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AASLD Guidelines for Treatment of Chronic Hepatitis B

November 26, 2015 10:14 PM

The American Association for the Study of Liver Diseases (AASLD) has released comprehensive guidelines for the treatment of chronic hepatitis B (CHB).

CHB affects more than 240 million people globally, causing significant morbidity and mortality. This document focuses on using antiviral therapy in chronic HBV infection and does not address other related and important issues, such as screening, prevention, and surveillance. For broader issues related to diagnosis, surveillance, and prevention as well as treatment in special populations (e.g., liver transplant recipients) that are not addressed by this guideline, the previous AASLD guideline and recent World Health Organization (WHO) guideline are excellent additional resources.

The AASLD formulated a list of discrete questions that physicians are faced with in daily practice.

These questions were:

  • Should adults with immune active CHB be treated with antiviral therapy to decrease liver-related complications?
  • Should adults with immune-tolerant infection be treated with antiviral therapy to decrease liver-related complications?
  • Should antiviral therapy be discontinued in hepatitis B e antigen (HBeAg)-positive persons who have developed HBeAg seroconversion on therapy?
  • Should antiviral therapy be discontinued in persons with HBeAg-negative infection with sustained HBV DNA suppression on therapy?
    In HBV-monoinfected persons, does entecavir therapy, when compared to tenofovir therapy, have a different impact on renal and bone health?
  • Is there a benefit to adding a second antiviral agent in persons with persistent low levels of viremia while being treated with either tenofovir or entecavir?
  • Should persons with compensated cirrhosis and low levels of viremia be treated with antiviral agents?
  • Should pregnant women who are hepatitis B surface antigen (HBsAg) positive with high viral load receive antiviral treatment in the third trimester to prevent perinatal transmission of HBV?
  • Should children with HBeAg-positive CHB be treated with antiviral therapy to decrease liver-related complications?

 

Natural History in Adults and Children

CHB has been traditionally characterized into four phases, reflecting the dynamic relationship between viral replication and evolution and the host immune response. These phases are of variable duration and not every person infected with CHB will evolve through all phases. Given the dynamic nature of CHB infection, serial monitoring of HBV DNA and alanine aminotransferase (ALT) levels is important to characterize the phase of infection. A single ALT and HBV DNA level are insufficient to assign phase of infection and/or need for treatment. Of note, some persons will be in the “gray zones,” meaning that their HBV DNA and ALT levels do not fall into the same phase. Longitudinal follow-up of ALT and HBV DNA levels and/or assessment of liver histology can serve to clarify the phase of infection.

  • Immune-tolerant phase: In this highly replicative/low inflammatory phase, HBV DNA levels are elevated, ALT levels are normal (<19 U/L for females and <30 U/L for males), and biopsies are without signs of significant inflammation or fibrosis. The duration of this phase is highly variable, but longest in those who are infected perinatally. With increasing age, there is an increased likelihood of transitioning from immune-tolerant to the HBeAg-positive immune-active phase.
  • HBeAg-positive immune-active phase: Elevated ALT and HBV DNA levels in conjunction with liver injury characterize this phase. Median age of onset is 30 years among those infected at a young age. The hallmark of transition from the HBeAg-positive immune-active to -inactive phases is HBeAg seroconversion. The rate of spontaneous seroconversion from HBeAg to antibody to HBeAg (anti-HBe) is less than 2% per year in children younger than 3 years of age and increases during puberty and among adults to 8% and 12% per year, respectively.
  • Inactive CHB phase: In this phase, HBV DNA levels are low or undetectable, ALT levels are normal, and anti-HBe is present. Liver histology shows minimal necroinflammation, but variable fibrosis reflecting previous liver injury during the HBeAg-positive immune-active phase. Among persons who undergo spontaneous HBeAg seroconversion, 67%-80% will continue to remain in the inactive CHB phase. Approximately 4%-20% of inactive carriers have one or more reversions back to HBeAg positive.
  • HBeAg-negative immune reactivation phase: Among those who seroconvert from HBeAg to anti-HBe positive, 10%-30% continue to have elevated ALT and high HBV DNA levels, and roughly 10%-20% of inactive carriers may have reactivation of HBV replication and exacerbations of hepatitis after years of quiescence. Most of these persons harbor HBV variants in the precore or core promoter region, and liver histology shows necroinflammation and fibrosis. Persons with HBeAg-negative CHB tend to have lower serum HBV DNA levels than those with HBeAg-positive CHB and are more likely to experience a fluctuating course.

