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По меньшей мере 600 тысяч человек, инфицированных вирусом гепатита В (HBV), ежегодно умирает во всем мире вследствие цирроза печени и гепатоцеллюлярной карциномы. В настоящее время эффективность противовирусной терапии HBV-инфекции ограниченна, поэтому основной целью лечения является предотвращение прогрессирования болезни печени, а не полная эрадикация HBV. При этом особое внимание уделяется не только исследованию новых препаратов, но также оптимизации существующих и поиску новых стратегий лечения хронического гепатита В (ХГВ). В связи с этим множество научных исследований посвящено взаимосвязи между генотипами HBV, прогрессированием ХГВ и эффективностью лечения. Известно о существовании 10 генотипов HBV (A-J), которые по-разному влияют на естественное течение заболевания, ответ на противовирусную терапию и развитие медикаментозной резистентности. Индивидуализированный подход к лечению HBV-инфекции с определением генотипа HBV может позволить лучше спрогнозировать развитие заболевания и оптимизировать стратегию лечения. В данном литературном обзоре обобщены результаты научных исследований, посвященных изучению влияния генотипов HBV на противовирусную терапию хронического вирусного гепатита В пегилированным интерфероном и нуклеозид(тид)ными аналогами.

Інфекція, спричинена вірусом гепатиту В (HBV), як і раніше, залишається глобальною проблемою охорони здоров’я і характеризується високим рівнем захворюваності та смертності. У процесі реплікації вірусу накопичуються численні мутації, які протягом філогенезу призводять до появи генотипів і субгенотипів HBV. На сьогодні налічується 10 різних генотипів HBV (A-J). Вони мають різне географічне поширення з досить вираженим переважанням тих чи інших генотипів залежно від регіону. В Україні, як і в інших європейських країнах, відзначається переважання генотипів A і D. Велика кількість досліджень вказує на те, що генотип HBV впливає на природний перебіг захворювання, схильність до хронізації, ймовірність сероконверсії HBeAg і відповідь на терапію пегільованим інтерфероном альфа. У даному літературному огляді узагальнені результати наукових досліджень, присвячених вивченню впливу генотипів HBV на природний перебіг захворювання. Наводяться дані про географічне поширення генотипів HBV в Україні та світі, аргументується важливість визначення генотипів HBV з точки зору їх впливу на перебіг та наслідки HBV-інфекції.

Hepatitis B virus (HBV) infection is one of the main causes of morbidity and mortality worldwide. Most children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by a high viral replication and a low-inflammation phase of infection, with normal or only slightly raised aminotransferases. Although a conservative approach in children is usually recommended, different therapies exist and different therapeutic approaches are possible. The main goals of antiviral treatment for children with chronic HBV infection are to suppress viral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma, although these complications are rare in children. Both United States Food and Drug Administration (US-FDA) and European Medicines Agency (EMA) have approved interferon alfa-2b for children aged 1 year and older, pegylated interferon alfa-2a and lamivudine for children aged 3 years and older, entecavir for use in children aged 2 years and older, and adefovir for use in those 12 years of age and older. Tenofovir disoproxil fumarate is approved by EMA for children aged 2 years and older and by US-FDA for treatment in children aged 12 years and older. Finally, EMA has approved the use of tenofovir alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of age. This narrative review will provide the framework for summarizing indications to antiviral therapy in the management of chronic HBV infection in children and adolescents.

Standard treatment of hepatitis delta virus (HDV) infection remains pegylated-interferon alfa (peg-IFN?) in most centers, which is not only associated with rather low efficacy but several adverse events. Hepatitis B core-related antigen (HBcrAg) is linked to intrahepatic covalently closed circular DNA levels and has previously been suggested as response predictor in IFN-based treatment of hepatitis B virus (HBV) mono-infection. This study aimed to investigate the value of HBcrAg in the management of patients with HBV/HDV co-infection undergoing peg-IFN? treatment. The Hep-Net-International-Delta-Hepatitis-Intervention Trial-2 study included 120 patients co-infected with HBV/HDV. Patients were treated for 96 weeks with peg-IFN? and either tenofovir or placebo. Ninety-nine patients with HDV-RNA results 24 weeks after end of treatment (FU24) were included in this analysis, of whom 32 patients (32.3%) had undetectable HDV RNA at FU24. HBcrAg was measured at baseline, week 12, 24, 48, 96, and FU24. HBcrAg levels showed no significant correlation with HDV RNA but were significantly linked to treatment outcome. HBcrAg levels < 4.5 log IU/mL at baseline, week 24, and week 48 had high negative predictive value (NPV) for achieving undetectable HDV RNA at FU24 (81.8%, 87.1% and 95.0%, respectively). Similarly, HBcrAg levels at week 96 were significantly higher in patients with viral relapse until FU24 (3.0 vs. 3.63 log IU/mL; P = 0.0089). Baseline, week 24, and week 48 HBcrAg levels were also associated with the likelihood of achieving HBsAg level < 100 IU/mL at FU24 (HBcrAg < 3.0 log IU/mL: NPV 91.7%, 90.4% and 92.3%, respectively). Test statistics improved when combining HBcrAg with additional viral and clinical parameters. Conclusion: HBcrAg is linked to treatment response to peg-IFN? in patients with HBV/HDV co-infection and could be a promising marker to determine treatment futility., Fujirebio Europe; Gilead Sciences; F. Hoffmann?La Roche; HepNet Study House

