Therapy For Viral Hepatitis Research Articles

Prevalence of hepatitis B among pregnant women in Libreville, Gabon

BackgroundHepatitis B virus (HBV) infection is one of the major public health problems worldwide. In pregnant women, there is a risk of mother-to-child transmission (vertical transmission) of the infection. The contaminated newborn will most often remain a chronic carrier. Gabon is part of the highly endemic area for hepatitis B. This study aims to determine the prevalence of hepatitis B in pregnant women at the Estuaire Regional Hospital of Melen, Libreville, Gabon.Material and methodsThe study was carried out at the Laboratory of the Center Hospitalier Régionale Estuaire Melen (CHREM), over a period of 5 years, from January 2018 to December 2022. It was a retrospective and prospective study ranging from January 2018 to December 2022. For the prospective study, the data was collected in the CHREM Laboratory library, by using registers and filing cabinets. For the prospective study, blood samples were taken and analyzed using Abbott Determine® HBsAg kits and the BioMérieux mini Vidas system. The variables studied were age, HBs status, profession, level of study, and residence. The data collected was entered into an Excel file (Microsoft Office 2016) and analyzed using XLSTAT 2016.4.01 and Epi Info™ 7.2.5 software and expressed as means and percentages.ResultsA total of 1615 pregnant women seen in the CHREM laboratory department were included in the study. Of which, 315 were diagnosed as HBsAg carriers, representing a prevalence of 8.36%. Depending on the year, the highest prevalence was observed in 2019 with 20 positive cases out of 267 women screened, i.e., 9.38%. Depending on the districts, the highest prevalence was found in the Essassa and Plein Ciel districts with 16.43% and 18.18%, respectively. According to the age groups, the highest prevalence was observed in the age group 26–30 with 10.16% (p = 0.075) out of 492 patients screened. Depending on the profession, the prevalence was higher among female students with 21.97% (p = 0.020). According to marital status, unmarried had the highest prevalence with 8.8% (p = 0.064). And according to nationality, women of Gabonese nationality had a higher prevalence with 9.52%.ConclusionAntenatal transmission of HBV is high in Libreville. The inaccessibility of antiviral therapy for viral hepatitis B makes the immunization of mothers and children a priority in Gabon.

Impact of viral hepatitis therapy in multiple myeloma and other monoclonal gammopathies linked to hepatitis B or C viruses.

Subsets of multiple myeloma (MM) and monoclonal gammopathies of undetermined significance (MGUS) present with a monoclonal immunoglobulin specific for hepatitis C virus (HCV), thus are presumably HCV-driven, and antiviral treatment can lead to the disappearance of antigen stimulation and improved control of clonal plasma cells. Here we studied the role of hepatitis B virus (HBV) in the pathogenesis of MGUS and MM in 45 HBV-infected patients with monoclonal gammopathy. We analyzed the specificity of recognition of the monoclonal immunoglobulin of these patients and validated the efficacy of antiviral treatment (AVT). For 18 of 45 (40%) HBV-infected patients, the target of the monoclonal immunoglobulin was identified: the most frequent target was HBV (n=11), followed by other infectious pathogens (n=6) and glucosylsphingosine (n=1). Two patients whose monoclonal immunoglobulin targeted HBV (HBx and HBcAg), implying that their gammopathy was HBV-driven, received AVT and the gammopathy did not progress. AVT efficacy was then investigated in a large cohort of HBV-infected MM patients (n=1367) who received or did not receive anti-HBV treatments and compared to a cohort of HCV-infected MM patients (n=1220). AVT significantly improved patient probability of overall survival (P=0.016 for the HBV-positive cohort, P=0.005 for the HCV-positive cohort). Altogether, MGUS and MM disease can be HBV- or HCV-driven in infected patients, and the study demonstrates the importance of AVT in such patients.

