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 Table of Contents    
REVIEW ARTICLE  
Year : 2009  |  Volume : 6  |  Issue : 1  |  Page : 55-79
Comparison of different Hepatitis B guidelines


Department of Gastroenterology, Apollo Gleneagles Hospital, Kolkata, India

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Date of Web Publication19-Feb-2011
 

   Abstract 

Hepatitis B is a global healthcare problem. An estimated one third of the global population have been infected with the hepatitis B virus (HBV). Various guidelines have been proposed for management of chronic hepatitis B. These guidelines have similarities and differences and are changed from time to time. Here, we have reviewed the management guidelines of chronic hepatitis B published after 2007 and highlighted the similarities and differences between their different recommendations.

Keywords: Adefovir dipivoxil, ALT, anti-HBe, antiviral resistance, Chronic Hepatitis B, diagnosis, Entecavir, Guidelines, HBeAg, HBsAg, HBV, HBV DNA, Interferon, screening, Telbivudine, Tenofovir disiproxil, treatment, prophyaxis.

How to cite this article:
Sethy PK, Goenka MK. Comparison of different Hepatitis B guidelines. Hep B Annual 2009;6:55-79

How to cite this URL:
Sethy PK, Goenka MK. Comparison of different Hepatitis B guidelines. Hep B Annual [serial online] 2009 [cited 2020 Jul 13];6:55-79. Available from: http://www.hepatitisbannual.org/text.asp?2009/6/1/55/76905



   Background Top


Guidelines are developed to assist healthcare providers in the recognition, diagnosis, and optimal management of patients with chronic hepatitis B (CHB). These guidelines are not intended to be prescriptive, and permit flexibility in interpretation. Also, the guidelines are evidence-based and incorporate expert medical opinion in addition to published information.

There have been rapid advances over the recent years, with revision of guidelines from time to time. Therefore, the most recently published versions represent the latest consensus view on optimal management.

The aim of this review is to highlight the significant recommendations from international and national guidelines, particularly those published from 2007 onwards, and outline the clinically relevant similarities and differences between their recommendations.


   Evolution of Chronic Hepatitis B Guidelines Top


Guidelines on the management of CHB have had to evolve to keep pace with therapeutic developments and the approval of new agents. Since the approval of interferon (IFN) for CHB in 1991, and the introduction of lamivudine (LVD) in 1998, five more agents have become available, adefovir (ADV) in 2002, pegylated IFN-α (pegIFN-α) and Entecavir (ETV) in 2005, telbivudine (LdT) in 2006, and tenofovir (TDF) in 2008. A key development influencing CHB management was made in 2001, when a threshold for initiating treatment, serum HBV DNA > 20,000 IU/ml, was somewhat arbitrarily set. [1] However, more recently, developed polymerase chain reaction (PCR)-based assays (e.g., Taqman assay in 2004) enable accurate quantification of lower levels of DNA. Guidelines have had to evolve, to incorporate a new understanding of the processes of CHB disease as well as new data on the therapeutic agents. This can be illustrated by considering the Asian-Pacific guidelines, which were first issued in 2000 [2] and revised in 2003. [3] The guidelines were subsequently revised again in 2005, following a large volume of new data on the treatment of CHB, for example, more studies on the events following the emergence of YMDD mutations, durability of response to LVD therapy, LVD therapy in patients with decompensated liver disease, in HBsAg positive patients undergoing chemotherapy or organ (other than liver) transplantation, and the role of hepatitis B virus (HBV) genotypes. The results of the Phase III clinical trial of ADV, ETV, pegIFN-α, and combination therapies had also become available or were emerging. [4]

In 2005, the finding that a biopsy revealed that patients with normal alanine aminotransferase (ALT) could have significant necroinflammation and fibrosis [5] and that patients with only slightly increased serum ALT were at increased risk of liver-related mortality, [6] meant that some of the guidelines published subsequently had recommended a more liberal use of biopsy in patients with CHB and normal ALT, particularly those aged > 40 years. There was also a tendency for the more recent guidelines to place less emphasis on the serum ALT level for deciding which patients should be treated.

