Publications by authors named "Kosh Agarwal"
Background And Aims: The aim of this systematic literature review (SLR) was to examine outcomes and associated predictors following nucleos(t)ide analog (NA) treatment cessation in adult patients with chronic hepatitis B virus infection.
Methods: The SLR was conducted according to PRISMA methodology. All included studies were quality assessed using appropriate scales or checklists.
Article Synopsis
- * This research analyzed microRNA profiles in plasma samples from various patient groups, finding that specific microRNAs (miR-24 and miR-27a) could differentiate between serious and less severe cases of liver disease.
- * The study suggests that miR-24 and miR-191, linked to inflammation and liver injury, could serve as important indicators of poor outcomes in liver disease, highlighting the need for more research on these microRNAs as potential biomarkers and treatment targets.
Background & Aims: Chronic hepatitis D (CHD) is the most severe form of chronic viral hepatitis, with a high risk of developing hepatocellular carcinoma (HCC) and liver-related mortality. Risk stratification is needed to guide HCC surveillance strategies and to prioritize treatment with antiviral agents.
Methods: We conducted a multicenter retrospective cohort of anti-hepatitis D virus (HDV)-positive individuals managed at sites in the Netherlands and the United Kingdom.
Background: In two phase 3 studies, tenofovir alafenamide (TAF) showed non-inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB).
Aims: Here, we report the studies' final 8-year results.
Methods: CHB patients (hepatitis B e antigen [HBeAg]-negative and HBeAg-positive) were randomised (2:1) to double-blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open-label (OL) TAF through year 8.
Article Synopsis
- MAFLD (Metabolic Associated Fatty Liver Disease) is the main cause of chronic liver problems, and it's super common in people with diabetes and obesity; around 70% of them can have it.
- This study wanted to find out how much diabetic patients know about MAFLD and how things like their ethnic backgrounds and habits affect their health.
- Out of the diabetic patients checked, over half had fat in their liver, but only about 31% knew about MAFLD, and 69% of those with serious liver issues had never even heard of it before.
Background: Phase 3 studies in patients with chronic hepatitis B have shown tenofovir alafenamide to have non-inferior efficacy to tenofovir disoproxil fumarate, with improved renal and bone safety. We conducted this study to evaluate the safety and efficacy of switching to tenofovir alafenamide in participants with chronic hepatitis B and renal or hepatic impairment.
Methods: This open-label, multicentre, phase 2 study was done in eight countries or territories at 30 sites.
Background & Aims: Functional cure for chronic hepatitis B (CHB) requires finite treatment. Two agents under investigation with the goal of achieving functional cure are the small-interfering RNA JNJ-73763989 (JNJ-3989) and the capsid assembly modulator JNJ-56136379 (JNJ-6379; bersacapavir).
Methods: REEF-2, a phase IIb, double-blind, placebo-controlled, randomized study, enrolled 130 nucleos(t)ide analogue (NA)-suppressed hepatitis B e-antigen (HBeAg)-negative patients with CHB who received JNJ-3989 (200 mg subcutaneously every 4 weeks) + JNJ-6379 (250 mg oral daily) + NA (oral daily; active arm) or placebos for JNJ-3989 and JNJ-6379 +active NA (control arm) for 48 weeks followed by 48 weeks off-treatment follow-up.
Background & Aims: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs).
Methods: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171).
Purpose: Tenofovir alafenamide (TAF) delivers the active metabolite more efficiently to target cells compared with tenofovir disoproxil fumarate (TDF). Recent studies suggest that TAF is efficacious in treatment naïve individuals who are co-infected with HBV/HIV and may have superior effects on HBV e antigen (HBeAg) seroconversion in this setting. The primary objective of this study was to explore the feasibility of switching from TDF to TAF in HBV/HIV co-infection.
View Article and Find Full Text PDFHarnessing the power of hepatitis B screening programmes: the I REACH OUT model.
Lancet Gastroenterol Hepatol
January 2024
Background & Aims: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown.
Methods: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain.
Nucleos(t)ide analogs are the cornerstone of treatment against hepatitis B virus; however, they have no direct effect on its transcriptional template (ie, covalently closed circular DNA) and so functional cure is rarely achieved. Over recent years, there has been a significant improvement in our understanding of the viral life cycle and its mechanisms of immune evasion. In this review article, we will explore novel therapeutic targets, discuss the latest data from clinical trials, and highlight future research priorities.
View Article and Find Full Text PDFArticle Synopsis
- - The study investigates how two antiviral treatments, tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), influence the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).
- - The results showed that patients treated with TAF had a significantly lower risk of HCC compared to those treated with TDF, with a Standard Incidence Ratio (SIR) of 0.32 versus 0.56, also highlighting that those without cirrhosis had a better risk profile.
- - Overall, both treatments reduced HCC risk in CHB patients, especially in those without cirrhosis, and many patients
Article Synopsis
- Patients who stop nucleos(t)ide analogue therapy for chronic hepatitis B risk viral rebound and severe liver flare-ups, requiring close monitoring.
- A study of 475 HBeAg-negative patients found that higher levels of both hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA 24 weeks after stopping treatment are linked to a greater risk of clinical relapse and lower chances of HBsAg loss.
- The study suggests that low levels of HBsAg and HBV DNA at follow-up can predict better outcomes, indicating potential criteria for determining the suitability of patients for finite therapy in hepatitis B treatment.
Introduction: The results from 2 phase 3 studies, through 2 years, in chronic hepatitis B infection showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. We report updated results through 5 years.
Methods: Patients with HBeAg-negative or HBeAg-positive chronic hepatitis B infection with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years.
Article Synopsis
- The study aimed to assess mortality rates in patients treated for hepatitis C using modern interferon-free, direct-acting antivirals and compare them to the general populace.
- A total of 21,790 patients treated between 2014 and 2019 were analyzed, categorized by liver disease severity, with follow-up ending either at death or by the end of 2019.
- Results showed a 7% mortality rate during follow-up, with deaths primarily from drug-related issues, liver failure, and liver cancer, and overall mortality rates significantly exceeded those of the general population, especially for patients with more advanced liver disease.
Article Synopsis
- The study investigates how pretreatment HBV DNA levels affect outcomes after stopping nucleotide analogue (NUC) therapy for chronic hepatitis B.
- Data were collected from 757 HBeAg-negative patients predominantly from Asia, analyzing their relapse rates and chances of HBsAg loss based on their HBV DNA levels before treatment.
- Results show that lower pretreatment HBV DNA (<20,000 IU/ml) significantly decreases the risk of clinical relapse and increases the likelihood of HBsAg loss, indicating that some patients may not need retreatment after NUC cessation.
Introduction: Liver transplantation (LT) remains integral to the management of end-stage chronic liver disease (CLD). However, referral thresholds and assessment pathways remain poorly defined. Distance from LT centre has been demonstrated to impact negatively on patient outcomes resulting in the development of satellite LT centres (SLTCs).
View Article and Find Full Text PDFChronic hepatitis B virus disproportionately affects migrant communities in high-income countries, reflecting increased migration from sub-Saharan Africa. Chronic hepatitis B virus is endemic in sub-Saharan Africa, yet the natural history of chronic infection experienced by patients remains incompletely understood, with evidence of variability across genotypes and regions within sub-Saharan Africa. Clinical guidelines recommending treatment thresholds are not specific to sub-Saharan African patients and are based on natural history studies from Western Pacific Asian countries.
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