258 Analysis of the Hepatic Microenvironment Before and After Direct-Acting Antiviral (DAA) Therapy for Viral Hepatitis C

OBJECTIVES/GOALS: The effect of the Direct-Acting Antiviral (DAA) on hepatic histopathological features from patients treated for HCV has not been thoroughly evaluated. The goals of this retrospective study were to determines differences between the liver biopsies collected before and after DAA treatment and correlated the histopathology with clinical outcome. METHODS/STUDY POPULATION: Spectral imaging was used to evaluate differences in intrahepatic macrophage (CD68, CD14, CD16, MAC 387, and CD163) and T cell (CD3, CD4, CD8, CD45, and FoxP3) phenotypes in paired liver biopsies collected from the same patient before (n=10) and after (n=10) achieving SVR (Figure 1). Imaging analysis and machine learning algorithms were used to evaluate changes in these key immune cells. We also compared differential gene expression of over 700 genes using RNA isolated from liver biopsies with NanoString. RESULTS/ANTICIPATED RESULTS: Multispectral imaging analysis showed a significant increase of proinflammatory/M1-like (e.g., CD14+) and anti-inflammatory/M2-like macrophage (e.g., CD163+) phenotypes in pre-treatment versus post-treatment biopsies, respectively. Gene expression analysis revealed enrichment of inflammatory (HLA-B, STAT1, CXCL10) and interferon induced-antiviral (ISG15, OAS3, MX1 and IFIT1) genes in the pre-treatment vs the post-treatment group. Cell deconvolution analysis also showed a significant increase of M1-like macrophages in the pre-treatment group when compared to the post-treatment group or controls. Upregulation of genes associated with cell proliferation and differentiation (c-KIT and Fos) was observed in the post-treatment biopsies of patients with persistent inflammatory infiltrates. DISCUSSION/SIGNIFICANCE: Protein and gene expression profiles observed in patients before DAA therapy showed a strong macrophage-mediated inflammatory response against HCV infection in the liver that shifted significantly to a tissue remodeling microenvironment after treatment.

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases.

The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

Potential Therapeutic Targets and Promising Agents for Combating NAFLD.

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is a growing cause of liver cirrhosis and liver cancer worldwide because of the global increases in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. Contrary to the advancements in therapies for viral hepatitis, effective treatments remain unestablished for patients with NAFLD. NAFLD, including NASH, is characterized by steatosis, inflammation, hepatic necrosis, and fibrosis. Despite our understanding of its pathophysiology, there are currently no effective treatments for NAFLD. In this review, we provide an update on the known pathophysiological mechanisms involved in the development of NAFLD and the role of hepatic stellate cells, and summarize the potential therapeutic agents, including natural products, for NAFLD.

Використання лікарських рослин як допоміжна терапія вірусних гепатитів

Вірусні гепатити становлять велику групу інфекційних захворювань людини, що характеризуються переважним ураженням печінки. Лікування вірусних гепатитів є складним завданням і обов’язково передбачає використання клінічних рекомендацій. Питання щодо лікування вірусних гепатитів лікарськими травами вивчається давно. У статті наводяться огляди результатів рандомізованих досліджень, які вивчали ефективність препаратів, що містять лікарські трави, у лікуванні вірусних гепатитів (Yarnell E., Abascal K. та iн). Огляд досліджень було проведено в регістрі контрольованих досліджень гепатобіліарної групи Кокрейн, бібліотеки Кокрейн, MEDLINE, EMBASE, BIOSIS, а також китайських та японських баз даних. Аналіз рандомізованих клінічних досліджень виявив доведену позитивну роль при лікуванні вірусних гепатитів таких лікарських трав: софори японської, розторопші плямистої, солодки, андрографіса волотистого, звіробою звичайного, плодів лимонника китайського, кореня кульбаби лікарської, кореня лопуха великого, кореневищ куркуми довгої, кореня шавлії червонокореневищної та ін. Автори цієї статті рекомендують групи рослин, що використовуються при лікуванні вірусних гепатитів, принципи, а також рецепти зборів лiкарських рослин, методику приготування і рекомендації щодо застосування приготованих препаратів — доза, частота прийому та тривалість фітотерапії для цієї групи пацієнтів. Вказується, на якому етапі захворювання і які трави можна додавати в збір залежно від загального стану та скарг хворого, збудника вірусного гепатиту і результатiв лабораторних дослiджень. Рекомендовано використання лікарських трав тільки як доповнення до основного лікування противірусними препаратами згідно з клінічними рекомендаціями щодо лікування вірусних гепатитів.

