| ID | 51 |
|---|---|
| Name | CHRONIC HEPATITIS B |
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| Introduction | Chronic hepatitis is mostly the continuum of acute hepatitis, where liver shows a chronic inflammatory reaction for more than 3-6 months duration, with a persistently raised serum aminotransferase levels. Serologically, the persistence of HBsAg after acute illness and appearance of IgG anti-HBc in the blood is the evidence of chronic hepatitis B infection (or carrier state). The presence of HBeAg & HBV-DNA in the serum, indicative of active viral replication; or absence of HBeAg and HBV-DNA in the serum and appearance of anti-HBe indicates low viral replication. In rare cases, in chronic hepatitis B IgG anti-HBc alone is the only evidence of chronic infection. In chronic hepatitis B, patient may be asymptomatic, but is highly infectious when markers of continuing viral replication (such as HBeAg, HBV-DNA or DNA polymerase) are present in the blood; and least infectious when these are absent and only anti-HBe is present. |
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| Treatment | Treatment of Chronic hepatitis B:1,2,26 In chronic hepatitis B patients, treatment is indicated if there is a high viral load in the serum with active viral replication (HBeAg and HBV-DNA positive) & presence of active hepatitis (raised serum aminotransferase levels and/or histological evidence of inflammation and fibrosis). Active chronic hepatitis B patients can be treated with recombinant human interferon (a-2b), or a long-acting pegylated interferon (a-2a) or an oral nucleoside (lamivudine) or nucleotide (adefovir) analogue. The aim of therapy is to acheive- i. reduction & maintenance of the serum HBV-DNA level to the lowest possible levels; ii. disappearance of HBeAg (if any) & subsequent apperance of anti-HBe in the serum (seroconversion) iii. normalization of the LFTs (ALT-serum aminotransferase) level; and iv. histologic improvement. 1. Treatment with recombinant human interferon-alfa: Interferon is the most effective in treating chronic hepatitis B with active viral replication (HBeAg and HBV-DNA positive) & raised aminotransferase levels. A dose of interferon (a-2b) 5 million units a day or 10 million units 3 times a week i.m for 4 months. Or, peginterferon a-2a, 150mcg subcutaneously once weekly for 48 weeks (4 months). About 40% of patients treated with above regimen (interferon/peginterferon) respond with disappearance of HBeAg and HBV-DNA from blood and normalization of serum aminotransferase levels, and followed by a subsequent appearance of anti-HBe. Besides, some of these responders may eventually become HBsAg-negative and rather develop anti-HBs and thus cured. But in case of chronic hepatitis B with HBeAg-negative, this response rate is lower, even after giving a longer course of treatment. Relapses are rare in complete responders who develop anti-HBe. Patients who develop cirrhosis, should not be treated with interferon, as it may cause a rise in serum transaminases and precipiate liver failure. Patients with chronic hepatitis B should also be treated with other antiviral drugs, because many patients may have high levels of viraemia and/or low transaminase levels, and are therfore not candidates for interferon therapy. 2. Treatment with oral antiviral agents: Currently, oral antiviral agents are used in the treatment of chronic HBV infection instead of interferon and has been found with better tolerance. These are more effective in reducing viral loads in HBeAg-negative chronic hepatitis B patients than those with HBeAg-positive chronic hepatitis B cases, as the pre-treatment viral loads are lower. But, relapse is frequent when treatment is stopped or due to drug resistance in long-term therapy. The drugs carrently used are- Lamivudine, Adefovir, Entecavir and Telbivudine, Tenofovir Lamivudine: Lamivudine, a nucleoside analogue drug acts by inhibiting HBV-DNA polymerase. The recommended dose is 100mg orally once daily with or without food, as a single dose for 1 year. This therapy results a complete suppression of serum HBV-DNA in about 93-100% patients with improvement of liver histology in 40% of patients and normalization of ALT levels in over 40% and seroconversion of HBeAg to anti-HBe in 17-21% of patients. But, about 15-30% of patients responding to lamivudine therapy may experience mild relapse with HBV replication when treatment is discontinued or due to drug resistance in prolonged therapy. Drug resistance may occur after 9 months of treatment by developing HBV-DNA polymerase mutants (known as ‘YMDD variants’) followed by a subsequent rise in viral load. Lamivudine is effective in improving liver function in patients with decompensated cirrhosis and may lessen the need for transplantation. Interferon and lamivudine combined therapy has no additional advantage over the use of any one alone. Adefovir: Adefovir, a nucleotide analogue drug that is phosphorylated first to yied active ingredient which inhibits HBV-DNA polymerase. Thus, it enhances the frequency of HBeAg seroconversion to anti-HBe and leads to histological improvement. Adefovir is effective in suppressing most of the lamivudine-induced DNA polymerase mutant viruses. Drug resistance usually occurs by developing HBV-DNA mutants at a lower rate than with lamivudine; 2% are identified after 2 years of treatment, but it increases to about 18% after 3 years of therapy. Relapse occurs on stopping treatment, so the optimum length of treatment remains indefinite. Adefovir should be used with caution in renal failure patient and doses interval should be adjusted with baseline creatinine clearance. The recommeded dose of adefovir is 10mg once daily, taken orally, without regard to food. Dose adjustment in renal failure: Please see in the therapeutic section. Entecavir: Entecavir, another nucleoside analog, is more effective than lamivudine and adefovir, has become a preferred first-line treatment for chronic hepatitis B with HBeAg-positive or negative patients. The recommended daily dose is 0.5mg orally for patients not resistant to lamivudine and Img for patients resistant to lamivudine. In HBeAg-positive patients 48 weeks of treatment with entecavir suppresses HBV-DNA levels in 67% to 80%. In HBeAg-negative chronic hepatitis, 1 year treatment with entecavir suppresses HBV-DNA levels in 90%. Anti-HBe seroconversion following a year of entecavir, occurs in about 21 %. Entecavir also improves histology (70%) and liver biochemistry. Antiviral resistance mutations occur in only 1% after 3 years of entecavir therapy. Telbivudine: Telbivudine (nucleoside analog), is also more effective than lamivudine and adefovir. The recommended dose is 600mg daily orally. In HBeAg-positive patients 48 weeks of treatment with telbivudine suppresses HBV-DNA levels in 60%. In HBeAg-negative chronic hepatitis, 1 year treatment with telbivudine suppresses HBV-DNA levels in 88%. Anti-HBe seroconversion following a year of telbivudine treatment occurs in 21%. Telbivudine also improves histology and liver biochemistry. Resistance to this drug may develop, particularly in patients who are resistant to lamivudine, and elevated creatine kinase levels are common in patients treated with telbivudine. Tenofovir: Tenofovir (another nucleotide analog), like entecavir, is also considered as a first-line drug for chronic hepatitis B patients because of its potency and low rate resistance. Recently, tenofovir could prove its superiority to adefovir, and a daily dose of 300mg had superior antiviral efficacy with a similar safety profile as compared with adefovir 10mg daily. In HBeAg-positive patients, tenofovir suppressed HBV-DNA to <400 copies/ml in 76% of patients, compared with 13% of those acheived with adefovir. |
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