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Bile acid sequestrants are the main agents used to treat bile acid malabsorption. Cholestyramine and colestipol, both in powder form, have been used for many years. Unfortunately many patients find them difficult to tolerate; although the diarrhea may improve, other symptoms such as pain and bloating may worsen. Colesevelam is a tablet and some patients tolerate this more easily. A proof of concept study of the farnesoid X receptor agonist obeticholic acid has shown clinical and biochemical benefit.
As of March 15, 2016, Novartis Pharmaceuticals is conducting a phase II clinical study involving a farnesoid X receptor agonist named LJN452.
Treatment is directed largely towards management of underlying cause:
- Replacement of nutrients, electrolytes and fluid may be necessary. In severe deficiency, hospital admission may be required for nutritional support and detailed advice from dietitians. Use of enteral nutrition by naso-gastric or other feeding tubes may be able to provide sufficient nutritional supplementation. Tube placement may also be done by percutaneous endoscopic gastrostomy, or surgical jejunostomy. In patients whose intestinal absorptive surface is severely limited from disease or surgery, long term total parenteral nutrition may be needed.
- Pancreatic enzymes are supplemented orally in pancreatic insufficiency.
- Dietary modification is important in some conditions:
- Gluten-free diet in coeliac disease.
- Lactose avoidance in lactose intolerance.
- Antibiotic therapy to treat Small Bowel Bacterial overgrowth.
- Cholestyramine or other bile acid sequestrants will help reducing diarrhoea in bile acid malabsorption.
Bacterial overgrowth is usually treated with a course of antibiotics although whether antibiotics should be a first line treatment is a matter of debate. Some experts recommend probiotics as first line therapy with antibiotics being reserved as a second line treatment for more severe cases of SIBO. Prokinetic drugs are other options but research in humans is limited. A variety of antibiotics, including tetracycline, amoxicillin-clavulanate, fluoroquinolones, metronidazole, neomycin, cephalexin, trimethoprim-sulfamethoxazole, and nitazoxanide have been used; however, the best evidence is for the use of rifaximin.
A course of one week of antibiotics is usually sufficient to treat the condition. However, if the condition recurs, antibiotics can be given in a cyclical fashion in order to prevent tolerance. For example, antibiotics may be given for a week, followed by three weeks off antibiotics, followed by another week of treatment. Alternatively, the choice of antibiotic used can be cycled.
The condition that predisposed the patient to bacterial overgrowth should also be treated. For example, if the bacterial overgrowth is caused by chronic pancreatitis, the patient should be treated with coated pancreatic enzyme supplements.
Probiotics are bacterial preparations that alter the bacterial flora in the bowel to cause a beneficial effect. Animal research has demonstrated that probiotics have barrier enhancing, antibacterial, immune modulating and anti-inflammatory effects which may have a positive effect in the management of SIBO in humans. "Lactobacillus casei" has been found to be effective in improving breath hydrogen scores after 6 weeks of treatment presumably by suppressing levels of a small intestinal bacterial overgrowth of fermenting bacteria. The multi-strain preparation VSL#3 was found to be effective in suppressing SIBO. "Lactobacillus plantarum", "Lactobacillus acidophilus", and "Lactobacillus casei" have all demonstrated effectiveness in the treatment and management of SIBO. Conversely, "Lactobacillus fermentum" and "Saccharomyces boulardii" have been found to be ineffective. A combination of "Lactobacillus plantarum" and "Lactobacillus rhamnosus" has been found to be effective in suppressing bacterial overgrowth of abnormal gas producing organisms in the small intestine.
Probiotics are superior to antibiotics in the treatment of SIBO. A combination of probiotic strains has been found to produce better results than therapy with the antibiotic drug metronidazole and probiotics have been found to be effective in treating and preventing secondary lactase deficiency and small intestinal bacteria overgrowth in individuals suffering from post-infectious irritable bowel syndrome. Probiotics taken in uncomplicated cases of SIBO can usually result in the individual becoming symptom free. Probiotic therapy may need to be taken continuously to prevent the return of overgrowth of gas producing bacteria. A study by the probiotic yogurt producer Nestlé found that probiotic yogurt may also be effective in treating SIBO with evidence of reduced inflammation after 4 weeks of treatment.