The risk of liver-related complications is variable. Among untreated adults with CHB, the cumulative 5-year incidence of cirrhosis is 8%-20%, and among those with cirrhosis, 5-year cumulative risk of hepatic decompensation is 20%, and risk of HCC is 2%-5%. Viral, host, and environmental factors influence risks of cirrhosis and HCC. HBV DNA levels, ALT levels, and HBeAg status are among the most important determinants of risk of progression to cirrhosis, whereas HBV DNA levels (>2,000 IU/mL), HBeAg status, and cirrhosis are key predictors of HCC risk. A biological gradient of risk has been shown in adults with HBV DNA levels above 2,000 IU/mL; a higher HBV DNA level is associated with progressively higher rates of cirrhosis and HCC.

 

The initial evaluation of persons with CHB should include

  • a thorough history and physical examination
  • emphasis on risk factors for coinfection, alcohol use, and family history of HBV infection and liver cancer
  • Laboratory tests should include
    • assessment of liver disease activity and function
    • markers of HBV replication
    • tests for coinfection with
      • hepatitis C virus (HCV)
      • hepatitis delta virus (HDV)
      • human immunodeficiency virus (HIV) in those at risk.

 

Owing to the fluctuating nature of CHB, the accuracy of one high HBV DNA level at a single time point in predicting prognosis is poor and regular monitoring of disease status is imperative to determine need for antiviral therapy. The upper limits of normal (ULNs) for ALT values based on healthy subjects are lower than laboratory values derived from all populations, including those with subclinical liver disease.

 

Determination of the stage of liver disease is important in guiding antiviral therapy decisions and need for surveillance.

  • Liver biopsy provides an assessment of the severity of necroinflammation and fibrosis, rules out other causes of liver disease, and may be especially useful for persons who lack clear-cut indications for treatment. Liver biopsy is regarded as the best method to assess the severity of inflammatory activity and fibrosis,
  • Noninvasive methods to assess fibrosis severity are also useful, but:
    • Acute-on-chronic exacerbations of hepatitis B may lead to overestimation of fibrosis stage by noninvasive tests, and different cutoffs for significant and advanced fibrosis depending on ALT levels have been proposed.
    • Serum markers of fibrosis, such as aspartate aminotransferase (AST)-to-platelet ratio index (APRI), FIB-4, FibroTest, and vibration-controlled transient elastography, have only moderate accuracy in identifying persons with significant fibrosis (fibrosis stage 2 or greater on the Metavir scale), but good diagnostic accuracy in excluding advanced fibrosis and may be useful aids in decision making.

 

Antiviral Therapy
The goals of antiviral treatment are to decrease the morbidity and mortality related to CHB. The achievement of a sustained suppression of HBV replication has been associated with normalization of serum ALT, loss of HBeAg with or without detection of (anti-HBe), and improvement in liver histology. Historically, the term “cure” was avoided in treatment of CHB, given that persistence of covalently closed circular DNA (cccDNA) in the nucleus of hepatocytes, even in persons with serological markers of resolved infection, poses a lifelong risk for reactivation of infection. However, an immunological cure may be defined by HBsAg loss and sustained HBV DNA suppression and a virological cure defined by eradication of virus, including the cccDNA form. The latter is not currently an attainable goal.

There are six therapeutic agents approved for the treatment of adults with CHB in the United States and five therapeutic agents approved for the treatment of children with CHB. Side effects are more frequent with interferon (IFN) therapy than with nucleos(t)ide analogs (NAs) therapy. Overall, all NAs have an excellent safety profile across a wide spectrum of persons with CHB, including those with decompensated cirrhosis and transplant recipients. For persons with HDV coinfection, the only effective treatment is pegylated interferon (Peg-IFN). For persons with HIV coinfection, treatment of HBV needs to be coordinated with HIV therapy given that several HBV drugs have anti-HIV activity (tenofovir, entecavir, lamivudine, and telbivudine).

