Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge

doi:10.1016/j.jcv.2016.02.026

Journal of Clinical Virology

Volume 78, May 2016, Pages 27-30

https://doi.org/10.1016/j.jcv.2016.02.026 Get rights and content

Highlights

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HBV reactivation occurred in HCV/HBV-coinfected persons during DAAs-based treatment.
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It occurred with various class of DAAs and in HCV genotype 1 or 4-infected patients.
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It occurred independently of the type of HBV infection: chronic, occult or resolved.
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HBV replication increased early during the interferon-free anti-HCV treatment.
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Close monitoring of HBV-coinfection may be warranted during any anti-HCV therapy.

Abstract

Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.

Section snippets

Why this case is important?

Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV), whether patients are treatment-naive or unsuccessfully pre-treated [1].

Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase), allow a rapid HCV clearance and increase rates of sustained virological response. Treatments incorporating only DAAs have superseded most previous regimens containing peginterferon and ribavirin [1].

Recently,

Case description

A HCV/HIV-coinfected 53-year-old man followed since 1988 in the Infectious Diseases Department of the Nice University Hospital presented for re-treatment of HCV genotype 4d infection. He was previously null responder to a bi-therapy incorporating peginterferon and ribavirin. Although liver stiffness was low (transient elastography using FibroScan = 7 kPa), HCV treatment was reconsidered because of cutaneous porphyria. Furthermore, his HIV infection (CDC class C3) was controlled since 2011, with a

Similar and contrasting cases in the literature

Reactivation of hepatitis B is characterized by an abrupt reappearance or rise of HBV DNA levels in the serum of a patient with previously resolved or inactive HBV infection. This increase of HBV replication, or “viral breakthrough”, is often accompanied by a “biochemical breakthrough”, i.e. reappearance of disease activity or a flare of hepatitis in previously inactive or minimal disease [7]. To our knowledge, four cases of HBV reactivation have just been reported in patients infected with

Discussion

Due to their transmission route, triple HCV/HBV/HIV infection can concern the same person. We reported herein HBV reactivation after initiation of DAAs regimen in a HCV genotype 4d/HIV coinfected patient having resolved HBV infection. The typical course of HBV reactivation was observed, with first viral breakthrough and then hepatitis cytolysis induced by the anti-HBV specific immune response (Fig. 1). In HBV/HIV-coinfected patient, HBV reactivation is known because of progressive

Conflict of interest statements

None declared.

Funding

None.

Acknowledgments

Dr C. Laffont and Dr P. Pugliese are kindly acknowledged for their teaching and their valuable advice. The authors would like to acknowledge the work of staff in Department of Virology.

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Cited by (114)

