Journal of Gastroenterology of Peru

CLINICAL GUIDELINES HEPATITIS B
Journal of Gastroenterology of Peru

ISSN 1022-5129 printed version
CLINICAL GUIDE
Clinical Practice Guideline for Diagnosis and Treatment of chronic hepatitis B virus hepatitis
Collaborated on Hepatitis B: - Peruvian Association for the Study of Liver - Society of Gastroenterology in Peru - Peruvian Society of Infectious and Tropical Diseases * Members of the collaborative group of the National Hepatitis B guide at the end of the article.
SUMMARY This guide sets out the technical criteria for the diagnosis and treatment of chronic hepatitis secondary to viral hepatitis B in order to help reduce the morbidity of this disease. Give definitions to understand the recommendations given here. Overview of epidemiology, associated risk factors, clinical aspects and diagnosis of chronic hepatitis B. They give management recommendations including special circumstances such as patients with cirrhosis, patients with HIV co-infection or coinfection with hepatitis C. The recommendations herein become national guidance for the management of chronic hepatitis B. Hepatitis KEY WORDS: chronic hepatitis, viral hepatitis B, User Guide, Treatment.
ABSTRACT This guide sets out the technical criteria for the Diagnosis and Treatment of Chronic viral hepatitis secondary to hepatitis B. The guide INTEND to reduce the Morbidity and Mortality of This Disease. The Practical Guide give definitions to help Understand the Terminology, describes epidemiology, Risk Factors, and Clinical Aspects and the diagnosis of chronic hepatitis B. Finally the guide give management recommendations for the special Circumstances Including Patients with cirrhosis Such as, Patients coinfected with HIV or coinfected with hepatitis C. The recommendations of the guide Become The national guide for the management of chronic hepatitis B. KEYWORDS: chronic hepatitis, viral hepatitis B, User Guide, Treatment.
JOURNAL OF GASTROENTEROLOGY 2011

I. PURPOSE Contribute to reducing morbidity and mortality from chronic hepatitis. II. OBJECTIVE The Clinical Practice Guideline is intended to establish the technical criteria for the prevention, diagnosis, treatment and control of chronic hepatitis. III. SCOPE This manual is applicable nationwide. IV. CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS TREATMENT OF CHRONIC HEPATITIS VIRUS OF HEPATITIS B 4.1. NAME AND CODE CIS: B18 chronic hepatitis B, 4.2. OTHER NAMES CIS: chronic hepatitis B B18.1 Without hepatic coma Without Delta Agent CIS: B18.0 Chronic Hepatitis Type B with hepatic coma Without Delta Agent V. GENERAL 5.1 DEFINITION The chronic hepatitis B is a liver disease caused by persistent infection with hepatitis B virus (HBV) that extends beyond 6 months. According to the type of virus is subdivided as follows: AND
a. HBeAg positive chronic hepatitis B (also called "wild HBV variant") is

defined by the presence of HBsAg 1, 2 and absence of HBeAg Anti-HBe 3. In these cases, HBV DNA is present in 4 high levels (> 10 6). Usually occurs in the first years of infection.
b. HBeAg negative chronic hepatitis B, occurs in two situations, whether

there are mutations at the core promoter or precore, and is characterized by positive HBsAg, HBeAg negative, anti-HBe positive and HBV-DNA present in low (< 10 6). It usually occurs in advanced stages of chronic infection. 5.1.1. Glossary of Terms Inactive Carrier State: Persistent infection of the liver without necroinflammatory activity signifi cannot, but with the presence of HBsAg (surface antigen, previously called Australian antigen). It is characterized by: - HBsAg (+)> 6 months. - HBeAg (-) and Anti-HBe (+)
- Serum HBV DNA <2,000 IU / ml (10,000 copies / ml) - Persistently normal transaminase levels - Liver biopsy with no significant inflammation. Hepatitis B resolved: It is a condition in which there is evidence of past infection with HBV and cured. It is characterized by normal transaminases as well as total Anticor presence of Anti-HBs5 positive and positive. Acute exacerbation: Condition in which a patient with chronic hepatitis transaminase elevation, so sudden has a clinical and biochemical features consistent with acute hepatitis. Transaminases rise more than twice the baseline. Reactivation of Hepatitis B: It is a condition in which a patient in chronic inactive carrier phase, suddenly presents important viral replication associated with hepatocellular damage which is characterized by elevated more than 10 times the normal limit or more than 2 times baseline transaminases. HBeAg clearance: The condition of serological HBeAg loss occurs in a previously positive to it. HBeAg Seroconversion: The condition occurs serological HBeAg loss and appearance of anti-HBe in a person with positive HBeAg and anti-HBe negative. HBeAg seroreversion: Reappearance of HBeAg in a person who was HBeAg negative and anti-HBe positive. 5.2. Etiology It is caused by HBV, a DNA virus classified within the family market Hepadnaviridae. There are eight genotypes (A, B, C, D, E, F, G, H), which are unevenly distributed geographically in the world. In Peru predominant genotype F. 5.3. PATHOPHYSIOLOGY Once the acute infection produced under certain conditions related to control of viral persistence of immunity occurs and is detected HBsAg for more than 6 months. People with compromised immune systems (infants, immune suppressed: people infected with the human immunodeficiency virus, rheumatologic diseases, chronic renal failure, cancer patients and transplant of organs or tissues) are at greater risk of going to chronicity. 5.4. Epidemiology It is estimated that worldwide more than 2,000 million people have been infected with Hepatitis B, and including more than 300 million are chronic carriers. 25% die from a direct consequence of the disease, either by cirrhosis, chronic active hepatitis or primary liver cancer. 80% of HCC cases registered worldwide have as causal to HBV, which according to WHO is the second leading cause of cancer in humans, after snuff. Peru is located between the countries of intermediate endemicity for HBV. ( Table 1 ). However, several studies indicate that the local prevalence estimates are