Sustained virological response (SVR) to the treatment of recurrent HCV in liver transplant recipients has excellent clinical outcomes; however, little is known about the effects on allograft histology. The study aimed to assess the histology of the allograft liver. In this single-center, retrospective cohort study, patients with recurrent hepatitis C (HCV) in allograft liver who were cured with antiviral therapy between 2010 and 2016 were identified. Biopsies were reviewed by two liver pathologists blinded to the treatment and SVR status. Paired analysis was performed to compare pre- and post-treatment histological features. Of the 62 patients analyzed, 22 patients received PEGylated interferon/ribavirin (IFN) therapy, while 40 patients received direct-acting antiviral agents (DAA). The mean age was 57 years, 24% were female, and 79% were Caucasian. RNA in situ hybridization testing for HCV and HEV was negative in all the tested patients. Significant reduction in the inflammatory grade of post-treatment biopsy specimens was noted in all subjects (n = 57; p

BackgroundRecurrent respiratory papillomatosis is a potentially life-threatening condition characterised by the growth of exophytic lesions within the larynx and trachea. The principal aim of management is maintenance of an adequate airway by surgical debulking. Several adjuvant therapies have been used to varying effect to reduce the burden of this disease and increase the interval between debulking procedures. The most severe cases present in children aged under three years, who are therefore most likely to need adjuvant therapies. The current evidence base on adjuvant treatments relating to children who present aged under three years has been reviewed.MethodsA literature review of articles in Cochrane, PubMed and Embase databases was carried out. Given the rarity of the condition in this age group, all the literature relates to case reports and case series.Results and conclusionThe following adjuvant therapies have been used in children who presented under three years of age: quadrivalent human papilloma virus vaccine, intralesional cidofovir, pegylated interferon, alpha-interferon, cimetidine and cetuximab.

Polycythemia vera (PV) is a relatively indolent myeloid neoplasm with median survival that exceeds 35 years in young patients, but its natural history might be interrupted by thrombotic, fibrotic, or leukemic events, with respective 20-year rates of 26%, 16%, and 4%. Current treatment strategies in PV have not been shown to prolong survival or lessen the risk of leukemic or fibrotic progression and instead are directed at preventing thrombotic complications. In the latter regard, two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors). All patients require phlebotomy to keep hematocrit below 45% and once-daily low-dose aspirin, in the absence of contraindications. Cytoreductive therapy is recommended for high-risk or symptomatic low-risk disease; our first-line drug of choice in this regard is hydroxyurea but we consider pegylated interferon as an alternative in certain situations, including in young women of reproductive age, in patients manifesting intolerance or resistance to hydroxyurea therapy, and in situations where treatment is indicated for curbing phlebotomy requirement rather than preventing thrombosis. Additional treatment options include busulfan and ruxolitinib; the former is preferred in older patients and the latter in the presence of symptoms reminiscent of post-PV myelofibrosis or protracted pruritus. Our drug choices reflect our appreciation for long-term track record of safety, evidence for reduction of thrombosis risk, and broader suppression of myeloproliferation. Controlled studies are needed to clarify the added value of twice- vs once-daily aspirin dosing and direct oral anticoagulants. In this invited review, we discuss our current approach to diagnosis, prognostication, and treatment of PV in general, as well as during specific situations, including pregnancy and splanchnic vein thrombosis.

