A case of acute exacerbation of chronic hepatitis C during the course of adrenal Cushing's syndrome

A 50-year-old woman with adrenal Cushing’s syndrome and chronic hepatitis C developed an acute exacerbation of chronic hepatitis C before adrenectomy. After administration of Glecaprevir/Pibrentasvir was started, her transaminase levels normalized promptly and a rapid virological response also was achieved. Then laparoscopic left adrenectomy was performed safely.

VIROLOGICAL RESPONSES OF VELPATASVIR/SOFOSBUVIR IN PATIENTS WITH HCV GENOTYPE 3

BACKGROUND & OBJECTIVE: The role of Velpatasvir/Sofosbuvir in the treatment of hepatitis C virus type 3 infection is evaluated in terms of virologic responses. i.e Rapid Virological Response (RVR) End of treatment response (ETR) and Sustained virological response (SVR 12). METHODOLOGY: This was a descriptive case study conducted in Liver OPD of Benazir Bhutto Hospital during 01 November 2018 to 30 April 2019 , in which 100 patients of HCV were enrolled, all of them had HCV genotype 3 infection. Every patient was treated with combination of Velpatasvir/Sofosbuvir 100mg/400 mg Once Daily as part of treatment regimen of HCV infection for 12 weeks. Pre-treatment HCV RNA QUANTITATIVE PCR was done, which was repeated on 4, 12 weeks of treatment and then 12 weeks post treatment. RESULTS: Among 100 patients, 51 (51%) were male and 49 (49%) were females. Mean age of patients was 43.2 ± 10.4 years (mean ± SD). Mean BMI of enrolled patients was 21.34 ± 2.40 kg/m2. 33% patients were cirrhotic while 67% were non cirrhotic. 53% patients were treatment experienced while 47% were treatment naïve. Rapid Virological Response (RVR) was achieved in 92%, End of treatment response (ETR) was achieved in 96%, while Sustained Virological response (SVR12) was achieved in 99% patients. The results were stratified according to age, gender and BMI. There was no effect of these parameters on the final results. CONCLUSION: Virological response (RVR, ETR, SVR12) of Velpatsvir /Sofosbuvir and Ribavirin is encouraging.

Immunomodulation of CXCL10 Secretion by Hepatitis C Virus: Could CXCL10 Be a Prognostic Marker of Chronic Hepatitis C?

Chemokine (C-X-C motif) ligand (CXCL)10 and other CXCR3 chemokines are involved in the pathogenesis of acute and “chronic hepatitis C virus (HCV) infection” (CHC). Here, we review the scientific literature about HCV and CXCL10. The combination of circulating CXCL10 and single nucleotide polymorphisms (SNPs) in IL-28B can identify patients with acute HCV infection most likely to undergo spontaneous HCV clearance and those in need of early antiviral therapy. In CHC, the HCV and intrahepatic interferon- (IFN-) γ drive a raised CXCL10 expression by sinusoidal endothelium and hepatocytes, thereby inducing the recruitment of CXCR3-expressing T cells into the liver; thus, CXCL10 plays an important role in the development of necroinflammation and fibrosis. Increased CXCL10 was significantly associated with the presence of active vasculitis in HCV-associated cryoglobulinemia, or with autoimmune thyroiditis in CHC. Pretreatment CXCL10 levels are predictive of early virological response and sustained virological response (SVR) to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy. The occurrence of SNPs adjacent to IL-28B (rs12979860, rs12980275, and rs8099917), and CXCL10 below 150 pg/mL, independently predicted the first phase viral decline and rapid virological response, which in turn independently predicted SVR. Directly acting antiviral agents-mediated clearance of HCV is associated with the loss of intrahepatic immune activation by IFN-α, associated by decreased levels of CXCL10. In conclusion, CXCL10 is an important marker of HCV clearance and successful therapy in CHC patients. Whether CXCL10 is a novel therapeutic target in CHC will be evaluated.