significantly different between regions and even within them in the different villages. So in the jungles of Peru, the endemicity is medium to high with prevalence ranging from 2.5% in population of Iquitos, up to 20% in native population. On the coast the prevalence ranges from 1 to 3.5%. In the mountains the studies agree as to the prevalence in this region, being lower in the towns of the western slope of the Andes, and medium to high valleys of the eastern slopes of the Andes, being particularly high in Huanta valleys and Abancay, located close to 2,400 meters above sea level.
5.5. RISK FACTORS ASSOCIATED 5.5.1. Environment: - In areas highly endemic, horizontal transmission is the most common form of infection. - If the infection occurs in newborns and children under 5 years, the probability that this progresses to chronicity is 90%. 5.5.2. Lifestyle: - Addiction to illegal drugs, especially intravenous use - Employees (as) sexual - Risk sexual behavior 5.5.3. History of other diseases or health conditions: - Multiple transfusions - Patients undergoing immunosuppressive therapy (eg chemotherapy) - Organ and Tissue Transplant - Hemodialysis Patients

VI. SPECIAL CONSIDERATIONS 6.1. CLINICAL 6.1.1. Signs and Symptoms The chronic form is usually asymptomatic, may occur occasionally general symptoms: fatigue, hyperoxia, dyspepsia, intolerance to alcohol. As the infection progresses to cirrhosis may occur: palmar erythema, collateral circulation, jaundice, ascites and edema. Sometimes the patient may present as acute hepatitis or the presence of tumor in the liver (hepatocellular carcinoma). 6.1.2. Chronological Interaction To consider the diagnosis of chronic hepatitis B six months must have elapsed from the acute episode if it had been recognized as such. However, in most cases there is no history of clinical symptoms of acute hepatitis, so the finding of HBsAg in an asymptomatic patient is considered as a marker of chronic hepatitis. In case of finding signs and symptoms of cirrhosis or liver cancer it indicates the time of infection has been extended (10 or more years). 6.1.3. Figure 1. Evolution of viral markers and ALT
6
in chronic hepatitis B
6.2. DIAGNOSIS 6.2.1. Diagnostic Criteria: The diagnosis of chronic hepatitis B is given by the presence of HBsAg for more than six months, with the common situations in which this diagnosis should be suspected as follows:
1. Incidental finding of impaired liver function tests 2. Monitoring of a patient with recent acute hepatitis B 3. History of contact with person carrying hepatitis B virus chronic infection
JOURNAL OF GASTROENTEROLOGY 2011 5
a. b. c. d. e. f.
B virus carrier mothers Sexual partner B virus carrier Accidental puncture with potentially contaminated material Addiction to illegal drugs Proceed in a geographical area of high prevalence for hepatitis B History of acute hepatitis of unidentified cause
4. Finding hepatic tumor

6.2.2. Differential Diagnosis
1. Chronic hepatitis C virus 2. Autoimmune liver disease (including autoimmune hepatitis, primary biliary
cirrhosis and primary sclerosing cholangitis)
3. Toxic hepatitis
6.3. Auxiliary tests 6.3.1. Clinical Pathology: He asked for the following laboratory tests:
1. 2. 3. 4. 5. 6. 7.
Quantitative HBsAg HBeAg Anticore Anti-HBe. TGP HBV DNA by real-time PCR6 HBV genotyping
6.3.2. In Pictures Abdominal ultrasound: Useful to evaluate the presence of liver cirrhosis and / or hepatocellular carcinoma. A normal ultrasound does not rule out chronic hepatitis. 6.3.3. Liver Biopsy Liver biopsy is recommended to determine the start of treatment in the following circumstances:
1. Patients after a period of 3-6 months remain HBeAg positive with HBV DNA
greater than 20,000 IU / mL (10 2 times the normal value.
5
copies / ml) and elevated SGPT less than
2. It is also recommended liver biopsy in the following situations:

- Male patients over 40 years without cirrhosis, regardless of level of TGP
- Family history of hepatocellular carcinoma. - When in doubt about the existence of liver disease co. If a liver biopsy showing fibrosis F2 (METAVIR classifi cation of) or A2 moderate inflammation (METAVIR) should be considered for treatment. See Annexes 4 and 5. 6.4. MANAGEMENT BY LEVEL OF COMPLEXITY and response capacity 6.4.1. General measures and preventive
a. b. c. d.
Avoid consumption of alcohol Avoid overweight (especially if the BMI is greater than 29) Controlled use of potentially hepatotoxic and immunosuppressive drugs. Proper management of other comorbidities if any (diabetes, hyperlipidemia, coinfection with other hepatotropic viruses).
e. Vaccination against hepatitis A in susceptible.

