Advances in the Treatment of Chronic Hepatitis B

Advances in the Treatment of Chronic Hepatitis B

Yurdaydin Cihan
US Gastroenterology Review 2007 - Issue II - October 2007
Published: October 2008
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Differences Between Chronic Hepatitis B and C
Treating chronic hepatitis B (CHB) is far more complex compared with dealing with chronic hepatitis C (CHC). In the latter, treatment for one year with pegylated interferons and ribavirin is the standard, and the search for new treatment modalities goes on for treatment optimization in terms of higher healthcare success and improved patient comfort. Undetectable serum hepatitis C virus (HCV) ribonucleic acid (RNA) by polymerase chain reaction (PCR) six months after treatment cessation is considered as cure from HCV infection. To use hepatitis B virus (HBV) DNA along the same line in hepatitis B treatment is not possible. Undetectable HBV DNA by PCR even after six months of treatment-free follow-up may still be followed by clinical relapse. The fact that the HBV is converted within the hepatocyte nucleus to covalently closed circular DNA (HBV cccDNA), which serves as the template for pre-genomic HBV RNA synthesis, and through reverse transcription to new HBV production, appears to be the main obstacle for achieving a cure through hepatitis B treatment. The last decade witnessed important progress and the emergence of alternative treatment options for patients suffering from CHB thanks to the translation of benchside work into clinical practice. We continue to witness a period where treatment alternatives are growing and where treatment indications may dare to cross some red lines of conventional teachings. Such proliferation in treatment options may have led to some confusion in the way hepatitis B is or should be treated. The division of current treatment algorithms in CHB into ‘finite curative treatment’ and ‘indefinite suppressive treatment,’ as suggested at the last Monothematic Conference on hepatitis B in Istanbul, may temper the confusion, or at least provide some orientation.1 This article aims to give a general overview of recent advances in hepatitis B treatment.

Phases of Chronic Hepatitis B Virus Infection—Hepatitis ‘e’ Antigen-positive versus Hepatitis ‘e’ Antigen-negative Chronic Hepatitis B
CHB infection in humans goes through different phases.2 The early phase is characterized by the presence of hepatitis ‘e’ antigen (HBeAg) in serum and high levels of HBV DNA. Depending on the age of HBV acquisition, this phase is accompanied by either normal alanine aminotransferase (ALT) or increased ALT levels and active liver disease. The former pattern is seen mostly in high endemic areas such as the Far East, where HBV acquisition occurs early in life, especially through vertical transmission at birth, and is termed the ‘immune tolerant phase.’ The latter pattern occurs when hepatitis B is transmitted later in life, either through horizontal transmission during childhood—as is the case in moderately endemic areas such as the Mediterranean basin—or through sexual transmission or intravenous drug use, as seen in low endemic areas such as West Europe or North America. This first phase is followed by ‘e’ antigen (eAg) seroconversion and the development of HBeAb in serum. HBeAg seroconversion can occur spontaneously, or may be treatmentinduced. Both occur very infrequently in persons who are in the ‘immune tolerant phase’ of the infection. In contrast, spontaneous HBeAg seroconversion is not an infrequent event after horizontal transmission, and can be further accelerated through treatment. The immune tolerant phase is followed years later by HBeAg-positive active liver disease at which point these patients are more prone to HBeAg seroconversion as well.

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