A prospective study of direct-acting antiviral effectiveness and relapse risk in HCV cryoglobulinemic vasculitis by the Italian PITER cohort.

Background and AimsMixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium‐term to long‐term period.Approach and ResultsDirect‐acting antiviral–treated cryoglobulinemic patients, consecutively enrolled in the multicentric Italian Platform for the Study of Viral Hepatitis Therapy cohort, were prospectively evaluated. Cumulative incidence Kaplan‐Meier curves were reported for response, clinical deterioration, relapse and relapse‐free survival rates. Cox regression analysis evaluated factors associated with different outcomes. A clinical response was reported in at least one follow‐up point for 373 of 423 (88%) patients with CV who achieved SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A full complete response (FCR) was reached by 164 (38.8%) patients in at least one follow‐up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration, 19 months). In patients who achieved FCR and had an available follow‐up (137 patients) a relapse was observed in 13% and it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24 months, respectively. After achieving SVR, a clinical nonresponse was associated with older age and renal involvement; a clinical deterioration/relapse was associated with high pretreatment rheumatoid factor values, and FCR was inversely associated with age, neuropathy, and high cryocrit levels.ConclusionIn patients with CV, HCV eradication may not correspond to a persistent clinical improvement, and clinical response may fluctuate. This implies an attentive approach to post‐SVR evaluation through prognostic factors and tailored treatment.

Mortality trends in chronic liver disease and cirrhosis from 1981 to 2015 in Taiwan

BackgroundGlobally, the morbidity and mortality rates for chronic liver disease and cirrhosis are increasing. The National Viral Hepatitis Therapy Program in Taiwan was implemented in 2003, but evidence regarding the program’s effect on the trends of mortality for chronic liver disease and cirrhosis is limited.MethodsWe analyzed mortality rates for chronic liver disease and cirrhosis in Taiwan for the period from 1981 to 2015. An autoregressive age–period–cohort model was used to estimate age, period, and cohort effects.ResultsAge-adjusted mortality rates for chronic liver disease and cirrhosis all displayed a flat but variable trend from 1981 to 2004 and a decreasing trend thereafter for both sexes. The age–period–cohort model revealed differential age gradients between the two sexes; mortality rates in the oldest age group (90–94 years) were 12 and 66 times higher than those in the youngest age group (30–34 years) for men and women, respectively. The period effects indicated that mortality rates declined after 2004 in both sexes. Mortality rates decreased in men but increased in women in the 1891–1940 birth cohorts and increased in both sexes in the birth cohorts from 1950 onward.ConclusionsThe National Viral Hepatitis Therapy Program in Taiwan may have contributed to the decrease in mortality rates for chronic liver disease and cirrhosis in adulthood.

From the Editor’s Desk...

From the Editor’s Desk...

Long-term effectiveness of population-wide multifaceted interventions for hepatocellular carcinoma in Taiwan

Taiwan has launched a series of population-wide interventions to prevent hepatocellular carcinoma (HCC) related to hepatitis B and C virus infection since 1984. We took this opportunity to investigate the impact of each intervention on the incidence and case-fatality rate of HCC, and assessed their relative contributions to the overall reduction in mortality during this period. Population-based registry data on HCC mortality and incidence from individuals aged 0 to 84 years between 1979 and 2016 were collected before (Period 1) and after universal hepatitis B vaccination from 1984 (Period 2), universal health care from 1995 (Period 3), and viral hepatitis therapy from 2003 (Period 4). A Bayesian Poisson regression model was used for mortality decomposition analysis to estimate the respective contributions of these interventions to the reduction in age-specific incidence and case-fatality rates. Mortality declined substantially in children, young- and middle-aged groups, but only slightly decreased in the elderly group. The declining trends in mortality were in part explained by incidence reduction and in part by a remarkable decline in case-fatality rate attributed to universal health care. Hepatitis B vaccination led to a 35.9% (26.8% to 44.4%) reduction in incidence for individuals aged 30 years or below, whereas antiviral therapy reduced the incidence of HCC by 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for individuals aged 30-49 years and 50-69 years, respectively. Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups. Since 1984, a series of population-wide interventions have been launched in Taiwan to prevent viral hepatitis-related hepatocellular carcinoma, including a universal hepatitis B vaccination program (from 1984), universal health care (from 1995), and a national viral hepatitis therapy program (from 2004). Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.

