Cirrhosis - Clinicals, Diagnosis, and Management

Gastroenterology

Clinicals - History

Fact Explanation
Asymptomatic Some patients are asymptomatic until the hepatic function is significantly impaired. Asymptomatic
Some patients are asymptomatic until the hepatic function is significantly impaired.
Yellowish discoloration of skin and sclera. Accumulation of bilirubin in the subcutaneous fat and in sclera. Yellowish discoloration of skin and sclera.
Accumulation of bilirubin in the subcutaneous fat and in sclera.
Hematemesis and or malena Esophageal varices develop secondary to portal hypertension. Often bleeding is massive because of defective coagulation secondary to reduced coagulation factor synthesis by the liver. Hematemesis and or malena
Esophageal varices develop secondary to portal hypertension. Often bleeding is massive because of defective coagulation secondary to reduced coagulation factor synthesis by the liver.
Reversed sleep wake cycle This is one of the earliest symptoms of hepatic encephalopathy (HE) and it is due to altered melatonin secretion. Reversed sleep wake cycle
This is one of the earliest symptoms of hepatic encephalopathy (HE) and it is due to altered melatonin secretion.
Impaired memory An early symptom of HE. Impaired memory
An early symptom of HE.
Personality changes Begins to appear from grade 2 HE. Personality changes
Begins to appear from grade 2 HE.
Inappropriate behavior This occurs in grade 3 HE. Inappropriate behavior
This occurs in grade 3 HE.
Coma Patients with severe hepatic encephalopathy may present with coma. Coma
Patients with severe hepatic encephalopathy may present with coma.
Abdominal pain Budd Chiary syndrome causes acute onset abdominal pain and symptoms of hepatic failure. Abdominal pain
Budd Chiary syndrome causes acute onset abdominal pain and symptoms of hepatic failure.
Constitutional symptoms Some patients present with non-specific symptoms like fatigue, malaise, anorexia, muscle wasting and loss of weight. Patients may gain weight due to ascites and generalized edema. Constitutional symptoms
Some patients present with non-specific symptoms like fatigue, malaise, anorexia, muscle wasting and loss of weight. Patients may gain weight due to ascites and generalized edema.
Presence of risk factors Harmful alcohol use is one of the leading causes of cirrhosis. Hepatitis B, C and nonalcoholic fatty liver disease (NAFLD) are all risk factors for cirrhosis. Presence of autoimmune hepatitis, primary and secondary biliary cirrhosis, alpha-1 antitrypsin deficiency, hemochromatosis, Wilson’s disease, chronic right heart failure (cardiac cirrhosis), tricuspid regurgitation, Budd Chiari syndrome and veno-occlusive diseases are other risk factors. Presence of risk factors
Harmful alcohol use is one of the leading causes of cirrhosis. Hepatitis B, C and nonalcoholic fatty liver disease (NAFLD) are all risk factors for cirrhosis. Presence of autoimmune hepatitis, primary and secondary biliary cirrhosis, alpha-1 antitrypsin deficiency, hemochromatosis, Wilson’s disease, chronic right heart failure (cardiac cirrhosis), tricuspid regurgitation, Budd Chiari syndrome and veno-occlusive diseases are other risk factors.