 

 
The guideline answers the above stated critical questions:

  • Should adults with immune active CHB be treated with antiviral therapy to decrease liver-related complications?
    • Treatment Intervention: Antiviral therapy
      Comparison: No treatment
      Outcome: Cirrhosis, decompensation, HCC, death, loss of HBsAg
    • Recommendations: The AASLD recommends antiviral therapy for adults with immune-active CHB (HBeAg negative or HBeAg positive) to decrease the risk of liver-related complications. The AASLD also recommends Peg-IFN, entecavir, or tenofovir as preferred initial therapy for adults with immune-active CHB.
  • Should adults with immune-tolerant infection be treated with antiviral therapy to decrease liver-related complications?
    • Treatment Intervention: Antiviral therapy
      Comparison: No treatment
      Outcome: Cirrhosis, decompensation, HCC, death, loss of HBsAg
    • Recommendations: The AASLD recommends against antiviral therapy for adults with immune-tolerant CHB. The AASLD suggests that ALT levels be tested at least every 6 months for adults with immune-tolerant CHB to monitor for potential transition to immune-active or -inactive CHB. The AASLD suggests antiviral therapy in the select group of adults >40 years of age with normal ALT and elevated HBV DNA (≥1,000,000 IU/mL) and liver biopsy showing significant necroinflammation or fibrosis.
  • Should antiviral therapy be discontinued in hepatitis B e antigen (HBeAg)-positive persons who have developed HBeAg seroconversion on therapy?
    • Treatment Intervention: Continued antiviral therapy
      Comparison: Stopping antiviral therapy
      Outcome: Cirrhosis, HCC, reactivation, seroreversion, decompensation, loss of HBsAg
    • Recommendations: The AASLD suggests that HBeAg-positive adults without cirrhosis with CHB who seroconvert to anti-HBe on therapy discontinue NAs after a period of treatment consolidation. The AASLD suggests indefinite antiviral therapy for HBeAg-positive adults with cirrhosis with CHB who seroconvert to anti-HBe on NA therapy, based on concerns for potential clinical decompensation and death, unless there is a strong competing rationale for treatment discontinuation.
  • Should antiviral therapy be discontinued in persons with HBeAg-negative infection with sustained HBV DNA suppression on therapy?
    • Treatment Intervention: Continued antiviral therapy
      Comparison: Stopping antiviral therapy
      Outcome: Reactivation, decompensation, loss of HBsAg
    • Recommendations: The AASLD suggests indefinite antiviral therapy for adults with HBeAg-negative immune-active CHB, unless there is a competing rationale for treatment discontinuation.
  • In HBV-monoinfected persons, does entecavir therapy, when compared to tenofovir therapy, have a different impact on renal and bone health?
    • Treatment Intervention: Tenofovir
      Comparison: Entecavir
      Outcome: Renal function, hypophosphatemia, bone health
    • Recommendations: The AASLD suggests no preference between entecavir and tenofovir regarding potential long-term risks of renal and bone complications.
  • Is there a benefit to adding a second antiviral agent in persons with persistent low levels of viremia while being treated with either tenofovir or entecavir?
    • Treatment Intervention: Continue therapy
      Comparison: Change or switch therapy
      Outcome: HBV resistance, clinical flare, decompensation, loss of HBeAg
    • Recommendations: The AASLD suggests that persons with persistent low-level viremia (<2,000 IU/mL) on entecavir or tenofovir monotherapy continue monotherapy, regardless of ALT. The AASLD suggests one of two strategies in persons with virological breakthrough on entecavir or tenofovir monotherapy: either switch to another antiviral monotherapy with high barrier to resistance or add a second antiviral drug that lacks cross-resistance.
  • Should persons with compensated cirrhosis and low levels of viremia be treated with antiviral agents?
    • Treatment Intervention: Antiviral therapy
      Comparison: No treatment
      Outcome: Decompensation, HCC, death
    • Recommendations: The AASLD suggests that adults with compensated cirrhosis and low levels of viremia (<2,000 IU/mL) be treated with antiviral therapy to reduce the risk of decompensation, regardless of ALT level. The AASLD recommends that HBsAg-positive adults with decompensated cirrhosis be treated with antiviral therapy indefinitely regardless of HBV DNA level, HBeAg status, or ALT level to decrease risk of worsening liver-related complications.
  • Should pregnant women who are hepatitis B surface antigen (HBsAg) positive with high viral load receive antiviral treatment in the third trimester to prevent perinatal transmission of HBV?
    • Treatment Intervention: Antiviral therapy in third trimester
      Comparison: No treatment
      Outcome: Cirrhosis, decompensation, HCC, death, loss of HBsAg CHB in the infant, maternal safety, fetal/infant safety
    • Recommendations: The AASLD suggests antiviral therapy to reduce the risk of perinatal transmission of hepatitis B in HBsAg-positive pregnant women with an HBV DNA level >200,000 IU/mL. The AASLD recommends against the use of antiviral therapy to reduce the risk of perinatal transmission of hepatitis B in the HBsAg-positive pregnant woman with an HBV DNA ≤200,000 IU/mL.
  • Should children with HBeAg-positive CHB be treated with antiviral therapy to decrease liver-related complications?
    • Treatment Intervention: Antiviral therapy
      Comparison: No treatment
      Outcome: Cirrhosis, decompensation, HCC, death, HBeAg seroconversion, loss of HBsAg
    • Recommendations: The AASLD suggests antiviral therapy in HBeAg-positive children (ages 2 to <18 years) with both elevated ALT and measurable HBV DNA levels, with the goal of achieving sustained HBeAg seroconversion. The AASLD recommends against use of antiviral therapy in HBeAg-positive children (ages 2 to <18 years) with persistently normal ALT, regardless of HBV DNA level.

