User talk:Pal Manickam

Non Alcoholic Fatty Liver Disease (NAFLD)

Definition:

A condition where liver is accumulated with fat and usually associated with metabolic conditions. Risk factors for NAFLD included obesity, diabetes and dyslipidemia. During the last decade NAFLD has reached epidemic proportions even in pediatric population.

Categories:

NAFLD is sub categorixed into non alcoholic fatty liver (NAFL) and non alcoholic steatohepatosis (NASH). NAFL has just fat accumulation whereas NASH has fat as well as inflammation of the liver tissues.

Prevalence of NAFLD:

Prevalence varies widely and it depends on age, sex and race of the population. Studies show that men are at highest risk for NAFLD, 31% in men Vs 16% in women. Compared to non-Hispanic whites, Hispanics have higher prevalence of NAFLD.

Who are at High Risk:

People with the following conditions are at high risk to develop NAFLD:

Obesity, type 2 diabetes mellitus, dyslipidemia, Hypothyroidism, Obstructive Sleep apnea, Hypopituitarism, Hypogonadism, Pancreato-duodenal resection.

When to Obtain a Liver Biopsy in Patients with NAFLD?

Liver biopsy will be needed when the diagnosis of liver disease is uncertain and other causes need to be ruled out.

Is there a screening test?!

Due to the increased morbidity and mortality, a screening test if present will be helpful. But, in most cases liver function will be normal and cannot be a good sensitive test. USG of liver will give more helpful information about the liver but it is expensive making screening test less affordable. So, high risk patients are offered USG of liver.

Management of NAFLD:

Initial step - Making the diagnosis:

1. Diagnosis of NAFLD requires that (a) there is hepatic steatosis by imaging or histology, (b) there is no significant alcohol consumption, (c) there are no other causes for hepatic steatosis, and (d) there are no co-existing causes for chronic liver disease.

2. Exclude other causes of hepatic steatosis like significant alcohol consumption, hepatitis C, medications, parenteral nutrition, Wilson’s disease, and severe malnutrition, other chronic liver disease including hemochromatosis, autoimmune liver disease and chronic viral hepatitis.

3. Liver biopsy is the gold standard for characterizing liver histology in patients with NAFLD. Due to procedural risk, cost, it should be performed in those who would benefit the most from diagnostic, therapeutic guidance, and prognostic perspectives.

Treatment:

Treatment of NAFLD includes treating liver disease as well as the associated metabolic co-morbidities such asobesity, hyperlipidemia, insulin resistance and T2DM. As patients with NAFLD without steatohepatitis have excellent prognosis from a liver standpoint, treatments aimed at improving liver disease should be limited to those with NASH. Lifestyle modification will reduce aminotransferases and improve hepatic steatosis when measured by ultrasound. Exercise programs consisted of 2 to 3 sessions a week of 30 – 60 minutes over a period of 6 to 12 weeks and showed liver fat content diminished without a significant change in body weight.

Effect of exercise and diet on NAFLD:

Studies have shown that weight loss generally reduces hepatic steatosis evidenced by USG/imaging studies. It can be done by low caloric diet alone or with increased physical activity. Loss of at least 3–5% of body weight appears to improve steatosis, but a greater weight loss (up to 10%) may be needed to improve necroinflammation. Exercise alone in adults with NAFLD may reduce hepatic steatosis.

Role of metformin in NASH:

Role of metformin is unclear NAFLD. Few studies have shown that metformin might help NASH and decrease aminotranferase levels. However, a open label study found that Metformin has no significant effect on liver histology and is not recommended as a specific treatment for liver disease in adults with NASH.

Pioglitazone and NASH:

Pioglitazone can be used to treat steatohepatitis in patients with biopsy-proven NASH. But, the caveat in the study which showed the benfit is that majority of the patients who took pioglitazone for NASH were non- diabetic and that long term safety and efficacy of this drug in patients with NASH is not established.

Oxidative stress and Vitamin E:

Vitamin E changes the liver histology in non-diabetic adults with biopsy-proven NASH and therefore it should be considered as a first-line pharmacotherapy for this patient population. However, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.

Other treatment considerations for NASH:

Statins can be used to treat dyslipidemia in patients with NAFLD and NASH. Until RCTs with histological endpoints prove their efficacy, statins should not be used to specifically treat NASH.

Ursodeoxy cholic acid is not recommended for the treatment of NAFLD or NASH.

Omega-3 fatty acids is not recommended for the specific treatment of NAFLD or NASH but they may be considered as the first line agents to treat hypertriglyceridemia in patients with NAFLD.

Patients with NAFLD should not consume heavy amounts of alcohol.

Foregut bariatric surgery is not contraindicated in otherwise eligible obese individuals with NAFLD or NASH (but with- out established cirrhosis).

Patients with NASH cirrhosis should be screened for gastroesophageal varices according to the AASLD/ACG practice guidelines.

Patients with NASH cirrhosis should be considered for HCC screening according to the AASLD/ACG practice guidelines. Do need to repeat liver biopsy in patients with NAFL or NASH.

To see a Specialist:

Patients with steatohepatitis on liver biopsy be followed by a hepatologist.

Patients with nonalcoholic fatty liver without steatohepatitis can be followed by a primary care physician, provided the diagnosis is clear.

Patients who develop cirrhosis and have complications (eg, ascites, variceal bleeding) or a model for end-stage liver disease (MELD) score ≥10 will be referred for a liver transplantation evaluation.