Clinicals - Examination

Fact Explanation
Abdominal examination The liver is usually not palpated because it is small and shrunken. Splenomegaly occurs due to portal hypertension. Portosystemic collaterals around the umbilicus dilates giving rise to caput medusa appearance. Ascites occurs due to cirrhosis and portal hypertension. Abdomen is distended and abdominal dullness is present. Depending on the amount of ascetic fluid, flank dullness, shifting dullness, horse shoe dullness and fluid thrill can be detected. Puddle sign is present in small fluid collections. Abdominal examination
The liver is usually not palpated because it is small and shrunken. Splenomegaly occurs due to portal hypertension. Portosystemic collaterals around the umbilicus dilates giving rise to caput medusa appearance. Ascites occurs due to cirrhosis and portal hypertension. Abdomen is distended and abdominal dullness is present. Depending on the amount of ascetic fluid, flank dullness, shifting dullness, horse shoe dullness and fluid thrill can be detected. Puddle sign is present in small fluid collections.
Pallor Secondary to recurrent bleeding episodes and nutritional deficiencies. Pallor
Secondary to recurrent bleeding episodes and nutritional deficiencies.
Jaundice Due to excessive accumulation of bilirubin. Jaundice
Due to excessive accumulation of bilirubin.
Muscle wasting Protein calorie malnutrition and recurrent infections play a role in the etiology of muscle wasting. Muscle wasting
Protein calorie malnutrition and recurrent infections play a role in the etiology of muscle wasting.
Scratch marks Patients develop pruritus due to retention of bile salts. Repetitive scratching causes scratch marks and polished nails. Scratch marks
Patients develop pruritus due to retention of bile salts. Repetitive scratching causes scratch marks and polished nails.
Peripheral edema Due to hypoalbuminemia. Peripheral edema
Due to hypoalbuminemia.
Spider telangiectasias Excess of estrogen in men is believed to be the reason for the development of spider telangiectasias, but the exact reason is not known. Spider telangiectasias
Excess of estrogen in men is believed to be the reason for the development of spider telangiectasias, but the exact reason is not known.
Palmar erythema Due to vasodilators which are not deactivated by the liver. Commonly seen in alcoholic cirrhosis. Palmar erythema
Due to vasodilators which are not deactivated by the liver. Commonly seen in alcoholic cirrhosis.
Fetor hepaticus Hyperammonemia causes fetor hepaticus. It is present in HE. Fetor hepaticus
Hyperammonemia causes fetor hepaticus. It is present in HE.
Impaired attention and concentration According to the West Haven classification minimal impairment is graded as grade 0. Mild lack of awareness and shortened attention span is grade 1. Disorientation belongs to grade 2 and somnolence, disorientation in time and place and marked confusion belongs to grade 3. Coma despite the responsiveness to painful stimuli is grade 4. Impaired attention and concentration
According to the West Haven classification minimal impairment is graded as grade 0. Mild lack of awareness and shortened attention span is grade 1. Disorientation belongs to grade 2 and somnolence, disorientation in time and place and marked confusion belongs to grade 3. Coma despite the responsiveness to painful stimuli is grade 4.
Impaired consciousness HE results due to reduced detoxification of ammonia and other neuro-toxic metabolites because of the liver failure. Impaired consciousness
HE results due to reduced detoxification of ammonia and other neuro-toxic metabolites because of the liver failure.
Hyperreflexia Pyramidal tract dysfunction in HE results in hyperreflexia which later becomes hypotonia with the development of coma. Hyperreflexia
Pyramidal tract dysfunction in HE results in hyperreflexia which later becomes hypotonia with the development of coma.
Hepatic flaps (asterixis) This sign is elicited by asking the patient to keep the hands outstretched and dorsiflexed. Presence of flaps favors the diagnosis of HE, but it can occur in various other metabolic abnormalities as well. Asterixis is absent in grade 0 HE and in grade 4. It is marked in grade 2 and 3 HE. Hepatic flaps (asterixis)
This sign is elicited by asking the patient to keep the hands outstretched and dorsiflexed. Presence of flaps favors the diagnosis of HE, but it can occur in various other metabolic abnormalities as well. Asterixis is absent in grade 0 HE and in grade 4. It is marked in grade 2 and 3 HE.
Transient focal neurologic deficits This is a rare finding of severe HE. Patients may manifest signs suggestive of focal neurological deficits. Transient hemiplegia is common. Transient focal neurologic deficits
This is a rare finding of severe HE. Patients may manifest signs suggestive of focal neurological deficits. Transient hemiplegia is common.
Cutaneous manifestations Jaundice, spider angiomata, skin telangiectasias, palmar erythema, leukonychia, and finger clubbing are present. Cutaneous manifestations
Jaundice, spider angiomata, skin telangiectasias, palmar erythema, leukonychia, and finger clubbing are present.
Pleural effusions In the presence of massive ascites pleural effusions can occur due to the direct flow of ascetic fluid in to the pleural cavity. Pleural effusions
In the presence of massive ascites pleural effusions can occur due to the direct flow of ascetic fluid in to the pleural cavity.
Signs suggestive of the etiology of cirrhosis Abdominal tenderness, hepatomegaly and ascites can be elicited in Budd Chiari syndrome. Neurological manifestations (chorea, Parkinsonism, dysarthria) and Kayser-Fleischer rings suggest Wilson’s disease. Acanthosis nigricans, obesity, high blood pressure and pheripheral stigmata of hyperlipidemia (xantholesma, xanthomata) all are suggestive of the possibility of metabolic syndrome and non-alcoholic fatty liver disease as the possible etiology. Tricuspid regurgitation and signs of right heart failure is found in cardiac cirrhosis. Signs suggestive of the etiology of cirrhosis
Abdominal tenderness, hepatomegaly and ascites can be elicited in Budd Chiari syndrome. Neurological manifestations (chorea, Parkinsonism, dysarthria) and Kayser-Fleischer rings suggest Wilson’s disease. Acanthosis nigricans, obesity, high blood pressure and pheripheral stigmata of hyperlipidemia (xantholesma, xanthomata) all are suggestive of the possibility of metabolic syndrome and non-alcoholic fatty liver disease as the possible etiology. Tricuspid regurgitation and signs of right heart failure is found in cardiac cirrhosis.