6.4.2. Therapy 6.4.2.1. Specific Treatment Tax Treatment: Defined by the specialist, gastroenterologist or infectious disease specialist with expertise in liver disease management and use of antiviral drugs and immune from the third level of care.
6.4.2.2. Types of Treatment There are two types of anti-HBV:
1. 180
Pegylated interferon alpha 2a gr. This drug is an immunomodulator with antiviral properties. Is used in adults for a finite time of 48 weeks.
2. Antivirals: These are drugs that prevent viral replication by interfering with
their life cycle, so that the virus can not make more copies of itself. These drugs are taken once a day orally. The time of therapy depends on the type B virus (HBeAg negative or positive) and HBeAg seroconversion. In cases where the infection is by the variant HBeAg +, therapy should be

maintained for at least 6 months after seroconversion to anti-HBe (+) and HBeAg (-) In cases of infection by the variant HBeAg (-) you will need to continue therapy indefinitely or until HBsAg seroconversion. Currently in the Peruvian market, there are three oral anti-HBV drugs:
I. II. III.
Lamivudine, approved in 1989 Entecavir, approved in 2005 Tenofovir, approved in 2008
6.4.2.3. Treatment Strategies Currently there are two treatment strategies: A. Pegylated interferon alfa-2a 180 gr.
It is a drug with antiviral and immunomodulatory properties. Comes in blister presentation subcutaneous (SC). The blisters need to be kept refrigerated between 2-8 C. On no account should be frozen as they lose all their activity under these conditions. The reconstituted solution takes maximum 24 hours in refrigeration (2-8 C, not frozen). After this time should be discarded. Pegylated IFN alfa-2a is applied to the dose of 180 every week for 48 weeks. gr subcutaneously

Adverse effects: Flu-like symptoms after each injection (fever, myalgia, headache), fatigue, hair loss to more serious effects such as leucopenia, neutropenia, thrombocytopenia, major depression, which can reach suicide, hypo-or hyperthyroidism, anemia, neurological disorders (tremors, paresthesia), diarrhea and others. Although treatment is ambulatory, needs to be monitored. See Appendix 1. The doses are regulated based on renal function, although no specific studies in HBV 135 was administered gr. subcutaneously once a week, as has been administered in cases of chronic HCV infection. See Annex 2.
The use of interferon is contraindicated in the following situations: Cirrhosis with signs of clinically significant portal hypertension, esophageal varices, ascites, jaundice and hepatic encephalopathy and functional impairment) Platelets <70,000 / mm Severe cardiac disease Neoplasia of any kind Insulin dependent diabetes mellitus uncontrolled Psoriasis Major Depression Addiction to alcohol and illicit drugs Uncontrolled seizure syndrome
3 3

Neutrophils <1,500 / mm

Pregnant women (women of childbearing age should use birth control during treatment and for 6 months thereafter. In the case of men who received treatment, this recommendation applies to your partner. Autoimmune Diseases Hypersensitivity to any of the known components of the drug. History of previous treatment with interferon unanswered.

B. Treatment with oral antivirals (nucleoside / nucleotide): These are drugs that help control HBV replication as interfering in their life cycle, so the virus can not make more copies of itself. These drugs come in tablets filing for administration orally once a day. The tablets should be stored in tightly closed container at a temperature of 25 C, with a permitted range between 15-30 C. The dose is adjusted based on renal function. The duration of treatment depends on the negative result for the viral load and HBeAg seroconversion by type B virus is decided to treat.
1. Entecavir (ETV) Administered at doses of 0.5 mg / day for patients with HBeAg-positive variant and 1mg/da for those infected with the variant HBeAg negative. It has high potency in reducing viral load and a high genetic barrier. A 6 years of treatment resistance is reported in 1.2% of untreated patients.
In patients who have previously received lamivudine without virologic

response, there is resistance to 7% in the first year of treatment (cross resistance).

Minimal side effects. Is virtually free of side effects, although rare cases have lactic acidosis. Take into consideration the reduction of dose in renal failure (Appendix 2).
2. Tenofovir (TNF) It is administered orally at doses of 300 mg. a day. It is the drug of choice in cases of resistance to lamivudine. It has a high genetic barrier, and 2-year study tracking no viral resistance has been reported. However, even there is no follow-up studies over time because the drug is relatively new. Well tolerated, the adverse effect of greater importance than has been reported is renal failure. If the patient has some degree of renal impairment, dosage should be corrected according to the corresponding table (see Appendix 2). The pharmacokinetics of tenofovir have not been evaluated in patients with creatinine clearance <10 mL / min without hemodialysis, therefore, not recommended.

3. Lamivudine (LMV) It is administered orally at doses of 100mg/day. It has high antiviral potency but low genetic barrier. In follow-up studies 5

years of treatment, 70% develop resistance. Has minimal side effects, so it is well tolerated.
The comparative analysis of the drugs used in therapy of chronic hepatitis B is shown in Annex 3. C. - chronic viral hepatitis B: HBeAg positive or without cirrhosis Compensated Cirrhosis Treatment is indicated if the following conditions:
1. HBV DNA levels 20,000 IU / mL or 10 5 copies / ml 2. Persistently elevated SGPT levels (more than 2 times the upper normal
value) for a period of 3 to 6 months. Guidelines before trying to follow: The patient who is not tax treatment should be monitored periodically by TGP and HBeAg tests:
1. Every 6 months, if you have previous values persistently normal TGP. 2. Every 3 months if their levels of TGP are oscillating or are between 1-2
times the normal value.
3. The marker HBeAg should be checked every 12 months. 4. If a liver biopsy showing fibrosis F2 (METAVIR classification) or A2
moderate inflammation (METAVIR) should be considered for treatment. See Annexes 4 and 5. In circumstances in which liver biopsy is indicated but is logistically or technically impossible to do, proceed to treatment with the antiviral of choice according to the logistics and the patient. Goals of treatment of HBV infection HBeAg The ideal objective is the eradication of HBsAg with the appearance of Anti-HBs antibody. However, since this is achieved in the minority of patients (1-3%), the practical objective in these cases is now Negativization VIRAL LOAD B virus determined by a highly sensitive diagnostic method, and the disappearance HBeAg with appearance of anti HBe (HBeAg seroconversion). Choice of treatment strategy Are considered first-line treatment in these patients: 180 Pegylated interferon alpha 2a gr Entecavir Tenofovir Lamivudine is not considered first choice because of its very high resistance.
You can choose any of the drugs mentioned and the decision should include an individualized analysis of the efficacy, safety and genetic barrier (rate of
10

