journal of gastroenterology of peru

8/3/2019 Journal of Gastroenterology of Peru

http://slidepdf.com/reader/full/journal-of-gastroenterology-of-peru 1/27

CLINICAL GUIDELINES HEPATITIS B

JOURNAL OF GASTROENTEROLOGY 2011 1

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 H epatitis B: - P eruvian Association f or the S tudy o f L iver - S ociety o f G astroenterology in P eru - P eruvian Society o f I n f ectious and Tropical D iseases * M embers o f the collaborative group o f the N ational H epatitis B guide at the end o f the article.

S UMMARY This guide sets out the technical criteria for the diagnosis and treatment of chronichepatitis secondary to viral hepatitis B in order to help reduce the morbidity of thisdisease. Give definitions to understand the recommendations given here. Overviewof epidemiology, associated risk factors, clinical aspects and diagnosis of chronichepatitis B. They give management recommendations including specialcircumstances such as patients with cirrhosis, patients with HIV co-infection orcoinfection with hepatitis C. The recommendations herein become nationalguidance for the management of chronic hepatitis B. Hepatitis

K EY WORD S: chronic hepatitis, viral hepatitis B, User Guide, Treatment.

AB S TRACT

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 theMorbidity and Mortality of This Disease. The Practical Guide give definitions to helpUnderstand the Terminology, describes epidemiology, Risk Factors, and ClinicalAspects and the diagnosis of chronic hepatitis B. Finally the guide givemanagement recommendations for the special Circumstances Including Patientswith cirrhosis Such as, Patients coinfected with HIV or coinfected with hepatitis C. The recommendations of the guide Become The national guide for themanagement of chronic hepatitis B.

K EYWORD S: chronic hepatitis, viral hepatitis B, User Guide, Treatment.





I. PURPO S E

Contribute to reducing morbidity and mortality from chronic hepatitis.

II. OBJECTIVE

The Clinical Practice Guideline is intended to establish the technical criteria for theprevention, diagnosis, treatment and control of chronic hepatitis.

III. S COPE

This manual is applicable nationwide.

IV. CLINICAL PRACTICE GUIDELINE S FOR THE DIAGNO S I S ANDTREATMENT OF CHRONIC HEPATITI S VIRU S OF HEPATITI S B

4.1. NAME AND CODE

CIS: B18 chronic hepatitis B,

4.2. OTHER NAME S

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:

a. HBeAg positive chronic hepatitis B (also called "wild HBV variant") isdefined by the presence of HBsAg 1, 2 and absence of HBeAg Anti-HBe 3. Inthese cases, HBV DNA is present in 4 high levels (> 10 6). Usually occurs inthe first years of infection.

b. HBeAg negative chronic hepatitis B, occurs in two situations, whetherthere are mutations at the core promoter or precore, and is characterizedby positive HBsAg, HBeAg negative, anti-HBe positive and HBV-DNApresent in low (< 10 6). It usually occurs in advanced stages of chronicinfection.

5.1.1. Glossary of Terms

Inactive Carrier S tate : Persistent infection of the liver without necro-inflammatory activity signifi cannot, but with the presence of HBsAg (surfaceantigen, 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 infectionwith HBV and cured. It is characterized by normal transaminases as well as totalAnticor presence of Anti-HBs5 positive and positive.

Acute exacerbation : Condition in which a patient with chronic hepatitistransaminase elevation, so sudden has a clinical and biochemical featuresconsistent with acute hepatitis. Transaminases rise more than twice the baseline.

Reactivation of Hepatitis B : It is a condition in which a patient in chronicinactive carrier phase, suddenly presents important viral replication associated withhepatocellular damage which is characterized by elevated more than 10 times thenormal limit or more than 2 times baseline transaminases.

HBeAg clearance : The condition of serological HBeAg loss occurs in a previouslypositive to it.

HBeAg S eroconversion : The condition occurs serological HBeAg loss andappearance of anti-HBe in a person with positive HBeAg and anti-HBe negative.

HBeAg seroreversion : Reappearance of HBeAg in a person who was HBeAgnegative 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 areunevenly distributed geographically in the world. In Peru predominant genotype F.

5.3. PATHOPHY S IOLOGY

Once the acute infection produced under certain conditions related to control of viral persistence of immunity occurs and is detected HBsAg for more than 6months. 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 atgreater risk of going to chronicity.