Investigations - Diagnosis

Fact Explanation
Full blood count Thrombocytopenia is seen with portal hypertension. Platelet counts less than 160,000 × 10(9)/L should raise the suspicion of cirrhosis in any patient. Full blood count
Thrombocytopenia is seen with portal hypertension. Platelet counts less than 160,000 × 10(9)/L should raise the suspicion of cirrhosis in any patient.
Hepatic transaminases Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated. Hepatic transaminases
Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated.
Prothrombin time Prolonged. Prothrombin time
Prolonged.
Serum bilirubin Often elevated. Higher the bilirubin levels in blood, higher the risk of spontaneous bacterial peritonitis. Serum bilirubin
Often elevated. Higher the bilirubin levels in blood, higher the risk of spontaneous bacterial peritonitis.
Serum albumin Reduced due to diminished hepatic synthesis. Serum albumin
Reduced due to diminished hepatic synthesis.
Liver biopsy Cirrhosis is a pathological diagnosis. Although imaging studies can suggest cirrhosis biopsy is necessary for confirmative diagnosis. Liver biopsy
Cirrhosis is a pathological diagnosis. Although imaging studies can suggest cirrhosis biopsy is necessary for confirmative diagnosis.
Ascetic fluid full report Differentiates ascites due to portal hypertension from other causes. In portal hypertension ascetic fluid is a transudate and protein content is less than 2.5g/dL and serum-ascites albumin gradient (SAAG) is greater than 1.1g/dL. Ascetic fluid full report
Differentiates ascites due to portal hypertension from other causes. In portal hypertension ascetic fluid is a transudate and protein content is less than 2.5g/dL and serum-ascites albumin gradient (SAAG) is greater than 1.1g/dL.
Abdominal imaging Ultrasound scan, CT and MRI can be used in assessing the hepatic architecture. Ultrasound scan has low sensitivity in detecting early cirrhosis. Ultrasound scan combined with Doppler can diagnose Budd Chiari syndrome. Abdominal imaging
Ultrasound scan, CT and MRI can be used in assessing the hepatic architecture. Ultrasound scan has low sensitivity in detecting early cirrhosis. Ultrasound scan combined with Doppler can diagnose Budd Chiari syndrome.

