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EASL releases Clinical Practice Guideline for the management of HBV

AMSTERDAM — The European Association for the Study of the Liver presented five new clinical practice guidelines for the diagnosis and management of various liver diseases at the International Liver Congress, including recommendations for the management of hepatitis B.

“Hepatitis B virus infections are major health threats that affect about 240 million individuals worldwide,” Frank Tacke, MD, PhD, member of the Clinical Practice Guidelines panel and EASL governing board member, said in a press release from the congress. “The updated EASL guidelines integrate the latest scientific advances on diagnosis and therapy of hepatitis B, thereby providing clear guidance to clinicians and patients for the management of this potentially life-threatening disease.”

Assessment of chronic HBV

In the new guideline, several previously defined states of chronic HBV have been designated into one of five phases. While all patients should be assessed for serum HBeAg, HBV DNA and alanine aminotransferase levels, the phases of chronic HBV are not necessarily sequential and patients may fall into an indeterminate gray area of chronic HBV phase. Management should be individualized.

While HBV genotype is not necessary in the initial evaluation, it may be useful for selecting patients to be treated with IFN for the probability of response to IFN therapy and the risk of hepatocellular carcinoma.

Comorbidities, including alcoholic, autoimmune, metabolic liver disease with steatosis or steatohepatitis; coinfection with hepatitis D, hepatitis C and HIV; and other causes of chronic liver disease should be systematically excluded from assessment.

Recommended endpoints of therapy include inducing long-term suppression of HBV DNA levels and HBeAg loss with or without anit-HBe seroconversion in chronic hepatitis patients, biochemical response defined as ALT normalization, and HBsAg loss with or without anti-HBs seroconversion.

“Patients who are not candidates for antiviral therapy should be monitored with periodical assessments of serum ALT and HBV DNA levels as well as for liver fibrosis severity by noninvasive markers,” the researchers wrote. “Patients with HBeAg-positive chronic HBV infection who remain untreated should ideally have ALT determinations at least every 3 months, HBV DNA determinations every 6 to 12 months and assessment of liver fibrosis every 12 months.”

Treatment strategies

There are two main treatment options for chronic HBV: nucleos(t)ide analog (NA) therapy or pegylated IFN (PegIFN).

NAs approved in Europe for HBV treatment include lamivudine, Hepsera (adefovir dipivoxil, Gilead), Tyzeka (telbivudine, Novartis), which are associated with a low barrier to HBV resistance; and Baraclude (entecavir, Bristol-Myers Squibb), Viread (tenofovir disoproxil fumarate, Gilead) and tenofovir alafenamide, which are associated with a high barrier to HBV resistance.

For patients with treatment-naive chronic hepatitis, the recommendation is for long-term administration of a potent NA with high barrier to resistance, regardless of the severity of liver disease. Patients under effective long-term NA therapy, especially those with cirrhosis, should remain under surveillance for HCC.

NA therapy should be discontinued after confirmation of HBsAg loss, with or without anti-HBs seroconversion and can be discontinued in non-cirrhotic HBeAg-positive chronic hepatitis patients who meet the following criteria: stable HBeAg seroconversion, undetectable HBV DNA and completed at least 12 months of consolidation therapy.

PegIFN therapy should be limited to patients with mild to moderate chronic hepatitis, potentially including selected patients with compensated cirrhosis but no portal hypertension. All patients undergoing PegIFN therapy should be followed regularly for full blood count, ALT, thyroid-stimulating hormone, serum HBV DAN and HBsAg levels. Patients who achieve virologic response should remain under long-term follow-up. Patients with HBeAg-positive chronic hepatitis should also have regular assessments for HBeAg and anti-HBe.

Special patient groups

The guideline offers specific recommendations for patients coinfected with HIV, HDV or HCV; patients with acute HBV; children; healthcare workers; pregnant patients; and dialysis and renal transplant patients.

Treatment of HCV with direct-acting antivirals may reactivate HBV; patients who meet the standard criteria for HBV treatment should receive NA therapy. Acute HBV is often resolved without treatment; however, severe acute HBV patients should be monitored closely. HBV is typically mild in children and most children do not meet standard treatment indications; for those who meet treatment criteria, the guideline recommends Baraclude, Viread, tenofovir alafenamide and PegIFN. In general, screening for HBsAg in the first trimester for pregnant patients is strongly recommended.

Future treatment options

Regarding the future of HBV treatment and potential cure, the researchers advise that due to the nature of HBV DNA’s integration into the host genome, a cure may not be feasible. However, in looking forward, combinations of antiviral therapy and immune modulatory therapy will likely be needed to achieve a considered cured state.

“Given the focused drug discovery effort and the potential of a future ‘cure’ strategy, it is important to be cognizant, when considering the current clinical management of [chronic hepatitis] patients, of the potential evolution of therapy in HBV,” the researchers wrote. “Patients who are willing to participate and/or are in phases of the disease that are not eligible for therapy within the current guidelines may be considered for clinical trial participation.” – by Talitha Bennett

References:

European Association for the Study of the Liver, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.03.021

Disclosure: Please see the full guideline for the researchers’ relevant financial disclosures.