Background: For Interleukin 28b Single nucleotide poly-morphism (SNP) rs8099917, the favourable T allele is asso-ciated with a higher SVR after PEG-IFN alpha/RBV therapy while the G allele is a risk factor for non-response. Aim of Study: To assess the value of Interleukin 28b (SNP) rs8099917 as a predictor of SVR. Patients and Methods: This study is a retrospective con-trolled study and was performed on a total number of 240 patients who were treated by PEG-IFN alpha/RBV for 48 weeks and (SNP) rs8099917 was done for the all patients. Results: TT genotype was more prevalent in SVR group than TG and GG genotypes. Conclusion: IL-28b single nucleotide polymorphism (SNP) rs8099917 is a strong pretreatment predictor of response to pegylated interferon and ribavirin therapy in egyptian patients chronically infected with HCV genotype 4.

Background and Aims Recent case series and retrospective studies have raised concerns that patients who receive direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection are at increased risk of developing varicella-zoster virus infection (VZV reactivation). We investigated the relationship between DAA treatment and VZV reactivation by analyzing pooled participant-level data from 37 clinical trials of DAA agents. Methods We obtained demographic, adverse event, and laboratory data from 13,816 participants in 37 clinical trials submitted to the Food and Drug Administration for approval of DAA agents for treatment of HCV infection. Participants received DAAs (n = 12,249), placebo (n = 997), pegylated interferon (n = 243), or a combination of DAAs and pegylated interferon (n = 327). Occurrence of VZV reactivation was identified using systematically reported adverse event data. HCV virologic response was evaluated by measurement of HCV RNA. Results VZV reactivation occurred in 9.9 cases per 1000 person-years of DAA treatment (95% CI, 6.8–14.0 per 1000 person years) and 13.8 cases per 1000 person-years of placebo (95% CI, 3.5–37.5 per 1000 person years). No participants in the pegylated interferon or combination DAA and pegylated interferon groups experienced VZV reactivation. Within the placebo-controlled trials there was no significant difference in VZV reactivation between DAA treatment and placebo. VZV reactivation was associated with age older than 40 years, female sex, and HIV coinfection. We did not find an association between time of virologic response and time to VZV reactivation. Conclusion In an analysis of data from 37 trials, we found no evidence for an association between DAA treatment for HCV infection and increased risk of VZV reactivation.

Introduction Hepatitis B virus (HBV) infection is associated with the onset of several major liver diseases. Inactive hepatitis B surface antigen (HBsAg) carriers (IHCs) may be successfully treated with PEGylated interferon-α2b (PEG-IFNα2b)-based antiviral therapy; however, studies on this treatment have been insufficient. In this study, we evaluated the efficacy and safety of PEG-IFNα2b treatment in IHCs. Methods Nineteen IHCs were treated with subcutaneous PEG-IFNα2b (180 μg/week) for 48 weeks (treatment group). Patients were followed up for 24 weeks after treatment discontinuation. Twenty untreated control patients were observed for 72 weeks (control group). HBsAg clearance (HBsAg

Ropeginterferon alfa-2b is a novel mono-pegylated human recombinant interferon (IFN) with the addition of N-terminal proline covalently attached by a 40-kDa polyethylene (peg) moiety. The present study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) profiles and safety of the product in healthy Chinese. Forty subjects were enrolled and treated with a single subcutaneous injection of either 180 mcg peg-IFN alfa-2a or 90, 180, and 270 mcg ropeginterferon alfa-2b. The mean Tmax of ropeginterferon alfa-2b was 92–141 h and the elimination half-life was 78–129 h. Dose-related, non-proportional increase in ropeginterferon alfa-2b exposure was observed, which was higher than for peg-IFN alfa-2a. The PD parameters were similar between each dose level of ropeginterferon alfa-2b. The mean Tmax of β2-microglobulin ranged from 118 to 132 h after a single dose of ropeginterferon alfa-2b. The average Emax was 3 mcg/ml in all dose levels and the mean AUEC0–t ranged from 1608 to 1775 h/mcg/ml. The TEAEs were comparable among each treatment group and no death nor drug-related SAE was reported. Ropeginterferon alfa-2b is safe and well tolerated after a single subcutaneous injection up to 270 mcg in healthy Chinese. www.chinadrugtrials.org.cn , CTR20190451.

This work explores the application of a physiologically structured population (PSP) framework in modeling hepatitis C virus (HCV) kinetics. To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated interferon, ribavirin, and telaprevir. By including both intracellular and extracellular processes of the HCV lifecycle, the model provided a description of the treatment effect on the intracellular HCV lifecycle. Combining PSP models with a nonlinear mixed effects approach in a single model permits a natural inclusion of the direct‐acting antiviral effect on intracellular processes, which can then be integrated with the viral kinetics within the host while accounting for the interindividual variability between patients. This should allow an exploration of the treatment effect within the entire chronic HCV‐infected population.

Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to

Objective: Silymarin is a natural extract from milk thistle (Silybum marianum), a natural herb that contains flavonoids. Silymarin also has anti-inflammatory properties and lipid peroxidation effects on human hepatocytes. It has also been used for the treatment of acute alpha-amanitin poisoning and chronic hepatitis C infection. Chronic Hepatitis D virus (HDV) infection is a severe health problem leading to fibrosis and hepatocellular carcinoma. Patients with chronic HDV infection can be treated with Peg-IFN with lower treatment success. Most patients with chronic HDV are unable or unwilling to use interferon (IFN)-based treatment due to liver cirrhosis. Our objective was to establish the long-term clinical outcomes with silymarin for interferon-experienced chronic HDV patients. Materials and Methods: We studied ten patients from one centre with interferon who experienced chronic HDV, of which 8 had cirrhosis, and 2 had chronic hepatitis who received HDV treatment with silymarin 600 mg/day after a median period of 12 months. Information collected included demographic, clinical, virologic, and outcomes data. MELD and Child-Pugh (CP) scores were also obtained. Friedman test was used to evaluate the laboratory parameters during the study period. Results: 10 chronic HDV patients (median age 54 yrs, six female, all of them previous null responders to Peg-IFN with mildly decompensated cirrhosis [CP 7 (range 6-11), MELD 11 (range 6-20] were followed for 12 months from the start of silymarin 600 mg/day. There was no decompensation of both MELD and CP scores among patients at the end of therapy. In addition, no patients stopped silymarin treatment early due to side effects. At the end of treatment, there was no significant change in prothrombin time (p= 0.949), AST (p=0.662) and AFP (p=0.983) levels and platelets counts (p=0.988) compared to the pre-treatment period (all p>0.005). Finally, HDV-RNA suppression was seen in all patients at the end of treatment (p=0.009). Conclusions: In the light of the presented data, silymarin seems to be effective in treating chronic HDV infection. Further research is needed for validation. The study is ongoing with a collection of data on sustained viral response.

CA Extern Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B surface antigen (HBsAg) seroconversion and inactivation of covalently closed circular DNA (cccDNA) in establishing functional cure were examined. Archived serum from the REP 401 study was analyzed using the Abbott ARCHITECT HBsAg NEXT assay (Chicago, IL), Abbott research use–only assays for HBsAg immune complexes (HBsAg ICs), circulating HBV RNA, and the Fujirebio assay for hepatitis B core-related antigen (HBcrAg; Malvern, PA). HBsAg became < 0.005 IU/mL in 23 participants during NAP exposure, which persisted in all participants with functional cure. HBsAg IC declined during lead-in TDF monotherapy and correlated with minor declines in HBsAg. Following the addition of NAPs and pegIFN, minor HBsAg IC increases (n = 13) or flares (n = 2) during therapy were not correlated with HBsAg decline, hepatitis B surface antibody (anti-HBs) titers, or alanine aminotransferase. HBsAg IC universally declined during follow-up in participants with virologic control or functional cure. Universal declines in HBV RNA and HBcrAg during TDF monotherapy continued with NAP + pegIFN regardless of therapeutic outcome. At the end of therapy, HBV RNA was undetectable in only 5 of 14 participants with functional cure but became undetectable after removal of therapy in all participants with functional cure. Undetectable HBV RNA at the end of therapy in 5 participants was followed by relapse to virologic control or viral rebound. Conclusion: Anti-HBs-independent mechanisms contribute to HBsAg clearance during NAP therapy. Inactivation of cccDNA does not predict functional cure following NAP-based therapy; however, functional cure is accompanied by persistent inactivation of cccDNA. Persistent HBsAg loss with functional cure may also reflect reduction/clearance of integrated HBV DNA. Clinicaltrials.org number NCT02565719.