Investigations - Management

Fact Explanation
Serum ammonia Increased in hepatic encephalopathy, but normal amounts do not exclude the possibility of hepatic encephalopathy. Serum ammonia
Increased in hepatic encephalopathy, but normal amounts do not exclude the possibility of hepatic encephalopathy.
Full blood count Leukocytosis suggests the possibility of spontaneous bacterial peritonitis. Full blood count
Leukocytosis suggests the possibility of spontaneous bacterial peritonitis.
Ascetic fluid full report In spontaneous bacterial peritonitis (SBP), polymorphonuclear cells increases (more than 250/mm3). Ascetic fluid full report
In spontaneous bacterial peritonitis (SBP), polymorphonuclear cells increases (more than 250/mm3).
Ascetic fluid culture Aids in isolating the organism causing SBP. Escherichia coli, Klebsiella species, Streptococcus pneumoniae, and other gram-negative enteric organisms are the common causes. Ascetic fluid culture
Aids in isolating the organism causing SBP. Escherichia coli, Klebsiella species, Streptococcus pneumoniae, and other gram-negative enteric organisms are the common causes.
Serum electrolytes and serum creatinine Detects hepato-renal syndrome. Serum electrolytes and serum creatinine
Detects hepato-renal syndrome.
Measurement of portal venous pressure Elevated in portal hypertension. This is an independent predictor of patients’ survival. Measurement of portal venous pressure
Elevated in portal hypertension. This is an independent predictor of patients’ survival.
Pulse oxymetry Patients with hepato-pulmonary syndrome (HPS) have low oxygen saturation (less than 70mm Hg). This is due to excess nitric oxide production and pulmonary artery vasodilatation. Pulse oxymetry
Patients with hepato-pulmonary syndrome (HPS) have low oxygen saturation (less than 70mm Hg). This is due to excess nitric oxide production and pulmonary artery vasodilatation.
Pulmonary capillary wedge pressure Increased in portopulmonary hypertension. Pulmonary capillary wedge pressure
Increased in portopulmonary hypertension.
Screening for hepatocellular carcinoma (HCC) Elevated alpha-feto protein and ultrasound scan, CT or MRI evidence of hepatic focal lesions should be looked for in screening of HCC. Screening for hepatocellular carcinoma (HCC)
Elevated alpha-feto protein and ultrasound scan, CT or MRI evidence of hepatic focal lesions should be looked for in screening of HCC.
Upper gastrointestinal endoscopy Regular variceal surveillance is indicated in all patients with cirrhosis. Upper gastrointestinal endoscopy
Regular variceal surveillance is indicated in all patients with cirrhosis.
Full blood count Anemia is a common finding due to chronic gastrointestinal bleeding, folate deficiency, B12 deficiency, hemolysis, and hypersplenism. Thrombocytopenia occurs secondary to hypersplenism and reduced synthesis of thrombopoietin. Full blood count
Anemia is a common finding due to chronic gastrointestinal bleeding, folate deficiency, B12 deficiency, hemolysis, and hypersplenism. Thrombocytopenia occurs secondary to hypersplenism and reduced synthesis of thrombopoietin.
Coagulation profile Synthesis of clotting factors is impaired resulting coagulopathy. Coagulation profile
Synthesis of clotting factors is impaired resulting coagulopathy.
Serum electrolytes Done as an assessment of fitness for surgery. Serum electrolytes
Done as an assessment of fitness for surgery.
Pulmonary capillary wedge pressure Measured to assess the pre-operative fitness before liver transplant. Pulmonary capillary wedge pressure
Measured to assess the pre-operative fitness before liver transplant.
PT/INR Used in calculation of MELD (Model for End Stage Liver Disease) score and Child-Pugh score. The MELD score predicts the short term (3 months) survival. PT/INR
Used in calculation of MELD (Model for End Stage Liver Disease) score and Child-Pugh score. The MELD score predicts the short term (3 months) survival.
Serum albumin Used in calculation of Child-Pugh score. Serum albumin
Used in calculation of Child-Pugh score.
Serum bilirubin Used in calculation of Child-Pugh score and MELD score. Serum bilirubin
Used in calculation of Child-Pugh score and MELD score.
Serum bilirubin Used in calculation of MELD score. Serum bilirubin
Used in calculation of MELD score.