Management of Gastroparesis

What is Gastroparesis?

Gastroparesis is slow emptying of the gastric contents presenting as nausea, vomiting, early satiety, and postprandial fullness. Many patients may be asymptomatic.

Epidemiology: Difficult to estimate its true prevalence due to asymptomatic in many people and its vague presentation common to many other diseases like nausea, vomiting. One study estimates the prevalence as 20 to 40 percent of diabetic patients might have gastroparesis.

Clinical Presentation:

Symptoms can be nausea, vomiting, early satiety, bloating and postprandial fullness

Diagnosis of Gastroparesis:

Diagnosis of gastroparesis is based on the combination of symptoms of gastroparesis, absence of gastric outlet obstruction or ulceration, and delay in gastric emptying.

Delay in gastric emptying need to be confirmed to make the diagnosis of gastroparesis. Scintigraphic gastric emptying of solids is the standard for the evaluation of gastric emptying and the diagnosis of gastroparesis. Most reliable method and parameter for diagnosis of gastroparesis is gastric retention of solids at 4 h measured by scintigraphy.

Alternative approaches for assessment of gastric emptying include wireless capsule motility testing and 13 C breath testing using octanoate or spirulina incorporated into a solid meal; they require further validation before they can be considered as alternates to scintigraphy for diagnosis of gastroparesis.

Rule out other condition that can cause Gastroparesis:

Condition that can mimick gastroparesis like thyroid dysfunction, neurological disease, prior gastric or bariatric surgery, and autoimmune disorders should be ruled out before diagnosing and treating gastroparesis.

Diabetes and Gastroparesis:

Markedly uncontrolled ( > 200 mg / dl) glucose levels may aggravate symptoms of gastroparesis and delay gastric emptying. Hence, good glycemic control should be a target for therapy; this may improve symptoms and the delayed gastric emptying.

Medication and Gastroparesis:

Medication-induced delay in gastric emptying, particularly from narcotic and anticholinergic agents and GLP-1 and amylin analogs among diabetics, should be considered in patients before assigning an etiological diagnosis. Narcotics and other medications that can delay gastric emptying should be stopped to establish the diagnosis with a gastric emptying test.

Gastroparesis can be associated with and may aggravate GERD. Evaluation for the presence of gastroparesis should be considered in patients with GERD that is refractory to acid-suppressive treatment.

Chronic usage of cannabinoid agents may cause similar symptoms. Patients presenting with symptoms of gastroparesis should be advised to stop usage of these agents.

Management of Gastroparesis:

First line of management for gastroparesis patients should include restoration of fluids and electrolytes, nutritional support and in diabetics, optimization of glycemic control.

Oral intake is preferable for nutrition and hydration. Patients should receive counseling from a dietician regarding consumption of frequent small volume nutrient meals that are low in fat and soluble fiber. If unable to tolerate solid food, then use of homogenized or liquid nutrient meals is recommended

If oral intake is insufficient, then enteral alimentation by jejunostomy tube feeding should be pursued. Indications for enteral nutrition : - unintentional loss of 10 % or more of the usual body weight during a period of 3 to 6 months, and / or repeated hospitalizations for refractory symptoms.

For enteral alimentation, postpyloric feeding is preferable to gastric feeding because gastric delivery can be associated with erratic nutritional support.

Good glycemic control should be the goal. Since acute hyperglycemia inhibits gastric emptying, it is assumed that improved glycemic control may improve gastric emptying and reduce symptoms. Pramlintide and GLP-1 analogs may delay gastric emptying in diabetics.

In addition to dietary therapy, prokinetic therapy should be considered to improve gastric emptying and gastroparesis symptoms like Metoclopramide which is the first line of prokinetic therapy and should be administered at the lowest effective dose. Risk of tardive dyskinesia has been estimated to be <1 %.

Patients should be instructed to discontinue therapy if they develop side effects including involuntary movements. For patients unable to use metoclopramide, domperidone can be prescribed with investigational new drug clearance from the FDA and has been shown to be as effective as metoclopramide in reducing symptoms without the propensity for causing central nervous system side effects; given propensity of domperidone to prolong corrected QT interval on electrocardiogram, a baseline electrocardiogram is recommended.

Erythromycin improves gastric emptying and symptoms from delayed gastric emptying. Administration of IV erythromycin should be considered when IV prokinetic therapy is needed in hospitalized patients . Oral treatment with erythromycin improves gastric emptying also. However, the long-term effectiveness of oral therapy is limited by tachyphylaxis.

Treatment with antiemetic agents should occur for improvement of associated nausea and vomiting but will not result in improved gastric emptying.

TCA can be considered for refractory nausea and vomiting in gastroparesis but will not result in improved gastric emptying and may potentially retard gastric emptying.

Intrapyloric injection of botulinum toxin is not recommended for patients with gastroparesis based on randomized controlled trials.

GES may be considered for compassionate treatment in patients with refractory symptoms, particularly nausea and vomiting. Symptom severity and gastric emptying have been shown to improve in patients with DG, but not in patients with IG or PSG.

Gastrostomy for venting and / or jejunostomy for feeding may be performed for symptom relief.

Completion gastrectomy could be considered in patients with PSG who remain markedly symptomatic and fail medical therapy.

Surgical pyloroplasty or gastrojejunosotomy has been performed for treatment for refractory gastroparesis. However, further studies are needed before advocating this treatment.

Partial gastrectomy and pyloroplasty should be used only in carefully selected patients.