Lawrence R. Schiller, MD, FACG

Helicobacter pylori:How to decide when to treat

Lawrence R. Schiller, MD,Digestive Health Associates of Texas

Baylor University Medical Center, Dallas

Why treat?

• Relieve symptomsE l f ti l d i– Example: functional dyspepsia

• Manage associated diseases– Examples: peptic ulcer disease, idiopathic

thrombocytopenic purpura, • Prevent disease complications

– Example: bleeding peptic ulcer• Prevent cancer

– Example: gastric adenocarcinoma

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

Peptic ulcer disease

• Helicobacter pylori infection predisposes to th d l t f ti lthe development of peptic ulcer

• About 20% of infected individuals develop PUD

• Continued H. pylori infection predisposes to recurrencerecurrence

• Gastric acid is a necessary co-factor• Gastric metaplasia in bulb leads to DU

Peptic ulcer disease

• Treatment promotes ulcer healing

• Treatment prevents ulcer recurrence

• Treatment reduces ulcer bleeding

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

Peptic ulcer disease

• Uncomplicated DU: no need to prolong PPI th H l i i t t dtherapy once H. pylori is treated

• GU and complicated GU: continue PPI until GU has healed or H. pylori eradication is confirmed in DU

• In patients with bleeding ulcer startIn patients with bleeding ulcer, start eradication treatment when oral feeding is restarted

Malfertheiner et al. Gut 2012;61:646-664.

Dyspepsia

• Uninvestigated dyspepsia in primary care– Some patients will be infected with H. pylori– If prevalence of H. pylori is high (>20%), a test-

and-treat strategy makes sense• Use non-endoscopic technique for diagnosis (urea

breath test or fecal antigen)T t if iti• Treat if positive

• Must be young enough to have low risk of gastric cancer

Malfertheiner et al. Gut 2012;61:646-664.

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

Functional dyspepsia

• H. pylori eradication produces long-term relief of dyspepsia in 8% of patients with H. pylori and functional dyspepsia– More successful than any other single treatment

tested

Malfertheiner et al. Gut 2012;61:646-664.

NSAIDs

• H. pylori + NSAIDs = increased ulcer risk• Eradication reduces risk of ulcer and

complications in NSAID naïve patients• Less clear if eradication is helpful in long-term

NSAID user continue PPI• Useful to treat before starting NSAID therapy• Useful to treat before starting NSAID therapy;

mandatory if history of ulcer

Malfertheiner et al. Gut 2012;61:646-664.

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

MALT lymphoma

• H. pylori eradication is first line treatment for l d t i MALT l hlow-grade gastric MALT lymphoma– Stage I/II lesions can be cured in 60—80%– If t(11,18) translocation is present, unlikely to

cured by H. pylori eradication and additional treatment may be needed

Malfertheiner et al. Gut 2012;61:646-664.

Extragastric diseases

• Unexplained iron deficiency anemia– Association in both adults and children– Eradication associated with increased hemoglobin

level

• Idiopathic thrombocytopenic purpura– Eradication led to increased platelet counts in 50%Eradication led to increased platelet counts in 50%

• Vitamin B12 deficiency• Poor drug absorption (thyroxine, l-dopa)

Malfertheiner et al. Gut 2012;61:646-664.

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

Cancer prevention

• H. pylori is the most common proven risk f t f di t i d ifactor for non-cardia gastric adenocarcinoma

• Eradication of H. pylori is the most promising strategy to reduce the incidence of gastric cancer

• Chronic active gastritis atrophy and intestinalChronic active gastritis, atrophy, and intestinal metaplasia are associated with the development of cancer

Malfertheiner et al. Gut 2012;61:646-664.

Cancer prevention

• H. pylori eradication abolishes the inflammatory response and may slow arrestinflammatory response, and may slow, arrest, or reverse atrophy in the corpus (but not the antrum)

• Intestinal metaplasia is irreversible• Eradication therapy has benefit in primary and

d tisecondary cancer prevention• Eradication therapy is most effective if

delivered before development of atrophy

Malfertheiner et al. Gut 2012;61:646-664.

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

Cancer prevention

• Screening may be cost-effective in populations ith hi h i k f t iwith a high risk of gastric cancer

– Early H. pylori eradication would be more cost-effective than life-time surveillance

– Screening young adults in China might reduce one of every 4 to 6 gastric cancers

– Not useful in U.S.

Malfertheiner et al. Gut 2012;61:646-664.

Cancer prevention

• Who should be considered for treatment?– 1o relatives of gastric cancer patients

• 2—3-fold increase with one relative• 10-fold increase with >1 relative

– Patients with severe pan-gastritis, corpus-predominant gastritis, severe atrophy

– (Patients with previously resected gastric neoplastic lesions)

Malfertheiner et al. Gut 2012;61:646-664.

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

Who should NOT be treated?

• Patients with gastroesophageal reflux diseaseg p g

• Patients on chronic PPI therapy

• Patients with intestinal metaplasiaPatients with intestinal metaplasia

Malfertheiner et al. Gut 2012;61:646-664.

Treatment tips

• Standard triple therapy– PPI + clarithromycin + metronidazole– PPI + clarithromycin + amoxicillin

• Sequential therapy– PPI + amoxicillin X 5 days, followed by– PPI + clarithromycin + metronidazole X 5 days– PPI + clarithromycin + metronidazole X 5 days

• Quadruple therapy– PPI + bismuth + tetracycline + metronidazoleMalfertheiner et al. Gut 2012;61:646-664.

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

Treatment tips

• Clarithromycin-containing triple therapy d d if i t t i 20%recommended if resistance rate is <20%

• Bismuth-containing quadruple therapy is alternative

• BID PPI therapy increases efficacy• Extending therapy from 7 to 10 14 days• Extending therapy from 7 to 10—14 days

improves success by ~5%

Malfertheiner et al. Gut 2012;61:646-664.

New treatment paradigm

• Because of frequency of clarithromycin and t id l i t t diti l imetronidazole resistance, traditional regimens

may be obsolete in most places• Preferred choices in U.S.:

– 14-day concomitant therapy– 14-day bismuth quadruple therapy14 day bismuth quadruple therapy– 14-day hybrid sequential-concomitant therapy

• Knowing local resistance pattern is essentialGraham DY, Lee Y-C, Wu M-S. Clin Gastroenterol Hepatol 2014;12:177-186.

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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Lawrence R. Schiller, MD, FACG

Treatment tips

• Levofloxacin-containing triple therapy is a l i if l fl i i t isalvage regimen if levofloxacin resistance is

not high in community• Antibiotic susceptibility should be assessed if

second-line therapy fails• Prove eradication with urea breath test orProve eradication with urea breath test or

fecal antigen test (not serology)

Malfertheiner et al. Gut 2012;61:646-664.Graham DY, Lee Y-C, Wu M-S. Clin Gastroenterol Hepatol 2014;12:177-186.

ACG/LGS Regional Postgraduate Course - New Orleans, LA Copyright 2014 American College of Gastroenterology

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