Gastroenterology Archives - Page 3 of 3

Gastroenterology

Monographs

Update on the Management of Gastro-Oesophageal Reflux Disease

This article discusses the latest recommended assessment, investigation and treatment of GORD as is relevant in the primary care setting.

Expert/s: Dr May Wong, Dr Harriet Wadsworth

Gastroenterology

Clinical Articles

Fatty liver Disease in Australian Women

Expert/s: Dr Linda Calabresi

Gastroenterology

Clinical Articles

The human microbiome is a treasure trove waiting to be unlocked

Bacteria are at the centre of all life forms on planet earth and are the essential building blocks that make living organisms the way they are. Both the mitochondrion — found in most organisms, which generates energy in the cell — and the chloroplast — the solar energy-harvester located in plants — can be traced to their bacterial ancestors. These specialized microbes laid the foundation for the biodiversity we live amongst.

Expert/s: Vasu Appanna

Gastroenterology

Clinical Articles

Probiotics Don’t Help in Kids’ Gastro

Giving children with acute gastroenteritis probiotics will not help them recover more quickly, according to two large randomised controlled trials. At least if the probiotic includes Lactobacillus rhamnosus. The research, published in the New England Journal of Medicine, provides solid evidence against the adjunctive treatment, which, as the study authors point out, has been recommended by many health professionals and authoritative bodies. “Many experts consider acute infectious diarrhoea to be the main indication for probiotic use,” they said. However, the two studies, both conducted on children aged three months to four years with a less than 72-hour history of acute vomiting and diarrhoea, failed to show any benefit of taking a five-day course of the probiotics. One of the studies conducted across six tertiary paediatric centres in Canada, involved almost 900 children with acute gastroenteritis randomly assigned to receive either a combination probiotic (L. rhamnosus and L. helveticus) or placebo. The other very similar study, this one involving US centres, included 970 children with gastroenteritis and tested the effectiveness of giving the single probiotic Lactobacillus rhamnosus against placebo. The results of the two trials, using almost identical outcome measures were the same – the probiotics did not make a difference. “Neither trial showed a significant difference in the duration of diarrhoea and vomiting, the number of unscheduled visits to a health provider or the duration of day-care absenteeism,” an accompanying editorial concluded. The role of probiotics in the management of gastroenteritis in children has been an area of controversy and contradiction not only among individual specialists but also among different expert bodies, with guideline recommendations varying from “not recommended” by the Centers of Disease Control and Prevention to “strongly recommended” by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. But now, it appears this grey area has now become very black and white. “Taken together, neither of these large, well-done trials provides support for the use of probiotics containing L. rhamnosus to treat moderate-severe gastroenteritis in children,” the editorial stated. The caveat, of course, is that this evidence while robust only applies to this particular probiotic. There might still be probiotics out there that do make a difference. The editorial author referred to a recent large randomised-controlled trial conducted in rural India that found giving healthy newborns the probiotic, L. planatarum in the first few days of life was associated with a significantly lower risk of sepsis and lower respiratory tract infection in the subsequent two months. So while these studies might appear to be the nail in the coffin for L. rhamnosus -containing probiotics, it is still a case of ‘watch this space’ with regard the role of probiotics more generally.

Reference

Schnadower D, Tarr PI, Casper TC, Gorelick MH, Dean JM, O'Connell KJ, et al. Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children. N Engl J Med. 2018 Nov 22; 379(21): 2002-2014. DOI: 10.1056/NEJMoa1802598 Freedman SB, Williamson-Urquhart S, Farion KJ, Gouin S, Willan AR, Poonai N, et al. Multicenter Trial of a Combination Probiotic for Children with Gastroenteritis. N Engl J Med. 2018 Nov 22; 379(21): 2015-26. DOI: 10.1056/NEJMoa1802597 LaMont JT. Probiotics for Children with Gastroenteritis. N Engl J Med 2018 Noc 22; 379(21): 2076-77. DOI: 10.1056/NEJMe1814089

Expert/s: Dr Linda Calabresi

Gastroenterology

Monographs

Traveller’s Diarrhoea

This article discusses the latest evidence on the incidence and prevalence of Traveller’s Diarrhoea, and how it is best prevented, assessed and treated.

Expert/s: Dr Bernard Hudson

Gastroenterology

Clinical Articles

Are We Missing Chronic Pancreatitis? Does it Matter?

