for 12weeks resulted in undetectable HCV RNA by PCR in 100% of the patients at the end of treatment. There was a significant improvement in portal hemodynamics 6 months after treatment as well as a significant correlation between Doppler indices and fibroscan. Conclusion: Doppler portal hypertensive parameters, as a marker of portal hypertension, were improved in parallel with the improvement in fibroscan values after viral clearance and its improvement in the current study mandate urgent treatment to avoid possible complications.

An observational retrospective cohort study of the effect of direct antiviral agents (DAAs) on glomerular filtration rate (GFR)

Background Hepatitis C virus (HCV) infection is known to be associated with high rates of liver related morbidities and mortality in the whole world. The interest of Public in HCV is growing, as more than 180 million people, (2.8%) of the global population, are infected with HCV. Aim of the Study To evaluate the effect of direct antiviral agents on glomerular filtrating rate (GFR). Patients and Methods The study performed on 120 subjects from the Hepatology outpatient clinic at Sharque elmadinah Hospital in Alexandria. Results The current results showed that the mean decrease in GFR in patients who received SOF/DAC were 5.21 ± 15.57 and 6.18 ± 16.13 after full 12 week regimen and after 1 year respectively while the mean decrease in patients SOF/SIM were 4.35 ± 14.9 and 3.57 ± 13.08 respectively. The decrease was not statistically significant in both regimens. Moreover, the mean GFR decrease in the only patient received SOF/Ribavirin was 12.8 and 30.9 after 12 weeks regimen and after one year respectively while for the only patient who received PAR/OMB/Rito/Ribavirin the decrease was 5.5 and 53.4 respectively. unfortunately, due to lack of sufficient patients number, the decrease an not be expressed statistically. Conclusion The new direct antiviral agents (sofosbuvir, daclatasvir and simeprevir) are effective and safe regarding glomerular filtration rate in patients with normal renal function. However, a meticulous monitoring of kidney function is mandatory during the course of these medications to early detect any untoward side effects. Moreover, such studies will yield beneficial data about the renal safety of these drugs if it could be performed on a larger scale of patients.

Clinical Outcomes After Treatment With Direct Antiviral Agents: Beyond The Virological Response in Patients With Previous HCV-Related Decompensated Cirrhosis

Background In HCV-infected patients with advanced liver disease, the direct antiviral agents (DAAS)-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with DAAs from the French ANRS CO22 HEPATHER cohort. Methods We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response (SVR) and its clinical benefits Results 559 patients met the identification criteria, of which 483 received DAA and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39·7 (IQR: 22·7–51) months. After adjustment for multivariate analysis, exposure to DAAs was associated with a decrease in all-cause mortality (HR 0·45, 95% CI 0·24–0·84, p = 0·01) and non-liver-related death (HR 0·26, 95% CI 0·08–0·82, p = 0·02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The SVR was 88%. According to adjusted multivariable analysis, SVR achievement was associated with a decrease in all-cause mortality (HR 0·29, 95% CI 0·15–0·54, p < 0·0001), liver-related mortality (HR 0·40, 95% CI 0·17–0·96, p = 0·04), non-liver-related mortality (HR 0·17, 95% CI 0·06–0·49, p = 0.001), liver transplantation (HR 0·17, 95% CI 0·05–0·54, p = 0.003), and hepatocellular carcinoma (HR 0·52, 95% CI 0·29–0·93, p = 0·03). Conclusion Treatment with DAAS is associated with reduced risk for mortality. Thus, DAA treatment should be considered for any patient with HCV-related decompensated cirrhosis.

Metabolic Evaluation in Patients With Hepatitis C Treated With Direct Antiviral Agents

Epidemiological data clearly indicate a link between hepatitis C virus (HCV) and altered glucose homeostasis.Objective: To evaluate the response of treatment with direct antiviral agents (DAAs) on metabolic variables of patients with hepatitis C.Methods: Observational, cross-sectional study in a sample of patients with hepatitis C starting therapy with DAAs followed on the hepatology division of Federal University of Rio de Janeiro State. Data were collected in two stages: before the start of therapy and between 12 and 52 weeks after obtaining the sustained virological response.Results: In the baseline assessment of the 97 patients selected, 19.3% were obese, 38.6% were overweight, 50% were hypertensive, 43.8% were pre-diabetic, 12.5% were diabetic, 31.2% were dyslipidemic, and 21.8% had metabolic syndrome. There was an increase in total cholesterol and LDL levels (p &lt; 0.001), and a non-significant reduction in blood glucose, glycated hemoglobin, insulin, and HOMA-IR levels after treatment. In the post-treatment, there was a reduction in fibrosis (p = 0.016), with a reduction in the levels of GGT, AST, and ALT (all with p &lt; 0.001), as well as in the FIB4 and APRI scores (both with p &lt; 0.001) and in the degree of fibrosis evaluated by elastography represented in kPa (p = 0.006). The blood glucose level was higher in patients with steatosis (p = 0.039) after treatment. There was a positive pre-treatment correlation between the degree of fibrosis (kPa) and FIB4 (r = 0.319, p = 0.004), APRI (r = 0.287, p = 0.010), and the NAFLD score (r = 0.275, p = 0.016).Conclusion: Patients with hepatitis C had a high prevalence of metabolic disturbance in the pre-treatment phase, but the therapy did not show beneficial effects, especially on glucose metabolism.