An elemental diet taken for two weeks is an alternative to antibiotics for eliminating SIBO. An elemental diet works via providing nutrition for the individual while depriving the bacteria of a food source. Additional treatment options include the use of prokinetic drugs such as 5-HT4 receptor agonists or motilin agonists to extend the SIBO free period after treatment with an elemental diet or antibiotics. A diet void of certain foods that feed the bacteria can help alleviate the symptoms. For example, if the symptoms are caused by bacterial overgrowth feeding on indigestible carbohydrate rich foods, following a FODMAP restriction diet may help.
The "treat empirically" route also has its difficulties, which have all come under wide debate and study. Recommendations are varied but seem to find some common ground around the notion that treatment should be individualized to the specific circumstances under which a patient has developed BLS since these circumstances affect the complex microbial make up of the affected bowel.
Tetracyclines have been the mainstay of treatment for BLS, but recent studies have concluded Rifaximin to be very effective in the treatment of BLS. One study by Di Stefano et al., however, concluded Metronidazole to be more effective than Rifaximin in the treatment of BLS.
Although it would seem to be the better way to go in terms of management, there has been recent criticism on the need for such testing because of reliability issues. However, it must be stated that there are options such as the glucose breath test and jejunal aspiration the explanations of which are beyond the scope of this current article.
Proton pump inhibitors (PPIs) used to suppress stomach acid production may cause bacterial overgrowth leading to IBS symptoms. Discontinuation of PPIs in selected individuals has been recommended as it may lead to an improvement or resolution of IBS symptoms.
For patients who do not adequately respond to dietary fiber, osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose can help avoid "cathartic colon" which has been associated with stimulant laxatives. Among the osmotic laxatives, doses of 17–26 g/d of polyethylene glycol have been well studied. Lubiprostone (Amitiza) is a gastrointestinal agent used for the treatment of idiopathic chronic constipation and constipation-predominant IBS. It is well tolerated in adults, including elderly patients. As of July 20, 2006, lubiprostone had not been studied in pediatric patients. Lubiprostone is a bicyclic fatty acid (prostaglandin E1 derivative) that acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements. Unlike many laxative products, lubiprostone does not show signs of tolerance, dependency, or altered serum electrolyte concentration.
Lymphocytic and collagenous colitis have both been shown in randomized, placebo-controlled trials to respond well to budesonide, a glucocorticoid. Budesonide formulated to be active in the distal colon and rectum is effective for both active disease and in the prevention of relapse. However, relapse occurs frequently after withdrawal of therapy.
Studies of a number of other agents including antidiarrheals, bismuth subsalicylate (Pepto-Bismol), mesalazine/mesalamine (alone or in combination with cholestyramine), systemic corticosteroids, cholestyramine, immunomodulators, and probiotics have shown to be less effective than budesonide for treating both forms of microscopic colitis.
Anti-TNF inhibitors. split ileostomy, diverting ileostomy, and subtotal colectomy are options for management of steroid-dependent or refractory microscopic colitis. Currently, the need to resort to surgery is limited considering the improvement of drug therapy options. However, surgery is still considered for patients with severe, unresponsive microscopic colitis.
Sulfasalazine has been a major agent in the therapy of mild to moderate ulcerative colitis for over 50 years. In 1977, Mastan S. Kalsi "et al." determined that 5-aminosalicylic acid (5-ASA and mesalazine) was the therapeutically active component in sulfasalazine. Since then, many 5-ASA compounds have been developed with the aim of maintaining efficacy but reducing the common side effects associated with the sulfapyridine moiety in sulfasalazine.
About 21% of inflammatory bowel disease patients use alternative treatments. A variety of dietary treatments show promise, but they require further research before they can be recommended.
- Melatonin may be beneficial according to "in vitro" research, animal studies, and a preliminary human study.
- Dietary fiber, meaning indigestible plant matter, has been recommended for decades in the maintenance of bowel function. Of peculiar note is fiber from , which seems to contain soluble constituents capable of reversing ulcers along the entire human digestive tract before it is cooked.
- Fish oil, and eicosapentaenoic acid (EPA) derived from fish oil, inhibits leukotriene activity, the latter which may be a key factor of inflammation. As an IBD therapy, there are no conclusive studies in support and no recommended dosage. But dosages of EPA between 180 and 1500 mg/day are recommended for other conditions, most commonly cardiac. Fish oil also contains vitamin D, of which many people with IBD are deficient.