 

Summary of Recommendations

  • The AASLD recommends antiviral therapy for adults with immune-active CHB (HBeAg negative or HBeAg positive) to decrease the risk of liver-related complications.
  • The AASLD recommends Peg-IFN, entecavir, or tenofovir as preferred initial therapy for adults with immune-active CHB.
  • The AASLD recommends against antiviral therapy for adults with immune-tolerant CHB.
  • The AASLD suggests that ALT levels be tested at least every 6 months for adults with immune-tolerant CHB to monitor for potential transition to immune-active or -inactive CHB.
  • The AASLD suggests antiviral therapy in the select group of adults >40 years of age with normal ALT and elevated HBV DNA (≥1,000,000 IU/mL) and liver biopsy showing significant necroinflammation or fibrosis.
  • The AASLD suggests that HBeAg-positive adults without cirrhosis with CHB who seroconvert to anti-HBe on therapy discontinue NAs after a period of treatment consolidation.
  • The AASLD suggests indefinite antiviral therapy for HBeAg-positive adults with cirrhosis with CHB who seroconvert to anti-HBe on NA therapy, based on concerns for potential clinical decompensation and death, unless there is a strong competing rationale for treatment discontinuation.
  • The AASLD suggests indefinite antiviral therapy for adults with HBeAg-negative immune-active CHB, unless there is a competing rationale for treatment discontinuation.
  • The AASLD suggests no preference between entecavir and tenofovir regarding potential long-term risks of renal and bone complications.
  • The AASLD suggests that persons with persistent low-level viremia (<2,000 IU/mL) on entecavir or tenofovir monotherapy continue monotherapy, regardless of ALT.
  • The AASLD suggests one of two strategies in persons with virological breakthrough on entecavir or tenofovir monotherapy: either switch to another antiviral monotherapy with high barrier to resistance or add a second antiviral drug that lacks cross-resistance.
  • The AASLD suggests that adults with compensated cirrhosis and low levels of viremia (<2,000 IU/mL) be treated with antiviral therapy to reduce the risk of decompensation, regardless of ALT level.
  • The AASLD recommends that HBsAg-positive adults with decompensated cirrhosis be treated with antiviral therapy indefinitely regardless of HBV DNA level, HBeAg status, or ALT level to decrease risk of worsening liver-related complications.
  • The AASLD suggests antiviral therapy to reduce the risk of perinatal transmission of hepatitis B in HBsAg-positive pregnant women with an HBV DNA level >200,000 IU/mL.
  • The AASLD recommends against the use of antiviral therapy to reduce the risk of perinatal transmission of hepatitis B in the HBsAg-positive pregnant woman with an HBV DNA ≤200,000 IU/mL.
  • The AASLD suggests antiviral therapy in HBeAg-positive children (ages 2 to <18 years) with both elevated ALT and measurable HBV DNA levels, with the goal of achieving sustained HBeAg seroconversion.
  • The AASLD recommends against use of antiviral therapy in HBeAg-positive children (ages 2 to <18 years) with persistently normal ALT, regardless of HBV DNA level.

 

Abbreviations

ALT alanine aminotransferase
anti-HBe antibody to HBeAg
anti-HBs antibody to HBsAg
APRI AST-to-platelet ratio index
AST aspartate aminotransferase
cccDNA covalently closed circular DNA
CHB chronic hepatitis B
HBV hepatitis B virus
HCV hepatitis C virus
HCC hepatocellular carcinoma
HIV human immunodeficiency virus
HDV hepatitis delta virus
HBsAg hepatitis B surface antigen
HBeAg hepatitis B e antigen
IFN interferon
NA nucleos(t)ide analog
Peg-IFN pegylated interferon

 

http://www.aasld.org/sites/default/files/guideline_documents/hep28156.pdf

http://onlinelibrary.wiley.com/doi/10.1002/hep.28156/full

http://aasldpubs.onlinelibrary.wiley.com/hub/

http://www.aasld.org

American Gastroenterological Association Institute Guidelines on the Management of Acute Diverticulitis

November 7, 2015 5:20 PM

The American Gastroenterological Association (AGA) Institute has issued updated guidelines regarding the management of acute diverticulitis. Routine use of antibiotics in uncomplicated diverticulitis is not recommended, and selective use is more appropriate. Patients who have not had a recent colon exam require colonoscopy after an episode of acute diverticulitis to rule out the possibility of malignancy.