In addition, the significance of serum HBV DNA as an indicator of a long-term outcome has been appreciated only relatively recently, [7] with data from the long-term prospective cohort studies released in 2005 - 2006, which show a strong relationship between elevated HBV DNA and a cumulative risk of cirrhosis and hepatocellular carcinoma (HCC). This information is beginning to cause a shift in thinking, with greater emphasis being placed on HBV DNA suppression and monitoring (using sensitive assays), and lower thresholds for initiating treatment (e.g., 2,000 IU/ml rather than 20,000 IU/ml). [8],[9]

Further information on the long-term use of LVD and ADV, Phase III results with ETV, pegIFN, and other agents, combination therapy with thymosin α-1 and IFN in adult patients, and IFN and LVD in pediatric patients, and the use of ADV or ETV in LVD-refractory disease, resulted in the Asian Pacific Association for the Study of the Liver (APASL) issuing an update to their guidelines in 2006, only 18 months after the publication of the previous version. [7] The guidelines are, however, already out of date again, because the LdT was approved after their formulation and publication.


   Overview of Similarities and Differences in Guideline Recommendations Top


Guidelines tend to have several features in common although the details and emphasis may vary between them. The guidelines generally focus on establishing which patients should be treated (based on serum HBV DNA and ALT levels), what treatments should be given, the duration for which a treatment should be administered, and the address resistance issues. [3],[8],[9],[10],[11],[12],[13],[14],[15] Differences between guidelines exist in the parameters used to decide whether a patient should receive treatment. Some of the guidelines have the same serum HBV DNA treatment threshold for HBeAg(+) and HBeAg(-) patients (although this level itself differs between guidelines, e.g., 2,000 IU/ml in the EASL [15] and German guidelines [9] and 20,000 IU/ml in the Dutch guidelines [10] ), whereas, others have a higher threshold for HBeAg(+) and HBeAg(-) patients (generally 20,000 and 2,000 IU/ml, respectively). An important area of difference is the emphasis placed on serum ALT, in deciding which patients should receive treatment. Some guidelines (e.g., AASLD, APASL) [8],[11] require ALT > 2 x ULN for the treatment to be initiated, whereas, the EASL guidelines only require elevated ALT (> ULN); others consider ALT to be unreliable (German) [9] as an indicator for treatment.

The AASLD [3] and Egyptian [5] guidelines recommend use of the revised, lower limits for the normal range of serum ALT concentration. The guidelines differ in their emphasis on biopsy. The EASL [15] and German guidelines [9] place more emphasis than the others on biopsy, while others recommend considering biopsy to guide treatment decisions in certain groups lacking, what they consider to be, a clear-cut indication for treatment. Differences exist between guidelines in the agents recommended; the Dutch, [10] German, [9] and Italian [13] guidelines recommend the use of pegIFN-α as the initial therapy, and the EASL [15] and Belgian [14] guidelines recommend pegIFN-α or an NA with high efficacy and low resistance, the AASLD [11] lists three preferred agents (pegIFN-α, ADV or ETV). Thymosin α-1 is considered an option by APASL; [8] however, the AASLD [11] and German [9] guidelines consider the data on thymosin α-1 conflicting and insufficient to recommend its use. The AASLD [11] guidelines recommend that IFN-α is not used in patients with compensated cirrhosis owing to the risk of hepatitis flares; some guidelines include it as an option in compensated disease, Italian [13] guidelines recommend it as a first-line therapy in compensated patients.


