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Corresponding author. This article has been cited by other articles in PMC. Abstract Despite the introduction of new nucleos t ide analogues in recent years, peginterferon is still recommended as a potential first-line treatment option by current practice guidelines for the management of chronic hepatitis B.
Introduction Chronic hepatitis B CHB is one of the most serious and prevalent infectious diseases worldwide. Goals of Antiviral Therapy The ideal outcome of treatment for any chronic infection is eradication of the infectious agent. Open in a separate window. Predictors of Response at Baseline Because treatment with PEG-IFN is expensive and is associated with considerable side-effects, identification of baseline parameters associated with the chance of achieving sustained response has gained attention recently, particularly concerning HBV genotype.
On-Treatment Predictors of Response Despite the availability of baseline predictors of response, considerable uncertainty remains as to whether an individual patient will benefit from PEG-IFN therapy. Predictors of Response at Baseline It is a major challenge to identify HBeAg-negative patients who are likely to benefit from PEG-IFN therapy before treatment is initiated or as early as possible during the treatment course.
On-Treatment Predictors of Response Because baseline predictors of response to PEG-IFN are poorly defined in HBeAg-negative patients, recent studies have focused on the identification of markers allowing on-treatment prediction of response. Potential Treatment Strategies Combination Therapy Combination therapy theoretically offers advantages compared to monotherapy, including a combination of immunomodulatory and antiviral effects, synergistic antiviral effects, and a higher barrier toward resistance.
Disclosure Dr. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author s and source are credited. Contributor Information Vincent Rijckborst, Email: ln. Hepatitis B virus infection.
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Pegylated interferons for chronic hepatitis B. Peters, MD, on June 14, Risk of end-stage liver disease and cancer increases with ongoing inflammation and HBV viremia in adults. Fibrosis can be reversible, and treatment can decrease fibrosis progression.
At present, chronic HBV infection can be controlled but not cured. Reactivation can occur even in patients who have lost hepatitis B surface antigen HBsAg. With regard to serologic markers in HBV infection, HBsAg indicates acute or chronic infection and is the first serologic marker to appear.
Infection is considered chronic if it persists for greater than 6 months. Its absence can indicate absence of ongoing replication; absence can also indicate mutations in the pre-core region of the e-antigen that prevent production of e-antigen. It is detectable after immunity conferred by HBV vaccination, and is occasionally seen in chronic carriers.
Anti-HBe antibody anti-HBe generally indicates that virus is no longer replicating. However, it can be found in patients with HBeAg mutations e-antigen-negative patients who have active disease. Management according to serologic findings can be summarized as follows. Patients who are anti-HBs-positive and anti-HBc-positive have evidence of past infection; in these cases, infection is latent but can reactivate in immunocompromised patients, with re-emergence of HBsAg.
Patients who are only anti-HBs-positive are immune or vaccinated. The European Association for the Study of the Liver EASL guidelines 2 differentiate chronic infection from chronic hepatitis, as shown in Table; in essence, chronic infection is having virus present in serum, and chronic hepatitis is present when there is evidence of liver damage.
ALT levels are normal in those with chronic infection and elevated in those with chronic hepatitis. In brief, patients with chronic infection have normal ALT level and no or low-level liver damage, whereas those with chronic hepatitis have elevated HBV DNA and ALT levels and evidence of ongoing necroinflammatory disease in the liver.
Treatment is directed at this latter group. Adapted from the European Association for the Study of the Liver guidelines. It should be noted that older patients may have cirrhosis with normal ALT levels. If ALT level increases, closer monitoring should be resumed and the potential need for therapy discussed.
Asian men aged 40 years or older, Asian women aged 50 years or older, sub-Saharan African people older than 20 years, and those with family history of HCC should be monitored for HCC. It should be noted that an elevated ALT level can be found in patients with HBV infection due to metabolic syndrome and non-alcoholic fatty liver disease.
Patients with HBV infection plus obesity or metabolic syndrome have a higher risk of cirrhosis than those with HBV infection alone. Weight gain or central adiposity rather than body mass index, since this may be normal in some patients— eg, patients of Asian decent may increase suspicion that ALT level is increasing in this context; however, liver biopsy may be needed to determine whether the ALT level increase is associated with HBV-related damage or steatosis.
There are no contraindications for use of statins in individuals with HBV infection or for other drugs used in treatment of metabolic syndrome eg, antihypertensive agents or antidiabetic agents, including metformin. Currently approved treatments for HBV infection consist of interferon alfa-2b, lamivudine, adefovir, entecavir, peginterferon alfa-2a, telbivudine, tenofovir disoproxil TDF , and tenofovir alaf-enamide TAF.
Figure 1A provides data for the efficacy of the first-line treatments by showing histology and fibrosis improvements with entecavir therapy.
Figure 1B shows data from different studies on the efficacy of entecavir and tenofovir compared with peginterferon in reducing HBV DNA to undetectable levels over the course of 3 years of treatment.
A: Histologic and fibrosis improvement with long-term entecavir treatment.
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