HEPATOLOGY Flashcards
Alcoholic Hepatitis - Definition
Inflammatory liver injury caused by chronic heavy intake of alcohol.
Alcoholic Hepatitis - Aetiology
One of the three forms of liver disease caused by excessive intake of alcohol, a spectrum that ranges from alcoholic fatty liver (steatosis) to alcoholic hepatitis and chronic cirrhosis. In alcoholic hepatitis, the liver histopathology shows centrilobular ballooning degeneration and necrosis of hepatocytes, steatosis, neutrophilic inflammation, cholestasis, Mallory hyaline inclusions (eosinophilic intracytoplasmic aggregates of cytokeratin inter- mediate filaments) and giant mitochondria.
Alcoholic Hepatitis - History
May remain asymptomatic and undetected unless they present for other reasons. May be mild illness with nausea, malaise, epigastric or right hypochondrial pain and a low-grade fever.
May be more severe with jaundice, abdominal discomfort or swelling, swollen ankles or GI bleeding. Women tend to present with more florid illness than men. There is a history of heavy alcohol intake (15–20 years of excessive intake necessary for development of alcoholic hepatitis). There may be trigger events (e.g. aspiration pneumonia or injury).
Alcoholic Hepatitis - Examination
Signs of alcohol excess: Malnourished, palmar erythema, Dupuytrens contracture, facial telangiectasia, parotid enlargement, spider naevi, gynaecomastia, testicular atrophy, hepatomegaly, easy bruising.
Signs of severe alcoholic hepatitis: Febrile (50% of patients), tachycardia, jaundice (>50% of patients), bruising, encephalopathy (e.g. hepatic foetor, liver flap, drowsiness, unable to copy a five-pointed star, disoriented), ascites (30–60% of patients), hepato- megaly (liver is usually mild–moderately enlarged and may be tender on palpation), splenomegaly.
Alcoholic Hepatitis - Investigations
Blood: FBC: low Hb, high MCV, high WCC, low platelets. LFT (high transminases, high bilirubin, low albumin, high AlkPhos, high GGT). U&E: Urea and K+ levels tend to be low, unless significant renal impairment. Clotting: Prolonged PT is a sensitive marker of significant liver damage.
Ultrasound scan: For other causes of liver impairment (e.g. malignancies).
Upper GI endoscopy: To investigate for varices.
Liver biopsy: Percutaneous or transjugular (in the presence of coagulopathy) may be helpful
to distinguish from other causes of hepatitis.
Electroencephalogram: For slow-wave activity indicative of encephalopathy.
MANAGEMENT
Acute: Thiamine, Vitamin C and other multivitamins (initially parenterally). Monitor and correct K+ , Mg2+ and glucose abnormalities. Ensure adequate urine output. Treat encephalopathy with oral lactulose and phosphate enemas. Ascites is managed by diuretics (spironolactone with or without frusemide (furosemide)) or therapeutic para- centesis. Glypressin and N-acetylcysteine for hepatorenal syndrome.
Nutrition: Nutritional support with oral or nasogastric feeding is important with increased caloric intake. Protein restriction should be avoided unless the patient is encephalopathic. Total enteral nutrition may also be considered as this improves mortality rate. Nutritional supplementation and vitamins (B group, thiamine, folic acid) should be started parenterally initially and then continued orally after.
Steroid therapy: Meta-analyses show that steroids reduce short-term mortality for severe alcoholic hepatitis.
Cirrhosis - Definition
End-stage of chronic liver damage with replacement of normal liver archi- tecture with diffuse fibrosis and nodules of regenerating hepatocytes. Decompensated when there are complications such as ascites, jaundice, encephalopathy or GI bleeding (see Liver failure).
Cirrhosis - Aetiology
Chronic alcohol misuse: Most common UK cause.
Chronic viral hepatitis: Hepatitis B/C are the most common causes worldwide. Autoimmune hepatitis.
Drugs: e.g. methotrexate, hepatotoxic drugs.
Inherited: a1-Antitrypsin deficiency, haemochromatosis, Wilsons disease, galactosaemia,
cystic fibrosis.
Vascular: Budd–Chiari syndrome or hepatic venous congestion.