The coronavirus 2019 (COVID-19) pandemic has resulted in 168 million cases and about 3.5 million deaths (as of May 26, 2021) during the last 18 months. These 18 months of the COVID-19 pandemic have been characterized by phases or waves of new cases, the emergence of new variants of the deadly virus, and several new complications. After providing emergency approval to several drugs and adherence to several public health measures with frequent full and partial lockdowns, the incidence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could not be contained till now on a global basis. Although prophylactic vaccines have inspired optimism, the scarcity of vaccines and several vaccine-related regulations indicate that the vaccine's benefit would not be reaching the people of developing countries anytime soon. In the course of our clinical practice, we used pegylated interferon (Peg-IFN) in 35 patients with chronic liver diseases (CLD), and we found that only two of them were infected with SARS-CoV-2 that was mild in nature. These two patients with CLD have a mild course of disease cured without any specific therapy. Patients with CLD are usually immune-compromised. However, three CLD patients remained free of SARS-CoV-2 although they had COVID-19 patients among their family members. Next, we accomplished two studies for assessing the immune-modulatory capacities of Peg-IFN, 1 and 12 injections following administration of Peg-IFN. The data revealed that peripheral blood mononuclear cells (PBMCs) of Peg-IFN-administered CLD patients produced significantly higher levels of some cytokines of innate immunity in comparison with the cytokines produced by PBMC of CLD patients before Peg-IFN intake. The pattern of cytokine responses and absence of infection of SARS-CoV-2 in 33 of 35 CLD patients represent some preliminary observations indicating a possible role of Peg-IFN in patients with CLD. The study may be extended to other chronic infections and cancers in which patients receive Peg-IFN. The role of Peg-IFN for pre- or postexposure prophylaxis in the acquisition of SARS-CoV-2 infection and influencing the natural course of COVID-19 remains to be clarified. How to cite this article Akbar SMF, Mahtab MA, Aguilar JC, et al. Role of Pegylated Interferon in Patients with Chronic Liver Diseases in the Context of SARS-CoV-2 Infection. Euroasian J Hepato-Gastroenterol 2021;11(1):27–31.

Enteral tubes are necessary for certain patients; however, medication absorption can be affected by this route of administration potentially resulting in decreased efficacy. All first-line treatments for Hepatitis C Virus (HCV) infection are only available as tablets and may have decreased absorption if administered via an enteral tube. This report describes the first case of a pegylated interferon and ribavirin treatment-experienced patient who successfully achieved HCV cure after 12 weeks of elbasvir/grazoprevir administered via percutaneous gastrostomy tube. We further review the available pharmacokinetic and clinical literature regarding administration via enteral feeding tubes for all first-line direct-acting antivirals (DAAs). The literature suggests that crushed administration can be considered for DAAs in patients with gastric access. However, caution should be exercised in patients with extragastric enteral tubes and in those with altered gastrointestinal tract anatomy.

Hepatitis delta virus (HDV) infection is a defective virus requiring hepatitis B virus (HBV) for its complete replication cycle. HDV is a small hepatotropic RNA virus and around 15 to 25 million people worldwide are living with chronic hepatitis delta (CHD) infection. However, the prevalence of HDV may be underestimated, and screening is frequently insufficient. HDV infection remains endemic in several regions including Central and West Africa, the Mediterranean basin, the Middle East, Eastern Europe, Northern Asia, certain areas of Southeast Asia and the Amazon basin of South America. The best preventive strategy to decrease HDV infection is to improve coverage of the prophylactic HBV vaccine. HDV infection may occur by HBV-HDV co-infection or superinfection, and the latter is usually more severe. CHD is associated with a higher risk of cirrhosis and hepatocellular carcinoma (HCC) compared to HBV mono-infection. Pegylated interferon alpha (PEG-IFNα) therapy is limited by moderate effectiveness (around 20%) and its adverse effects. The entry inhibitor, bulevirtide (BLV, Hepcludex® ), which was recently approved in Europe at a dose of 2 mg in sub-cutaneous injection per day, is indicated for the treatment of CHD in adult patients with compensated liver disease and positive HDV viremia. BLV can be administrated in monotherapy or in combination with PEG-IFNα. Nucleos(t)ide analogues can be used in combination for underlying HBV infection. The optimal treatment duration has not yet been determined and treatment should be continued if a clinical benefit is observed. There are other promising therapies such as IFN lambda (IFNλ) (immunomodulator), lonafarnib (prenylation inhibitor) and nucleic acid polymers (Inhibitors of HBsAg release). In this review, we will present an update on CHD and future promising treatments.

Interferon (IFN) is a multifaceted immunomodulator that is effective against many diseases, including chronic hepatitis B and chronic hepatitis C infection. IFN defends against viral infection, but may also cause various side effects, such as ulcerative colitis (UC). Herein, we present a case of UC triggered by pegylated interferon alpha-2b (PEG-IFN-α-2b) therapy in a patient with concurrent chronic hepatitis B (CHB) infection. The diagnosis was based on typical clinical symptoms, colonoscopy findings, colonic mucosal biopsy, and histopathology. Accordingly, treatment with mesalazine was initiated without stopping PEG-IFN-α-2b. Fortunately, UC relieved gradually without compromising the effects of treatment. Simultaneously, we conducted a literature review of previously published case reports on the side effect of UC in patients with underlying chronic hepatitis. Various reactions have been reported, including induction, exacerbation, and no change. This is the first report of UC triggered by PEG-IFN-α-2b in a CHB patient. We recommend that physicians pay attention to the rare side effect of UC during administration of PEG-IFN-α-2b. Mesalazine can relieve UC with sustained use of PEG-IFN-α-2b.