5.4. Epidemiology

It is estimated that worldwide more than 2,000 million people have been infectedwith Hepatitis B, and including more than 300 million are chronic carriers. 25% diefrom a direct consequence of the disease, either by cirrhosis, chronic activehepatitis or primary liver cancer. 80% of HCC cases registered worldwide have ascausal to HBV, which according to WHO is the second leading cause of cancer inhumans, 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





VI. S PECIAL CON S IDERATION S

6 .1. CLINICAL

6 .1.1. S igns and S ymptoms

The chronic form is usually asymptomatic, may occur occasionally generalsymptoms: fatigue, hyperoxia, dyspepsia, intolerance to alcohol. As the infectionprogresses to cirrhosis may occur: palmar erythema, collateral circulation,

jaundice, ascites and edema. Sometimes the patient may present as acutehepatitis 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 fromthe acute episode if it had been recognized as such. However, in most cases thereis no history of clinical symptoms of acute hepatitis, so the finding of HBsAg in anasymptomatic 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. DIAGNO S I S

6 .2.1. Diagnostic Criteria :

The diagnosis of chronic hepatitis B is given by the presence of HBsAg for morethan six months, with the common situations in which this diagnosis should besuspected 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





a. B virus carrier mothers b. Sexual partner B virus carrier c. Accidental puncture with potentially contaminated material d. Addiction to illegal drugs

e. Proceed in a geographical area of high prevalence for hepatitis B f. 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. Quantitative HBsAg 2. HBeAg 3. Anticore 4. Anti-HBe. 5. TGP 6. HBV DNA by real-time PCR6 7. HBV genotyping

6 .3.2. In Pictures

Abdominal ultrasound: Useful to evaluate the presence of liver cirrhosis and / orhepatocellular 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 followingcircumstances:

1. Patients after a period of 3-6 months remain HBeAg positive with HBV DNAgreater than 20,000 IU / mL (10 5 copies / ml) and elevated SGPT less than2 times the normal value.

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 A2moderate inflammation (METAVIR) should be considered for treatment. SeeAnnexes 4 and 5.

6 .4. MANAGEMENT BY LEVEL OF COMPLEXITY and response capacity

6 .4.1. General measures and preventive

a. Avoid consumption of alcohol b. Avoid overweight (especially if the BMI is greater than 29) c. Controlled use of potentially hepatotoxic and immunosuppressive drugs. d. 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. S pecific Treatment

Tax Treatment: Defined by the specialist, gastroenterologist or infectious diseasespecialist with expertise in liver disease management and use of antiviral drugsand 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 animmunomodulator with antiviral properties. Is used in adults for a finitetime of 48 weeks.

2. Antivirals : These are drugs that prevent viral replication by interfering withtheir life cycle, so that the virus can not make more copies of itself. Thesedrugs are taken once a day orally. The time of therapy depends on the typeB virus (HBeAg negative or positive) and HBeAg seroconversion. In caseswhere the infection is by the variant HBeAg +, therapy should be





maintained for at least 6 months after seroconversion to anti-HBe (+) andHBeAg (-)

In cases of infection by the variant HBeAg (-) you will need to continue therapyindefinitely or until HBsAg seroconversion.

Currently in the Peruvian market, there are three oral anti-HBV drugs: I. Lamivudine, approved in 1989

II. Entecavir, approved in 2005 III. Tenofovir, approved in 2008

6 .4.2.3. Treatment S trategies

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. Thereconstituted solution takes maximum 24 hours in refrigeration (2-8 º C,not frozen). After this time should be discarded.

Pegylated IFN alfa-2a is applied to the dose of 180 gr subcutaneouslyevery week for 48 weeks.

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, needsto 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, ashas 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, esophagealvarices, ascites, jaundice and hepatic encephalopathy and functionalimpairment)

Platelets <70,000 / mm 3

Neutrophils <1,500 / mm3

Severe cardiac disease Neoplasia of any kind Insulin dependent diabetes mellitus uncontrolled Psoriasis Major Depression Addiction to alcohol and illicit drugs Uncontrolled seizure syndrome





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 isshown in Annex 3.

C. - chronic viral hepatitis B : HBeAg positive or without cirrhosisCompensated 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. SeeAnnexes 4 and 5.