   Similarities and Differences in Guideline Treatment Recommendations Top


There are significant differences between guidelines in the parameters used to decide if a patient should receive treatment and in the agents recommended . Similarities and differences of all guidelines are summarized in [Table 1],[Table 2],[Table 3],[Table 4],[Table 5]. One of the key differences between the guidelines is the importance of liver biopsy in treatment decisions. For example, the Belgian [14] guidelines go to the extent of using serum HBV DNA and the ALT threshold as indicators for biopsy, not treatment; treatment decisions are then based on the biopsy results. Biopsy is mandatory in patients with elevated ALT, and should be considered in patients aged > 35 - 40 years with normal ALT exceeding the HBV DNA threshold. Similarly, the EASL [15] and both the Turkish VHSD and Turkish TASL guidelines advocate biopsy to determine whether treatment is warranted, and the German guidelines view it as important for all patients. Although other guidelines also recognize the usefulness of biopsy, they tend to recommend biopsy only in certain patient groups, in order to help in decision-making. [8],[10],[11],[16],[17],[18],[19],[20],[21]
Table 1: Similarities and differences in guideline treatment recommendations1

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Table 2: Similarities and differences in guideline treatment recommendations2

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Table 3: Similarities and differences in guideline treatment recommendations3

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Table 4: Similarities and differences in guideline treatment recommendations4

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Table 5: Similarities and differences in guideline treatment recommendations5

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Another area of difference is the emphasis placed on serum ALT in deciding which patients should receive treatment. Although they detail certain groups in which biopsy should be considered, to give the decision about whether to treat, the AASLD [11] , Italian, [13] and Romanian [17] guidelines recommend treatment when serum ALT is > 2 x ULN (in conjunction with serum HBV DNA). The German [9] guidelines have a stronger focus on the HBV DNA level (in conjunction with biopsy, considered desirable in all patients, or raised ALT), and consider serum ALT levels not to be a reliable parameter for assessing disease activity [particularly in HBeAg(-) patients]. In contrast, the EASL [15] guidelines recommend either raised HBV DNA (> 2,000 IU/ml) or raised ALT (> ULN), in conjunction with a biopsy, for treatment.

The EASL [15] and German guidelines [9] recommend a threshold HBV DNA level of > 2,000 IU/ml in both HBeAg(+) and HBeAg(-) patients, above which, treatment should be considered, whereas, other guidelines, such as APASL, [8] Egyptian, [12] Greek, [20] HBV Treatment Algorithm, [21] and Italian [13] guidelines use this threshold only in HBeAg(-) patients and a cut-off of >20,000 IU/ml in HBeAg(+) patients. The AASLD [11] guidelines require a HBV DNA of >20,000 IU/ml in both HBeAg(+) and HBeAg(-) disease, using the > 2,000 IU/ml level only to recommend consideration of biopsy in HBeAg(-) patients with borderline or minimally elevated serum ALT.

Interestingly, the AASLD [11] and Egyptian [12] guidelines specifically recommend use of the revised, lower limits for the normal range of serum ALT concentration. This could have important consequences on the decision of whether or not to treat certain patients. First-line therapeutic agents differ somewhat between the guidelines, with the Dutch, [10] Egyptian, [12] [only HBeAg(+)] German, [9] and Italian [13] guidelines recommending the use of pegIFN-α as first-line therapy, whereas, the EASL [15] and Belgian [14] guidelines recommend pegIFN-α or an NA with high efficacy and low resistance. The AASLD [11] lists three preferred agents (pegIFN-α, ADV or ETV), the APASL [8] guidelines recommend the use of ADV, ETV, LdT, LVD or (peg)IFN-α, and the HBV Treatment Algorithm [21] recommends pegIFN-α, ETV or TDF. In addition, thymosin α-1 is considered by APASL [8] to be an option; however, the AASLD [11] and German [9] guidelines consider the data on thymosin α-1 to be conflicting and insufficient to recommend its use.