In the pilot NCT01935089 trial, we tested whether pegylated interferon alpha2b (Peg-IFN-α2b) with antiretroviral therapy (ART) was safe and could impact HIV and immune measures in blood and in gut-associated lymphoid tissue (GALT). Twenty HIV-1(+) ART-suppressed individuals received 1 μg/kg/week Peg-IFN-α2b with ART for 20 weeks, with intermediate 4-week analytical ART interruption (ATI). Safety, immune activation, HIV viral load and integrated HIV DNA in blood, and HIV RNA and DNA in gut biopsies were measured. A total of 7/20 participants experienced grade 3–4 adverse events, while 17/20 participants completed the study. Of the 17 participants who completed the study, 8 remained suppressed during ATI, while all 17 were suppressed at end of treatment (EoT). As expected, treatment increased activation of T and natural killer (NK) cells and IFN-stimulated molecule expression on monocytes in periphery. While circulating CD4(+) T cells showed a trend for a decrease in integrated HIV DNA, GALT showed a significant decrease in HIV-1 RNA(+) cells as measured by in situ hybridization along with a reduction in total HIV DNA and cell-associated RNA by EoT. The observed decrease in HIV-1 RNA(+) cells in GALT was positively associated with the decrease in activated NK cells and macrophages. This study documents for the first time that 20 weeks of immunotherapy with Peg-IFN-α2b+ART (inclusive of a 4-week ATI) is safe and results in an increase in blood and GALT immune activation and in a significant decrease in HIV-1 RNA(+) cells in GALT in association with changes in innate cell activation.

Myeloproliferative neoplasms are a common cause of splanchnic vein thrombosis, which causes significant morbidity and mortality. Indefinite anticoagulation is the mainstay of therapy, and vitamin K antagonists (VKAs) are routinely used since hematologists have the most experience with this drug class. The role of direct oral anticoagulants (DOACs) is promising, but still undergoing evaluation. Cytoreduction with hydroxyurea or pegylated interferon is often used when cytosis is present, but their roles are yet to be defined when the complete blood count is normal. Janus kinase (JAK) inhibition may have a complementary role in reducing splenomegaly and portal hypertension.

Objective: The purpose behind this study was to determine the frequency of erectile dysfunction in patients receiving pegylated interferon and ribavirin for the treatment of chronic hepatitis C. Study Design: Prospective observational study. Setting: Department of Gastroenterology and Hepatology, Medical Unit III, Services Hospital, Lahore. Period: Six months from 10st July 2017 to 9th January 2018. Materials and Methods: We have evaluated a total of 130 patients through a consecutive sampling technique who were admitted or visited Out-Patient-Department (OPD) with an underlying diagnosis of hepatitis C virus infection and advise to take anti viral regime (Pegylated interferon and ribavirin combination therapy) for HCV treatment and followed after 12 weeks and 24 weeks for erectile dysfunction. Results: A total of 130 patients with HCV infection were included. The overall mean age of the patients was 37.4±9.6 years. The overall frequency of erectile dysfunction was 83.07%. Among them, equal percentage of patients at 12 and at week 24 did not have erectile dysfunction (N = 76, 58.5%). While severe erectile dysfunction was surprisingly more common at week 12 (14.61%, N = 19) than at week 24 (13.07%, N = 17) of treatment. Significant association of severe erectile dysfunction was only observed at week 12 in age group 40 – 60 years (p

Background Direct-Acting agents (DAAs) target and inhibit essential viral replication proteins. They have revolutionized the treatment of Hepatitis C virus (HCV) infection reaching high levels of sustained virologic response. However, the detection of basal resistance-associated substitutions (RASs) to DAAs in naïve patients could be important in predicting the treatment outcome in some patients exhibiting failures to DAA-based therapies. Therefore, the aim of this work was to evaluate the presence of RASs as minority variants within intra-host viral populations, and assess their relationship to response to therapy on a multiple times relapser patient infected chronically with HCV. Case presentation A male HCV infected-patient with a genotype 1a strain was evaluated. He had previously not responded to dual therapy (pegylated interferon-α plus ribavirin) and was going to start a direct-acting agent-based therapy (DAAs). He showed no significant liver fibrosis (F0). Viral RNA was extracted from serum samples taken prior and after therapy with DAAs (sofosbubir/ledipasvir/ribavirin). NS5A and NS5B genomic regions were PCR-amplified and the amplicons were sequenced using Sanger and next-generation sequencing (NGS) approaches. RASs were searched in in-silico translated sequences for all DAAs available and their frequencies were determined for those detected by NGS technology. Sanger sequencing did not reveal the presence of RASs in the consensus sequence neither before nor after the DAA treatment. However, several RASs were found at low frequencies, both before as well as after DAA treatment. RASs found as minority variants (particularly substitutions in position 93 within NS5A region) seem to have increased their frequency after DAA pressure. Nevertheless, these RASs did not become dominant and the patient still relapsed, despite perfect adherence to treatment and having no other complications beyond the infection (no significant fibrosis, no drug abuse). Conclusions This report shows that some patients might relapse after a DAA-based therapy even when RASs (pre- and post-treatment) are detected in very low frequencies (