Safety and Efficacy of Antiviral Therapy of Chronic Hepatitis C in Chronic Kidney Disease and Hemodialysis Patients

Background and Aims: To assess the efficacy and tolerability of sofosbuvir-based antiviral therapy for viral hepatitis C (HCV) patients with chronic kidney disease and on maintenance hemodialysis.
 Methods: We retrospectively reviewed all treated patients with HCV from January 2015 to November 2020. They were treated either with standard Interferon/Ribavirin or with Sofosbuvir combined to Daclatasvir or to Ledipasvir. We evaluated the sustained virologic response at 12 weeks (SVR12). Data were analyzed using SPSS 20.00.
 Results: Out of 61 patients, the mean age of our patients was 56,8±12,56 years and 42,6% were males. Six patients had eGFR< 60 ml/mn/1,73 m2 (9,8%) and 26 patients were on maintenance hemodialysis (42,6%). The majority had genotype 1 and overall SVR12 was 70,1% with a rate of 75% in the Sofosbuvir-regimen subgroup. The adverse events were minor. On multivariate analysis, genotype, viral load and rapid virologic response were independent factors that significantly predicted treatment success.
 Conclusion: Sofosbuvir-based regimen appears to be safe and efficious in patients with chronic kidney disease and on maintenance hemodialysis, especially in countries with limited resources.

About antiviral effects of vitamin D

Preventing infectious diseases is very important in obstetric and gynaecological practice. Vitamin D is a complex regulator of innate and adaptive immunity. It is known that lack of vitamin D reduces antibacterial and antiviral immunity, stimulates the development of pathologies associated with chronic systemic inflammation. Evidence from evidence-based medicine indicates the importance of using vitamin D preparations to support immunity. The results of fundamental and clinical studies have shown that chronic inflammation and congenital immunity disorders resulting from vitamin D deficiency significantly reduce the body’s resistance not only to tuberculosis, but also to viral hepatitis, acute respiratory infections, papillomavirus and herpesvirus. In addition to a pronounced antibacterial effect, vitamin D is also characterized by its antiviral action. By increasing the expression of interferon-alpha, cathecidine, defensin and antiviral microRNA, vitamin D activates various mechanisms of congenital antiviral immunity. Studies show the need to compensate for vitamin D deficiency for successful therapy of viral hepatitis, respiratory infections, human papillomavirus (HPV) and herpesvirus. In the present article the molecular fundamentals of antiviral action of vitamin D are sequentially considered, as well as the results of fundamental and clinical studies indicating the action of vitamin D against the viruses of hepatitis, herpes, RSV, Epstein-Barr, human papillomavirus, the possibility of using vitamin D in the treatment of these and other viral pathologies is considered. The authors analyzed data on the effect of vitamin D on immunity functions and antiviral protection of the human body.

Report from Hokkaido Chapter Educational Seminar: Greatly Advanced Therapies for Viral Hepatitis

Report from Hokkaido Chapter Educational Seminar: Greatly Advanced Therapies for Viral Hepatitis

The impact of national viral hepatitis therapy program and hepatitis B vaccination program on mortality from acute and chronic viral hepatitis in Taiwan.

