|Sábado, octubre 25, 2014

Invitado Internacional: Tratamiento de Hepatitis B  

Hepatitis B Treatment: new directions for future therapy

MARÍA H.SJÖGREN, M.D., MPH, CLINICAL GASTROENTEROLOGIST, DEPARTMENT OF CLINICAL INVESTIGATION,
 WALTER REED ARMY MEDICAL CENTER, WASHINGTON D.C. TOMADO DE RESÚMENES DE CONGRESO DE
ACTUALIZACIÓN EN GASTROENTEROLOGÍA, CELEBRADO ENTRE EL 23 -25 DE MARZO DE 2001 EN EL WALTER
REED ARMY MEDICAL CENTER, WASHINGTON D.C., CON AUTORIZACIÓN DEL AUTOR. TRADUCCIÓN: LUIS 
ALEJANDRO OROZCO, GASTROENTERÓLOGO, ENDOSCOPISTA, CLÍNICA PASTRANA, ISS, BOGOTÁ, D.C.

Introducción

Chronic infection with the hepatitis B virus (HBV) is a common occurrence in the world. Worldwide, approximately 400 million subjects were HBV-infected by the year 2000, with 1.25 million of them located in the United States (1). In the USA, HBV infection is responsible for 5 to 10% of all causes of chronic liver disease and approximately 200 cases of fulminant hepatitis per year. HBV causes the major morbidity and mortality when it progresses to cirrhosis and hepatocellular carcinoma.

The goal of therapy is to halt the progression of liver injury by suppressing viral replication and eliminating infection. When a sustained loss of HBeAg and HBV DNA is achieved, a biochemical, clinical and histological remission ensues. The HBV precore mutant deserves particular mention. The HBV precore mutant is devoid of the capacity to generate HBeAg; therefore infected subjects are HBeAg and anti-HBe negative but still are HBV DNA-positive. In these cases the goal of therapy is to eliminate viral replication and induce a HBV DNA-negative status.

All HBV-infected subjects with active viral replication should be treated unless there are contraindications for therapy. Even if there is minimal evidence of hepatic inflammation, the presence of persistent viremia foretells liver disease sometime in the future.

The indications for therapy are (2):

  • Detectable HBeAg and HBV DNA for at least 6 months
  • Increased serum ALT level
  • Liver biopsy showing chronic inflammation

Liver biopsy is not an absolute requirement,but may be useful. Once therapy starts,the patients need to be monitored at monthly visits where HBV DNA, HBeAg,anti-HBe and serum ALT status are evaluated.

The preferred method to test for HBV DNA during therapy is the liquid hybridization assay. The polymerase chain reaction (PCR) assays are uniquely sensitive and may detect HBV even in subjects who have a complete clinical remission of HBV infection.

Medications for Treatment of Chronic HBV Infection (3)

  1. Interferon alpha
  2. Antiviral agents or nucleoside analogues
  3. Immunomodulator therapy

Non-HBV specific
Thymosin
Interleukin-2
Interleukin-12
Levamisole
HBV-specific
Pre-S or S peptide vaccination
Cytotoxic lymphocyte epitope vaccination
DNA vaccination

Interferon a

Interferon alfa-2b was approved in 1992 for the treatment of chronic HBV infection. The recommended doses are 5 million units (MU)injected subcutaneously (SC) every day for 16 weeks or 10 MU injected SC three times a week for 16 weeks. In two-thirds of treated subjects a transient flare of ALT is observed usually between weeks 4 -12 of therapy or after therapy is discontinued. This flare is believed to be a result of immunemediated clearance of HBV-infected hepatocytes. Interferon has been successful in about one third of treated patients. The addition of a 6-week “priming ” of prednisone before starting interferon did not result in a higher remission rate (4). The use of prednisone in the treatment of HBV is discouraged.

A meta-analysis of 16 randomized clinical trials (5) have shown that 33% of treated subjects lose HBeAg and 32% lose HBV DNA.These rates compared favorably to controls, which showed 12 and 17% loss of these virological markers (p<0.001). In general, the sustained response following interferon therapy is 30 to 40%.

Table summarizes results of reference 4.

Treatment Group HBeAg/ HBV DNA loss HBsAg loss
Interferon alfa-2b 5MU/day for 16 weeks 37% 12%
Prednisone for 6 weeks followed by interferon alfa 2b 5MU/day for 16 weeks 36% 11%
Control 7% (p <0.001) 0% p<0.024)

Long-term benefit (prevention of cirrhosis or increased survival)has not been adequately assessed. A limited study of 103 interferon-treated patients showed a 95% 5 year survival rate in subjects who had a sustained remission, and less than 50%among those who did not (6).

Side effects of interferon therapy are well known, among them are fever, malaise, myalgia, granulocytopenia and thrombocytopenia. In less than 5%, thyroid suppression or significant psychiatric side effects may be observed. If the side effects are serious enough, interferon doses are modified or in rare situations, discontinued permanently.

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