resistance). Pegylated interferon alpha 2a has the advantage of having a finite duration (48 weeks). The ideal candidate is a young patient without cirrhosis, with viral load below 10 7 IU / ml, genotype A or B, HBeAg positive and high TGP more than 3 times the normal value. Before a thorough study should be discarded comorbidities that could worsen during use, taking into account the list of adverse effects and contraindications of the drug. It is important to note that this strategy will need training in subcutaneous application of blisters (preferably by the patient to avoid infection by puncture) and refrigerated storage facilities for the same. If there are doubts about compliance with these conditions is not considered a suitable candidate to receive interferon. Patients who have contraindications or high risk of not tolerating or failing to comply with interferon therapy, or who have received no response, are tributaries to receive tenofovir or entecavir. Tenofovir also be preferred in patients who have previously received lamivudine. Entecavir is preferred in patients with known renal disease, comorbidity (diabetes mellitus, hypertension, known history of glomerulopathy) or need for drugs that predispose to develop nephropathy. Patients with creatinine clearance <60% should start treatment with Entecavir. Monitoring during treatment with pegylated interferon alpha 2a Before starting treatment should be performed baseline visit, including history, physical examination and ancillary tests including complete blood count, liver profile, alpha-fetoprotein (AFP), abdominal ultrasonography, values of thyroid hormones (TSH, T3 and T4), glucose and creatinine. It is important to have baseline HBV DNA TGP. The visits should be 1 time per week during the first month of therapy and then monthly. Each visit will include a thorough history (presenting research on side effects), physical examination and laboratory blood count, platelet count and TGP. They carry out checks on viral load at week 12, 24, 48 (third, sixth and twelfth month of therapy), and 6 months after the last dose of the drug. Markers will be asked HBeAg and Anti HBe at weeks 24 and 48 of treatment and at 6 months after treatment ends. If the week 12 viral load decreased to <1log 10 IU / ml, it is considered that there is NO PRIMARY RESPONSE (also called primary failure). In this case the drug should be discontinued and Tenofovir or Entecavir will start in his place. If the week 24 viral load is <2.000 IU / ml is considered to exist virologic response. If after 6 months of the last dose of Interferon control of viral load is undetectable, it is considered SVR. If you also have achieved HBeAg seroconversion, treatment was considered successful.

11

HBsAg will be sought 24 weeks (6 months) after HBeAg seroconversion.
Monitoring during treatment with oral antivirals Before starting treatment should be performed baseline visit, including history, physical examination and auxiliary tests, including AFP, abdominal ultrasonography, complete blood count, glucose, urea and creatinine. Is essential to have TGP levels, markers of viral replication and HBV DNA at baseline. The visits should be every month until the sixth month and then every 3 months. Each visit will include thorough history and physical examination and laboratory tests: CBC, SGPT, and creatinine. In the case of Tenofovir also be added urea, creatinine clearance calculated and simple urine test. In case of any changes in renal function with use of tenofovir, discontinue it and start treatment with Entecavir. (Annex 2: adjustment in renal impairment). They carry out checks on viral load at week 12, 24 and 48 of treatment.

Response to Treatment If the week 12 viral load decreased to <1log 10 IU / ml, it is considered that there is an absence of primary response. In these cases we must add another drug with a high genetic barrier (Entecavir or tenofovir). If the week 48 viral load is undetectable by real-time PCR, it is considered that there Virologic Response at end of treatment and the chances of achieving HBeAg seroconversion is high. Continue treatment. If the week 48 viral load has dropped by more than 1log10 IU / ml but still detectable virologic response is considered PART. We recommend adding another drug high genetic barrier (Entecavir or tenofovir). From week 48 of treatment viral load controls will be every 6 months. If it detects a rise> 1log IU / ml compared to the lowest level reported for the patient sees a virological relapse. In this case, genotyping is indicated (analysis of resistance). There should be adequate to assess medication adherence. If adherence is adequate, it is likely that you are generating resistance to antiviral employee. We recommend adding another oral antiviral high genetic barrier. They seek to maintain an undetectable viral load values in order to reduce the chances of resistance. Treatment is continued until 6 months after achieving seroconversion (HBeAg loss and appearance of anti HBe). HBeAg

The HBeAg seroconversion rate increases in direct proportion to the time of therapy.
12
13

D. Chronic Viral Hepatitis B: HBeAg negative. Without cirrhosis and / or with compensated cirrhosis. For the treatment should take into account the following criteria: Levels of HBV DNA 2000 IU / mL or 10 4 copies / ml persistently elevated SGPT levels (more than 2 times upper normal value) for a period of 3 months. Guidelines before trying to follow:
1. The patient who is not tax treatment should be monitored periodically by

