Treatment of chronic hepatitis B
The components of the concept of "response to treatment" are now defined and standardized.
- Biochemical response (it is understood that before the treatment the patient had elevated ALT level) - normalization of ALT indices against the background of therapy.
- The histological response is an improvement in histological activity by 2 points (according to the IGA scale, the histological activity index is 0-18 points) without worsening the fibrosis score or improving with this indicator when comparing liver biopsy results before and after treatment.
- Virological response - reducing the level of viral load in the blood to an undetectable level (depends on the sensitivity of the method and test system used) and the disappearance of HBeAg in a patient with HBeAg in the blood before treatment.
- The full answer is the presence of biochemical and virological response criteria and the disappearance of HBeAg.
The following notions are also highlighted: the response to treatment on the background of therapy, the constant response to the background of therapy (throughout the course), the response at the end of the therapy (at the end of the planned course of treatment), a stable response after the end of therapy at the sixth month and a stable response after the end of therapy on the 12th month.
The following terms are also used when characterizing exacerbations:
- virological exacerbation (breakthrough) - the appearance or increase in viral load of HBV DNA by more than 1xIg10 (tenfold increase) after reaching a virologic response against antiviral therapy;
- virological breakdown (rebound) - an increase in the level of viral load of HBV DNA greater than 20 000 IU / ml or an increase in the level of viral load of HBV DNA is greater than it was registered before treatment against the background of continuing antiviral therapy. The duration of treatment, including after reaching the ultimate goal of treatment (consolidating the result, consolidating therapy), depends on the variant of chronic viral hepatitis B and the type of drug being treated.
Treatment of chronic hepatitis B is carried out with interferon preparations or with nucleoside analogues.
In Ukraine, 2 types of interferon preparations (standard interferon alpha, pegylated interferon alfa-2) and 3 nucleoside analogs have been registered for treatment of chronic hepatitis B: lamivudine, entecavir and telbivudine.
Treatment with standard interferon is recommended for patients with chronic hepatitis B with low viral load and an elevated level of aminotransferases in the blood serum (more than 2 norms), since with a high level of viral load and normal ALT indices, treatment is ineffective. Treatment with standard interferon in patients with HBe-positive chronic hepatitis B allows achieving seroconversion of HBeAg / anti-HBe in 18-20% of patients, a stable biochemical response is recorded in 23-25% of patients, and a virological response to treatment is in 37% of patients. In 8% of patients who responded to treatment, it is possible to achieve a complete response to therapy (disappearance of HBsAg). With HBeg-negative chronic hepatitis B, despite a greater percentage responding to therapy, in the treatment (60-70% of the virologic and biochemical response), a persistent response is recorded only in 20% of patients, and in most cases, an acute event is observed after the therapy is withdrawn. Treatment is carried out for 16 weeks at a dose of 5 million IU daily or 10 million IU three times a week subcutaneously.
Pegylated interferon alfa-2 has the same indications as standard interferon, but the effectiveness of treatment is higher in terms of seroconversion rate (27-32%). Treatment is carried out for 48 weeks at a dose of 180 mcg 1 time per week subcutaneously.
Treatment with lamivudine
In patients with HBe-positive chronic hepatitis B, HBeAg / anti- HBe seroconversion is achieved in 16-18% of cases with 100 mg of the drug administered orally once a day during the year and in 27% of cases with the drug for 2 years. Improvement of the histological pattern of the liver was recorded irrespective of seroconversion in approximately 50% of patients. In patients with HBeAg-negative chronic hepatitis B, against the background of lamivudine treatment for 48-52 weeks, a virological and biochemical response is noted in 70% of patients, but after reversal of therapy in 90% of patients, a return to viremia and increased activity of ALT are recorded. Improvement of the histological pattern of the liver is also recorded in more than half of the patients after the annual course of therapy. A complete virologic response, as a rule, is not recorded. Combination therapy with interferon and lamivudine showed no advantages over monotherapy with pegylated interferons.
A significant disadvantage of lamivudine therapy is a high probability of resistance to the drug (17-30% at 2 years) due to mutation of the virus. Treatment can be completed after 6 months after achieving seroconversion (6 months of consolidated therapy). Treatment is carried out at a dose of 100 mg daily per os. Lamivudine is characterized by a good safety profile.