   Metrics Used to Compare Guidelines Top


These are the metrics used to compare guideline recommendations:

  • Screening
  • Diagnosis
  • Treatment
    • Recommended treatments
    • Which patients to treat
    • Treatment endpoints
    • On-treatment monitoring
    • When to stop therapy
  • Resistance
    • Management of antiviral resistance
    • Prevention and monitoring of resistance
    • Treatment modification following resistance
  • Management of special populations


Some guidelines identify populations at high risk for HBV infection and recommend that they should be tested for HBV. This process, known as screening, can help aid in the early detection of HBV-infected individuals. Some guidelines also provide diagnostic criteria (e.g., HBV DNA and ALT levels), which are used to define when a patient has CHB. This diagnosis can then help to define how this patient should be managed.


   Screening Top


The AASLD, [11] German, [9] HBV Treatment Algorithm, [21] and both Turkish [18],[19] guidelines, list groups / individuals at increased risk of CHB, in whom screening is recommended; screening is not specifically addressed in other guidelines. Many guidelines are designed to only provide recommendations for the management of HBV infections, so they do not cover screening or diagnosis of patients. The AASLD, [11] German, [9] HBV Treatment Algorithm, [21] and both Turkish guidelines [18],[19] recommend screening for HBV in high-risk groups. These groups can broadly be divided into individuals with an increased risk of acquiring the viral infection (e.g., contacts of HBsAg positive individuals) or groups at increased risk through medical reasons (e.g., dialysis or immunocompromised patients), although the exact definitions vary between the guidelines.


   Diagnosis Top


The AASLD, [11] EASL, [15] German, [9] HBV Treatment Algorithm, [21] and Turkish guidelines [18],[19] give detailed information on the diagnosis of CHB, which is not addressed in other guidelines [Table 6]. Guidelines differ in their recommendations regarding biopsy. The German [9] guidelines state that biopsy is considered an important procedure in the diagnosis and prognosis of chronic hepatitis, and should be obtained in all patients with chronic HBV infection. The EASL [15] guidelines recommend biopsy to assist the decision, to start treatment, and to evaluate other possible causes of the disease. In contrast, the AASLD [11] guidelines consider biopsy to be most useful in people who do not meet clear-cut guidelines for treatment.
Table 6: Diagnosis of CHRONIC HEPATITIS B

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   Treatment of Naive CHB Patients Top


Recommended first-line treatments overlap to a certain extent between the guidelines, although there are some notable differences between them . PegIFN-α (or IFN-α) is recommended as first-line therapy by the Dutch, [10] Egyptian [12] [HBeAg(+) patients only], German, [9] and Italian [13] guidelines. The APASL [8] and both Turkish [18],[19] guidelines suggest that any of the licensed agents may be used. The AASLD [11] guidelines list the preferred treatments as pegIFN-α, ADV, and ETV, whereas, the HBV Treatment Algorithm [21] recommends ETV, TDF, and pegIFN-α as first-line. Both the AASLD [11] and the HBV Treatment Algorithm [21] do not recommend LVD and LdT owing to the risk of development of resistant strains, and both prefer pegIFN-α over standard IFN-α. The German [9] guidelines recommend the use of a more potent agent, where disease indicators are particularly high (i.e., HBV DNA > 2 x 10 8 IU/ml). The EASL [15] guidelines recommend the use of potent NAs with a high barrier to resistance, that is, ETV or TDF. The APASL [8] guidelines are the only ones to state that thymosin α-1 can be used.

Treatment options of few important guidelines for naοve CHB patients are summarized in [Table 7].
Table 7: Treatment of naïve CHRONIC HEPATITIS B patients

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   Treatment of LVD-Resistant [LVD-r] Patients Top


In cases of antiviral resistance, guidelines recommend that medications should be switched or add-on therapy used, according to the resistance profiles of the agents. The most common management options in LVD-resistant patients are to either switch therapy over to ETV or add-on ADV [Table 8].
Table 8: Treatments of Lamivudine resistant patients

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   Treatments of ADV-Resistant [ADV-r] Patients Top
In cases of antiviral resistance, guidelines recommend that medications be switched or add-on therapy be used, according to the resistance profiles of the agents. The management of ADV resistance is dependent on when the ADV therapy was initially administered, that is, as initial therapy or after the emergence of LVD resistance. The EASL [15] guidelines recommend different rescue therapies, which are dependant on the specific mutations present [Table 9].
Table 9: Treatments of Adefovir resistant patients

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Which patients to treat?