In Taiwan, the national hepatitis B virus vaccination program and national viral hepatitis therapy program were implemented to control the infections of hepatitis viruses and their progressive illnesses. Studies have evaluated the impacts of two national health programs on many liver-related diseases, but not on acute and chronic viral hepatitis. The purpose of this study was to evaluate the impact on the mortality of acute and chronic viral hepatitis. Poisson regression models were used to estimate the adjusted rate ratios of the different period groups and corresponding 95% confidence intervals for childhood, adulthood and elderhood, and to estimate the adjusted rate ratios of vaccinated cohorts and corresponding 95% confidence intervals. Compared with period of 2000-2003, the adjusted rate ratios for period groups of 2008-2011 and 2012-2015 reported a significantly increasing risk of acute and chronic viral hepatitis mortality, except for the childhood and female adulthood. For population without vaccination, the adjusted rate ratios of acute and chronic viral hepatitis B mortality were 0.99 (95% CIs 0.88-1.12), 1.30 (95% CIs 1.17-1.45) and 1.42 (95% CIs 1.28-1.55) for periods of 2004-2007, 2008-2011 and 2012-2015, respectively, comparing with unimplemented period of national viral hepatitis therapy program. Compared with 1967-1983 cohorts, the adjusted rate ratio of 1984-2000 cohorts was 0.46 (95% CIs 0.28-0.75), and the adjusted rate ratios were 0.49 (95% CIs 0.28-0.87) and 0.35 (95% CIs 0.11-1.05) for male and female, respectively. This study revealed the significantly higher mortality rates of acute and chronic viral hepatitis during the implemented period of national viral hepatitis therapy program, comparing the unimplemented period. Such ineffectiveness may be attributable to the low coverage rate. The national vaccination program was currently an effective strategy for controlling the mortality of viral hepatitis.

Highlights from the 3rd international HIV/viral hepatitis Co-infection meeting - HIV/viral hepatitis: improving diagnosis, antiviral therapy and access

The International AIDS Society convened the 3rd International HIV/Viral Hepatitis Co-Infection Meeting on 17 July 2016 as part of the pre-conference program preceding the 21st International AIDS Conference held in Durban, South Africa. The meeting brought together a diversity of scientific, technical and community interests to discuss opportunities and challenges for increased prevention, diagnosis and treatment of viral hepatitis in people living with HIV, particularly in low- and middle-income settings.The objectives of the meeting were:To review the latest therapeutic developments in viral hepatitis;To identify challenges such as high cost of medications for hepatitis C virus (HCV) and risk of developing viral resistance, and successes, such as the provision of HCV treatment in community-based settings, movements to reduce drug costs and increasing access, in relation to scaling up diagnosis, screening, antiviral treatment and prevention of viral hepatitis;To advance the agenda for elimination of viral hepatitis as a public health problem.Discussions centred around the six key interventions outlined by the World Health Organization Global Health Sector Strategy on Viral Hepatitis 2016–2021: hepatitis B virus (HBV) vaccination (including birth dose); safe injection practices plus safe blood; harm reduction among people who inject drugs; safer sex practices; hepatitis B treatment; and hepatitis C cure.This article summarizes the main issues and findings discussed during the pre-conference meeting. One of the recommendations from the meeting delegates is universal implementation of birth dose vaccination for HBV without further delay to prevent mother-to-child transmission of infection. There is also the need to implement screening and treatment of hepatitis among pregnant women. A call was made for concerted efforts to be put together by all stakeholders towards addressing some of the structural barriers, including criminalization of drug use, discrimination and stigma that people living with viral hepatitis face. Finally, the need for greater advocacy was highlighted to enable access to therapy of viral hepatitis at lower cost than currently prevails. Implementation of these resolutions will help in achieving the target of eliminating viral hepatitis as a public health threat.

ETIOTROPIC THERAPY OF VIRAL HEPATITIS

Treatment of chronic viral hepatitis is not a fully resolved problem, especially in children. There are no convincing criteria for recovery. The paper presents various schemes used for etiotropic therapy of viral hepatitis at the present stage — interferons and antiviral drugs. For the treatment of hepatitis B, synthetic nucleoside and nucleotide analogues are used as an antiviral therapy, in the case of hepatitis C — ribavirin and protease and polymerase inhibitors. In children, interferon therapy remains important with the use of domestic drugs, including rectal forms of interferon administration (VIFERON®). At the same time, active research is underway to study non-interferon regimens for the treatment of chronic viral hepatitis in pediatric practice, but so far the choice of drugs for non-interferon therapy is limited to individual drugs. With hepatitis B, it is a lamivudine, prescribed from 3 years (the reception of which is accompanied by frequent development of resistance) and — tenofovir (appointed from 12 years). With hepatitis C, ribavirin can be administered from 3 years.