The answer to both these questions is yes according to Dr Darren Pavey, gastroenterologist and senior lecturer at the University of NSW. Speaking at the Healthed General Practice Education seminar in Sydney recently, Dr Pavey said there was good international research suggesting that many cases of chronic pancreatitis were going undiagnosed and the condition was far more prevalent than previously recognised. Overseas studies including cohorts of randomly selected adult patients suggest a prevalence of between 6-12%, with the condition being more likely among patients with recent onset type 2 diabetes, excess alcohol intake, smokers and those over 40 years of age, he said. And in response to the question of whether it is important to diagnose this condition, Dr Pavey said chronic pancreatitis not only caused immediate symptoms usually including pain, diarrhoea and weight loss but commonly had longer-term consequences such as pancreatic exocrine insufficiency (where there is less than 10% pancreatic function) and an increased risk of diabetes, malnutrition and even pancreatic cancer. Certainly, an incentive to diagnose and treat earlier rather than later. Part of the challenge in recognising the condition is that the classic triad of symptoms, namely abdominal pain, diarrhoea and weight loss are common to a variety of medical conditions including IBD and IBS. What’s more, abdominal pain, which many doctors would have thought had to be present with pancreatitis does not always occur in chronic pancreatitis especially when it is idiopathic which is the more common variety of chronic pancreatitis. In fact, pain is only present in about half the cases of idiopathic chronic pancreatitis. Idiopathic pancreatitis constitute 55% of all cases, the other 45% being alcohol-related. Abdominal pain tends to be a more consistent feature of alcoholic chronic pancreatitis. So if you have a patient in the right age group (about 40 to 60 years), who has chronic diarrhoea, weight loss and maybe abdominal pain and you suspect they might have chronic pancreatitis what do you do? The most common screening test for chronic pancreatitis is now a faecal elastase-1 stool test, requiring a single formed stool sample, said Dr Pavey. The test has a high specificity and sensitivity (both over 90%) and is readily available to Australian GPs, although it does not attract a Medicare rebate and costs approximately $60. The test is positive if the concentration of faecal elastase is less than 200mcg/g. In terms of imaging, CT is usually the option of first choice with signs of calcification and atrophy being pathognomonic of significant chronic pancreatitis. Aside from the need to stop drinking and smoking, treatment revolves around replacement of the pancreatic enzymes, which is available as a capsule taken orally (Creon). The deficiency of these enzymes is the chief cause of the diarrhoea, malabsorption, and weight loss so replacing them not only alleviates the symptoms but will also help prevent some of significant sequelae associated with this ongoing condition. Interestingly, a study of patients newly diagnosed with pancreatic cancer, showed that 66% had pancreatic exocrine insufficiency at diagnosis, and after two months this prevalence grew to 93% Dr Pavey advises starting patients with known chronic pancreatitis on 25,000 lipase units (Creon) with every meal and 10,000 units with every snack, and recommends patients eat six smaller meals during the day rather than three larger meals. This replacement therapy would then be titrated up to 40,000 units with a meal and 25,000 units for a snack. For those whose need was greater, replacement could even be increased to 80,000 units per meal. There was no need to put patients on a reduced fat diet when they were on pancreatic enzyme replacement therapy however they often had a highly acidic upper gastrointestinal environment and required acid suppression treatment. In conclusion, Dr Pavey advises clinicians to have a high index of suspicion for this poorly-recognised but important condition. “[Doctors] should be aware of the problem of underdiagnosing this condition and have a low threshold for checking faecal elastase and assessing pancreatic insufficiency,” he said.

Expert/s: Dr Linda Calabresi

Gastroenterology

Clinical Articles

The Gut Microbiome – Fad or The Future?