The guidelines differ in the parameters used to guide treatment decisions [Table 10],[Table 11],[Table 12]. The German [9] guidelines differ from the others in the lesser emphasis given to serum ALT as an indicator of the need for treatment, and the AASLD [11] and Dutch [10] guidelines differ from the others in maintaining a threshold HBV DNA level for treatment, of > 20,000 IU/ml, in HBeAg(-) patients. A serum ALT level of > 2 x ULN is used by the AASLD, [11] APASL, [8] Egyptian, [12] and Italian [13] guidelines as a cut-off for treatment, in conjunction with HBV DNA levels [> 20,000 IU/ml or, in the APASL, [8] Egyptian [12] and Italian [13] guidelines, > 2,000 IU/ml in HBeAg(-) patients]; biopsy can be considered in certain groups not reaching the ALT threshold and the results used to guide treatment decisions; the APASL [8] guidelines also indicate that biopsy can be considered if clinically indicated in HBeAg(-) patients with normal ALT and HBV DNA < 2,000 IU/ml.
Table 10: Which patient to treat?

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Table 11: Which patient to treat?

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Table 12: Which patient to treat?

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The HBV Treatment Algorithm [21] uses elevated ALT levels and a HBV DNA cut-off of ≥ 20,000 IU/ml [for HBeAg(+) patients] or ≥ 2,000 [for HBeAg(-) patients] for treatment; biopsy can be considered if ALT is normal, in conjunction with increased HBV DNA. The German [9] guidelines place a greater emphasis on serum HBV DNA, using a low threshold for therapy, > 2,000 IU/ml, in all patients. The guidelines consider the ALT level to be an unreliable parameter for assessing disease activity, particularly in HBeAg(-) patients, and thus there is only limited use for deciding indication for treatment. The EASL [15] guidelines use a low HBV DNA threshold of > 2,000 IU/ml and a low ALT threshold of > ULN, for treatment in all patients; this is accompanied by a biopsy. The German, [9] Belgian, [14] and both Turkish [18],[19] guidelines place a greater emphasis on the use of biopsy, to indicate a need for treatment.

On-treatment monitoring

Recommendations for monitoring on-treatment responses are included in all the major guidelines. The recommendations for monitoring vary slightly in detail, but the ultimate aim is to advocate regular monitoring in order to gauge the response to therapy and identify the emergence of resistance, so that modifications can be made if necessary.

Treatment endpoints

Where stated, treatment endpoints are broadly similar across guidelines and are divided into virological, biochemical, and histological endpoints. The AASLD [11] guidelines define several different timings for assessment, which are separated into two categories: On-therapy (during therapy) assessments: maintained (persist throughout the course of treatment); end-of-treatment (at the end of a defined course of therapy), Off-therapy (after discontinuation of therapy) assessments: sustained (SR-6; six months after discontinuation of therapy); sustained (SR-12; 12 months after discontinuation of therapy).

The EASL [15] guidelines recommend monitoring the HBV DNA levels after 12 weeks of treatment, to verify the primary response; monitoring is dependent on the therapy used. Responses are defined according to HBV DNA and / or HBe levels. The HBV Roadmap and HBV Treatment Algorithm [21] propose monitoring HBV DNA levels at week 24, in order to assess the response. German [9] guidelines note that a response to therapy under continuous antiviral treatment must be differentiated from a sustained response after stopping the therapy. In most studies this was determined six or 12 months after the termination of therapy. The Turkish VHSD [18] guidelines additionally define responses according to when they are achieved: end of treatment response (response at treatment discontinuation) and permanent response (response 6 - 12 months after treatment discontinuation).