In circumstances in which liver biopsy is indicated but is logistically or technicallyimpossible 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-HBsantibody. However, since this is achieved in the minority of patients (1-3%), thepractical objective in these cases is now Negativization VIRAL LOAD B virusdetermined by a highly sensitive diagnostic method, and the disappearance HBeAgwith 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 anindividualized analysis of the efficacy, safety and genetic barrier (rate of





resistance).

Pegylated interferon alpha 2a has the advantage of having a finite duration (48weeks). The ideal candidate is a young patient without cirrhosis, with viral loadbelow 10 7 IU / ml, genotype A or B, HBeAg positive and high TGP more than 3times the normal value. Before a thorough study should be discarded comorbiditiesthat could worsen during use, taking into account the list of adverse effects andcontraindications of the drug.

It is important to note that this strategy will need training in subcutaneousapplication of blisters (preferably by the patient to avoid infection by puncture) andrefrigerated storage facilities for the same. If there are doubts about compliancewith these conditions is not considered a suitable candidate to receive interferon.

Patients who have contraindications or high risk of not tolerating or failing tocomply with interferon therapy, or who have received no response, are tributariesto 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 (diabetesmellitus, hypertension, known history of glomerulopathy) or need for drugs thatpredispose 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, includinghistory, physical examination and ancillary tests including complete bloodcount, 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 countand TGP.

They carry out checks on viral load at week 12, 24, 48 (third, sixth andtwelfth 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 treatmentand at 6 months after treatment ends.

If the week 12 viral load decreased to <1log 10 IU / ml, it is consideredthat there is NO PRIMAR Y RESPONSE (also called primary failure). In thiscase the drug should be discontinued and Tenofovir or Entecavir will start inhis place.

If the week 24 viral load is <2.000 IU / ml is considered to exist virologicresponse.

If after 6 months of the last dose of Interferon control of viral load isundetectable, it is considered SVR.

If you also have achieved HBeAg seroconversion, treatment was consideredsuccessful.





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, includinghistory, 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 atbaseline.

The visits should be every month until the sixth month and then every 3months.

Each visit will include thorough history and physical examination andlaboratory tests: CBC, SGPT, and creatinine. In the case of Tenofovir alsobe added urea, creatinine clearance calculated and simple urine test.

In case of any changes in renal function with use of tenofovir, discontinue itand start treatment with Entecavir. (Annex 2: adjustment in renalimpairment).

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 consideredthat there is an absence of primary response. In these cases we mustadd another drug with a high genetic barrier (Entecavir or tenofovir).

If the week 48 viral load is undetectable by real-time PCR, it is consideredthat 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 stilldetectable virologic response is considered PART. We recommend addinganother 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 forthe patient sees a virological relapse. In this case, genotyping is indicated(analysis of resistance). There should be adequate to assess medicationadherence. If adherence is adequate, it is likely that you are generatingresistance to antiviral employee. We recommend adding another oralantiviral high genetic barrier.

They seek to maintain an undetectable viral load values in order to reducethe chances of resistance.

Treatment is continued until 6 months after achieving HBeAgseroconversion (HBeAg loss and appearance of anti HBe).

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





D. Chronic Viral Hepatitis B : HBeAg negative. Without cirrhosis and / orwith compensated cirrhosis.

For the treatment should take into account the following criteria: Levels of HBVDNA 2000 IU / mL or 10 4 copies / ml persistently elevated SGPT levels (morethan 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 byTGP and HBeAg tests:

I. Every 6 months, if you have previous values persistently normal TGP. II. 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. HBV DNA 10 4 copies or 2.000 IU / ml and ALT less than 2 timesthe upper normal value.

II. HBV DNA 10 3 copies / ml and <10 4 IU / ml with high TGP. III. When in doubt about the existence of hepatic comorbidity.

If a liver biopsy showing fibrosis ( F2 METAVIR histological classification) ormoderate to severe inflammation ( A2, METAVIR) should be considered fortreatment.

Treatment goals HBeAg negative HBV

The ideal objective is the eradication of HBsAg with the appearance of Anti-HBsantibody. However, since this is achieved in a minority of patients (1%), thepractical objective in this patient group is to keep the viral load measured by PCRin 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 anindividualized analysis of the efficacy, safety and genetic barrier (rate of resistance).

Pegylated interferon alpha 2a has the advantage of having a fixed period (48weeks). The ideal candidate is a young patient without cirrhosis, with viral loadbelow 10 7 IU / ml, genotype A or B, HBeAg positive and elevated transaminasesmore than 3 times the normal value.