Which bacteria are colonising your gut is becoming increasingly important, Australian researchers say. More and more evidence is suggesting the gut microbiota has a significant role in both the cause and the cure of a wide range of gastrointestinal and hepatic diseases and conditions. According to a review in The Medical Journal of Australia, research shows that particular types of bacteria colonising the gut have been associated the development of inflammatory bowel disease (IBD), metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steato-hepatitis (NASH), obesity and diabetes. We know that the bowel starts to be colonised by bacteria in utero. The make-up of an individual’s gut microbiota then depends on factors such as mode of delivery, breast-feeding, diet, illness and exposure to antibiotics. By the age of three, the gut microbiota resembles that of an adult. Observational studies have suggested a strong association between alterations in the microbiota because of environmental factors, and an increased risk of diseases. For instance, IBD was very rare in traditional Chinese populations, but studies have shown exposure to Western diets and medicines from a young age has increased the prevalence of this disease. “Asian adults who migrate from countries of low prevalence to countries of high prevalence do not have an increased risk of developing IBD, but their children experience the IBD incidence of their new country of residence,” the review authors said. Stronger evidence comes from studies into the exact nature of bacteria colonising the gut. It appears both the specific bacteria and the diversity of bacteria are important in disease pathogenesis. “For example, the presence of Proteus species at the time of Crohn’s disease resection is associated with early disease recurrence, while the presence of Faecalibacterium prauznitzii is protective against recurrence,” they said. Researchers have also found significant differences in the microbiota of people who develop severe alcoholic hepatitis and those who maintain normal hepatic function despite drinking the same amount of alcohol. Most importantly in the investigation of the role of the gut microbiota, is the emerging evidence that by altering the bacterial colonies in the gut we can alter the course of the disease. The classic example of this, of course, was the discovery of Helicobacter Pylori as the cause of peptic ulcer disease with treatment of this, dramatically changing health outcomes. But since then a lot of the research focus has been on faecal microbiota transplants (or poo transplants as they are commonly known). Mice studies have shown that a mouse will become fat if given a transplant of faecal bacteria from a fat donor mouse. Similarly, a similar result has been shown in a single trial of FMT from lean to obese humans, lowering triglyceride levels and increasing insulin sensitivity. FMT has also been shown to be an effective therapy for recurrent C.difficile infection and in active ulcerative colitis. And while the application of FMT as a treatment continues to be explored, investigators are also looking at how the microbiota can be changed through dietary means and how this can be used therapeutically. While probiotics have not been shown to be effective in the majority of inflammatory diseases, an anti-inflammatory diet combined with liquid formulated enteral nutrition has shown some success in Crohn’s disease. In short, the review authors suggest that the current interest in the gut microbiome is justified and has the potential to provide important therapeutic options in the future. “Microbial manipulation is an effective therapy, likely to have broadening implications,” they concluded. Reference White LS, Van den Bogaerde J & Kamm M. The gut microbiota: cause and cure of gut diseases. Med J Aust. 2018 Oct 1; 209(7): 312-16. Available from: https://www.mja.com.au/journal/2018/209/7/gut-microbiota-cause-and-cure-gut-diseases doi: 10.5694/mja17.01067