When to stop IFN therapy

The guidelines vary somewhat in their recommendations regarding duration of IFN-α therapy [Table 13]. The AASLD [11] and APASL [8] guidelines recommend a longer period of treatment for HBeAg(-) than HBeAg(+) patients, whereas, the Belgian, [14] Dutch, [10] EASL, [15] German, [9] Polish, [16] and Turkish TASL [19] guidelines recommend the same duration of treatment for HBeAg(-) and HBeAg(+) patients.
Table 13: When to stop IFN therapy?

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When to stop NA therapy

The guidelines vary somewhat in their recommendations regarding the duration of NA therapy, but generally recommend a period of consolidation treatment in HBeAg(+) patients after HBeAg seroconversion and prolonged treatment in HBeAg(-) patients [Table 14]. HBeAg seroconversion is a key milestone for the cessation of therapy in HBeAg(+) patients, whereas, indefinite treatment is generally recommended in HBeAg(-) patients, unless there is HBsAg seroconversion.
Table 14: When to stop NA therapy?

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Management of patients with cirrhosis

Treatment of patients with cirrhosis with detectable serum HBV DNA is recommended, although the HBV DNA threshold and agents recommended vary. All guidelines recommend the treatment of compensated cirrhosis, mostly recommending NA treatment, either as a monotherapy or combination therapy. Only the EASL [15] and Italian [13] guidelines recommend that IFN may be used in compensated patients; all guidelines note that IFN is contraindicated in decompensated cirrhosis. In a decompensated disease, all guidelines recommend treatment of patients with detectable serum HBV DNA, and all agree that IFN-α should not be used in this patient group.

Management in immunosuppressive / cytotoxic chemotherapy

Prophylactic treatment to prevent reactivation of HBV replication during immunosuppressive therapy or cytotoxic chemotherapy is recommended in all guidelines (no recommendations currently in Dutch, [10] Egyptian [12] or Polish [16] ). Prophylactic treatment is generally recommended in HBsAg positive individuals, prior to or at the onset of chemotherapy, and continuing it for a period after that, to prevent viral relapse [Table 15].
Table 15: Management in immunosuppressive / cytotoxic chemotherapy

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Management of children

Children with CHB who have persistently elevated serum ALT can be considered for therapy with IFN-α or an NA [Table 16]. The guidelines that address this area are broadly similar in recommending that treatment be considered in children with long-term disease, bearing indicators of likelihood of response to therapy (persistently elevated serum ALT). Treatment is recommended with either IFN-α or LVD.
Table 16: Management of children

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   Conclusion Top
The primary goal of the therapy for CHB is to halt disease progression and prevent long-term complications of cirrhosis, with suppression of hepatitis B. Guidelines are developed to assist healthcare providers in the recognition, diagnosis, and management of CHB. These recommendations provide a data-supported approach to manage these patients. This review on the comparison of different guidelines on CHB, has tried to compare different aspects on the management of CHB. Some aspects such as acute hepatitis B and drug resistance have not been addressed in this review. Few issues, for example, the role of HBV genotyping and combination therapy are yet to be settled. Finally, alternative agents under active investigation for CHB treatment may likely improve the outcome in the future.