If you choose to pegylated interferon alpha 2a, previously ruled out a detailedstudy 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 subcutaneousapplication of blisters (preferably by the patient to avoid accidental puncturetransmission) and refrigerated storage facilities for the same. If there are doubtsabout compliance with these conditions is not considered a suitable candidate toreceive pegylated interferon alfa 2a.

Patients who have contraindications or high risk of not tolerating or failing tocomply with therapy with pegylated interferon alfa 2a, or that you have receivedno 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 / orpatients with known renal disease, comorbidity, or need for drugs that predisposeto develop nephropathy.

Monitoring during treatment with pegylated interferon alpha 2a

Before starting treatment should conduct an initial evaluation that includeshistory, physical examination and aids such as AFP, abdominalultrasonography, 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 bloodcount, ALT, albumin, glucose, creatinine, triglycerides).

They carry out checks on viral load at week 12, 24, 48 (third, sixth andtwelfth 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 isconsidered that there is NO primary response, so this drug should bediscontinued and Tenofovir or Entecavir will start in his place.

If the week 24 viral load is <2.000 IU / ml is considered to exist v irologic 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 viralresponse.





Monitoring during treatment with oral antivirals

Before starting treatment should conduct an initial evaluation that includeshistory, 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 alsobe added, calculated creatinine clearance (see Annex 6) and simple urinetest.

In case of any changes in renal function with use of tenofovir, discontinue itand 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 youshould assess whether there is inadequate compliance with medication. If adherence is adequate, it is likely that you are generating resistance toantiviral employee. In these cases it is recommended to add another oralantiviral high genetic barrier.

They seek to maintain an undetectable viral load values in order to reducethe chances of resistance.

Treatment is continued until the disappearance of HBsAg and theappearance 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 S pecial Cases

A. - Treatment of Patients with Decompensated Cirrhosis HBeAg Positiveand Negative

These patients should be treated in specialist units. Treatment is indicated onlydetected the presence of hepatitis B virus with real-time PCR to prevent recurrentreactivation. 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).





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 afterimmunosuppressive 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 thefollowing:

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 HBVDNA is undetectable by PCR in real time. This therapy should becontinued until 12 months after completion of the immunosuppressivescheme.

4. In patients with detectable viral load and expected to receiveimmunosuppressive therapy for long periods, even when the level is normalTGP should start antiviral treatment with high potency and high geneticbarrier for the high risk of inducing resistance: Tenofovir or Entecavir .

5. Patients with negative HBsAg, anti-HBc positive, antiHBs> 10 IU / mL withno detectable HBV DNA should be watched (viral load at 12 weeks) duringchemotherapy or immunosuppressive therapy, antiviral treatmentcommencing only be detected seroreversion before altering the liver profile.

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 themother, but even if it has positive viral load greater than 2000 IU / mL. On theother hand, the presence of advanced liver disease (cirrhosis) significantlyincreases 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 pregnantwomen in the first consultation.

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





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 aspecialized unit and should be evaluated by trained obstetrician in casesof high complexity.

3. If the HBeAg or viral load is positive, the mother should be referred to aspecialist for a decision on antiviral therapy in the third trimester of pregnancy. Be used lamivudine, 100 mg. a day in one shot, 4 weeks beforethe calculated date of birth occurs.

4. If viral load is negative at the time of evaluation, does not require antiviraltherapy to the mother in the third quarter.

5. All HBsAg positive pregnant women should be monitored monthly for thefirst 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 preferablywithin the first 12 hours after birth. The scheme to be completed is theusual fi gure in the national immunization program.

b. Application of hyperimmune globulin (HBIg) to the newborn within 24hours of delivery (0.5 mL intramuscularly as a single dose). Be placed ina different area than the application of the vaccine. The dose is appliedregardless of birth weight.

c. If the child weighs less than 2 kg the dose should be applied first monthafter birth because the newborn has an immature immune system. Thisinitial dose should not be considered as dose 1, then therecommendation is that it needs to comlete the conventionalvaccination. In these cases the child will receive 04 doses.

d. In the first 24 hours should determine the baseline liver profile andwhether the child is a carrier of HBsAg. If the child is a carrier of HBsAgshould be referred to the reference level personnel trained in childrenwith chronic hepatitis B.

e. If there is a carrier of HBsAg, to determine the infection status orimmunoprotection be determined HBsAg and anti-HBs at 9 and 18months after birth to assess whether there has been contagion, or if thechild is actually protected.

f. NOT RECOMMENDED determine serum anti-core, as this can bedetected 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 2months 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 HBsAgcarrier mothers or stop breastfeeding.





j. All children under 19 years and have not been vaccinated should receivetriple 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 HBVmeet one of the following criteria:

When HBV DNA greater than or equal to 2.000 IU / mm 3, with elevatedtransaminases

In cases where the level of TGP is normal, should be evaluated by liverbiopsy histologic damage (necroinflammation determination or fibrosis) orby an alternative method for deciding on treatment.

