Showing posts with label Gastro-enterology. Show all posts
Showing posts with label Gastro-enterology. Show all posts

Tuesday, September 22, 2015

, , ,

Alcoholic liver disease

 INTRODUCTION 
Chronic and excessive use of alcohol is one of the major causes of liver disease.

90% of daily heavy drinkers (>60 g alcohol/day) as well as binge drinkers have fatty liver but a smaller percentage (10-35%) of drinkers progress to alcoholic hepatitis which is a precursor for cirrhosis.

The long-term risk is 9 times higher in patients with alcoholic hepatitis compared to those with fatty liver alone.

Some population-based surveys have documented that men must drink 40 to 80 g of alcohol daily and women must drink 20 to 40 g daily for 10 to 12 years to achieve a significant risk of liver disease.

Liver pathology consists of 3 major lesions that are progressive and rarely exist in a pure form:
1) fatty liver (usually reverses quickly with abstinence),
2) alcoholic hepatitis and
3) cirrhosis.

histologic staging alcoholic liver disease


Prognosis of severe alcoholic liver disease (ALD) is bad. Mortality of patients with alcoholic hepatitis concurrent with cirrhosis id nearly 60% at 4 years.

Although alcohol is a direct hepatotoxin, it is unclear why only 10-20% of alcoholics will develop alcoholic hepatitis. It appears to involve a complex interaction of facilitating factors like drinking patterns, diet, obesity and gender.

 EPIDEMIOLOGY 
Harmful use of alcohol results in 2.5 million deaths each yr. Most of the mortality is due to cirrhosis. The mortality is declining now because of decreased consumption of alcohol in the Western countries except in the U.K, Romania, Russia and Hungary.

 ETIOLOGY 
a) Quantity and duration of alcohol intake - are the most important risk factors. Time taken to develop liver disease is directly related to the amount of alcohol consumed.
b) There is no clear role of the type of beverage and the pattern of drinking.
c) Genetic - some people are genetically predisposed  for alcoholism and subsequently to the ill effects of alcohol on the liver.
d) Gender - It is a strong determinant for ALD. Women are more susceptible to alcoholic liver injury. They develop advanced liver disease with substantially less alcohol intake. Gender-dependent differences may be due to the effects of estrogen, proportion of body fat and gastric metabolism of alcohol.
e) Chronic infection with Hepatitis C virus - It is an important comorbidity in the progression of ALD to cirrhosis in chronic and excessive drinkers. Even moderate alcohol intake of 20-50 g/day increases the risk of cirrhosis and hepatocellular cancer. Intake of more than 50 g/day decreases the efficacy of interferon-based antiviral therapy.

 PATHOGENESIS 
It is unclear but what is known is that alcohol can act as a direct hepatotxin and malnutrition does not play a major role.
- Alcohol is metabolised to acetyldehyde which in turn initiates an inflammatory cascade that results in a variety of metabolic responses.
- Steatosis from lipogenesis, fatty acid synthesis and depression of fatty acid oxidation occur secondary to effects on sterol regulatory transcription factor (SRTF) and peroxisome proliferator-activated receptor alpha (PPAR-alpha).
- Intestinal derived endotoxin initiates a pathogenic process through toll-like receptor-4 and TNF-alpha. This facilitates hepatocyte apoptosis and necrosis.
- Cell-injury endotoxin also activates innate and adaptive immunity pathways. There is release of pro-inflammatory cytokines (TNF-alpha) and proliferation of T/B cells.
- Production of toxic protein-aldehyde adducts, generation of reducing equivalents and oxidative stress also contribute to liver injury.

Finally hepatocyte injury and impaired regeneration are associated with stellate cell activation and collagen production which are key events in fibrogenesis. The resulting fibrosis causes architectural derangement of the liver and the associated pathophysiology.

 PATHOLOGY 
Fatty liver is the initial and most common histologic response to hepatotoxic stimuli, including excess alcohol ingestion. Accumulation of fat within the perivenular hepatocytes coincides with the location of alcohol dehydrogenase. Continuing alcohol ingestion results in deposition of fat throughout the entire hepatic lobule.

Alcoholic fatty liver - traditionally regarded as benign but appearance of steatohepatitis and certain features like giant mitochondria, perivenular fibrosis and microvesicular fat are associated with progressive liver injury.