Efficacy of Atorvastatin Plus Pegylated Interferon and Ribavirin Versus Pegylated Interferon and Ribavirin Alone in Chronic Hepatitis C Patients with Genotype-3a

Chronic hepatitis C infection has created a huge burden of disease causing serious healtheffects. The combination therapy used to treat hepatitis C virus (HCV) infection includes Pegylatedinterferon and Ribavirin. As cholesterol biosynthesis plays a pivotal role in HCV replication, the use ofvarious statins has been associated with higher sustained viral response Objective: To compare theefficacy of atorvastatin plus pegylated interferon and ribavirin versus pegylated interferon and ribavirinalone in patients of chronic hepatitis C with genotype-3a Methods: This Randomized controlled trial wasconducted at outpatient department, Mayo Hospital Lahore for six months i.e. May to November 2017.After ethical approval, 60 patients of ages 25 to 55 years of either gender with chronic hepatitis C withgenotype 3a were included in the study. Informed consent was taken from all patients. Then patients wererandomly allocated into two groups “A” and “B” using random number table. Patients in Group A receivedstandard of care treatment for chronic hepatitis C i.e. pegylated interferon and ribavirin while the patientsin Group B also received tab atorvastatin along with the standard treatment. Patients were follow up for 4week. Blood samples were collected and HCV RNA detection. All this information were entered inproforma Results: In standard therapy group, the mean age of patients was 39.50±8.39years. Inatorvastatin plus standard therapy group, the mean age of patients was 34.30±6.78years. In standardtherapy group, there were 25 (83.3%) males and 5 (16.7%) females. In atorvastatin plus standard therapygroup, there were 16 (53.3%) males and 14 (46.7%) females. After 4 weeks, Rapid Virological Response(RVR) was achieved in 4 (13.3%) patients in standard therapy group while in 14 (46.7%) in atorvastatin plusstandard therapy group. The difference was significant (p<0.05) Conclusions: Atorvastatin incombination with Pegylated interferon and ribavirin have better efficacy as compared to Pegylatedinterferon & ribavirin alone in chronic hepatitis C-3a.

Impact of IL28B genetic variant's and viral genotype on treatment outcome of hepatitis C infected patients

Introduction: Viral genotype and variation in host genes involved in the immune response may predict the treatment response in patients infected with HCV. The present study was designed to determine the distribution pattern of HCV and host genotypes in Chronic Hepatitis C (CHC) patients and their association with virological response and other risk factors. Methodology: Two hundred and fifty (n = 250) HCV positive patients were included in the study. HCV and Interleukin 28B (IL28B) genotyping was carried out by PCR-RFLP. Results: Viral genotype 3 was the predominant genotype seen in 187 (74.8%) patients. Wild genotype predominated in rs12979860, rs12980275 and rs8099917 SNP of IL28B gene. A significant difference was found in end stage virological response (EVR) between HCV genotype 1 infected patients with wild and variant genotype for rs12980275 and rs8099917 SNPs respectively (P < 0.05). On multivariate analysis all the SNPs were found to be associated with each other (P < 0.05) with rs12980275 SNP associated with history of Jaundice (P < 0.05). Viral genotype 3 was significantly associated with age (< 50 years) and rapid virological response (RVR) while as viral genotype 1 was significantly associated with history of surgery on multivariate analysis (P < 0.05). Conclusions: The viral genotype and IL28B polymorphisms are important factors to personalize antiviral therapy of patients with CHC.

Role of Direct Antiviral Agents in Treatment of Chronic Hepatitis C Infection in Renal Transplant Recipients

Background. Since the introduction of direct antiviral agents (DAAs), morbidity of HCV has considerably decreased but still no guidelines have been formulated in renal transplant recipients (RTRs). We studied efficacy and tolerability of direct antiviral agents in RTRs.Methods. This prospective observational study was conducted at Army Hospital Research & Referral, Delhi, from June 2016 to May 2017. Forty-five HCV infected RTRs with stable graft function were included.Results. Median time between renal transplantation and the start of anti-HCV therapy was 36 months (1–120 months). The majority (66.7%) were infected with genotype 3. Baseline median HCV RNA level was 542648 IU/ml (1189–55028534 IU/ml). Sofosbuvir-Ribavirin combination (24 weeks) was given to 30 patients including 3 cirrhotics, Ledipasvir-Sofosbuvir combination to 8 patients, and Daclatasvir-Sofosbuvir combination to 7 patients, including 2 cirrhotics. Rapid virological response was observed in 29 patients treated with Sofosbuvir/Ribavirin, all 8 patients on Sofosbuvir/Ledipasvir, and all 7 patients on Sofosbuvir/Daclatasvir. End treatment response and sustained virological response (12 weeks) were achieved in all patients irrespective of genotype or treatment regimen. Decrease in mean HCV RNA level and transaminase level was statistically significant (p<0.01). Ribavirin was significantly associated with anaemia (p=0.032).Conclusions. DAA regimens are well tolerated and highly efficacious. Response to DAA is good irrespective of genotype, drug combination, initial HCV RNA level, age or sex of patient, or graft age. However, Sofosbuvir/Ledipasvir and Sofosbuvir/Daclatasvir combination is preferable.