Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat

Zachou, Kalliopi; Sarantopoulos, Alexandros; Gatselis, Nikolaos; Vassiliadis, Themistoklis; Gabeta, Stella; Stefos, Aggelos; Saitis, Asterios; Boura, Panagiota; Dalekos, George Ν.

doi:10.4254/wjh.v5.i7.387

Cited by 35 publications

(24 citation statements)

References 19 publications

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“…These findings indicate that rituximab may have a role in the treatment of at least refractory AIH. Rare, but serious, side effects have been reported with rituximab administration, including late‐onset neutropenia, interstitial pneumonitis, HBV reactivation, intestinal perforation and possible multifocal leucoencephalopathy …”

Section: Management and Outcomementioning

confidence: 99%

Review article: autoimmune hepatitis - current management and challenges

Zachou

Muratori

Koukoulis³

et al. 2013

Aliment Pharmacol Ther

171

202

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SUMMARY BackgroundAutoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by interface hepatitis, hypergammaglobulinaemia, circulating autoantibodies and a favourable response to immunosuppression. AimTo review recent advancements in understanding aetiopathogenesis, clinical, serological and histological features, diagnostic criteria and treatment strategies of AIH. MethodsPublished studies on AIH extracted mainly from PubMed during the last 15 years. ResultsAutoimmune hepatitis has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations are variable ranging from no symptoms to severe acute hepatitis and only seldom to fulminant hepatic failure. Autoimmune attack is perpetuated, possibly via molecular mimicry mechanisms, and favoured by the impaired control of regulatory T-cells. A typical laboratory finding is hypergammaglobulinaemia with selective elevation of IgG, although in 15-25% of patients -particularly children, elderly and acute cases -IgG levels are normal. Liver histology and autoantibodies, although not pathognomonic, still remain the hallmark for diagnosis. Immunosuppressive treatment is mandatory and life-saving; however, to meet strict response criteria, the conventional therapy with prednisolone with or without azathioprine is far from ideal. ConclusionsAutoimmune hepatitis remains a major diagnostic and therapeutic challenge. The clinician, the hepato-pathologist and the laboratory personnel need to become more familiar with different expressions of the disease, interpretation of liver histology and autoimmune serology. According to the strict definition of treatment response issued by the 2010 AASLD guidelines, many patients are nonresponders to conventional treatment. Newer immunosuppressive agents targeting pathogenetic mechanisms can improve patient management, which needs to be tailored on a case-by-case basis.

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Section: Management and Outcomementioning

confidence: 99%

Review article: autoimmune hepatitis - current management and challenges

Zachou

Muratori

Koukoulis³

et al. 2013

Aliment Pharmacol Ther

171

202

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“…The absence of HBsAg and the presence of anti‐HBs are generally accepted as serological recovery from acute HBV infection. Reactivation of HBV in OBI or RBI patients who received immunosuppressive treatment has been reported . Therefore, HBV replication can persist at low levels in the liver for decades in cases of RBI …”

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confidence: 99%

“…Reactivation of HBV in OBI or RBI patients who received immunosuppressive treatment has been reported. 14,15 Therefore, HBV replication can persist at low levels in the liver for decades in cases of RBI. 16 This study was conducted to determine the prevalence of OBI and RBI in children receiving complete passive-active immunoprophylaxis for HBV and to characterize the clinical course of OBI/RBI and identify the genomic mutations that might be associated with the pathogenesis of OBI in the immunized children.…”

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confidence: 99%

Occult hepatitis B virus infection in immunized children born to carrier mothers

Yokoyama

Kumagai

Takahashi

et al. 2017

Pediatrics International

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“…HBV reactivation may occur as long as 2 years after stopping the immunosuppresive regimen, which suggests that follow up should be extended [Zachou et al 2013]. However, some experts recommend preemptive lamivudine treatment in all patients who are HBsAg -or anti-HBc + who receive monoclonal antibodies (antiCD20, antiCD52), combined regimens for haematological malignancies (fludarabine, allogenic or autologous bone marrow transplantations, hematopoietic stem cell transplantations, induction of acute leukaemias) in patients with antiHBs -if close monitoring is not possible [Mandala et al 2013] or in Asian patients.…”

Section: Preemptive Treatmentmentioning

confidence: 99%

Hepatitis B virus treatment beyond the guidelines: special populations and consideration of treatment withdrawal

Vallet-Pichard

Pol

2014

Therap Adv Gastroenterol

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Abstract:The goal of chronic hepatitis B (CHB) treatment is to improve survival by preventing disease progression to decompensated cirrhosis and hepatocellular carcinoma which is the cause of over 1 million deaths annually. The risk of disease progression is reduced when a sustained reduction of hepatitis B virus (HBV) DNA to undetectable levels and suppression of HBV replication are obtained which can result in regression of liver fibrosis and may even reverse cirrhosis. However, even if HBsAg loss occurs, HBV is not completely eradicated by treatment, and long-term therapy is required in patients who are HBeAg -and HBeAg + who do not maintain off-treatment virological suppression and in those with advanced liver disease. The recently updated European Association of the Study of the Liver (EASL) clinical practical guidelines for HBV have clarified, first, how to treat HBV (interferon or the most potent oral drugs with optimal resistance profiles, i.e. entecavir and tenofovir disoproxil fumarate, should be used as first-line monotherapies); second, who should be treated (CHB in patients with significant liver disease but also patients who are HBsAg + and are receiving immunosuppressive treatment, patients coinfected with HBV and human immunodeficiency virus, mothers who are HBsAg + with high viral load in late pregnancy associated with sero vaccination to reduce the risk of vertical transmission of HBV; and third, when to stop antiviral therapies. The aim of this review was to clarify how to treat HBV and who should be treated, as well as when to stop treatment. Although the answer to these questions is clear for pegylated interferon, it is more debatable for nucleos(t)ide analogues (anti-HBe seroconversion, HBsAg loss or anti-HBs seroconversion with undetectable HBV DNA are clear indications to discontinue treatment but sustained undetectable HBV DNA in patients who are anti-HBe + without significant fibrosis might be another indication).

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Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat

Abstract: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.

Cited by 35 publications

References 19 publications

Review article: autoimmune hepatitis - current management and challenges

Review article: autoimmune hepatitis - current management and challenges

Occult hepatitis B virus infection in immunized children born to carrier mothers

Hepatitis B virus treatment beyond the guidelines: special populations and consideration of treatment withdrawal

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