SM Journal of Hepatitis Research and Treatment

Archive Articles

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The Impact of IL28B Single Nucleotide Polymorphism on Antiviral Response in HCV Genotype 2 or 3

Background and Aim: This study aimed to relate the impact of IL-28B SNP in HCV genotype 2 (GT2) and 3 (GT3) associated with the degree of liver fibrosis, according to Metavir score and sustained virologic response (SVR).

Methods: This cross-sectional study conducted between January 2012 and December 2014, which involved 103 patients treated in the center of application and monitoring of injectable drugs from the city of Rio Grande/ RS-Brazil. The analysis of the region rs12979860 IL-28B, PCR was performed according to the technique of Moreira et al, 2012.

Results: Caucasian patients showed 3.15 times greater chance of having SVR than the non-Caucasian ones (p = 0.046). Patients with higher degrees of fibrosis (F3/F4) obtain lower rates of SVR. Among the GT3, SVR was 84% in patients with lower degrees of fibrosis (F0/F1/F2) and 67.7% in patients with higher degrees of fibrosis. The GT3 showed fibrosis F3/F4 almost twice more than those with GT2 (59.7% versus 33.3%). Patients with a IL-28B CC genotype had about 3.8 times higher chance to present SVR compared to those patients with IL-28B TT genotype. The chance for advanced fibrosis in patients with TT genotype of the IL-28B was 3.6 times higher than in patients with CC genotype.

Conclusions: The results obtained in this study indicate the need of permanent search for predictive response factors to antiviral treatment of genotype 3 patients, especially those with higher degrees of fibrosis, even in the age of direct-acting antivirals.

Deise Machado dos Santos¹, Nayle Maria Oliveira da Silva²*, Rubens Caurio Lobato³, Luanna Elisa Liebscher Vidal⁴, Elisa Moraes Batista⁵, Mateus da Rocha Rodrigues⁶, Carolina Fischer Cunha⁶, Andrea Delfino Torres⁷, Vanusa Pousada da Hora⁸, Andre Felipe Andrade dos Santos⁹ and Ana Maria Barral de Martinez⁸


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A Single-Center Experience with Liver Transplantation from Donation after Cardiac Death

Background and Objective: Liver transplantation (LT) is an effective treatment method for terminal liver disease but is limited by a lack of donors. Donation after cardiac death (DCD) would effectively alleviate this shortage. Here we summarize our experience with LT using DCD in our hospital.

Methods: We retrospectively analyzed the mortality and adverse reactions of 13 patients who underwent LT for terminal liver disease and their donors in our hospital between November 2011 and August 2013.

Results: The surgeries were successful in all 13 cases. The 1-, 2-, and 3-year survival rates were 92%, 85%, and 72%, respectively.

Conclusions: LT from DCD for patients with terminal liver disease will be an effective treatment method.

Jiangfa Li¹#, Shoutang Zhou²#, Zhenghang Li¹#, Jianhua Gong¹, Junyi Wang¹, Jianchao Wang¹, Bo Li¹, Syed Abdul Tahir¹ and Songqing He¹,³*


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A Systematic Review And Meta-Analysis of Ribavirin with Newer Directly Acting Antivirals in the Treatment of HCV

Background: In the current era of interferon free oral Directly Acting Antivirals (DAAs), Ribavirin (RBV) is widely used. A relevant question in focus is the value of RBV to date, from the accrual of data from all clinical studies and real world data. We aimed to assess the efficacy of DAAs in combination with RBV compared with DAAs without RBV, and discuss pertinent literature.

Methods: We identified studies through a systematic review of PubMed, Embase, Clinical Trials.gov, meeting abstracts and a national HCV database repository (HCV Target). We used cumulative random effects meta-analysis to combine effect estimates from the data.

Findings: We included 19 studies that met the inclusion criteria. The meta-analysis of HCV patients comprised data for 9350 patients (DAAs with RBV=3371, DAAs alone=5979). The baseline characteristics were similar between the two groups. In cumulative meta-analysis adjusted for age, sex, previous treatment failure, IL28 beta genotype, and male sex no factor was associated with a statistically significant increase in SVR 12.The use of RBV with DAA for HCV was not associated with a significant increase in SVR 12 rates compared with the use of DAA alone in all patients OR of 0.90 (95% CI 0.53-1.53; p=0.7), in the subgroup of cirrhotic patients OR of 0.99 (95% CI 0.53-1.85; p=0.98), in the subgroup of treatment experienced patients OR of 1.19 (95% CI 0.80- 1.75; p=0.65) and in the subgroup of G3 patients OR of 0.97 (95% CI 0.25-3.71; p=0.96). The adverse effects of RBV appears to be mostly non-fatal but contributes to significant morbidity.

Interpretation: Although the use of RBV with DAAs is common in the era of IFN free therapy, its synergistic effect with DAAs in clinical studies to achieve superior SVR 12 rates remains inconclusive. Therefore the use of RBV with DAAs needs to cautiously reconsidered in all patients with HCV, especially in those at risk for serious adverse events.

Mark M Aloysius¹#, Niraj J Shah²*#, Nimy John³, Ked Fortuzi⁴, Elona Shehi⁴, Robert S Brown⁴ and Patrick P Basu⁴


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HDV Coinfection Rates in Moroccan Chronic Hepatitis B Patients

The infection of Viral Hepatitis D (HDV) is life-threatening due to the chronically infected hepatitis B virus carriers which lead to the sudden acute hepatitis or severe chronic active hepatitis. Thus, an active surveillance of these patients with HDV co-infection is an important step to reduce the risk of hepatitis clinical complications. At present, we aimed to update the Moroccan sero-prevalence for HDV in these individuals and determine the status of hepatitis in chronic HBV carriers.

Methods: A one year follow-up was performed for 280 chronic HBV carriers and all patients were youngadults and adults. The anti-HDV antibodies (Total IgG and IgM Abs), while HBeAg and anti-HBe antibodies were additionally assessed by DiaSorin. The HBV-DNA levels were measured by Cobas Ampliprep Cobas TaqMan 48: KIT CAPA-G/CTM HBV V2.0 72 TESTS CE-IVC. The HDV-RNA detection and/or viral load quantification were performed in France in Avicenne laboratory of virology, as it has been described by Lunel-Fabiani.

Results: Only 2 (0.8%) individuals among chronic HBV infected individuals had been in contact with hepatitis D virus and have anti-HDV antibodies and both were HDV-RNA negative while 278 (99.2%) had a negative serology anti-HDV antibodies. 98% of chronic HBV individuals were HBeAg-negative with very low DNA HBV levels and five patients had “isolated anti-HBc” profile carriers with low DNA HBV levels. Two patients with a positive HBeAg had elevated ALT with higher HBV DNA loads.

Conclusion: A low prevalence of HDV in Moroccan chronic HBV carriers was demonstrated by this study, while 35% of patients with negative HBeAg were established as inactive carriers.

Nadia Kandoussi¹*, Rachid Abi², Jalal Kasouati², Reda Tagajdid², Safae Elkochri², Bouchra Elmchichi², Hicham Elannaz², Nadia Touil² and Saad Mrani²


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Predictors of Sustained Virologic Response and Failure of First DAA Therapy in Chronic Hepatitis C Patients

Telaprevir and Boceprevir were the first US Food and Drug Administration (FDA) approved NS3/4A protease inhibitors of Chronic Hepatitis C infection in 2011. Despite their discontinuation from the US market 3 years after their approval by the US FDA, both protease inhibitors left a great impact in the treatment approach of Chronic Hepatitis C. Both antiviral agents allowed a dramatic improvement in SVR rates compared to the old dual regimen of Pegylated interferon and ribavirin. However, there were associated significant adverse outcomes. Randomized clinical trials may have limited generalizability in terms of efficacy, safety, and tolerability of these drugs in everyday outpatient setting. Our prospective cohort study of 113 Chronic Hepatitis C patients, who were treated outside of a controlled trial, showed different efficacies and safety profiles compared to what was described in controlled trials of Telaprevir and Boceprevir. In addition, our analysis identified no significant predictors of end of treatment response or sustained virologic responses at weeks 12 and 24 following treatment completion. This does not correspond with data from recent studies. Research studies conducted outside of a controlled trial about new chronic hepatitis C therapies that have obtained FDA approval is important as newer antiviral agents are being reviewed by the FDA.

Omar Y Mousa¹*, Chang H Kim², Ly Elaine Pham³, Scott A Zela¹, Chukwuma I Egwim¹ and Victor Ankoma Sey¹


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Determination of Pharmacokinetics and Pharmacodynamics of Lamivudine After Highdoses in Duck Hepatitis B Virus-Infected Pekin Ducks

Purpose: The Duck Hepatitis B Virus (DHBV)-infected Pekin duck model has been shown to be a reference model for the evaluation of anti-HBV treatments. The purpose of the current study was to characterize the pharmacokinetic and pharmacodynamic profiles of lamivudine, a potent nucleoside inhibitor of HBV replication, in DHBV-infected Pekin ducks.

Methods: Lamivudine serum concentrations were measured by LC-ESI-MS/MS following the administration of 80mg/kg IV, 200 mg/kg IM and 480 mg/kg PO of lamivudine to DHBV-infected Pekin ducks. Whereas, DHBV viremia levels were measured by real-time-PCR before, during and after 6-week lamivudine treatment of 40mg/ kg IM daily, or 100 or 200 mg/kg PO daily.

Results: The average apparent total body clearance and volume of distribution of lamivudine were 0.29 L/ hr/kgand0.65 L/kg, respectively. The average area under the concentration-time curve was 318, 661 and 1344 µg.hr/mL for 80mg/kg IV, 200 mg/kg IM and 480 mg/kg PO of lamivudine, respectively. 6-week lamivudine treatment of 100 mg/kg and 200 mg/kg PO were indifferently able to significantly lower DHBV titers compared with control and 40 mg/kg IM groups. However, the latent suppression of DHBV titers after the termination of lamivudine treatment was significantly more in 200 mg/kg PO compared with 100 mg/kg PO.

Conclusions: Our results suggest that the optimum dose of lamivudine against chronic HBV is higher than the current recommended dose in human.

Anwar Anwar-Mohamed¹˒²*, Ahmed A El-Sherbeni², Lesley Poirier³#, Mohammadali Fakheri³#, Amirali Fakheri³, Janelle Johnson³, Darren Hockman³, Deanna M Santer³, Karl Fischer¹˒³, Mohammed A Sarhan³, Ayman El Kadi², D Lorne Tyrrell¹˒³, and Michael Houghton¹˒³