Management and treatment of lactose malabsorption

Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world's population, while secondary hypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen causes gastrointestinal symptoms. The condition is known as lactose intolerance. In patients with lactase nonpersistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenousβ-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation. In this review the usefulness of these approaches is discussed and a therapeutic management with a flow chart is proposed.     

Breath tests and irritable bowel syndrome

Breath tests are non-invasive tests and can detect H2and CH4 gases which are produced by bacterial fermentation of unabsorbed intestinal carbohydrate and are excreted in the breath.These tests are used in the diagnosis of carbohydrate malabsorption,small intestinal bacterial overgrowth,and for measuring the orocecal transit time.Malabsorption of carbohydrates is a key trigger of irritable bowel syndrome(IBS)-type symptoms such as diarrhea and/or constipation,bloating,excess flatulence,headaches and lack of energy.Abdominal bloating is a common nonspecific symptom which can negatively impact quality of life.It may reflect dietary imbalance,such as excess fiber intake,or may be a manifestation of IBS.However,bloating may also represent small intestinal bacterial overgrowth.Patients with persistent symptoms of abdominal bloating and distension despite dietary interventions should be referred for H2 breath testing to determine the presence or absence of bacterial overgrowth.If bacterial overgrowth is identified,patients are typically treated with antibiotics.Evaluation of IBS generally includes testing of other disorders that cause similar symptoms.Carbohydrate malabsorption(lactose,fructose,sorbitol)can cause abdominal fullness,bloating,nausea,abdominal pain,flatulence,and diarrhea,which are similar to the symptoms of IBS.However,it is unclear if these digestive disorders contribute to or cause the symptoms of IBS.Research studies show that a proper diagnosis and effective dietary intervention significantly reduces the severity and frequency of gastrointestinal symptoms in IBS.Thus,diagnosis of malabsorption of these carbohydrates in IBS using a breath test is very important to guide the clinician in the proper treatment of IBS patients.     

Molecularly defined adult-type hypolactasia in school-aged children with a previous history of cow＇s milk allergy

AIM: To assess the role of lactase non-persistence/persistence in school-aged children and their milk-related symptoms. METHODS: The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years (SE = 0.02, 93 boys) participating in a follow-up study for cow's milk allergy. The parents were asked to assess their children's milk consumption and abdominal symptoms. RESULTS: The presence of allergy to cow's milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood (lactase non-persistence). The frequency of the C/C-13910 genotype (16%) was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children (90%) in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping (P< 0.004 when compared to the other genotypes). CONCLUSION: Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow's milk allergy.     

Molecularly defined adult-type hypolactasia among working age people with reference to milk consumption and gastrointestinal symptoms

AIM: To study milk consumption and subjective milk- related symptoms in adults genotyped for adult-type hypolactasia. METHODS: A total of 1900 Finnish adults were genotyped for the C/T-13910 variant of adult-type hypolactasia and filled in a structured questionnaire concerning milk consumption and gastrointestinal problems. RESULTS: The C/C-13910 genotype of adult-type hypolactasia was present in 18% of the study population. The prevalence of the C/C-13910 genotype was higher among subjects who were undergoing investigations because of abdominal symptoms (24%, P < 0.05). Those with the C/C-13910 genotype drank less milk than subjects with either the C/T-13910 or the T/T-13910 genotype of lactase persistence (18% vs 38%; 18% vs 36%, P < 0.01). Subjects with the C/C-13910 genotype had experienced more gastrointestinal symptoms (84%) during the preceding three-month period than those with the C/T-13910 (79%, P < 0.05) or the T/T-13910 genotype (78 %, P < 0.05). Only 9% (29/338) of the subjects with the C/C-13910 genotype consumed milk and reported no symptoms from it.CONCLUSION: Gastrointestinal symptoms are more common among adults with the C/C-13910 genotype of adult-type hypolactasia than in those with genotypes of lactase persistence.     

Hydrogen breath test for the diagnosis of lactose intolerance, is the routine sugar load the best one？

AIM： To evaluate the prevalence of lactose intolerance （LI） following a load of 12.5 g in patients diagnosed as high-grade malabsorbers using the hydrogen breath test （HBT）-25. METHODS： Ninety patients showing high-grade malabsorption at HBT-25 were submitted to a second HBT with a lactose load of 12.5 g. Peak hydrogen production, area under the curve of hydrogen excretion and occurrence of symptoms were recorded. RESULTS： Only 16 patients （17.77%） with positive HBT-25 proved positive at HBT-12.5. Hydrogen production was lower as compared to HBT-25 （peak value 21.55 parts per million （ppm） ± 29.54 SD vs 99.43 ppm ± 40.01 SD; P 〈 0.001）. Symptoms were present in only 13 patients. The absence of symptoms during the high-dose test has a high negative predictive value （0.84） for a negative low-dose test. The presence of symptoms during the first test was not useful for predicting a positive low-dose test （positive predictive value 0.06-0.31）. CONCLUSION： Most patients with a positive HBT-25 normally absorb a lower dose of lactose and a strict lactose restriction on the basis of a ＂standard＂ HBT is, in most instances, unnecessary. Thus, the 25 g lactose tolerance test should probably be substituted by the 12.5 g test in the diagnosis of LI, and in providing dietary guidelines to patients with suspected lactose malabsorption/intolerance.     

Breath test for differential diagnosis between small intestinal bacterial overgrowth and irritable bowel disease： An observation on non-absorbable antibiotics

AIM： To estimate the prevalence of small intestine bacterial overgrowth （SIBO） among patients with an earlier diagnosis of irritable bowel disease （IBS） in our geographical area, and to collect information on the use of locally acting non-absorbable antibiotics in the management of SIBO. METHODS： A non-interventional study was conducted in 73 consecutive patients with a symptom-based diagnosis.. RESULTS： When the patients underwent a ＂breath test＂, 33 （45.2%） showed the presence of a SIBO. Arcer treatment with rifaximin 1200 mg/d for seven days in 32 patients, 19 （59.4%） showed a negative ＂breath test＂ one week later as well as a significant reduction of symptoms, thus confirming the relationship between SIBO and many of the symptoms claimed by patients. In the other 13 patients, ＂breath test＂ remained positive, and a further cycle of treatment with ciprofloxacin 500 mg/d was given for 7 additional days, resulting in a negative ＂breath test＂ in one patient only. CONCLUSION： （1） about half of the patients with a symptomatic diagnosis of IBS have actually SIBO, which is responsible for most of the symptoms attributed to IBS; （2） only a ＂breath test＂ with lactulose （or with glucose in subjects with an intolerance to lactose） can provide a differential diagnosis between IBS and SIBO, with almost identical symptoms; and （3） the use of non-absorbable antibiotics may be useful to reduce the degree of SIBO and related symptoms; it must be accompanied, however, by the correction of the wrong alimentary habits underlying SIBO.     

Lactase non-persistence and milk consumption in Estonia

INTRODUCTION Lactase enzyme hydrolyses lactose to glucose and galactose facilitating their absorption through the gut wall. Adult- type hypolactasia (lactase non-persistence, primary lactose malabsorption) is the most common enzyme def iciency in the worl…     

Diagnostic approach to patients with acute idiopathic and recurrent pancreatitis,what should be done？

Acute recurrent pancreatitis （ARP） is a common clinical condition that may be difficult to diagnose. Endoscopic ultrasound （EUS） is proposed to be a safe first line test of choice in the majority of patients. When interventions are needed to remove biliary stones, evaluate sphincter of Oddi or pancreas divisum, endoscopic retrograde cholangiopancreatography （ERCP） is recommended. Magnetic resonance cholangiopancreatography （MRCP） can be a suitable alternative from a diagnostic standpoint although may not be widely available. Finally, genetic testing is increasingly used to detect certain mutations that are associated with this diagnosis.     

Non-invasive assessment of liver fibrosis:Between prediction/prevention of outcomes and cost-effectiveness

The assessment of the fibrotic evolution of chronic hepatitis has always been a challenge for the clinical hepatologist. Over the past decade, various noninvasive methods have been proposed to detect the presence of fibrosis, including the elastometric measure of stiffness, panels of clinical and biochemical parameters, and combinations of both methods. The aim of this review is to analyse the most recent data on non-invasive techniques for the evaluation of hepatic fibrosis with particular attention to costeffectiveness. We searched for relevant studies published in English using the Pub Med database from 2009 to the present. A large number of studies have suggested that elastography and serum markers are useful techniques for diagnosing severe fibrosis and cirrhosis and for excluding significant fibrosis in hepatitis C virus patients. In addition, hepatic stiffness may also help to prognosticate treatment response to antiviral therapy. It has also been shown that magnetic resonance elastography has a high accuracy for staging and differentiating liver fibrosis. Finally, studies have shown that non-invasive methods are becoming increasingly precise in either positively identifying or excluding liver fibrosis, thus reducing the need for liver biopsy. However, both serum markers and transient elastography still have "grey area" values of lower accuracy. In this case, liver biopsy is still required to properly assess liver fibrosis. Recently, the guidelines produced by the World Health Organization have suggested that the AST-to-platelet ratio index or FIB-4 test could be utilised for the evaluation of liver fibrosis rather than other, more expensive non-invasive tests, such as elastography or Fibro Test.     

Irritable bowel syndrome and small intestinal bacterial overgrowth:Meaningful association or unnecessary hype

Irritable bowel syndrome(IBS)is a common condition characterized by abdominal pain or discomfort,bloating,and altered stool form and passage.Small intestinal bacterial overgrowth(SIBO)is a condition in which there is overgrowth of bacteria in small bowel in excess of 105colony forming units per milliliter on culture of the upper gut aspirate.Frequency of SIBO varied from 4%-78%among patients with IBS and from 1%-40%among controls.Higher frequency in some studies might be due to fallacious criteria[postlactulose breath-hydrogen rise 20 PPM above basal within 90 min(early-peak)].Glucose hydrogen breath test(GHBT)has a low sensitivity to diagnose SIBO.Hence,studies based on GHBT might have under-estimated frequency of SIBO.Therefore,it is important to analyze these studies carefully to evaluate whether the reported association between IBS and SIBO is over or under-projected.This review evaluates studies on association between SIBO and IBS,discordance between different studies,their strength and weakness including methodological issues and evidence on therapeutic manipulation of gut flora on symptoms of IBS.     

Management of constipation in the elderly： Emerging therapeutic strategies

A number of new, novel strategies for managing constipation in the elderly have emerged over the past few years. Prucalopride is one such new agent that is highly effi cacious in managing chronic constipation. In fact, Camilleri et al in a recent study reported that the average number of bowel movements increased by at least one in nearly 47% of the patients who were administered a dose of 4 mg. Lubiprostone is another new agent recently approved by the FDA that shows efficacy in managing the symptoms of constipation. Neostigmine has also been successfully used for the management of recalcitrant constipation. Most of these studies have used subcutaneous neostigmine. Symbiotic yogurt containig components, such as Bifidobacterium and fructoligosaccharide, have also been recently shown to be highly effective in improving symptoms of constipation. Elderly patients especially those in hospices and nursing homes are often on opiods for pain management. Constipation secondary to opioid use is extremely common in nursing homes. Subcutaneous methylnaltrexone has recently been shown to be highly effective in the management of opioid-related constipation, and was recently approved by the FDA. Sacral nerve stimulation is another emerging strategy. A recent analysis by Mowatt et al supports the eff icacy of this technique. Botulinum toxin is another agent that has already been successfully used for the management of chronic, refractory constipation in children and may be very effective for elderly constipation. Further larger studies are needed to confi rm the fi ndings noted in these studies. Constipation is clearly a major issue in the elderly and these new, emerging strategies will hopefully improve the quality of life and relieve the symptoms of constipation in this population.     