TGP and HBeAg tests:
I. II.
Every 6 months, if you have previous values persistently normal TGP. Every 3 months if their levels of TGP are oscillating or are between 1-2 times the upper normal value.
2. The marker HBeAg should be checked every 12 months. 3. It is recommended to determine the HBV DNA levels every 6 months if
normal TGP.
4. Liver biopsy is recommended to determine the start of treatment in the

following circumstances:
I. II. III.
HBV DNA 10 4 copies or 2.000 IU / ml and ALT less than 2 times the upper normal value. HBV DNA 10
3
copies / ml and <10
IU / ml with high TGP.
When in doubt about the existence of hepatic comorbidity.
If a liver biopsy showing fibrosis ( F2 METAVIR histological classification) or moderate to severe inflammation ( A2, METAVIR) should be considered for treatment. Treatment goals HBeAg negative HBV The ideal objective is the eradication of HBsAg with the appearance of Anti-HBs antibody. However, since this is achieved in a minority of patients (1%), the practical objective in this patient group is to keep the viral load measured by PCR in real-time undetectable levels. Choice of treatment strategy Are considered first-line treatment in these patients: Pegylated Interferon alfa-2a, entecavir and tenofovir. You can choose any of the drugs mentioned and the decision should include an individualized analysis of the efficacy, safety and genetic barrier (rate of resistance). Pegylated interferon alpha 2a has the advantage of having a fixed period (48 weeks). The ideal candidate is a young patient without cirrhosis, with viral load below 10 7 IU / ml, genotype A or B, HBeAg positive and elevated transaminases more than 3 times the normal value.
14

If you choose to pegylated interferon alpha 2a, previously ruled out a detailed study will comorbidities that may worsen during use, taking into account the list of adverse effects and contraindications of the drug. Annex 1. It is important to note that this strategy will need training in subcutaneous application of blisters (preferably by the patient to avoid accidental puncture transmission) and refrigerated storage facilities for the same. If there are doubts about compliance with these conditions is not considered a suitable candidate to receive pegylated interferon alfa 2a. Patients who have contraindications or high risk of not tolerating or failing to comply with therapy with pegylated interferon alfa 2a, or that you have received no response, are tributaries to receive oral antiviral Tenofovir or Entecavir. Tenofovir is preferred in patients who have previously received lamivudine. Entecavir is preferred in patients who have previously received adefovir and / or patients with known renal disease, comorbidity, or need for drugs that predispose to develop nephropathy. Monitoring during treatment with pegylated interferon alpha 2a Before starting treatment should conduct an initial evaluation that includes history, physical examination and aids such as AFP, abdominal ultrasonography, blood count, thyroid hormones, glucose and creatinine. There should be the baseline ADNVHB TGP. Controls should be once a week during the first month of therapy and then monthly. Each visit will include a thorough history (investigating the occurrence of adverse effects), physical examination and laboratory (complete blood count, ALT, albumin, glucose, creatinine, triglycerides). They carry out checks on viral load at week 12, 24, 48 (third, sixth and twelfth month of treatment), and 6 months after the last dose of drug. If the week 12 viral load has decreased less than 1log (10 IU / ml), it is considered that there is NO primary response, so this drug should be discontinued and Tenofovir or Entecavir will start in his place. If the week 24 viral load is <2.000 IU / ml is considered to exist virologic response. Continue to complete 48 weeks treatment. If after 6 months of the last dose of pegylated interferon alpha 2a control of viral load is undetectable, is considered SVR. HBsAg will be sought 24 weeks (6 months) after achieving sustained viral response.

15
Monitoring during treatment with oral antivirals Before starting treatment should conduct an initial evaluation that includes history, physical examination and laboratory tests such as CBC, AFP, abdominal ultrasound, blood glucose, urea and creatinine. It is very important to have ADNVHB TGP levels at baseline. Evaluations should be conducted every 2 months to monitor the fi n compliance. Each evaluation will include a thorough history, physical examination and laboratory blood count, SGPT, and creatinine. In the case of Tenofovir also be added, calculated creatinine clearance (see Annex 6) and simple urine test. In case of any changes in renal function with use of tenofovir, discontinue it and start treatment with Entecavir. (Creatinine clearance less than 60%). They carry out checks on viral load at week 12, 24 and 48 of treatment. From week 48 of treatment viral load controls will be every 6 months. If it detects a rise> 1log 10 IU / ml compared to the lowest level reported for the patient is considered that there is viral reactivation. In this case you should assess whether there is inadequate compliance with medication. If adherence is adequate, it is likely that you are generating resistance to antiviral employee. In these cases it is recommended to add another oral antiviral high genetic barrier. They seek to maintain an undetectable viral load values in order to reduce the chances of resistance. Treatment is continued until the disappearance of HBsAg and the appearance of antibody. Since the latter condition occurs in 1% of cases, the patient may receive treatment on an indefinite nida.

6.4.2.2. Treatment in Special Cases A. - Treatment of Patients with Decompensated Cirrhosis HBeAg Positive and Negative These patients should be treated in specialist units. Treatment is indicated only detected the presence of hepatitis B virus with real-time PCR to prevent recurrent reactivation. Oral antivirals should be used with high genetic barrier and low rate of resistance (Entecavir first, it must be present in cirrhotic patients the presence of nephropathy associated with underlying cirrhosis and hepatorenal syndrome).
16

Patients can experience clinical improvement in a period of 3 to 6 months. B. - B Virus Infection in Cases of immunosuppressive therapy It has been shown in some retrospective studies and case series during or after immunosuppressive therapy is increased risk of reactivation of hepatitis B virus infection and even death have been reported cases of liver failure. In this regard, and for purposes of this guide is considered as immunosuppressive therapy to the following:
1. Use of chemotherapeutic drugs and radiation therapy. 2. Use of biological therapy has depressant effects on cellular and humoral
immunity
3. Using high-dose corticosteroids and maintenance