 
   References Top

1.Consensus statements on the prevention and management of hepatitis B and hepatitis C in the Asia-Pacific region. Core Working Party for Asia-Pacific Consensus on Hepatitis B and C. J Gastroenterol Hepatol 2000;15:825-41.  Back to cited text no. 1
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2.Liaw YF, Leung N, Guan R, Lau GK, Asian-Pacific Consensus Working Parties on Hepatitis B. Asian-Pacific consensus statement on the management of chronic hepatitis B: An update J Gastroenterol Hepatol 2003;18:239-45.  Back to cited text no. 2
    
3.Liaw YF, Leung N, Guan R, Lau GK, Merican I, McCaughan G, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: A 2005 update. Liver Int 2005;25:472-89.  Back to cited text no. 3
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4.ACT-HBV Asia-Pacific Steering Committee Members. Chronic hepatitis B: Treatment alert. Liver Int 2006;26:47-58.  Back to cited text no. 4
    
5.Weiss J, Wu H, Farrenkopf B, Schultz T, Song G, Shah S, et al. Real time TaqMan PCR detection and quantitation of HBV genotypes A-G with the use of an internal quantitation standard. J Clin Virol 2004;30:86-93.  Back to cited text no. 5
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6.Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: An update. Clin Gastroenterol Hepatol 2006;4:936-62.  Back to cited text no. 6
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7.Kim HC, Nam CM, Jee SH, Han KH, Oh DK, Suh I. Normal serum aminotransferase concentration and risk of mortality from liver diseases: Prospective cohort study. Br Med J 2004;328:983.  Back to cited text no. 7
    
8.Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: A 2008 update. Hepatol Int 2008;2:263-83.  Back to cited text no. 8
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9.Cornberg M, Protzer U, Dollinger MM, Petersen J, Wedemeyer H, Berg T, et al. Prophylaxis, diagnosis and therapy of hepatitis B virus (HBV) infection: The German guidelines for the management of HBV infection. Z Gastroenterol 2007;45:1281-328.  Back to cited text no. 9
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10.Buster EH, van Erpecum KJ, Schalm SW, Zaaijer HL, Brouwer JT, Gelderblom HC, et al. Netherlands Association of Gastroenterologists and Hepatologists: Treatment of chronic hepatitis B virus infection - Dutch national guidelines. Neth J Med 2008;66:292-306.  Back to cited text no. 10
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11.Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507-39.  Back to cited text no. 11
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12.Waked I, Salama M, Zayed N. Egyptian Guidelines 2008.  Back to cited text no. 12
    
13.Carosi G, Rizzetto M. Treatment of chronic hepatitis B: Recommendations from an Italian workshop. Dig Liver Dis 2008;40:603-17.  Back to cited text no. 13
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14.Colle I, Adler M, Brenard R, Henrion J, Langlet P, Michielsen P, et al. Management and treatment of chronic hepatitis B virus: Belgian Association for the Study of the Liver (BASL) 2007 guidelines. Acta Gastroenterol Belg 2007;70:389-420.  Back to cited text no. 14
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15.European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of chronic hepatitis B. J Hepatol 2009;50:227-42.  Back to cited text no. 15
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16.Juszczyk J, Boroñ-Kaczmarska A, Cianciara J, Flisiak R, G³adysz A, Halota W, et al . Polish Experts Group on HBV. Therapeutic recommendations on 2008 year (antiretroviral treatment of chronic hepatitis B). Przegl Epidemiol 2008;62:379-81.  Back to cited text no. 16
    
17.Nicolaescu GE, Ciurchea V. Official J Romania 2008;257:413-8.  Back to cited text no. 17
    
18.Balik I, Tabak F. Turkish VHSD guidelines 2007.  Back to cited text no. 18
    
19.Akarca US. Chronic Hepatitis B A guideline to Diagnosis, Approach, Management and Follow-up 2007 Turkish Association for Study of the Liver. Turk J Gastroenterol 2008;19:207-30.  Back to cited text no. 19
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20.The Viral Hepatitis Committee Members KEELPNO (National Disease Centre), 2008.  Back to cited text no. 20
    
21.Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol 2008;6:1315-41.  Back to cited text no. 21
[PUBMED]  [FULLTEXT]  

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Correspondence Address:
Pradeepta Kumar Sethy
Apollo Gleneagles Hospital, 58, Canal Circular Road, Kolkata-700 058
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-9747.76905

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14], [Table 15], [Table 16]



 

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