Patients with a history of acute diverticulitis may benefit from a fiber-rich diet or fiber supplementation, and do not need to avoid nuts, seeds, and popcorn. Patients with a history of acute diverticulitis may safely take aspirin but should avoid non-aspirin NSAIDs. Mesalamine, rifaximin, and probiotics all have no proven benefit after an episode of acute diverticulitis. Patients should be advised to exercise.

Recommendations

The AGA suggests:

  • that antibiotics should be used selectively, rather than routinely, in patients with acute uncomplicated diverticulitis.
  • that colonoscopy be performed after resolution of acute diverticulitis in appropriate candidates to exclude the misdiagnosis of a colonic neoplasm if a high-quality examination of the colon has not been recently performed.
  • against elective colonic resection in patients with an initial episode of acute uncomplicated diverticulitis. The decision to perform elective prophylactic colonic resection in this setting should be individualized.
  • a fiber-rich diet or fiber supplementation in patients with a history of acute diverticulitis.
  •  against routinely advising patients with a history of diverticulitis to avoid consumption of seeds, nuts, and popcorn.
  • against routinely advising patients with a history of diverticulitis to avoid the use of aspirin.
  • advising patients with a history of diverticulitis to avoid the use of nonaspirin NSAIDs if possible.
  • against the use of mesalamine after acute uncomplicated diverticulitis.
  • against the use of rifaximin after acute uncomplicated diverticulitis.
  • against the use of probiotics after acute uncomplicated diverticulitis.
  • advising patients with diverticular disease to consider vigorous physical activity.

Important discussion points:

  • Antibiotics:
    Until recently, antibiotics have been the cornerstone of treatment of patients with acute diverticulitis. The emerging belief that acute diverticulitis may be more inflammatory than infectious, as well as increasing concerns about the overuse of antibiotics have led to the recommendation of selective and individualized antibiotic use. The current data are of low quality, and recommendations could change as further studies are performed. These recommendations should not be generalized to complicated patients (ie, those with abscesses or fistulas), those with signs of severe infection or sepsis, immunosuppressed patients, or patients with other significant comorbidities.
    Furthermore, outpatient management without antibiotics has not been studied.
  • Colonoscopy:
    Observational studies of patients with imaging-proven diverticulitis who subsequently underwent colonoscopy detected a small number of colorectal cancers (15/1000 patients) and advanced adenomas (38/1000 patients). Absence of a mass lesion on CT scan does not exclude the possibility of an underlying colonic neoplasm. Evidence of alternative, non-neoplastic explanations for the index presentation, such as inflammatory bowel disease or ischemic colitis, was either infrequently identified or not reported. Although an increased risk of recurrent diverticulitis or colonic perforation is a concern in patients undergoing colonoscopy after an episode of acute diverticulitis, this was not reported as an adverse event.
  • Elective Colonic Resection:
    Approximately 20% of patients with acute uncomplicated diverticulitis experience a recurrent episode of diverticulitis in the following 5 years. The risk of future diverticular complications and need for emergency surgery among patients treated medically without colonic resection is low (<5%). Approximately 10% of patients with elective sigmoid resection after an episode of acute diverticulitis experience short-term complications of surgery, including wound infection, anastomotic leak, and cardiovascular/thrombotic events. Such postoperative risks are increased in patients older than 65 years of age. Long-term complications of abdominal distention, cramping, altered defecation, and fecal incontinence are reported in 25% of patients after elective surgery. The rates of recurrent diverticulitis appear to be higher in younger patients and the operative risks are lower, but the data do not support elective surgery in this subgroup when presenting with acute uncomplicated diverticulitis.