Hallmarks of alcoholic hepatitis include: (hepatocyte injury)
a) ballooning degeneration,
b) spotty necrosis,
c) polymorphonuclear infiltrate and
d) fibrosis in the perivenular and perisinusoidal space of Disse.

Mallory-Denk bodies are often present in florid cases but these are neither specific nor necessary to establish the diagnosis.

 CLINICAL FEATURES 
Usually the patients are asymptomatic.
Hepatomegaly is often the only clinical finding.
It is very important to assess the drinking history and estimate how much alcohol is consumed per day and for how long.
1 beer, 4-5 ounces of wine, 1.5 oz of 40% liquor and 1 ounce (approximately 30 mL) of 80% spirits all have around 12 g of alcohol.

Alcohol content of various beverages

- Patients with fatty liver may have:
1) right upper quadrant discomfort,
2) nausea and
3) rarely jaundice.

- Patients with alcoholic hepatitis may have:
1) fever
2) spider nevi
3) jaundice
4) abdominal pain.
We can also see portal hypertension, ascites and variceal bleeding even in the absence of cirrhosis.

 LABORATORY FINDINGS 
These are most identified through routine screening tests.

Fatty liver - laboratory abnormalities are non-specific
Modest elevation of AST, ALT, GGTP are seen. Triglycerides and bilirubin may also be increased.

Alcoholic hepatitis
a) increased AST and ALT - by 2-7 fold but rarely greater than 400 IU.
b) AST/ALT ratio greater than 1.
c) hyperbilirubinemia
d) modest increase in alkaline phosphatase

If synthetic function is deranged then the condition is more serious. Hypoalbuminemia and coagulopathy are more common in advanced liver disease.

Ultrasonography is also a useful investigation as it can determine the size of the liver and detect any fatty infiltration. If it demonstrates portal vein flow reversal, ascites and intraabdominal venous collaterals then the condition has less potential for complete reversal.

Below is an ultrasonographic picture of hepatic steatosis. Fatty infiltration produces an increased reflectivity of hepatic parenchyma, known as ‘bright liver pattern’. This feature can be assessed by comparing liver parenchyma with the right kidney’s cortex, which normally presents an echogenicity equal to or slightly lower than that of the liver. Severe steatosis produces a strong attenuation in the deepest liver sections, resulting in poor explorability.

bright liver with posterior attenuation



 PROGNOSIS 
Critically ill patients with alcoholic hepatatis have short term (30-day) mortality rates exceeding 50%.
A Discriminant Function (DF) above 32 and a Model for End-stage Liver Disease (MELD) greater than 21 is associated with poor prognosis.
Worse prognosis if there is associated:
a) ascites,
b) variceal hemorrhage,
c) deep encephalopathy and
d) hepatorenal syndrome.

mortality alcoholic liver disease


 TREATMENT 
a) Complete abstinence from alcohol is the mainstay for treatment.
b) Patients with severe alcoholic hepatitis i.e. DF>32 and MELD>21 should be given Prednisone 40mg/day or Prednisolone 32mg/day for 4 weeks followed by tapering over 4 weeks.
c) Alternatively Pentoxifylline, a non-specific TNF inhibitor, can be used in a dosage of 400mg 3 times per day for 4 weeks.
d) Liver transplantation is an accepted indication for treatment in selected and motivated patients with end-stage cirrhosis.

Below is an algorithm showing how to manage alcoholic hepatitis:
algorithm alcoholic hepatitis


N.B Monoclonal antibodies that neutralize serum TNF-alpha should not be used as studies have reported an increase in the number of deaths secondary to infections and renal failure.

First published on: 23 September 2015

Wednesday, June 27, 2012

,

Aminotransferases (Transaminases)


Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are measured by the serum glutamic-oxaloacetic  transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) respectively. They are important markers of hepatocellular injury.

Normal values:  (varies from lab to lab but on average)
ALT : 7-41 U/L
AST: 12-38 U/L

AST can be found in various tissues like cardiac/skeletal muscles, kidney, brain and liver.
ALT is limited primarily to the liver and thus ALT is a more specific reflection of hepatocellular disease than AST.

The highest elevations of both enzymes are seen in viral, toxin-induced and ischemic hepatitis. On the other hand, alcoholic hepatitis usually gives a lower raise of around < 300 U/L. 