Expert/s: Dr Linda Calabresi

Gastroenterology

Clinical Articles

What Is Lymphocytic Oesophagitis

The importance of eosinophils and neutrophils infiltrating oesophageal squamous epithelium as markers for reflux, eosinophilic oesophagitis, and infection are well entrenched, although traditionally less attention has been paid to lymphocytes. Small numbers of lymphocytes are normally seen in oesophageal epithelium including CD4 helper and CD8 positive cytotoxic lymphocytes. However, isolated increases in lymphocytes in the oesophageal epithelium, outside the context of entities such as lichen planus and graft versus host disease, have been less well recognised until recently. The criteria for a diagnosis of lymphocytic oesophagitis, where lymphocyte numbers are markedly increased with few or no eosinophils, is not strictly defined since this is still a reaction pattern and not a specific diagnosis per se, and thresholds vary from study to study. The strictest definition requires at least 50 intraepithelial or peripapillary lymphocytes per HPF with few or no granulocytes. The term lymphocytic oesophagitis was originally coined in 2005 by Rubio et al to describe a histological reaction pattern in the oesophagus of a series of 20 patients. The patients had a high number of peripapillary lymphocytes and a lack of neutrophils and eosinophils. The papillae are projections of lamina propria, containing capillaries, which project a short distance into the epithelium of the normal oesophagus. The pattern of lymphocytic oesophagitis showed an association with Crohn’s disease, though not a completely specific one. Of the 20 patients, 11 were age 17 or younger and of these, eight (40%) had Crohn’s disease; 20% had manifestations of reflux and the remainder a mixture of conditions including coeliac, gastroduodenitis, and Hashimoto’s thyroiditis. A similar study of 40 patients in 2008 was unable to confirm these findings. Looking at it from a different angle, Ebach et al studied 60 paediatric patients with known Crohn’s disease and control groups and found an association. Lymphocytic oesophagitis which was found in 28% of patients with Crohn’s disease (mean age 13.3) but in only 2/30 patients with ulcerative colitis. A 2014 study of 580 paediatric patients confirms the association with Crohn’s disease, but also shows the non-specific nature of lymphocytic oesophagitis. This found 31 patients with lymphocytic oesophagitis and 49 with Crohn’s disease. Six of the 31 lymphocytic oesophagitis patients (19%) and 43 of the 514 non- lymphocytic oesophagitis patients (8.4%) had Crohn’s disease. The remaining lymphocytic oesophagitis patients had other diagnoses with no significant clinical correlates. Conversely, lymphocytic oesophagitis was identified in 12.2% of the patients with Crohn’s disease. Thus, there were still more lymphocytic oesophagitis patients without Crohn’s disease than with Crohn’s disease. In adults, the association with Crohn’s disease is not seen but there appears to be an association with oesophageal dysmotility. A 2011 study of over 129,000 patients from a large outpatient private GI pathology lab service revealed lymphocytic oesophagitis in only 119 patients, 60% female. Most patients had symptoms of oesophageal disease such as dysphagia or odynophagia, with dysphagia being the most common complaint, and around 20% complaining of reflux. Endoscopically, around a third of patients were suspected of having eosinophilic oesophagitis (including ‘feline oesophagus’ where the oesophagus has rings resembling that of a cat’s oesophagus), around 20% were normal, 18% had features suggestive of reflux, and 10% had stricture. However, none had Crohn’s disease or an association with Helicobacter gastritis. Although this study drew no firm conclusions as to the nature of lymphocytic oesophagitis in adults, the prevalence of dysphagia as a presenting complaint, and the number of patients with findings reminiscent of eosinophilic oesophagitis were noted. The association with dysmotility is enhanced by the finding that in adult patients, a lymphocytic oesophagitis with a complete absence of granulocytes was mostly seen in older female patients who presented with dysphagia and had an oesophageal motility disorder. CD4- and CD8-predominant lymphocytic oesophagitis occurs with roughly equal frequency. However, patients with CD4-predominant lymphocytic oesophagitis are more likely to be female (71%), and have a motility disorder (90% of those tested). This suggests a new entity of ‘dysmotility lymphocytic oesophagitis’. In summary, the reaction pattern of lymphocytic oesophagitis appears to be real, however, the term cannot be used as a wastebasket and true increased numbers of intraepithelial lymphocytes must be seen. Clinical and endoscopic correlations determine the significance of any pathologist comment on increased numbers of lymphocytes in the epithelium.
General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

Expert/s: Dr David Palmer

Gastroenterology

Clinical Articles

Coeliac disease testing

Coeliac disease is a common disorder affecting the gastrointestinal tract, secondary to an immunologic reaction to gluten. At present it can only be managed by lifelong avoidance of gluten, and thus presents a challenge for patients and their health care professionals.

Epidemiology

Coeliac disease was first characterised in the late 1940s with diarrhoea and failure to thrive in young children. The wartime shortage of wheat, and adoption of a gluten-free surrogate diet, allowed their symptoms to improve. When wheat was re-introduced into their diets their condition worsened again. Initially thought to be a rare disease of children, we now recognise coeliac disease to be prevalent in adults, including the elderly. Data from the UK reveal that the most common age group diagnosed is between 30 and 45, with more people over 60 than those under 16 years (Coeliac UK: www.coeliac.co.uk). The illness occurs in people of European, Turkish, Middle Eastern, Egyptian and Indian backgrounds. It appears to be rare in sub-Saharan Africa and South-East Asia. There is debate over mass screening in populations such as in the UK and Scandinavia, where the disease incidence approaches 1%. The Gastroenterological Society of Australia (GESA) recommends screening in persons with Type 1 diabetes mellitus, Down syndrome, Turner syndrome, immunoglobulin A (IgA) deficiency, or a family history of coeliac disease, where the condition may be as common as 1 in 10.