Hepatitis B Reactivation Following Eradication of HCV with Direct-Acting Antiviral Drugs (DAAs) in a Cohort of Patients from Different Institutions in Egypt
2022, Journal of Clinical and Experimental Hepatology
Concerns about HBV reactivation (HBVr) have been raised with the introduction of DAA for HCV treatment. The aim of the study was to assess the risk of HBVr in chronic HCV patients during or after DAA.
A cohort of 166 chronic HCV patients who were treated with SOF-based DAA regimens and initially positive for HBcAb total were evaluated; 10 HBsAg-positive, 156 had past HBV exposure (HBsAg-negative/HBcAb-positive). Laboratory investigations, including liver functions tests, HBV-DNA, LSM by Transient elastography, and ARFI together with serum markers of fibrosis; APRI and FIB-4 were done at baseline and after 12 weeks of DAAs therapy. HBV-DNA levels and liver functions were monitored for assessment of HBVr.
Virological HBVr was diagnosed by ≥ 1 log10 IU/ml HBV-DNA levels in 2/166 patients (1.2%) among the whole HCV cohort, who were initially positive for HBsAg; 20%. Clinical HBVr (>3 folds liver enzyme elevation) was detected in one patient with virological HBVr. Conversely, none of past HBV-infected patients experienced HBVr. All patients achieved SVR12 and had a significant decline in serum transaminases, bilirubin, APRI, and LSM measurements after HCV eradication.
HBVr might be considered after successful eradication of HCV following DAAs therapy, especially among patients who are positive for HBsAg, while past HBV infection does not seem to be a predisposing condition to HBVr.
High hepatitis C treatment uptake among people with recent drug dependence in New South Wales, Australia
2021, Journal of Hepatology
High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence.
HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence.
57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24–2.36), recent incarceration (aOR 1.10; 95% CI 1.01–1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13–1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72–0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69–0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78–0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82–0.98), HBV coinfection (aOR 0.69; 95% CI 0.59–0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84–0.98).
These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination.
To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.
Consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B virus infection (2020)
2020, Gastroenterologia y Hepatologia
La infección por el virus de la hepatitis B (VHB) continúa siendo un problema global de salud pública. La vacunación frente al VHB, introducida en España en la década de 1990, constituye el método más eficaz para reducir la incidencia de la enfermedad. No obstante, la migración procedente de países donde la prevalencia de la infección es alta contribuye a que en nuestro país la tasa esté aún entre el 0,5 y el 1%. El espectro de la enfermedad crónica ocasionada por el VHB es muy variable y abarca desde el portador inactivo a pacientes con hepatitis crónica, cirrosis y carcinoma hepatocelular. A pesar de que en los últimos años no se han producido grandes avances en el desarrollo clínico de nuevos fármacos para el tratamiento de la hepatitis B crónica, los cambios en la epidemiología, en el conocimiento de la historia natural, métodos diagnósticos e indicaciones de tratamiento aconsejan la actualización del documento de consenso de la Asociación Española para el Estudio del Hígado (AEEH) sobre el tratamiento de la infección por el VHB publicado en el año 2012. El documento de la AEEH revisa el tratamiento de la hepatitis B crónica y establece como mejor pauta la administración prolongada de un análogo de nucleós(t)ido con alta barrera genética a la resistencia (entecavir, tenofovir o tenofovir alafenamida). El interferón-pegilado constituye una alternativa en pacientes con enfermedad hepática poco avanzada, pero su aplicabilidad es limitada por su baja eficacia y efectos adversos frecuentes. En todos los pacientes se debe evaluar el riesgo de progresión a enfermedad hepática avanzada y de desarrollo de carcinoma hepatocelular. Determinados subgrupos de pacientes con infección crónica por VHB deben ser incluidos en programas de vigilancia para el diagnóstico precoz de carcinoma hepatocelular, que constituye en el momento actual la principal complicación de la enfermedad.
Hepatitis B virus (HBV) infection remains a global public health problem. HBV vaccination is the most effective tool to reduce the incidence of HBV disease. Despite there has not been new clinical developments for the treatment of chronic hepatitis B in the last few years, changing epidemiology and current insights on natural history, diagnostic tools and therapy indications make necessary an update of the former version of the consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B infection published in 2012. The current document updates the management of chronic hepatitis B. The treatment of choice is the long-term administration of a nucleos(t)ide analogue with high barrier to resistance (entecavir, tenofovir or tenofovir alafenamide). Pegylated interferon may be an option in patients with non-advanced liver disease, but its applicability is limited due to the low efficacy and poor tolerability. All patients must be monitored for the risk of progression to advanced liver disease and development of hepatocellular carcinoma.
New aspects in epidemiological surveillance in relation to viral diseases in haemodialysis
2020, Nefrologia
Pharmacology Update for the Treatment of Hepatitis C Virus
2020, Nursing Clinics of North America
Citation Excerpt :
For this reason, all patients initiating HCV DAA therapy should be assessed for HBV coinfection with HBsAg, hepatitis B surface antibody, and hepatitis B core antibodies testing.29 Confirmation of HBV infection in an HCV/HIV coinfected individual requires additional treatment with an antiretroviral HBV agent.29 HCV infection is linked to 43% increased risk of the development of chronic kidney disease (CKD).30
Efficacy and safety of direct-acting antiviral agent regimens in a real-world cohort of adult Chinese patients with chronic hepatitis C virus infection
2020, Liver Research
To investigate the safety and efficacy of direct-acting antiviral (DAA) regimens in a cohort of Chinese patients with chronic hepatitis C virus (HCV) infection.
A total of 222 adult Chinese patients were enrolled and treated via DAA regimens in accordance with HCV management guidelines. Treatment responses were evaluated 4 weeks after treatment, at the end of treatment (EOT) and 12 weeks post-treatment. Virological responses, biochemical responses, model for end-stage liver disease (MELD) and Child-Pugh (CP) scores were recorded.
A total of 218 patients (98.2%) achieved sustained virological response 12 weeks post-treatment and 4 patients relapsed. The combined number of rapid virological responses for all six regimens was 170/222 (76.6%), and 221/222 (99.6%) had achieved virological responses by the end of treatment. In decompensated cirrhosis patients the baseline mean CP score was 6.8 ± 1.3 and the mean MELD score was 10.1 ± 3.3. Compared with the mean CP score at baseline, the mean score is significantly lower at the end of treatment (5.7 ± 1.3) and 12 weeks post-treatment (5.6 ± 1.0). Estimated glomerular filtration rates did not differ significantly from baseline during the treatment or 12 weeks post-treatment. The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 42/172 (24.4%), and in patients with decompensated cirrhosis it was 8/22 (36.4%). The most frequently reported adverse events were elevated indirect bilirubin, fatigue and rash. There were no cases of serious adverse events, death or treatment discontinuation because of adverse events.
DAA regimens were highly effective and well tolerated irrespective of HCV genotype, cirrhosis, liver or kidney transplantation, hepatocellular carcinoma, HCV/hepatitis B virus co-infection, or renal failure.

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Case reportDirect-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge

Highlights

Abstract

Section snippets

Why this case is important?

Case description

Similar and contrasting cases in the literature

Discussion

Conflict of interest statements

Funding

Acknowledgments

Lancet Lond. Engl.

J. Clin. Virol.

J. Biol. Chem.

J. Hepatol.

Biochem. Biophys. Res. Commun.

J. Hepatol.

Clin. Microbiol. Infect.

Virology

EASL recommendations on treatment of hepatitis C

J. Hepatol.

Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus

Hepatology

Hepatitis B virus reactivation during successful treatment of hepatitis C virus with sofosbuvir and simeprevir

Clin. Infect. Dis.

Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report

J. Med. Case Reports

Case report
Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge