In the next in this series sharing expert insights on the most common advice and guidance (A&G) requests in key specialties, gastroenterology fellow Dr Michael Colwill, consultant gastroenterologist Dr Andrew Poullis and GP Dr Jessica Hemingway highlight the 10 most common requests received in their gastroenterology A&G service and explain how these are managed
Note all 10 requests feature hypothetical cases created for illustrative purposes
1. Persistent dyspepsia on high-dose omeprazole
Q: A 44-year-old has persistent dyspepsia despite high dose omeprazole (20mg twice a day). He has no red flag symptoms warranting a two-week-wait referral. Is adding famotidine the correct next step? Are famotidine and omeprazole synergistic? And which one would you stop first if his symptoms improve?
A: In patients who suffer from persistent dyspepsia despite omeprazole 20mg BD, the first approach should be to review whether the patient is compliant with medication and is taking it at least 30 minutes before eating. Ensure that conservative measures have been addressed – eg, stopping smoking, alcohol reduction, avoidance of NSAIDs, dietary changes to exclude triggers, exercise and weight loss. Testing of Helicobacter pylori is also reasonable but this requires patients to have stopped their PPI for 2 weeks. If all these issues have been addressed then adding famotidine 20mg OD is a reasonable next step. Combined famotidine and omeprazole has been shown to have an increased impact on gastric pH compared to monotherapy. Review the history to confirm the diagnosis and look for signs of differentials such as functional dyspepsia or eosinophilic oesophagitis (eg, intermittent dysphagia, atopy history). Persisting symptoms after a trial of famotidine are an indication for referral to gastroenterology for routine gastroscopy and consideration of other differentials.
2. Hepatitis B surface antigen negative and core antibody positive
Q: This 24-year-old is a new patient to the practice and a Somali refugee. She has been screened by the health inclusion team and bloods showed she is hepatitis B surface antigen negative but core antibody positive. Hepatitis C and HIV screening is negative, and she has normal liver function tests. Does she need to be referred to hepatology?
A: A negative surface antigen and positive core antibody suggests that the patient has previously cleared the virus. However, the surface antibody status should also be checked as well. If positive then this is consistent with cleared natural infection and subsequent immunity. If the surface antibody is negative then they should be referred routinely to a hepatologist for further investigation. It should be noted that if the patient has been vaccinated against hepatitis B in the past, they will have a positive surface antibody result but will be negative for surface antigen and core antibody. An ultrasound can be performed to ensure no evidence of cirrhosis, although that is unlikely given clinical presentation. If the patient needs immunosuppression treatment at any point in the future, they should be referred to hepatology services for consideration of prophylactic nucleoside analogue therapy. Immunosuppression has been shown to lead to reactivation of previous infection which can lay dormant in hepatocytes, the nucleoside analogue therapy ensures that if this occurs, viral load and subsequent hepatic inflammation remains low. Ensure this is clearly explained to the patient and documented in their notes.
3. Crohn’s disease and low B12
Q: This 57-year-old man presented with fatigue and was found to have a marginally low total vitamin B12 of 172pg/mL, but a normal haemoglobin, folate and ferritin. He has a diagnosis of Crohn’s disease on azathioprine and tells me he has not had a flare in 7 years. Would you commit this man to lifelong B12 injections? I was considering a trial of oral B12 and then rechecking bloods in three months.
A: Patients with Crohn’s disease are at risk of multiple vitamin deficiencies because of active disease and subsequent impaired absorption (particularly if the terminal ileum is affected as this is where B12 is absorbed) but also because of previous surgeries they may have had such as a terminal ileal resection. They are also more likely to suffer from autoimmune atrophic gastritis which can predispose to B12 malabsorption.
Given the result here is borderline low and rest of his markers are normal, there are a few options. It is reasonable to repeat his tests including a serum methylmalonic acid (MMA) which, if high, confirms B12 deficiency. Oral replacement and monitoring his response at 3 months is reasonable given the otherwise normal test. Test for intrinsic factor antibodies and parietal cell antibodies to investigate possible pernicious anaemia. If tests are positive, consider referring him for a gastroscopy as he is over 50 years old; patients with pernicious anaemia and B12 deficient are at risk of atrophic gastritis which is a risk factor for gastric cancer. Check coeliac autoantibodies to assess for possible coeliac disease. Helicobacter pylori infection can damage parietal cells, reducing production of intrinsic factor leading to impaired B12 absorption, so testing for this with a stool antigen is also worth considering. Intramuscular replacement is indicated if the patient does not respond to oral treatment.