AST/ALT ratio is a useful indicator.
a) A ratio of > 2 is highly suggestive of alcohol-induced hepatic injury.
b) A ratio of > 1 and cirrhosis is often seen in patients of chronic hepatitis B infections.
c) A ratio of < 1 is commonly seen in acute/chronic viral hepatitis or in extra hepatic biliary obstruction.

Elevated AST or ALT are not definitive predictive indices of histologic findings. Instead serial measurements may reflect the extent of damage and give information about the progression of the disease.

A decrease in previously elevated enzymes does not always indicate recovery. In cases of fulminant hepatic failure, a decrease in the level of enzymes indicates that there is a low hepatic reserve after overwhelming hepatocyte necrosis. i.e. there is so much damage that the remaining normal hepatocytes are releasing only a small amount of the enzymes upon insult.
False low levels are seen in patients with uremia and chronic renal failure undergoing dialysis. False elevation is seen in patients treated with erythromycin.

Monday, March 12, 2012

, ,

Barrett's esophagus

Definition:
Barrett’s esophagus is characterized by an intestinal metaplastic change in the lining mucosa of the esophagus in response to chronic gastro­esophageal reflux. 
The condition is named after Norman Barrett, an Australian surgeon who drew attention to the columnar-lined esophagus in 1950.
It is still not well understood why some people develop esophagitis and others develop Barrett’s esophagus often without significant esophagitis. 

Pathology:
In Barrett’s esophagus the junction between squamous esophageal mucosa and gastric mucosa moves proximally. The columnar epithelium is more acid resistant than the squamous epithelium. So this metaplasia appears to be a protective adaptation. The patient of chronic reflux esophagitis will find his symptoms decrease when he has developed Barrett's esophagus.

Incidence:
It is mainly seen in white man and the prevalence increases with age. 
Several types of gastric-type mucosa may be found in the lower esophagus. When intestinal metaplasia occurs there is an increased risk of adenocarcinoma of the esophagus of the order of 25 times that of the general population. A recent (Dec 2011) large scale study in Denmark however shows that the incidence of adenocarcinoma in Barrett’s esopahgus is actually much lower i.e. around 7 times that of general population.

Clinical features:
The patient will have all the complaints of reflux esophagitis. Heartburn, described as a substernal burning sensation that moves from the region of the xiphoid up toward the neck. Regurgitation, water-brash and  odynophagia may be the other symptoms.

Diagnosis:
Barrett’s esophagus is diagnosed by endoscopic examination and  2  criteria  must  be  fulfilled.
1) The endoscopist must ascertain that columnar epithelium lines the distal esophagus.
2) Biopsy specimens of that columnar epithelium must show evidence of metaplasia.

To ascertain that columnar epithelium lines the distal esophagus, the endoscopist first must locate the esophagogastric junction (EGJ, which is recognized as the most proximal extent of the gastric folds) and then determine that columnar epithelium extends above the EGJ into the esophagus. Endoscopically, columnar epithelium has a reddish color and velvet-like texture that can be distinguished readily from normal esophageal squamous epithelium, which is pale and glossy.
There is disagreement among experts regarding the histologic type of epithelium required to confirm that there is evidence of metaplasia in the esophagus.
Virtually all would agree that the finding of an intestinal type epithelium with goblet cells (which has been called intestinal metaplasia, specialized intestinal metaplasia or specialized columnar epithelium) is clear evidence of metaplasia.

Treatment:
Patients who are found to have Barrett’s esophagus may be submitted to regular screening endoscopy with multiple biopsies every year or two in the hope of finding dysplasia or in situ cancer rather than allowing invasive cancer to develop and cause symptoms. There is as yet no general agreement about the benefits of screening endoscopy, nor about the ideal frequency of endoscopy. 
When Barrett’s esophagus is discovered the treatment is that of the underlying GERD. Several methods of ablation of Barrett’s mucosa are under active study, including laser, photodynamic therapy and argon beam plasma coagulation. In conjunction with high-dose PPI treatment or an antireflux operation these endoscopic methods can restore the squamous lining of the esophagus. It is not yet known whether this reduces the risk of malignant transformation since there are often remnants of glandular mucosa underneath the new squamous lining.