Background The progress of liver diseases may not stop after viral eradication. This study aimed to provide data on long-term prognosis of patients with hepatitis C virus (HCV) infection who underwent pegylated interferon plus ribavirin (PR) regimen and achieved a sustained virological response 24 weeks post-treatment (SVR24). Methods Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up. Baseline characteristics were profiled. The incidence of hepatocellular carcinoma (HCC), progression of liver disease (increase in liver stiffness or occurrence of decompensated complication), and HCV recurrence was all monitored. The accumulative and annualized incidence rates (AIRs) of these adverse events were analyzed, and the risk factors were also examined. Results In total, 151 patients reached a median follow-up time of 103 weeks. Among them, two had an incidence of HCC during the surveillance with AIR of 0.68% (95% CI: 0.00-1.63%). Six patients showed progression of liver disease with AIR of 2.05% (95% CI: 0.42%-3.68%). Three patients who had risky behaviors encountered HCV reinfection. The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients, including HCC and progression of liver disease (AIR: 6.17% vs. 1.42%, P = 0.039). Conclusions The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period, but the risk level was low. Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones. HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.

Hepatitis C is the liver disease caused by the Hepatitis C virus (HCV) which can lead to serious health problems such as liver cancer. In this research work, the non‐linear model of HCV having three state variables (uninfected hepatocytes, infected hepatocytes and virions) and two control inputs has been taken into account, and four non‐linear controllers namely non‐linear PID controller, Lyapunov Redesign controller, Synergetic controller and Fuzzy Logic‐Based controller have been proposed to control HCV infection inside the human body. The controllers have been designed for the anti‐viral therapy in order to control the amount of uninfected hepatocytes to the desired safe limit and to track the amount of infected hepatocytes and virions to their reference value which is zero. One control input is the Pegylated interferon (peg‐IFN‐α) which acts in reducing the infected hepatocytes and the other input is ribavirin which blocks the production of virions. By doing so, the uninfected hepatocytes increase and achieve the required safe limit. Lyapunov stability analysis has been used to prove the stability of the whole system. The comparative analysis of the proposed nonlinear controllers using MATLAB/Simulink have been done with each other and with linear PID. These results depict that the infected hepatocytes and virions are reduced to the desired level, enhancing the rate of sustained virologic response (SVR) and reducing the treatment period as compared with previous strategies introduced in the literature.

Hepatitis D virus (HDV) is a dependent virus that relies on hepatitis B virus for its replication and transmission. Chronic hepatitis D is a severe form of viral hepatitis that can result in end stage liver disease. Currently, pegylated interferon alpha is the only approved therapy for chronic HDV infection and is associated with significant side effects. Liver transplantation (LT) is the only treatment option for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis due to coinfection with HDV. As LT for HDV and hepatitis B virus coinfection is uncommon in the United States, most data on the long-term impact of LT on HDV are from international centers. In this review, we discuss the indications and results of LT with treatment options in HDV patients.

Background:: Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease, with chronically infected making up approximately 1% of the global population. Of those infected, 70% (55-85%) will develop chronic HCV infection. Chronic HCV infection causes substantial morbidity and mortality, with complications including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and eventually death. Objective:: Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct-acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects. Methods:: We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug-drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation. Results:: We present a comprehensive overview of specific direct-acting antiviral metabolism and drug-drug interaction issues in different settings. Conclusion:: Despite its complex pharmacokinetics and the possibility of drug-drug interactions, direct-acting antivirals are highly efficacious in providing viral clearance, which is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with tight control of immunosuppressive therapy.

