The New Times (Kigali)

30 November 2012

Rwanda: Know When You Need to Start Treatment for Chronic Hepatitis B Infection

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Vaccination against highly contagious Hepatitis B has been on high note in the country of recent. People have been screened for this virus and those found infected have panicked to seek solutions on how and when to seek medical solutions for their health.

It is important to understand that the approach to start chronic Hepatitis B treatment has changed significantly in recent years largely due, to the advent of new medications, more sensitive laboratory, and increased understanding of the natural history of chronic Hepatitis B.

The decision to start therapy is not always clear cut and normally requires careful interpretation of clinical, laboratory, and histological investigations.

Chronic Hepatitis B infection can be divided into 3 phases that involves; the immune-tolerant phase, the immune-clearance phase, and the residual or inactive phase. In some individuals, a fourth phase termed as Hepatitis B e antigen (HBeAg)-negative for chronic Hepatitis B carriers occurs.

The immune-tolerant phase typically occurs in individuals from endemic areas where Hepatitis B is most often acquired perinatally. In this phase, viral replication is high, the HBeAg is present and Hepatitis viral load (HBV DNA) is elevated. This is because the developing immune system does not mount a response to the Hepatitis B (HBV) infection. However, sometimes the liver function tests detected as serum alanine aminotransferase (ALT) is normal and liver inflammation is minimal in such circumstances.

In some patients, there is a more vigorous cytotoxic T-cell response that could rise, and this terminates the immune-clearance phase. What happens actually here is that the liver is massively attacked by the virus and injures the liver cells called the hepatocytes. The outcome is that there is hepatocyte necrosis or death of liver cells that occurs and this makes the liver function enzymes to increase (elevated ALT levels) as a result of increased liver inflammation. The liver tissues begin to die out in a process termed as fibrosis.

Options for the treatment of Hepatitis B have expanded significantly since the introduction of interferon alfa in recent decades.

Currently approved therapies can be divided into interferon agents such as the standard interferon alfa-2b and pegylated-interferon alfa-2a. The oral nucleotide drugs such as lamivudine, adefovir, entecavir, and telbivudine. Most recently tenofovir is also recommended as a treatment option for chronic Hepatitis and this drug is given in combination with lamivudine.

The interferons have both antiviral and immunomodulatory effects, and can be administered for finite durations, with virtually no risk for resistance. They confer the highest rates of HBsAg clearance.

In HBeAg-positive chronic Hepatitis B, standard interferon alfa is given for 4 months, while pegylated-interferon alfa is administered for one year. In HBeAg-negative chronic hepatitis B, therapy with either agent should be administered for at least one year.

One of the major drawbacks to interferon therapy is its high incidence of adverse effects, including most commonly flu-like symptoms, fatigue, and depression

Nucleotide medications have the advantage of oral administration and tend to be more effective at suppressing HBV DNA and normalising liver enzyme levels. However, they must be taken for longer periods of time and carry a risk for resistance. Lamivudine has been found to have high viral resistance and this is why its given in association with Tenofovir.

Recent scientific studies suggest that entecavir is the most potent agent in reducing HBV DNA levels over a 1-year period. Adefovir is considered the least potent of the approved oral drugs for hepatitis B.

For patients with HBeAg-positive chronic Hepatitis B, nucleotide drugs should be administered until at least six months after HBeAg sero-conversion, in association with undetectable serum HBV DNA by a primalase chain reaction.

For patients with HBeAg-negative chronic Hepatitis B, because of the high rate of relapse even when serum HBV DNA is undetectable, therapy with nucleotide drugs should be considered indefinitely.

First-line therapy in both HBeAg-positive and HBeAg-negative chronic Hepatitis B consists of interferon Alfa, pegylated interferon Alfa, adefovir or entecavir. Lamivudine or telbivudine are less favored due to their high rates of resistance.

Tenofovir like entecavir is potent and associated with low rates of resistance.

In patients with compensated cirrhosis, first-line therapy consists of entecavir and adefovir; adefovir can be used either as monotherapy or in combination with a nucleoside drug and most commonly lamivudine.

In decompensated cirrhosis, therapy using 2-drug combinations with adefovir is preferred. The advantages of using the combination of adefovir and lamivudine, for instance, are rapid viral suppression and a decreased risk of developing resistance.

Tenofovir will likely replace adefovir as the preferred initial therapy because of its better efficacy in achieving viral suppression, as well as its low rates of resistance.

The writer is a doctor at the Rwanda Military Hospital - Kanombe.

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