In conclusion, the AGA states that the management of acute diverticulitis has undergone meaningful changes over the past decade, including more judicious use of antibiotics and surgery as well as preliminary and ongoing investigations into medical therapies to decrease symptoms and reduce recurrence.

http://www.gastro.org/guidelines

http://www.gastrojournal.org/article/S0016-5085(15)01432-8/abstract

http://www.gastrojournal.org/article/S0016-5085(15)01432-8/fulltext

The Role of Upper Gastrointestinal Biopsy to Evaluate Dyspepsia in the Adult Patient in the Absence of Visible Mucosal Lesions

November 1, 2015 8:25 PM

American Gastroenterological Association Institute Guideline on the Role of Upper Gastrointestinal Biopsy to Evaluate Dyspepsia in the Adult Patient in the Absence of Visible Mucosal Lesions

This document presents the official recommendations of the American Gastroenterological Association (AGA) on the role of upper gastrointestinal biopsy to evaluate dyspepsia in the absence of mucosal lesions. The guideline was developed by the AGA’s Clinical Practice Guidelines Committee and approved by the AGA Governing Board.
The authors of these guidelines present evidence-based recommendations for performing biopsies of normal mucosa in patients with dyspepsia who are undergoing EGD. The authors take into consideration the different segments of the upper GI tract as well as patient factors such as immune system status.  Please make sure to review the entire paper as linked.

Esophagus:

  • In patients undergoing EGD for dyspepsia as the sole indication, the AGA recommends against obtaining routine biopsies of the normal-appearing esophagus or GE junction regardless of immune status.

Stomach:

  • In immunocompetent patients undergoing EGD for dyspepsia as the sole indication, the AGA recommends obtaining routine biopsies of the normal appearing gastric body and antrum for the detection of HP infection if the HP infection status is unknown.
  • In immunocompromised patients undergoing EGD for dyspepsia as the sole indication, the AGA recommends obtaining routine biopsies of the normal-appearing gastric body and antrum for the detection of HP infection if the HP infection status is unknown.
  • When obtaining biopsies from the normal-appearing gastric body and antrum for the detection of HP infection, the AGA suggests following the 5-biopsy Sydney System with all specimens placed in the same jar.
  • When biopsies are obtained from the normal-appearing gastric body and antrum for the detection of HP infection, the AGA suggests not obtaining automatic special staining of the specimens.

Duodenum:

  • In patients undergoing EGD for dyspepsia as the sole indication, and in the absence of signs or symptoms associated with an increased risk of celiac disease, the AGA suggests not obtaining routine biopsies of the normal-appearing duodenum to detect celiac disease.
  • In immunocompromised patients undergoing EGD for dyspepsia as the sole indication, the AGA suggests obtaining routine biopsies of the normal-appearing duodenum for the detection of GVHD in post−allogeneic tissue transplantation patients and for opportunistic infections.
  • When biopsies are obtained from the normal-appearing duodenum, the AGA suggests not performing routine special staining of the specimens.

Clarifications:

  • The updated Sydney System protocol includes specimens from the lesser and greater curve of the antrum within 2−3 cm of the pylorus, from the lesser curvature of the corpus (4 cm proximal to the angularis), from the middle portion of the greater curvature of the corpus (8 cm from the cardia), and one from the incisura angularis. Although a 3-biopsy protocol (1 each from greater curvature of the corpus and antrum and 1 from incisura) also identifies 100% of HP, equivalency of the 3- vs 5-biopsy protocol cannot be definitively established. Given that the time and cost of specimen preparation and processing from the pathology standpoint are the same for a 3- vs 5-biopsy protocol, a conditional recommendation was made to follow the 5-biopsy protocol.
  • Regarding Celiac disease the AGA argues that Celiac disease can be present in patients with endoscopically normal duodenum. The prevalence of biopsy-proven celiac disease among patients with dyspepsia is not significantly different from that in the US general population in which screening for celiac disease is not recommended. One must consider the potential for false-positive biopsy diagnosis in this setting, particularly when only early-grade celiac changes (eg, Marsh I−II) are detected. The AGA argues that this recommendation is primarily dependent on very-low-quality prevalence data, and thus a conditional recommendation is warranted (the possibility exists that the true prevalence of celiac disease among patients presenting with dyspepsia might be higher than what the current literature suggests, this recommendation might need to be updated when higher-quality evidence becomes available). Biopsy of the normal-appearing duodenum might be appropriate in patients who are at high risk for celiac disease, as specified by a previous AGA guideline on the diagnosis and management of celiac disease. If the suspicion for celiac disease is high, biopsies of the normal-appearing duodenum can be of value even if serologies (obtained while the patient is on a gluten-free diet) are negative.

http://www.gastro.org/guidelines/2015/10/19/endoscopic-biopsies
http://www.gastrojournal.org/article/S0016-5085%2815%2901065-3/pdf