Before initiating therapy in any of the cases mentioned above must:
1. Evaluated serology for active or past infection with hepatitis B virus by

determining HBsAg and anti-HBc.
2. Should receive the hepatitis B vaccine in non-protected (antiHBs level of

negative or less than 10 IU / mL).
3. In candidates for chemotherapy and immunosuppressive therapy who are

HBsAg positive should be performed:
a. Viral load, which will serve as a baseline for follow-up marker b. Should be treated with Lamivudine 100 mg. a day in a single dose of 4
to 8 weeks before starting immunosuppressive therapy if baseline HBV DNA is undetectable by PCR in real time. This therapy should be continued until 12 months after completion of the immunosuppressive scheme.
4. In
patients with detectable viral load and expected to receive immunosuppressive therapy for long periods, even when the level is normal TGP should start antiviral treatment with high potency and high genetic barrier for the high risk of inducing resistance: Tenofovir or Entecavir . no detectable HBV DNA should be watched (viral load at 12 weeks) during chemotherapy or immunosuppressive therapy, antiviral treatment commencing only be detected seroreversion before altering the liver profile.
5. Patients with negative HBsAg, anti-HBc positive, antiHBs> 10 IU / mL with
C. - B Virus Infection in Pregnancy It has been demonstrated in several epidemiological studies that the major risk of infection in early childhood is a state of chronic hepatitis B virus infection in the mother, but even if it has positive viral load greater than 2000 IU / mL. On the other hand, the presence of advanced liver disease (cirrhosis) significantly increases the risk of maternal morbidity and the likelihood of preterm birth, morbidity and mortality of the product. Therefore you must:
1. MADE HBV infection screening by determination of HBsAg in all pregnant

women in the first consultation.
2. Should pregnant women in those proven positive HBsAg should:

JOURNAL OF GASTROENTEROLOGY 2011 17
a. Determine the presence of HBeAg b. If HBeAg negative should be determined HBV DNA viral load c. Define if there is chronic liver disease using non-invasive tests:
ultrasound, blood count, platelet count, prothrombin time, albumin, bilirubin.
d. If proven liver cirrhosis, should immediately refer the patient to a

specialized unit and should be evaluated by trained obstetrician in cases of high complexity.
3. If the HBeAg or viral load is positive, the mother should be referred to a

specialist for a decision on antiviral therapy in the third trimester of pregnancy. Be used lamivudine, 100 mg. a day in one shot, 4 weeks before the calculated date of birth occurs.
4. If viral load is negative at the time of evaluation, does not require antiviral
therapy to the mother in the third quarter.
5. All HBsAg positive pregnant women should be monitored monthly for the
first 6 months after delivery, the risk of reactivation of hepatitis B.
6. In children born to HBsAg carrier mothers: a. The first dose of hepatitis B virus vaccine should be placed preferably
within the first 12 hours after birth. The scheme to be completed is the usual fi gure in the national immunization program.
b. Application of hyperimmune globulin (HBIg) to the newborn within 24

hours of delivery (0.5 mL intramuscularly as a single dose). Be placed in a different area than the application of the vaccine. The dose is applied regardless of birth weight.
c. If the child weighs less than 2 kg the dose should be applied first month
after birth because the newborn has an immature immune system. This initial dose should not be considered as dose 1, then the recommendation is that it needs to comlete the conventional vaccination. In these cases the child will receive 04 doses.
d. In the first 24 hours should determine the baseline liver profile and
whether the child is a carrier of HBsAg. If the child is a carrier of HBsAg should be referred to the reference level personnel trained in children with chronic hepatitis B.
e. If there is a carrier of HBsAg, to determine the infection status or

immunoprotection be determined HBsAg and anti-HBs at 9 and 18 months after birth to assess whether there has been contagion, or if the child is actually protected.
f. NOT RECOMMENDED determine serum anti-core, as this can be

detected up to 24 months after birth, these being of maternal (transplacental immunity)
g. If the child is HBsAg negative and anti-HBs title is less than 10 mIU /
mL, the child should receive a new vaccination course (03 doses) and 2 months after the last dose should determine the level of anti-HBs.
h. If the child is HBsAg negative and anti-HBs title is greater than 10 mIU /
mL CHILD is immunized and does not require additional monitoring.
i.
NOT RECOMMENDED elective Caesarean section in cases of HBsAg carrier mothers or stop breastfeeding.
18
CLINICAL GUIDELINES HEPATITIS B j.

All children under 19 years and have not been vaccinated should receive triple vaccination scheme.
D - Treatment of coinfection HIV / HBV In these cases must be taken into consideration: The HBV DNA level The serum level of CD4 The need for antiretroviral therapy for HIV infection. The severity of liver disease. Do not forget that in patients with chronic hepatitis B, HIV progresses rapidly to liver cirrhosis.
I. Indications for Treatment: Treatment should be considered in all patients coinfected with HIV and chronic HBV meet one of the following criteria: When HBV DNA greater than or equal to 2.000 IU / mm transaminases
3,
with elevated
In cases where the level of TGP is normal, should be evaluated by liver biopsy histologic damage (necroinflammation determination or fibrosis) or by an alternative method for deciding on treatment. If HBV DNA is less than 2,000 IU should be assessed to consider the histological damage and treatment. In cases of compensated cirrhosis and HBV DNA-positive, even with less than 2,000 IU / mm 3 be considered for HBV treatment, independent of CD4 count should be the start of HAART therapy. In patients with decompensated cirrhosis regardless of the value of HBV DNA will initiate HAART. HAART should be initiated with two active drugs for HBV.