- Short chain fatty acid (butyrate) enema. The epithelial cells in the colon uses butyrate from the contents of the intestine as an energy source. The amount of butyrate available decreases toward the rectum. Inadequate butyrate levels in the lower intestine have been suggested as a contributing factor for the disease. This might be addressed through butyrate enemas. The results however are not conclusive.
- Herbal medications are used by patients with ulcerative colitis. Compounds that contain sulfhydryl may have an effect in ulcerative colitis (under a similar hypothesis that the sulfa moiety of sulfasalazine may have activity in addition to the active 5-ASA component). One randomized control trial evaluated the over-the-counter medication "S"-methylmethionine and found a significant decreased rate of relapse when the medication was used in conjunction with oral sulfasalazine.
- Helminthic therapy is the use of intestinal parasitic nematodes to treat ulcerative colitis, and is based on the premises of the hygiene hypothesis. Studies have shown that helminths ameliorate and are more effective than daily corticosteroids at blocking chemically induced colitis in mice, and a trial of intentional helminth infection of rhesus monkeys with idiopathic chronic diarrhea (a condition similar to ulcerative colitis in humans) resulted in remission of symptoms in 4 out of 5 of the animals treated. A randomised controlled trial of Trichuris suis ova in humans found the therapy to be safe and effective, and further human trials are ongoing.
- Curcumin (turmeric) therapy, in conjunction with taking the medications mesalamine or sulfasalazine, may be effective and safe for maintaining remission in people with quiescent ulcerative colitis. The effect of curcumin therapy alone on quiescent ulcerative colitis is unknown.
Some individuals may benefit from diet modification, such as a reduced fat diet, following cholecystectomy. The liver produces bile and the gallbladder acts as reservoir. From the gallbladder, bile enters the intestine in individual portions. In the absence of gallbladder, bile enters the intestine constantly, but in small quantities. Thus, it may be insufficient for digestion of fatty foods. Postcholecystectomy syndrome treatment depends on the identified violations that led to it. Typically, the patient is recommended dietary restriction table with fatty foods, enzyme preparations, antispasmodics, sometimes cholagogue.
If the pain is caused by biliary microlithiasis, oral ursodeoxycholic acid can alleviate the condition.
A trial of bile acid sequestrant therapy is recommended for bile acid diarrhoea.
Prevention of radiation injury to the small bowel is a key aim of techniques such as brachytherapy, field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy. Medications including ACE inhibitors, statins and probiotics have also been studied and reviewed.
The treatment for bile reflux is the same as the treatment for acidic reflux. In general, everything that can
reduce acidic reflux can reduce bile reflux. Examples include lifestyle modification, weight reduction, and the avoidance of eating immediately before sleep or being in the supine position immediately after meals. In addition, smoking has been found to be a factor in the development of acidic reflux. Thus, all of these factors should be applied to bile reflux as well.
Likewise, drugs that reduce the secretion of gastric acid (e.g., proton pump inhibitors)
or that reduce gastric contents or volume can be used to treat acidic bile reflux. Because prokinetic drugs increase the motility of the stomach and accelerate gastric emptying, they can also reduce bile reflux. Other drugs that reduce the relaxations of the lower esophageal sphincter, such as baclofen, have also proven to reduce bile reflux, particularly in patients who are refractory to (medically unresponsive to) proton pump inhibitor therapy.
Medications used in managing biliary reflux include bile acid sequestrants, particularly cholestyramine, which disrupt the circulation of bile in the digestive tract and sequester bile that would otherwise cause symptoms when refluxed; and prokinetic agents, to move material from the stomach to the small bowel more rapidly and prevent reflux.
Biliary reflux may also be treated surgically, if medications are ineffective or if precancerous tissue is present in the esophagus.
There are many tools for investigating stomach problems. The most common is endoscopy. This procedure is performed as an outpatient and utilizes a small flexible camera. The procedure does require intravenous sedation and takes about 30–45 minutes; the endoscope is inserted via the mouth and can visualize the entire swallowing tube, stomach and duodenum. The procedure also allows the physician to obtain biopsy samples. In many cases of bleeding, the surgeon can use the endoscope to treat the source of bleeding with laser, clips or other injectable drugs.
In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others.