Management - Supportive

Fact Explanation
Health education Public awareness should be raised about the common and preventable causes of cirrhosis, like harmful use of alcohol, hepatitis B and C infection, and non-alcoholic fatty liver disease. Patients with cirrhosis should be advised to restrict salt and protein intake. Nutritional supplements or healthy balanced diet with low protein is indicated. Regular physical exercise will help to delay and prevent the muscle wasting. Health education
Public awareness should be raised about the common and preventable causes of cirrhosis, like harmful use of alcohol, hepatitis B and C infection, and non-alcoholic fatty liver disease. Patients with cirrhosis should be advised to restrict salt and protein intake. Nutritional supplements or healthy balanced diet with low protein is indicated. Regular physical exercise will help to delay and prevent the muscle wasting.
Treatment of causative factors Auto-immune hepatitis is treated with immunosuppression (prednisone and azathioprine). Interferon and other antiviral agents are used to treat chronic viral hepatitis. Phlebotomy is indicated in hemochromatosis. Primary biliary cirrhosis is treated with ursodeoxycholic acid. Trientine, penicillamine and zinc is used in the treatment of Wilson’s disease. Anticoagulation with intravenous heparin followed by oral warfarin or subcutaneous low-molecular-weight heparin is indicated in Budd Chiari syndrome. Angioplasty and or stent placement will re-establish the vessel patency. Treatment of causative factors
Auto-immune hepatitis is treated with immunosuppression (prednisone and azathioprine). Interferon and other antiviral agents are used to treat chronic viral hepatitis. Phlebotomy is indicated in hemochromatosis. Primary biliary cirrhosis is treated with ursodeoxycholic acid. Trientine, penicillamine and zinc is used in the treatment of Wilson’s disease. Anticoagulation with intravenous heparin followed by oral warfarin or subcutaneous low-molecular-weight heparin is indicated in Budd Chiari syndrome. Angioplasty and or stent placement will re-establish the vessel patency.
Management of hepatorenal syndrome Intravenous fluid, albumin or fresh frozen plasma administration are helpful measures. Hemodialysis may be needed in refractory renal failure. Liver transplantation is carried out as the final option of treatment. Management of hepatorenal syndrome
Intravenous fluid, albumin or fresh frozen plasma administration are helpful measures. Hemodialysis may be needed in refractory renal failure. Liver transplantation is carried out as the final option of treatment.
Management of hepatic encephalopathy Lactulose (30mL once or twice a day) administration and treatment of any infection or precipitating factor (hypovolemia, metabolic disturbances, gastrointestinal bleeding, infection, constipation) should be done. Lactulose can reduce the intestinal absorption of ammonia and also facilitate the quick passage of intestinal contents reducing the duration of absorption. L-ornithine L-aspartate, sodium benzoate are other available treatment options.
Nutritional needs should be supplied via a nasogastric tube to prevent the risk of aspiration. Other supportive care include, urinary catheterization, maintaining skin and oral hygiene.
Management of hepatic encephalopathy
Lactulose (30mL once or twice a day) administration and treatment of any infection or precipitating factor (hypovolemia, metabolic disturbances, gastrointestinal bleeding, infection, constipation) should be done. Lactulose can reduce the intestinal absorption of ammonia and also facilitate the quick passage of intestinal contents reducing the duration of absorption. L-ornithine L-aspartate, sodium benzoate are other available treatment options.
Nutritional needs should be supplied via a nasogastric tube to prevent the risk of aspiration. Other supportive care include, urinary catheterization, maintaining skin and oral hygiene.
Management of ascites Dietary sodium restriction, diuretics and therapeutic abdominal paracenthesis are treatment options. Peritoneovenous, portosystemic and transjugular intrahepatic portosystemic shunts are also helpful. Spironolactone (50-300mg once daily) is the diuretic of choice in management of ascites. Spironolactone is used either alone or in combination with furosemide in severe ascites. Intravenous albumin and vasopressin (V2 receptor antagonists) are used in the management of ascites. Management of ascites