Immunopathology

The pathologic understanding of coeliac disease has advanced considerably over the past 10 years, although our understanding is still incomplete. In some individuals, when gluten is digested the peptides cross the intestinal mucosa where they are recognised by the mucosa-associated lymphoid tissue. Those individuals with HLA-DQ2 or -DQ8 are able to process the gluten peptides, resulting in presentation of gliadin/gluten peptides on the surface of antigen-presenting cells. Over 99% of coeliac patients have HLA-DQ2 or -DQ8, and homozygotes for DQ2/8 are more likely than heterozygotes to develop the disease, and more severely. For the peptides to be presented to T cells, they must first be deamidated by a ubiquitous enzyme, tissue transglutaminase (tTG). Tissue transglutaminase alters the gluten-derived peptide so that it remains in the binding site of the HLA molecule, and allows an immune response to occur against the enterocytes that carry the HLADQ2/8-gluten peptide complex. Tissue transglutaminase is present in an active form outside cells; its usual role is to help maintain the extra-cellular matrix. Several isoenzymes of tTG exist throughout the body, tTG2 being present in the GI tract. It is the presence of IgA antibodies to this enzyme— anti-tTG2 antibodies (hereafter ‘tTG antibodies’)—that have become the gold standard serologic marker for coeliac disease. It remains uncertain why antibodies to tTG develop in coeliac patients, although research suggests that tTG can become cross-linked to the gluten peptide and cause specific tTG antibodies to develop, through a process termed ‘epitope spreading’. Tissue transglutaminase antibodies have been shown to pre-date the development of the histologic changes of coeliac disease. It is clear that antibodies to tTG are not pathogenic in most patients, as many cells in the body contain similar tTG. However, in dermatitis herpetiformis, a disease long associated with coeliac disease, these antibodies develop against tTG3 (whereas in coeliac disease they are directed against tTG2). In dermatitis herpetiformis, these tTG3 antibodies may well be pathogenic, leading to classic cutaneous lesions.

Serologic testing

IgA tTG antibodies are now considered the gold standard in the detection of coeliac disease, giving a sensitivity of around 95%, and a specificity of around 90%. IgA tTG antibodies become negative 9–12 months after the introduction of a gluten-free diet. In children less than 2 years of age, IgA production is not mature and may result in false negative IgA tTG. This is especially true for those less than one year of age. At present, all serologic diagnoses should be confirmed by histologic diagnosis, as false positives can occur. Although several studies in children have indicated that very high IgA anti-tTG results may not need to be confirmed by biopsy, Australian guidelines indicate the need for histologic confirmation. IgG tTG antibodies may also be detected in coeliac patients, though they have similar problems to IgG anti-gliadin antibodies (AGA, discussed below), with a poor sensitivity and specificity, despite initial enthusiasm for their utility. Older serologic tests for coeliac disease were based on antibodies directed against gliadin—anti-gliadin antibodies (IgA AGA and IgG AGA). Like all food antibodies, they have relatively poor sensitivity (false negatives) and particularly poor specificity (false positives), especially given that they are a group of antibodies (polyclonal), rather than being directed against a single epitope. The indication for IgA AGA is very limited and should largely be consigned to history. However, these antibodies can be used to monitor early adherence to a gluten-free diet as they become negative 6–9 months after the diet is introduced. IgG AGA, however, remains of use in IgA-deficient patients in whom IgA tTG and IgA AGA are not produced. IgG against deamidated gliadin is of use in IgA-deficient patients in whom IgA tTG and IgA AGA are not produced. This is a modified test, using a gliadin peptide (small piece of protein) that had been altered to more closely resemble the natural peptide found in wheat. IgA deficiency is defined as ‘undetectable or barely detectable’ serum IgA. IgG AGA are also of use in children less than two years of age (and especially children under one), in whom the ability to produce IgA antibodies has not fully developed. All patients with IgA deficiency in whom coeliac disease is suspected should undergo a small bowel biopsy, regardless of the IgG AGA and other testing conducted. It is suggested they be referred to a gastroenterologist, as other diseases such as chronic giardia and autoimmune enteritis may occur. One theory to explain why IgA deficiency is associated with the development of coeliac disease is that IgA is involved in the neutralisation of foreign antigens at mucosal surfaces, and these deficient individuals have greater transmucosal passage of gliadin fragments. Another type of antibody, IgA endomysial antibodies, has also been used to test for the disease in the past. These antibodies were first detected in monkey oesophagus; it is now recognised that the antigen being detected by this method was tTG. These antibodies are highly specific (~ 100%) but have a slightly lower sensitivity (~ 90%) than IgA tTG. Endomysial antibodies are sometimes used in children under two years of age.

Tissue typing

In selected cases, HLA-DQ typing may be of benefit. In patients who are predisposed to the development of coeliac disease, a negative test would essentially rule out the diagnosis. A positive result, on the other hand, would not significantly alter the chance of the person having coeliac disease. In Down syndrome and Turner syndrome patients, this would alleviate the need for life-long screening. Tissue typing may be of value in infants (less than two years), to exclude disease, as serologic markers are less reliable. HLA-DQ typing in relatives of coeliac patients may also be of use, although they are highly likely to have DQ2/8 present, whether or not they also have the disease. As DQ2 is independently associated with IgA deficiency and Type 1 diabetes, tissue typing would be less beneficial in such cases.

General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

Expert/s: Dr Daman Langguth