Medical treatments include the use of hyperbaric oxygen which has beneficial effects in radiation proctitis or anal damage. Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and vitamin B12 or vitamin D supplements, together with bile acid sequestrants for bile acid diarrhea and possibly antibiotics for small intestinal bacterial overgrowth. Probiotics have all been suggested as another therapeutic avenue.
Endoscopic therapies including argon plasma coagulation have been used for bleeding telangiectasia in radiation proctitis and at other intestinal sites, although there is a rick of perforation. Sucralfate enemas look promising in proctitis.
Surgical treatment may be needed for intestinal obstruction, fistulae, or perforation, which can happen in more severe cases. These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common.
Optimal treatment usually produces significant improvements in quality of life.
Smoking has been linked to a variety of disorders of the stomach. Tobacco is known to stimulate acid production and impairs production of the protective mucus. This leads to development of ulcers in the majority of smokers.
Chronic stomach problems have also been linked to excess intake of alcohol. It has been shown that alcohol intake can cause stomach ulcer, gastritis and even stomach cancer. Thus, avoidance of smoking and excess alcohol consumption can help prevent the majority of chronic stomach disorders.
One of the most causes of chronic stomach problems is use of medications. Use of aspirin and other non-steroidal anti-inflammatory drugs to treat various pain disorders can damage lining of the stomach and cause ulcers. Other medications like narcotics can interfere with stomach emptying and cause bloating, nausea, or vomiting.
The majority of chronic stomach problems are treated medically. However, there is evidence that a change in life style may help. Even though there is no specific food responsible for causing chronic stomach problems, experts recommend eating a healthy diet which consists of fruits and vegetables. Lean meat should be limited. Moreover, people should keep a diary of foods that cause problems and avoid them.
Treatment of collagenous colitis is often challenging. Typically, one or more of the following therapeutic agents are used:
- Bismuth agents, including Pepto-Bismol
- 5-aminosalicylic acid
- Budesonide
- Immunosuppressants, including azathioprine
- Corticosteroids
Pilot-scale studies have shown some evidence of possible benefit for both "Boswellia serrata" extract and specific strains of probiotics in the treatment of collagenous colitis, although larger sample sizes are needed to confirm the results.
Bile acid malabsorption, known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy and bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective.
No pharmacologic treatment has been approved by the U.S. Food and Drug Administration for PSC. Some experts recommend a trial of ursodeoxycholic acid (UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13-15 milligrams per kilogram) of UDCA for PSC.
Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritics (e.g. bile acid sequestrants such as (cholestyramine)); antibiotics to treat episodes of acute cholangitis; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (vitamin A, vitamin D, vitamin E, and vitamin K).
ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile duct cancer (cholangiocarcinoma).
Liver transplantation is the only proven long-term treatment of PSC, although only a fraction of individuals with PSC will need it. Indications for transplantation include recurrent bacterial cholangitis, decompensated cirrhosis, hepatocellular carcinoma, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some will experience disease recurrence afterward.
Proton pump inhibitors (such as omeprazole and lansoprazole) and histamine H2-receptor antagonists (such as famotidine and ranitidine) are used to slow acid secretion. Once gastric acid is suppressed, symptoms normally improve.
Laparoscopic cholecystectomy has been used to treat the condition when due to dyskinesia of the gallbladder.
Symptoms may persist after cholecystectomy, and have been linked to the use of proton pump inhibitors.
Osteopathic treatment, oral magnesium supplementation with 325 mg and the use of digestive enzymes caused improvement in one case.
The prognosis for lymphocytic colitis and collagenous colitis is good, and both conditions are considered to be benign. The majority of people afflicted with the conditions recover from their diarrhea, and their histological abnormalities resolve, although relapses commonly occur if maintenance treatment is not continued.
Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure.
Extrahepatic cholestasis can usually be treated by surgery.
Pruritis in cholestatic jaundice is treated by Antihistamines, Ursodeoxycholic Acid, Phenobarbital
Cholesterol gallstones can sometimes be dissolved with ursodeoxycholic acid taken by mouth, but it may be necessary for the person to take this medication for years. Gallstones may recur, however, once the drug is stopped. Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP). Gallstones can be broken up using a procedure called extracorporeal shock wave lithotripsy (often simply called "lithotripsy"), which is a method of concentrating ultrasonic shock waves onto the stones to break them into tiny pieces. They are then passed safely in the feces. However, this form of treatment is suitable only when there is a small number of gallstones.