Exhaled breath analysis in hepatology: State-of-the-art and perspectives

Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained increasing attention in the context of hepatology,following the good results obtained in other fields of medicine.After the first studies that led to the identification of selected VOCs for pathophysiological purposes,subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical application.Specific VOC patterns were found to discriminate subjects with liver cirrhosis,to rate disease severity,and,eventually,to forecast adverse clinical outcomes even beyond existing scores.Preliminary results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver disease.However,clinical translation is still hampered by a number of methodological limitations,including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained results.Given the low-cost and easy execution at bedside of the new technologies(e-nose),larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.     

Subtypes of functional dyspepsia

Functional dyspepsia is a common clinical condition characterised by chronic or recurrent upper abdominal pain or discomfort commonly associated with a variety of associated gastrointestinal symptoms and a normal endoscopy. To standardise research-based approaches, an initial categorisation of into sub groups was agreed to, based on clusters of symptoms. However the early expectation that these subgroups would be associated with distinct pathophysiologies amenable to specific therapy has not been realised. A classification based on the most troublesome symptom has been suggested but the utility of this is also unclear. More recent data suggest that some of the pathophysiologic dysfunctions may be associated with specific symptoms and so provide a better tool for grouping patients. But this approach remains incomplete as current insights into the pathogenesis are still too limited for this to be satisfactory. In conclusion, no classification provides for an adequate treatment-based approach to the syndrome of functional dyspepsia. As a consequence treatment remains largely empiric.     

Postoperative Crohn＇s disease recurrence： A practical approach

Crohn＇s disease is a chronic inflammatory condition that may involve any segment of the gastrointestinal tract. Although several drugs have proven efficacy in inducing and maintaining disease in remission, resectional surgery remains as a cornerstone in the management of the disease, mainly for the treatment of its stenosing and penetrating complications. However, the occurrence of new mucosal （endoscopic） lesions in the neoterminal ileum early after surgery is almost constant, it is followed in the mid-term by clinical symptoms and, in a proportion of patients, repeated intestinal resections are required. Pathogenesis of postoperative recurrence （POR） is not fully understood, but luminal factors （commensal microbes, dietary antigens） seem to play an important role, and environmental and genetic factors may also have a relevant influence. Many studies tried to identify clinical predictors for POR with heterogeneous results, and only smoking has repeatedly been associated with a higher risk of POR. Ileocolonoscopy remains as the gold standard for the assessment of appearance and severity of POR, although the real usefulness of the available endoscopic score needs to be revisited and alternative techniques are emerging. Several drugs have been evaluated to prevent POR with limited success. Smoking cessation seems to be one of the more beneficial therapeutic measures. Aminosalicylates have only proved to be of marginal benefit, and they are only used in lowrisk patients. Nitroimidazolic antibiotics, although efficient, are associated with a high rate of intolerance and might induce irreversible side effects when used for a long-term. Thiopurines are not widely used after ileocecal resection, maybe because some concerns in giving immunomodulators in asymptomatic patients still remain. In the era of biological agents and genetic testing, a well-established preventive strategy for POR is still lacking, and larger studies to identify good clinical, serological, and genetic predictors of early POR as well a     

Is liver biopsy necessary in the management of alcoholic hepatitis?

Acute alcoholic hepatitis(AAH)is characterised by deep jaundice in patients with a history of heavy alcohol use,which can progress to liver failure.A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure.Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered.Liver biopsy remains the only reliable method to make an accurate diagnosis.However,there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy.We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH.In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor.Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions,we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology.Italso adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology.Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH.     

How much can be inferred from the left main coronary artery?