4. Asymptomatic mild anaemia
Q: A 74-year-old woman is mildly anaemic, with a haemoglobin of 112g/L and 109g/L on two blood tests six weeks apart. Her MCV is normal. Her haematinics, including iron binding studies, folate and B12, are normal and she is asymptomatic with no visible blood loss and no weight loss. A FIT is negative and a urine dip was negative for blood. Given the anaemia is unexplained does she warrant a referral for an OGD and colonoscopy?
A mild non-iron deficient anaemia, particularly in the absence of GI symptoms and with a negative FIT, is unlikely to be from a gastrointestinal source and therefore does not justify endoscopic investigation. Given the anaemia is mild, and assuming no cause is found, then repeating the blood tests in 2-3 months is a reasonable strategy and if a further fall is noted then a referral to haematology, rather than gastroenterology, with close follow-up in primary care in the meantime, is indicated. If there is an ongoing clinical concern, for example a strong family history of colorectal cancer then, as per NICE guidance DG56, referral to secondary care under the lower GI two-week rule pathway can be considered.
5. Rising ferritin
Q: This 65-year-old woman has a rising ferritin over 12 months and it is now 960ng/mL. She was reviewed by the rapid diagnostics clinic nine months ago to rule out a malignancy given the rising ferritin. She has a history of type 2 diabetes, hypertension and hypercholesterolaemia. Her liver ultrasound performed four months ago showed fatty liver with possible early fibrosis. Could the fatty liver explain her ferritin? Should we consider referring to gastroenterology or possibly haematology for haemochromatosis testing?
A: Ferritin is the cellular storage protein for iron but is also an acute phase reactant that, along with transferrin, helps to orchestrate cellular defence against oxidative stress and inflammation. Because of this it can be raised in multiple conditions including acute infection, liver disease, metabolic syndrome, viral hepatitis, any chronic inflammatory state or multiple haematological disorders.
Haemochromatosis is included in the differential and in the first instance iron binding studies should be performed. If the transferrin saturation (TSAT) is less than 45% then haemochromatosis is very unlikely and other causes as described should be looked for. If the TSAT is above 45% then referral to hepatology for investigation of possible haemochromatosis is indicated. In some services haematology manages this condition and appropriate referral should be based upon local policy.
Importantly, as the patient also has multiple risk factors for metabolic dysfunction-associated steatotic liver disease and given the changes of fatty liver on the ultrasound, a FIB-4 or enhanced liver fibrosis (ELF) should be performed as per local guidance. Refer to hepatology if indicated. She should also be given lifestyle advice with regards to maintaining healthy weight, dietary and lifestyle measure to manage her liver disease as well as tight control of her diabetes.
6. Positive CLO test for H pylori
Q: This 41-year-old woman had a routine oesophagogastro duodenoscopy (OGD) for persistent epigastric pain which was largely normal although a small area of ‘irregularity’ was biopsied. The report states the CLO (Campylobacter-like organism) test for Helicobacter pylori was positive, but the biopsy taken did not show any evidence of malignancy. She has ongoing pain, and I am wondering whether we should treat her with triple therapy? If so is one week of treatment sufficient? Do you ever recommend doing a test of cure?
A: The CLO test is a rapid test done at the time of OGD that tests for the urease enzyme found in Helicobacter pylori. This indicates that H pylori infection is present and therefore should be treated. The lack of atypia or concerning features on histology is reassuring. This suggests the patient does not need any further procedures, unless the endoscopist has specific concerns. Triple therapy as per national guidance is effective and eradicates the infection, if taken correctly and the course completed, in over 90% of patients. The triple therapy regimen requires 7 days of treatment; longer courses are only recommended for third-line treatment regimens. Routine re-testing is not advocated but if symptoms persist then a repeat stool antigen test for H pylori, off PPI, can be performed and subsequent treatment given if there is persisting infection. A longer course of PPI can be considered to help treat any residual gastritis symptoms. If second- and third-line treatments fail, then referral to gastroenterology is indicated for a repeat procedure to biopsy and culture and treat, based upon sensitivities.
7. Statin for fatty liver
Q: This 38-year-old woman has had a liver ultrasound that demonstrates fatty liver and a persistently mildly raised ALT (105 U/L) and AST (85 U/L). Her BMI is 39kg/m2 and she is pre-diabetic. Her full lipid profile demonstrates a total cholesterol of 7.0mmol/L and a non-HDL cholesterol of 4.9mmol/L. Should we be prescribing a statin to treat her fatty liver? Can we safely initiate a statin given her liver function tests?
A: Statins are known to cause mild derangement in aminotransferases but these rises are nearly always clinically insignificant. Guidance from NHS England suggests that provided the AST and ALT are less than 3 times the upper limit of normal there is no contraindication to starting a statin if indicated, but that these blood tests should be repeated at 1 month and if they remain elevated but less than 3 times the upper limit of normal then continue with the statin and repeat at 6 months. If they go above this threshold, stop the statin and consider restarting at a lower dose or consider an alternative therapy.
