1 Proton pump inhibitor in liver cirrhosis:
Tradition vs. Evidence based practice
I Dewa Nyoman Wibawa
Div.Gastroentero-hepatology, Dept.of Internal Medicine, Udayana Univ., School of Medicine/Sanglah Gen. Hospital.
Introduction
The recommendation on the saftey use of most drugs in cirrhosis based largerly on experiences and/or expert opinion because most drugs have not been well studied in cirrhosis with dosing recommendations often based on pharmacokinetic changes. Most drugs can be used safely in cirrhosis, including those that are potentially hepatotoxic, but lower doses or reduced dosing frequency is often recommended.
Proton pump inhibitors (PPI) have been related to an increased risk of infection in cirrhosis including spontaneous bacterial peritonitis (SBP) and should be used with care.
PPIs, which reduce acid secretion, could increase the risk of gastrointestinal (GI) infections by raising the pH of the stomach and making it more prone to colonization by various pathogenic bacteria. The PPIs can disrupt the gut microbiota too, they change the bacterial growth, including abnormal bacterial counts and overt small intestinal bacterial overgrowth (SIBO). Moreover, gastric acid influences not only the upper gut flora, but also lower intestinal microbiota. The number of bacteria in small and large bowel increases as a result of gastric hypochlorhydric conditions. Previous case control studies have found an increased risk of GI infections in patients taking PPIs. Increased ammonia-producing enteric bacteria in patients with cirrhosis is also shown to be a risk factor for hepatic encephalopathy (HE).
Moreover there are convincing papers suggesting that acid secretion is reduced in patients with liver cirrhosis.
Proton pump inhibitor in liver cirrhosis
PPIs or Acid-suppressant medications are prescribed quite frequently in patients with cirrhosis. Indeed, PPIs were the most frequently prescribed class of medication prescribed to cirrhotics (given to approximately 40% of 400 patients). Lucena et al. reported that nearly one-fourth of the 568 patients in their series were prescribed these medications on admission and 35% on discharge. Ulcer-healing drugs accounted for 12% (n = 2377) of all medications prescribed, with both PPIs and H2 blockers being utilized chronically.
2 that only about 10% of more than 1309 patients were eligible for analysis, most of whom had inadequate records and medicationsto lists to review. Moreover, the risk was apparentonly for those patients taking PPIs in the previous 7 days, and why the investigators included patients already on antibiotics was not clearly stated. Terg also mentions that the data on the association of PPIs and bacterial overgrowth have been conflicting.
Although daily fluoroquinolone use as primary prophylaxis to high-risk patients with cirrhosis has been shown to substantially reduce the risk of SBP as reported in various meta-analyses, it is unknown whether or not the use of a fluoroquinolone (or other antibiotic) in this setting would mitigate the SBP risk associated with acid suppression in the same population. Since about two-thirds of cirrhotics were found to have no documented indication for the use of a PPI, we join the recommendation by Terg that acid-suppressive medications be used only when clinically indicated in the cirrhotic patient at high risk for SBP and other infections (especially those with ascites). While the riskof SPB was significantly lower in those taking PPIs formore than 90 days, the risk may not be completely eliminated in such patients, and the safety of chronic useof PPIs and H2 blockers in cirrhosis deserves additional study, both in terms of design and duration.
Tradition
PPI are very effective in inhibiting acid secretion and are extensively used in many acid related diseases. They are also often used in patients with cirrhosis sometimes in the absence of a specific acid related disease, with the aim of preventing peptic complications in patients with variceal or hypertensive gastropathic bleeding receiving multidrug treatment. Contradicting reports support their use in cirrhosis and evidence of their efficacy in this condition is poor. In a minority of patients, PPIs may be prescribed without clear indications or because of their propensity to develop upper gastrointestinal symptoms.
Evidence –based practice
One study reported patients with SBP had a significantly higher rate of pre-hospital PPI use (60.8%) compared with cirrhotic patients without SBP (42.2%; P=0.03). On multivariate analysis, PPI use was the only factor independently associated with SBP (OR 2.09 [95% CI 1.04 to 4.23]; P=0.04). Thirty-five (35%) patients in both groups had no documented indication for PPI use in their charts. Forty-five percent of the remaining cirrhotic patients with SBP had an inappropriate indication, as defined in the protocol, for PPI use compared with 25% of controls.
Cirrhotic patients with SBP were twice as likely to have taken PPIs than patients without SBP. These findings reinforce the association between PPI use and SBP observed in other studies. A high percentage of cirrhotic patients were taking a PPI without any documented indication.
3 patients taking PPI is still missing, the prescription of PPI in cirrhotics should be considered carefully taking into account its potential adverse effects.
Summary
We need more paper provides further evidence that PPIs are associated with a worse outcome in cirrhotic patients. More studies are required to clarify the mechanisms of increased mortality in this patient group and at what stage (and for what indication) the risks may outweigh benefits in cirrhosis. In the meantime, it is essential that clinicians are aware of the potential deleterious effects of PPIs in cirrhotic patients. The use of this class of drugs seems more habit related than evidence based eventually leading to an increase in health costs.
Further Readings
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