Peginterferon Lambda-1a, a New Therapeutic for Hepatitis C Infection, from Bench to Clinic.

Chronic infection with hepatitis C virus (HCV) is estimated to affect approximately 3% of the world's population and cause 350,000 deaths each year. For a number of years, the standard of care has been combination therapy with recombinant alfa interferons—originally as native proteins but more recently as polyethyleneglycol-modified derivatives—and ribavirin, with the recent addition of an NS3 protease inhibitor for HCV genotype 1. However, therapeutic alfa interferons are associated with a significant burden of treatment-limiting adverse events, including musculoskeletal and influenza-like symptoms, hematologic cytopenias, autoimmune disease, fatigue, and other neurologic events. In 2003, a team at ZymoGenetics (now a fully owned subsidiary of Bristol-Myers Squibb) and a second, independent group simultaneously identified a new class of interferons—the type III lambda interferons—with near-identical activity to the type I alfa interferons in hepatocytes but with an unrelated and less ubiquitous receptor. Subsequent evaluation of the type III interferon system demonstrated antiviral activity against HCV in vitro with limited activity in peripheral blood mononuclear cells and other nonhepatocyte cell types, supporting its development as a potentially better-tolerated therapy for viral hepatitis. Peginterferon lambda-1a (Lambda) is an investigational type III therapeutic agent originally developed at ZymoGenetics that is currently in Phase 3 studies for the treatment of HCV. In this review, we describe the selection of the Lambda molecule and its preclinical and early clinical development, and how the resulting data have helped to establish the differentiated safety profile for Lambda—with fewer influenza-like and musculoskeletal symptoms and less hematologic toxicity than the alfa interferons—that was seen in later studies.

Real life Egyptian experience of efficacy and safety of Simeprevir/Sofosbuvir therapy in 6211 chronic HCV genotype IV infected patients.

Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy. This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12weeks course of daily combination of sofosbuvir (400mg) and simeprevir (150mg). Patients were closely monitored for treatment safety and efficacy. Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%). Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV.

Ly6Chi monocytes regulate T cell responses in viral hepatitis

Viral hepatitis remains a global health challenge despite recent progress in the development of more effective therapies. Although virus-specific CD8+ and CD4+ T cell responses are essential for viral clearance, it remains largely unknown what regulates T cell-mediated viral clearance. Thus, a better understanding of the regulation of anti-viral T cell immunity would be critical for the design of more effective therapies for viral hepatitis. Using a model of adenovirus-induced hepatitis, here we showed that adenoviral infection induced recruitment of Ly6Chi monocytes to the liver in a CCR2-dependent manner. These recruited Ly6Chi monocytes suppressed CD8+ and CD4+ T cell responses to adenoviral infection, leading to a delay in viral clearance. In vivo depletion of Ly6Chi monocytes markedly enhanced anti-viral T cell responses and promoted viral clearance. Mechanistically, we showed that induction of iNOS and the production of NO by Ly6Chi monocytes are critical for the suppression of T cell responses. In addition, a contact-dependent mechanism mediated by PD-1 and PD-L1 interaction is also required for T cell suppression by Ly6Chi monocytes. These findings suggest a critical role for Ly6Chi monocytes in the regulation of T cell immunity in viral hepatitis and may provide new insights into development of more effective therapies for treating viral hepatitis based on targeting the immunosuppressing monocytes.

Long-term clinical observation. viral hepatitis B: from diagnosis to treatment selection in different periods of illness

Therapy for viral hepatitis B at the present stage depends on the stage of the disease, activity of the viral process, the extent of liver tissue fibrosis and concomitant pathological processes. The high level of liver cells fibrosis in combination with viral processes are known to promote the formation of hepatocellular carcinoma. Under our supervision over 5 years there is the patient with HBV infection and high levels of fibrosis: from the acute period ofdiseases till now. Performing long-term antiviral therapy allowed to significantly reduce the level offibrosis, however, despite the prolonged use of modern antivirals, we have twice watched ”viral breakthrough”, that necessitated stopping treatment.