With regards to her metabolic dysfunction-associated liver disease (MASLD), which is recognised as part of the metabolic syndrome, the most important aspect is lifestyle modification as well as tight control of risk factors (hypertension, diabetes, cholesterol).
Whilst statins are effective in addressing dyslipidaemia and reducing cardiovascular events, there is no evidence that they are independently beneficial to MASLD. If the patient meets criteria for a statin for other indications, then there is no contraindication, and it will provide her with a longer-term protective benefit. Given the deranged LFTs, she should have a FIB-4 or ELF score performed as per local protocol and if indicated should be referred to hepatology. If her FIB-4 or ELF is not elevated sufficiently to necessitate referral then these should be rechecked every three years whilst her metabolic risk factors are addressed.
8. Adalibumab and Covid
Q: This 33-year-old has a diagnosis of Crohn’s and is well controlled with adalimumab injections which she administers herself. She recently had Covid and was unsure whether to hold her injections. Are there any ‘sick day rules’ for the drug?
A: Adalimumab is usually administered fortnightly by the patient but can also be increased to weekly injections for severe disease. Anti-TNFa drugs such as adalimumab have been shown to put patients slightly more at risk of severe infections. Given this, if her next dose is due it is reasonable to wait until her symptoms have resolved and she is feeling better. If she had a bacterial infection, such as LRTI or UTI, and was being given antibiotics then holding the adalimumab whilst on the antibiotics and restarting 1-2 weeks after the course of treatment is completed is a reasonable approach. In this situation, given her diagnosis of Crohn’s and immunosuppressive medication, she would be eligible for Covid-19 anti-viral therapy such as remdesivir or sotrovimab if indicated clinically.
9. New diagnosis of IBS
Q: This 36-year-old has been diagnosed with irritable bowel syndrome (IBS) by my colleague and is struggling with her symptoms despite following a FODMAP diet. I plan to refer her to a dietitian but wonder if all patients with a new diagnosis of IBS should be referred for a one-off assessment?
A: IBS is common, affecting between 5% and 15% of the population, and the troublesome and sometimes persistent nature of the symptoms can cause a lot of concern. The BSG have provided thorough guidelines on initial management including steps that can be taken in primary care. These include simple lifestyle advice, dietary advice, probiotics and medications tailored to their symptoms. Examples include loperamide for diarrhoea, laxatives for constipation and anti-spasmodics for pain (either buscopan, peppermint capsules or mebeverine). However, if patients’ symptoms are refractory to first-line treatment, there is diagnostic doubt or atypical features of clinical concern, then a referral to secondary care gastroenterology is indicated.
10. Chronic constipation
Q: A 69-year-old man has longstanding chronic severe constipation, and we are struggling to treat it. He has tried ispaghula husk, lactulose and is now on 6 sachets of macrogol a day and still only producing type 2 stools. Glycerol suppositories have not helped and senna and bisacodyl caused abdominal cramps. His FIT is negative, and his weight is stable. What would you recommend next? Would you recommend trialling prucalopride?
A: Chronic constipation, particularly refractory to therapy, should be carefully assessed to delineate if this is primary constipation, ie, due to slow colonic transit, IBS or dyssynergic defecation, or secondary to any of the conditions below:
- Endocrine – diabetes, hypercalcaemia, hypothyroidism.
- Neurologic – Parkinson’s, spinal cord injury, autonomic neuropathy.
- Myogenic – myositis, scleroderma, amyloidosis.
- Drugs – opioids, TCAs, iron, anti-epileptics, anticholinergic or dopaminergic, some antihypertensives.
If secondary causes have been ruled out and the history and examination, including a DRE, does not raise any red flags, then lifestyle factors should be assessed and modified as required. Increasing fluid intake to 2L of fluid per day, exercise and a gradual increase in fibre to 25g/day will help most patients.
In this case, multiple laxatives have been trialled and there are no alarm symptoms. If lifestyle changes fail to work then prucalopride is a reasonable option. For this man, start at 2mg OD and review the response at 28 days. If he was a more frail individual then 1mg OD, increased if required to 2mg OD, would be a safe approach. Another option is linaclotide, which is an agonist of guanylate cyclase receptors and increases intestinal fluid and transit. Start this at 290mcg OD 30 minutes before food and review the response at 4 weeks. If any red flag features develop then urgent referral to lower GI two-week-wait services is indicated. If non-alarm symptoms remain persistent, refer to gastroenterology.
Dr Michael Colwill is a Gastroenterology Fellow and Dr Andrew Poullis is a Consultant Gastroenterologist at St George’s Hospital, London. Dr Jessica Hemingway is a GP in South London