II. Recommended schemes. See Table 5 .
19

III. Precautions in use of antiretrovirals in patients co-infected HIV / HBV: There is no evidence to contraindicate absolutely, the use of any antiretroviral agent in HIV-infected patients with viral hepatitis (DEIS). Use with caution: o o o Nucleoside RTIs: Didanosine, Abacavir, Zidovudine, Stavudine Non-nucleoside RTIs: nevirapine PIs: Ritonavir, Atazanavir
IV. Patients co-infected HIV / HBV lamivudine-containing HAART Add Tenofovir monotherapy in patients with lamivudine and undetectable HIV viral load. If there is resistance to lamivudine with evidence of detectable HIV viral load assessment is recommended by expert committees and ability to perform genotyping.
V. Duration of treatment with oral antiviral In HBeAg (+) and HBV DNA undetectable, continue until 12 months after seroconversion from HBeAg to anti-HBe. In HBeAg (-), treatment will be for indefinite time nest
VI. Special cases Will be discussed in the Committee of Experts or a Medical Board at the relevant ruling to define the treatment. E. - Virus C Coinfection There is insufficient evidence to indicate the specific therapy of coinfection with HBV / HCV. The current recommendation is to treat the infection that predominates. If HBV DNA levels are undetectable or low, and HCV-RNA is elevated, refer the patient to a specialist. If you have HBV DNA 104UI/ml undetectable HCV-RNA and will address the virus, pursuant to the provisions of this guide If the levels of HBV DNA and HCV RNA are both high, they refer the patient to a specialist. Regular monitoring is required TGP HCV RNA HBV-DNA during and after treatment, as dominant virus suppression can lead to reactivation of previously suppressed virus. The reactivation of HBV during antiviral treatment will be handled by adding pursuant to the provisions of this guide.

F. - Co-infection with Delta Virus (HVD) Suspect HDV superinfection in all patients with chronic HBV infection coming from areas with high endemicity for hepatitis B virus, and present or sudden decompensation.
20

Coinfection HBV / HDV is confi rms by the presence of serum HDV-Ag. The primary objective of this co-infection treatment is to suppress the replication VHD. Treatment should be decided by a medical board in a specialized center. The best strategy to eradicate this virus is universal vaccination against HBV.

6.4.3. Adverse effects and treatment (see Annexes 1 and 3) 6.4.4. Warning Signs Clinical: Presence of severe fatigue, nausea, vomiting, jaundice, ascites, encephalopathy and gastrointestinal bleeding. Laboratory tests show deterioration of liver function tests: Prolongation of prothrombin time, decreased albumin level, elevated SGPT level of severe hyperbilirubinemia. 6.4.5. Criteria for discharge Usually the patient with chronic HBV infection, even without specific antiviral therapy should be under regular surveillance permanently. However, in some cases may be considered clinical and laboratory criteria to indicate high: - Improved clinical - Standardization biochemical - Conversion of Anti-HBs HBsAg 6.4.6 Forecast The outcome will depend on the response to antiviral treatment used and the absence of viral resistance to the drug used. 6.5. COMPLICATIONS Liver cirrhosis: In these cases it will be according to the complications presented by the patient. Hepatocellular Carcinoma: In these cases, the patient should be evaluated in a specialized center to determine the type of therapy specifi ca. 6.6. BENCHMARKS and counter The benchmarks are based on the presence of clinical warning signs (severe fatigue, nausea, vomiting, jaundice, ascites, encephalopathy and gastrointestinal bleeding) and / or deterioration of liver function tests (coagulopathy, hypoalbuminemia, hyperbilirubinemia, Severe elevation TGP) requiring hospitalization and other complications that can not be settled in the area of
21

application of this guide. 6.7 flowchart for the management of chronic hepatitis B HBeAg positive and HBeAg negative. (A) Management of Patients with HBeAg positive chronic hepatitis B without cirrhosis
(B) Management of Patients with HBeAg negative chronic hepatitis B without cirrhosis
22
(C) Treatment of cirrhotic patients HBeAg positive and HBeAg negative Chronic Hepatitis B
ANNEX N 1. Side Effects of Treatment with Interferon
23
APPENDIX No. 2. Dose adjustment of drugs for infection with hepatitis B virus
Annex 3. Comparative Analysis of the treatments used in the therapy of chronic hepatitis B
24

Annex 4. METAVIR Histological Classification
ANNEX N 5. Histological Staging System according to Ishak chronic hepatitis
25