Treatment with entecavir
Entecavir most efficiently and quickly suppresses HBV replication within 48 weeks of treatment (67 and 90% efficacy with HBe-positive and HBe-negative chronic hepatitis B, respectively) and with more than 70% efficiency in the formation of biochemical remission with both forms of chronic hepatitis B The effect of a rapid reduction in the level of viral load is also recorded in patients with initially high replicative activity. The histological response is recorded in 70-72% of patients with HBe-positive and HBe-negative chronic hepatitis B after 48 weeks of therapy. The frequency of HBe / anti-HBe seroconversion after a year of therapy does not exceed 21%, but it increases with prolonged duration of treatment (11% of patients continued treatment for another year). An important advantage of entecavir is the low probability of development of resistance to treatment (less than 1% after 5 years of therapy). The optimal duration of treatment is not determined. Treatment with entecavir is carried out at a dose of 0.5 mg daily per os. The duration of consolidation therapy for HBe-positive viral hepatitis B is recommended for at least 6 months. For patients with developed resistance or refractoriness to lamivudine treatment is carried out at a dose of 1.0 mg daily for at least 6 months. Entecavir is characterized by a good safety profile.
Treatment with telbivudine
Telbivudine is characterized by effective suppression of HBV replication within 48 weeks of treatment (60 and 88% efficacy in HBe-positive and HBe-negative chronic hepatitis B, respectively, and with more than 70% efficiency in the formation of biochemical remission with both forms of chronic viral hepatitis B). Histological response is recorded in 65-67% of patients with HBe-positive and HBe-negative chronic hepatitis B. The frequency of seroconversion of HBe, anti-HBe after a year of therapy does not exceed 23%. The risk of developing resistance to telbivudine), significantly less than lamivudine, but higher than with treatment with entecavir (8-17% after 2 years of therapy). Telbivudine is characterized by a good safety profile. Treatment with telbivudine is carried out at a dose of 600 mg daily per os. The duration of consolidation therapy for HBe-positive viral hepatitis B is recommended for at least 6 months.
Patients with chronic hepatitis B are able to work. Observation of infectious diseases is recommended; polyclinic, a specialist in the hepatology center. In the case of enzymatic: exacerbations of the disease recommend exemption from work, with increased ALT activity of more than 10 norms, hospitalization is recommended. Patients with cirrhosis of the liver are limited able to work in the absence of decompensation and are unable to work if there are symptoms of decompensation of the disease.
Entecavir (Baracluda) is an analogue of guanosine nucleoside with powerful and selective activity against hepatitis B virus DNA polymerase. It quickly and strongly suppresses viral replication to an undetectable level, and is also characterized by a low level of resistance.
Indications for use. The drug is indicated for the treatment of adult patients with chronic hepatitis B, accompanied by compensated liver function, signs of active viral replication and inflammation of the liver.
Currently, the clinical efficacy of entecavir has been established in six Phase II-III clinical trials, and another twelve Phase II-IV studies are planned to study the efficacy of entecavir in selected patient categories, and to determine comparative efficacy with other antiviral drugs. It should be noted that most of the clinical trials of entecavir have been conducted with the participation of Russian research centers.
Based on the results of registration clinical trials involving a total of about 1700 patients with chronic hepatitis B, entecavir demonstrated the maximum ability to suppress the replication of hepatitis B virus and a minimal risk of developing resistance, especially in patients who had not previously received nucleoside analogues.
Baraklad is well tolerated, has a high safety profile, as well as lamivudine, it is convenient to use (one tablet per day). Based on this, the drug is included in current recommendations for the treatment of patients with chronic hepatitis B as a first-line drug (eg, recommendations of the American Association for the Study of Liver Disease, 2007, recommendations of the European Association for Liver Disease, 2008).
Method of administration and dose. Baraklad should be taken orally on an empty stomach (that is, not less than 2 hours after meals and not later than 2 hours before the next meal). The recommended dose of Baraccluda is 0.5 mg once a day. Refractory to lamivudine patients (that is, patients with an anamnesis with viremia of the hepatitis B virus persisting against lamivudine therapy, or patients with confirmed resistance to lamivudine), it is recommended that 1 mg of entecavir be administered once a day.