Purpose: To present a patient with Rosai-Dorfman Disease (RDD), a histiocytic proliferative disorder typified by lymphadenopathy with rare ocular manifestations, who developed panuveitis that responded to pegylated interferon.Methods: Descriptive case report of a patient with RDD with multi-organ involvement including ocular manifestations including bilateral panuveitis with choroidal masses.Results: A 54-year-old African American woman with known systemic RDD of the breast, lung, and gastrointestinal tract presented with panuveitis with choroidal masses in both eyes. Her systemic and ocular disease initially responded well to oral and topical steroid therapy. Later, however, her systemic disease progressed with multiple muscular and bony lesions. Systemic therapy was switched to pegylated interferon, a cytokine with antiviral, antitumor and immunomodulatory activity. After 14 months of therapy with pegylated interferon, the patient's systemic and ocular disease stabilized.Conclusion: Rosai-Dorfman disease may be complicated by panuveitis and choroidal masses that may respond to pegylated interferon with stabilization of systemic and ocular manifestations. A multi-disciplinary approach is essential given the unique diagnostic and management challenges of RDD.

Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients. Methods Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg–IFN–α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24). Results SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg–IFN–α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively. Conclusion Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg–IFN–α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.

Background The causal link of sustained virologic response (SVR) with outcome has been challenged. With improved SVR rates with direct-acting antivirals (DAAs), the benefit of SVR would be expected to diminish if the association with outcome is not causal. Methods Data were collected for patients starting treatment with interferon (IFN) or DAAs between June 2006 and December 2016. To control for disease severity, criteria for the IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial determined IFN-eligibility. Clinical events were decompensation, hepatocellular carcinoma, liver transplantation, and all-cause mortality. Results In 1078 IDEAL-eligible patients, 1306 treatments occurred (52% IFN, 49% DAAs). Cirrhosis was present in 30% DAAs vs 21% IFN (P Conclusions In IFN-eligible patients, SVR is more commonly achieved with DAAs and confers a similar clinical benefit as in those treated with IFN. The reduced event-rate with DAAs compared to IFN, despite similar disease severity, confirm that SVR alters prognosis leading to improved clinical outcomes.

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg

The pegylated interferon plus ribavirin combination therapy has been used as the primary treatment for chronic hepatitis C (CHC) but fails to produce a sustained viral response (SVR) in many patients. In recent years, the treatment of CHC has been rapidly changing because of the introduction of direct-acting antivirals (DAAs), which have a high cure rate. However, retreatment of patients after failure of the first DAA therapy is difficult. We report two rare cases of CHC that showed acquired SVR with other DAA combinations after failure to daclatasvir and asunaprevir.

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The study aimed to evaluate the efficacy of pegylated interferon (Peg-IFN) alfa-2a treatment for seroclearance of HBs antigen (HBsAg) in HBe antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. This retrospective study investigated 16 HBeAg-negative CHB patients who received Peg-IFN alfa-2a weekly for 48 weeks. Thereafter, the patients were followed-up for 48 weeks after the end of therapy. The following criteria were also used for inclusion: HBV-DNA

Background. To explore the role of natural killer (NK) cells in the process of hepatitis B virus (HBV) clearance and whether their phenotype is related to antiviral treatment outcome in chronic hepatitis B (CHB) patients. Method. We performed a single-center prospective cohort study to analyze changes of NK cells at weeks 12 and 24 from baseline in CHB patients who received PEGylated-interferon- (PEG-IFN-) α-2a versus entecavir. The frequencies of NK, CD56bright, CD56dim, IFNAR2+, NKp46+, NKp46bright, and NKp46dim NK cells and mean fluorescence intensity (MFI) of receptors NKp46 and IFNAR2 on the surface of NK cells were measured. Subgroup analyses were performed by comparing treatment responders versus nonresponders with aforementioned parameters in each group. Results. In PEG-IFN-α-treated patients, posttreatment CD56bright NK cell frequency increased, but CD56dim NK cell frequency decreased. Additionally, receptor NKp46 and IFNAR2 expression enhanced. In entecavir-treated patients, although NK cell frequency increased, CD56bright and CD56dim NK cell frequencies and IFNAR2 expression did not differ between baseline and posttreatment. In subgroup analyses, posttreatment CD56bright NK cell frequency and IFNAR2 expression significantly increased in PEG-IFN-α responders from baseline, while changes were absent in PEG-IFN-α nonresponders and entecavir treatment responders. Among patients with HBV viremia after entecavir therapy, NK cell frequency significantly increased, whereas NKp46bright and IFNAR2+ NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline. Conclusions. In CHB patients, PEG-IFN-α treatment significantly enhanced NK cell frequency and function when compared to entacavir. Positive treatment responses to either interferon or entecavir were associated with NK cell function improvement. This trial is registered with clinical trial registration no. NCT03208998.