Dietary sodium restriction, diuretics and therapeutic abdominal paracenthesis are treatment options. Peritoneovenous, portosystemic and transjugular intrahepatic portosystemic shunts are also helpful. Spironolactone (50-300mg once daily) is the diuretic of choice in management of ascites. Spironolactone is used either alone or in combination with furosemide in severe ascites. Intravenous albumin and vasopressin (V2 receptor antagonists) are used in the management of ascites.
Management of variceal bleeding Nonselective beta blockers (propranolol, nadolol) are indicated to reduce portal hypertension. Endoscopic treatment options like banding, injection of scleroscents are indicated in treatment of esophageal varices. Management of variceal bleeding
Nonselective beta blockers (propranolol, nadolol) are indicated to reduce portal hypertension. Endoscopic treatment options like banding, injection of scleroscents are indicated in treatment of esophageal varices.
Antibiotic prophylaxis of spontaneous bacterial peritonitis (SBP) Patients with a history of SBP are given antibiotic prophylaxis with norfloxacin (400mg daily) and trimethoprim-sulfamethoxazole (5 days a week) to prevent the recurrence of SBP. Patients with gastrointestinal bleeding are prescribed norfloxacin (400mg orally twice per day) for 7 days to minimize the risk of SBP. Antibiotic prophylaxis of spontaneous bacterial peritonitis (SBP)
Patients with a history of SBP are given antibiotic prophylaxis with norfloxacin (400mg daily) and trimethoprim-sulfamethoxazole (5 days a week) to prevent the recurrence of SBP. Patients with gastrointestinal bleeding are prescribed norfloxacin (400mg orally twice per day) for 7 days to minimize the risk of SBP.
Treatment of SBP Antibiotics should be prescribed for the treatment. Treatment of SBP
Antibiotics should be prescribed for the treatment.
Management of abdominal hernia Massive ascites can cause umbilical and inguinal hernias. Umbilical hernia should not be repaired unless it is irreducible, or strangulated, since the risk of elective risk is significantly higher than the risk of complications of the umbilical hernia. Management of abdominal hernia
Massive ascites can cause umbilical and inguinal hernias. Umbilical hernia should not be repaired unless it is irreducible, or strangulated, since the risk of elective risk is significantly higher than the risk of complications of the umbilical hernia.
Treatment of anemia These include hematinic, erythropoietin or blood transfusion. Treatment of anemia
These include hematinic, erythropoietin or blood transfusion.
Zinc sulfate (220mg orally twice daily) Zinc deficiency is seen in many patients with cirrhosis. It is also effective in preventing muscle cramps. Zinc is indicated in patients with Wilson’s disease as well. Zinc sulfate (220mg orally twice daily)
Zinc deficiency is seen in many patients with cirrhosis. It is also effective in preventing muscle cramps. Zinc is indicated in patients with Wilson’s disease as well.
Treatment of osteoporosis Vitamin D and oral calcium supplements are indicated for patients with increased risk. Treatment of osteoporosis
Vitamin D and oral calcium supplements are indicated for patients with increased risk.
Vaccination Patients with cirrhosis should be vaccinated against hepatitis A, influenza and pneumococci. These infections increase the morbidity and mortality in patients with cirrhosis. Vaccination
Patients with cirrhosis should be vaccinated against hepatitis A, influenza and pneumococci. These infections increase the morbidity and mortality in patients with cirrhosis.

Management - Specific

Fact Explanation
Liver transplantation Severe cardiomyopathy, pulmonary disease, active alcohol abuse, malignancy other than HCC and sepsis are contraindications for liver transplantation. Liver transplantation
Severe cardiomyopathy, pulmonary disease, active alcohol abuse, malignancy other than HCC and sepsis are contraindications for liver transplantation.

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