Atherosclerotic diseases is a diffuse process that involves the coronaries, carotids, renals and all other peripheral arteries owing to the systemic nature of atherosclerotic pathophysiology. This systemic precipitants that promote aggressive atherogenesis have been confirmed in multiple studies showing a relationship between atherosclerotic disease in one vascular bed with disease in another. However, the strength of this relationship varies from patient to patient. Thus, the practical utility of the diffuse nature of atheresclerosis is questionable. Ge and colleagues have proposed the use of left main (LM)coronary artery disease as a potential marker for left anterior descending (lAD) atherosclerotic disease. At first thought, this seems useless since the evaluation of the LM (by angiography or IVUS) can just as easily be performed in the LAD so why bother searching for such a surrogate? However, newer (non-invasive) imaging modalifies are making great gains and will be able to reliably image the LM sooner than the LAD (especially the distal LAD) so such a surrogate could have practical applications.……     

Giardia lamblia infection in patients with irritable bowel syndrome and dyspepsia： A prospective study

AIM:To evaluate the prevalence of Giardia lamblia(G.lamblia)infection in patients with irritable bowel syndrome(IBS)and dyspepsia and to establish which is the mostaccurate test to diagnose the infection in this setting.METHODS:One hundred and thirty-seven patients whoconsecutively attended the Outpatient GastroenterologyClinic for the first time between January 2002 and De-cember 2003 due to symptoms of IBS and/or dyspepsiawere recruited.All patients underwent clinical evaluation,first-step haematology and chemistry tests,serologic as-says for celiac disease,lactose-H2 breath test,abdominalultrasonography,and esophagogastroduodenoscopy.Helicobacter pylori status was evaluated.In patients withsymptoms of IBS older than 45 years,colonoscopy wasalso performed.In all patients,duodenal biopsies andstool samples were examined for trophozoites and cystsof G.lamblia by several methods.RESULTS:G.lamblia was identified in 9 patients.Thefollowing diagnoses were also made:IBS(100/137,73%),functional dyspepsia(62/137,45%),organicdyspepsia(33/137,24%),and lactose intolerance(75/137,55%).A significant association was foundbetween giardiasis and H pylori infection(X~2=6.632,OR=12.4,CI=1.5-68.1).There were no symptomsthat reliably allowed the recognition of giardiasis.Direct search of the parasite in duodenal biopsy andstool sample examinations gave concordant results inall cases while histological examination of duodenal biopsies displayed a low sensitivity(e.g.,22.2%).CONCLUSION:In this consecutive series,diagnosisof G.lamblia infection accounted for 6.5% of patientswith IBS and dyspepsia.Duodenal biopsies for diag-nosis of giardiasis may be unnecessary if stool sampleexamination is performed.     

Managing gastroesophageal reflux disease in children: The role of endoscopy

Gastroesophageal reflux disease (GERD) is a growing problem in the pediatric population and recent advances in diagnostics and therapeutics have improved their management, particularly the use of esophago-gastroduodenoscopy (EGD). Most of the current knowledge is derived from studies in adults; however there are distinct features between infant onset and adult onset GERD. Children are not just little adults and attention must be given to the stages of growth and development and how these stages impact the disease management. Although there is a lack of a gold standard test to diagnose GERD in children, EGD with biopsy is essential to assess the type and severity of tissue damage. To date, the role of endoscopy in adults and children has been to assess the extent of esophagitis and detect metaplastic changes complicating GERD; however the current knowledge points another role for the EGD with biopsy that is to rule out other potential causes of esophagitis in patients with GERD symptoms such as eosinophilic esophagitis. This review highlights special considerations about the role of EGD in the management of children with GERD.     

Long-term symptom development of functional bowel disease and the effects of lactose-restricted diet on the symptoms

正Objective To explore the long-term symptom development in functional bowel disorders(FBD)and the effects of lactose-restricted diet on the symptoms.Methods From January 2008 to December 2010,805patients with FBD were included.Among them 245patients who completed lactose hydrogen breath test and     

Role of probiotics,prebiotics and synbiotics in chemoprevention for colorectal cancer

Colorectal cancer is the third most common form of cancer. Current treatments are all associated with a high risk of complications and a low success rate. Recently, synbiotics have been proposed as a new preventive and therapeutic option. There is no direct experimental evidence for cancer suppression in humans as a result of the consumption of pro-, pre- or synbiotics. However, there is a wealth of evidence emerging from laboratory studies. The mechanisms by which pro-, pre- and synbiotics may inhibit colon cancer are now beginning to be understood and will be addressed in the present review.