If HBV DNA is less than 2,000 IU should be assessed to consider thehistological damage and treatment.

In cases of compensated cirrhosis and HBV DNA-positive, even with lessthan 2,000 IU / mm 3 be considered for HBV treatment, independent of CD4count 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 .





III. Precautions in use of antiretrovirals in patients co-infected HIV / HBV :

There is no evidence to contraindicate absolutely, the use of anyantiretroviral agent in HIV-infected patients with viral hepatitis (DEIS).

Use with caution:

o Nucleoside RTIs: Didanosine, Abacavir, Zidovudine, Stavudine o Non-nucleoside RTIs: nevirapine o PIs: Ritonavir, Atazanavir

IV. Patients co-infected HIV / HBV lamivudine-containing HAART

Add Tenofovir monotherapy in patients with lamivudine and undetectableHIV viral load.

If there is resistance to lamivudine with evidence of detectable HIV viralload assessment is recommended by expert committees and ability toperform 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. S pecial cases

Will be discussed in the Committee of Experts or a Medical Board at the relevantruling to define the treatment.

E. - Virus C Coinfection

There is insufficient evidence to indicate the specific therapy of coinfectionwith HBV / HCV. The current recommendation is to treat the infection thatpredominates.

If HBV DNA levels are undetectable or low, and HCV-RNA is elevated, referthe patient to a specialist.

If you have HBV DNA 104UI/ml undetectable HCV-RNA and will addressthe virus, pursuant to the provisions of this guide

If the levels of HBV DNA and HCV RNA are both high, they refer the patientto a specialist.

Regular monitoring is required TGP HCV RNA HBV-DNA during and aftertreatment, as dominant virus suppression can lead to reactivation of previously suppressed virus.

The reactivation of HBV during antiviral treatment will be handled by addingpursuant to the provisions of this guide.

F. - Co-infection with Delta Virus (HVD)

Suspect HDV superinfection in all patients with chronic HBV infectioncoming from areas with high endemicity for hepatitis B virus, and present orsudden decompensation.





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 S igns

Clinical :

Presence of severe fatigue, nausea, vomiting, jaundice, ascites, encephalopathyand 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 antiviraltherapy should be under regular surveillance permanently. However, in some casesmay 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 theabsence of viral resistance to the drug used.

6 .5. COMPLICATION S

Liver cirrhosis: In these cases it will be according to the complications presentedby the patient.

Hepatocellular Carcinoma: In these cases, the patient should be evaluated in aspecialized center to determine the type of therapy specifi ca.

6 . 6 . BENCHMAR KS and counter

The benchmarks are based on the presence of clinical warning signs (severefatigue, nausea, vomiting, jaundice, ascites, encephalopathy and gastrointestinalbleeding) and / or deterioration of liver function tests (coagulopathy,hypoalbuminemia, hyperbilirubinemia, Severe elevation TGP) requiringhospitalization and other complications that can not be settled in the area of





application of this guide.

6 .7 flowchart for the management of chronic hepatitis B HBeAg positiveand HBeAg negative.

(A) Management of Patients with HBeAg positive chronic hepatitis B

without cirrhosis

(B) Management of Patients with HBeAg negative chronic hepatitis Bwithout cirrhosis





(C) Treatment of cirrhotic patients HBeAg positive and HBeAg negativeChronic Hepatitis B

ANNEX N º 1. Side Effects of Treatment with Interferon





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 chronichepatitis B





Annex 4. METAVIR Histological Classification

ANNEX N º 5. Histological Staging System according to Ishak chronic hepatitis





III. BIBLIOGRAPHY

1. Lok AS, McMahon BJ, Practice Guidelines Committee, American Association forthe 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: Update2009. Hepatology 2009, 50 (3) :661-2