III. BIBLIOGRAPHY 1. Lok AS, McMahon BJ, Practice Guidelines Committee, American Association for the Study of Liver Diseases (AASLD). Chronic hepatitis B: update of recommendations. Hepatology. 2004 Mar, 39 (3) :857-61 2. Lok AS and McMahon BJ. AASLD Practice Guidelines: Chronic hepatitis B: Update 2009. Hepatology 2009, 50 (3) :661-2 3. McMahon BJ, Dienstag JL. Hepatitis B Virus Infection. NEJM 2008, 358:14861500. 4. Perillo RP, Schiff ER, Davis GL, Bodenheimer HC, Lindsay K, Payne J, et al. A randomized, controlled trial of interferon alfa 2-b alone and after-prednisone withdrawal for the Treatment of chronic hepatitis B. N Eng J Med 1990,323.295301 5. Wong DK, Cheung AM, O `Rourke K, Naylor CD, Detsky AS, Heathcote J. Effect of alpha-interferon Treatment in Patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis.Ann Intern Med 1993; 119312-323. 6. Zoulim F, puppy R. Hepatitis B: re fl ections on the current approach to antiviral therapy. J Hepatol 2008; 48 (suppl1): S2-S19. 7. Bonino F, Marcellin P, Lau GK, Hadziyannis S, Jin R, Piratvisuth T, et al. Predicting response to peginterferon alpha-2a, lamivudine and the two HBeAgnegative for Combined chronic hepatitis B. Gut 2007, 56:699-705 8. Fried MW, Piratvisuth T, Lau GKK, Marcellin P, Chow WC, Cooksley G et al.HBe Ag and hepatitis B virus DNA as outcome predictors DURING therapy with peginterferon alfa-2a for HBe Ag-positive chronic hepatitis B. Hepatology 2008, 47:428-434 9. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, M et al.Long Rizetto-term therapy with adefovir for HBeAg-negative dipovoxil chronic hepatitis B for up to 5 years. Gastroenterology 2006, 131:1743-1751. 10. Flink HJ, van Zonnevald M, Hansen BE, Mann RA, Schalm SW, Janssen HL, HBV 99-01 Study Group. Treatment with Peg-interferon alpha 2-b for chronic hepatitis B HBeAgpositive: HBsAg loss is associated with HBV genotype. Am J Gasttoenterol 2006, 101. 297-303 11. Yuen MF, Fong DY, Wong DK, Yuen JC, Lai CL. Hepatitis B Virus DNA Levels at week 4 of lamivudine Treatment Predicts the 5-year ideal response. Hepatology 2007, 46:1695-1703 12. Marcellin P, Lau GK, Bonino F, Farsi P, Hadziyannis S, Jin R, et al. Peg interferon alfa-2a alone, lamivudine alone, and the two in combinationin Patients wih chronic HBe Ag-negative hepatitis B. N Eng J Med 2004; 351:1206-1217 13. Zarski JP, Bohn B, Bastie A, et al. Characteristics of Patients with Dual Infection by hepatitis B and C viruses. J Hepatol 1998, 28 (1): 27. 14. National Institutes of Health Consensus Development Conference. Statement:
26

Management of Hepatitis C. Hepatology 2002:36 (Suppl1) :3-20. 15. Senturk et al. Chronic hepatitis C combination therapy Responds poorly to hepatitis B in chronic carriers. The Neth Journ Med 2008; 66 (5) :192-195. 16. Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H. A Treatment algorithm for the management of chronic hepatitis B virus Infection in the United States: 2008 update. Clin Gastroenterol Hepatol 2008; 6 (12) :131541. 17. Daruich J, Gadano A, Fainbom H, et al. Clinical Practice Guidelines: Guidelines for Treatment of Latin American Chronic Hepatitis B. Latin American Gastroenterological Acta 2007, 37 (3) :168-177. 18. Al-Mahtab M, Rahman S, Akbar SM, Khan IF, Uddin M, Karim F, Ahmed F. Combination therapy with antiviral drugs and hepatitis B vaccine in asymptomatic and detected incidentally, chronic hepatitis B virus carriers at Bangladesh. Viral Immunol. 2010 Jun, 23 (3) :335-8. 19. Haddad R, Martinelli Ade L, Uyemura SA, Yokosawa J. Hepatitis B virus genotyping Among Patients with chronic hepatitis B with lamivudine resistance to Treatment in the City of Ribeiro Preto, State of So Paulo. Rev Soc Bras Med Trop 2010; 43 (3) :224-8. 20. He XX, Chang Y, Jiang HJ, Tang F, Meng FY, Xie QH, Li PY, Song YH, Lin JS .. Persistent effect of IFNAR-1 genetic polymorphism on the long-term pathogenesis of chronic HBV Infection. Viral Immunol. 2010, 23 (3) :251-7. 21. Wu B, Li T, Chen H, Shen J. Cost-Effectiveness of Nucleoside Analog Therapy for Hepatitis B in China: A Markov Analysis. Value Health. 2010 April 30. [Epub ahead of print] 22. Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B Immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database of Systematic Reviews 2006, Issue 2. Art No.: CD004790. DOI: 10.1002/14651858.CD004790.pub2. 23. Centers for Disease Control and Prevention. A comprehensive immunization strategy to Eliminate Transmission of Hepatitis B Virus Infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part 1: Immunization of Infants, Children, and Adolescents. MMWR 2005, 54 (No. RR-16): [inclusive page numbers]. 24. Ayoub WAS, Keeffe EB. Review article: current antiviral therapy of chronic hepatitis B. Aliment Pharmacol There. 2008 Jul, 28 (2) :167-77. 25. European Association For The Study Of The Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol. 2009 Feb, 50 (2) :22742. 26. Liaw YF, Leung N, Guan R, Lau GK, Merican I, Mc-B. Asian-Paci fi c consensus statement on the man-caugh G, Gane E, Kao JH, Omata M, Asian-Paci fi c agement of chronic hepatitis B: a 2005 update. Liver consensus update working party on chronic hepatitis Int 2005, 25 (3) :472-89.
27

Journal of Gastroenterology of Peru

Diunggah oleh

Informasi Dokumen

Deskripsi Asli:

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Journal of Gastroenterology of Peru

Diunggah oleh

Hak Cipta:

Format Tersedia

CLINICAL GUIDELINES HEPATITIS B