3. McMahon BJ, Dienstag JL. Hepatitis B Virus Infection. NEJM 2008, 358:1486-1500.

4. Perillo RP, Schiff ER, Davis GL, Bodenheimer HC, Lindsay K, Payne J, et al. Arandomized, controlled trial of interferon alfa 2-b alone and after-prednisonewithdrawal for the Treatment of chronic hepatitis B. N Eng J Med 1990,323.295-301

5. Wong DK, Cheung AM, O `Rourke K, Naylor CD, Detsky AS, Heathcote J. Effectof 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 antiviraltherapy. 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 HBeAg-negative 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.HBeAg and hepatitis B virus DNA as outcome predictors DURING therapy withpeginterferon 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.LongRizetto-term therapy with adefovir for HBeAg-negative dipovoxil chronic hepatitis Bfor up to 5 years. Gastroenterology 2006, 131:1743-1751.

10. Flink HJ, van Zonnevald M, Hansen BE, Mann RA, Schalm SW, Janssen HL, HBV99-01 Study Group. Treatment with Peg-interferon alpha 2-b for chronic hepatitis BHBeAgpositive: HBsAg loss is associated with HBV genotype. Am J Gasttoenterol2006, 101. 297-303

11. Yuen MF, Fong D Y, Wong DK, Yuen JC, Lai CL. Hepatitis B Virus DNA Levels atweek 4 of lamivudine Treatment Predicts the 5-year ideal response. Hepatology2007, 46:1695-1703

12. Marcellin P, Lau GK, Bonino F, Farsi P, Hadziyannis S, Jin R, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combinationin Patientswih 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 Infectionby hepatitis B and C viruses. J Hepatol 1998, 28 (1): 27.

14. National Institutes of Health Consensus Development Conference. Statement:




Management of Hepatitis C. Hepatology 2002:36 (Suppl1) :3-20.

15. Senturk et al. Chronic hepatitis C combination therapy Responds poorly tohepatitis 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 inthe United States: 2008 update. Clin Gastroenterol Hepatol 2008; 6 (12) :1315-41.

17. Daruich J, Gadano A, Fainbom H, et al. Clinical Practice Guidelines: Guidelinesfor Treatment of Latin American Chronic Hepatitis B. Latin AmericanGastroenterological 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 asymptomaticand detected incidentally, chronic hepatitis B virus carriers at Bangladesh. ViralImmunol. 2010 Jun, 23 (3) :335-8.

19. Haddad R, Martinelli Ade L, Uyemura SA, Yokosawa J. Hepatitis B virusgenotyping Among Patients with chronic hepatitis B with lamivudine resistance toTreatment in the City of Ribeirão Preto, State of São Paulo. Rev Soc Bras Med Trop2010; 43 (3) :224-8.

20. He XX, Chang Y, Jiang HJ, Tang F, Meng F Y, Xie QH, Li P Y, Song YH, Lin JS ..Persistent effect of IFNAR-1 genetic polymorphism on the long-term pathogenesisof chronic HBV Infection. Viral Immunol. 2010, 23 (3) :251-7.

21. Wu B, Li T, Chen H, Shen J. Cost-Effectiveness of Nucleoside Analog Therapyfor Hepatitis B in China: A Markov Analysis. Value Health. 2010 April 30. [Epubahead of print]

22. Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B Immunisation fornewborn infants of hepatitis B surface antigen-positive mothers. Cochrane Data-base of Systematic Reviews 2006, Issue 2. Art No.: CD004790. DOI:10.1002/14651858.CD004790.pub2.

23. Centers for Disease Control and Prevention. A comprehensive immunizationstrategy to Eliminate Transmission of Hepatitis B Virus Infection in the UnitedStates: 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 chronichepatitis B. Aliment Pharmacol There. 2008 Jul, 28 (2) :167-77.

25. European Association For The Study Of The Liver. EASL Clinical PracticeGuidelines: management of chronic hepatitis B. J Hepatol. 2009 Feb, 50 (2) :227-42.

26. Liaw YF, Leung N, Guan R, Lau GK, Merican I, Mc-B. Asian-Paci fi c consensusstatement on the man-caugh G, Gane E, Kao JH, Omata M, Asian-Paci fi c agementof chronic hepatitis B: a 2005 update. Liver consensus update working party onchronic hepatitis Int 2005, 25 (3) :472-89.

journal of gastroenterology of peru

Documents