Chronic biliary diseases: Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC),
biliary atresia.
Cryptogenic: In 5–10%.
Non-alcoholic steatohepatitis (NASH) increased risk of developing cirrhosis. NASH is associated
with obesity, diabetes, total parenteral nutrition, short bowel syndromes, hyperlipidaemia
and drugs, e.g. amiodarone, tamoxifen.
Decompensation can be precipitated by infection, GI bleeding, constipation, high-protein
meal, electrolyte imbalances, alcohol and drugs, tumour development or portal vein thrombosis.
Cirrhosis - History
Early non-specific symptoms: Anorexia, nausea, fatigue, weakness, weight loss. Symptoms caused by lowe liver synthetic function: Easy bruising, abdominal swelling, ankle
oedema.
Reduced detoxification function: Jaundice, personality change, altered sleep pattern,
amenorrhoea.
Portal hypertension: Abdominal swelling, haematemesis, PR bleeding or melaena.
Cirrhosis - Examination
Stigmata of chronic liver disease (ABCDE): Asterixis (liver flap). Bruises. Clubbing. Dupuytrens contracture. Erythema (palmar). Jaundice, gynaecomastia, leukonychia, parotid enlargement, spider naevi, scratch marks, ascites (shifting dullness and fluid thrill), enlarged liver (shrunken and small in later stage), testicular atrophy, caput medusae (dilated superficial abdominal veins), splenomegaly (indicating portal hypertension).
Cirrhosis - Investigations
Blood: FBC: low Hb, low platelets as a result of hypersplenism. LFTs: May be normal or often high transaminases, AlkPhos, GGT, bilirubin, low albumin. Clotting: Prolonged PT (low synthesis of clotting factors). Serum AFP: High In chronic liver disease, but high levels may suggest hepatocellular carcinoma.
Other investigations: To determine the cause, e.g. viral serology (HBsAg, HBsAb, HCV ab), a1-antitrypsin, caeruloplasmin (Wilsons disease), iron studies: serum ferritin, iron, total iron binding capacity (haemochromatosis), antimitochondrial antibody (PBC), antinuclear antibodies (ANA), SMA (autoimmune hepatitis).
Ascitic tap: Microscopy, culture and sensitivity, biochemistry (protein, albumin, glucose, amylase) and cytology. If neutrophils >250/mm3, this indicates spontaneous bacterial peritonitis (SBP).
Liver biopsy: Percutaneous or transjugular if clotting deranged or ascites present. Histo- pathology: Periportal fibrosis, loss of normal liver architecture and nodular appearance. Grade refers to the assessment of degree of inflammation, whereas stage refers to the degree of architectural distortion, ranging from mild portal fibrosis to cirrhosis.Imaging: Ultrasound, CT or MRI (to detect complications of cirrhosis such as ascites, hepatocellular carcinoma, and hepatic or portal vein thrombosis, to exclude biliary obstruction), MRCP (if PSC suspected).
Endoscopy: Examine for varices, portal hypertensive gastropathy.
Child–Pugh grading: Class A is score 5–6, Class B is score 7–9, Class C is score 10–15.
Cirrhosis - Management
Treat the cause if possible, avoid alcohol, sedatives, opiates, NSAIDs and drugs that affect the liver. Nutrition is very important and if intake is poor, dietitian review and enteral supplements should be given; nasogastric feeding may be indicated.
Treat the complications:
Encephalopathy: Treat infections. Exclude a GI bleed. Lactulose, phosphate enemas and avoid sedation.
Ascites: Diuretics (spironolactonefurosemide), dietary sodium restriction (88meq or 2g/day), therapeutic paracentesis (with human albumin replacement IV). Monitor weight daily. Fluid restriction in patients with plasma sodium <120mmol/L. Avoid alcohol and NSAIDs.
SBP: Antibiotic treatment (e.g. cefuroxime and metronidazole), prophylaxis against recurrent SBP with ciprofloxacin.
Surgical: Consider insertion of TIPS to relieve portal hypertension (if recurrent variceal bleeds or diuretic-resistant ascites) although it may precipitate encephalopathy. Liver transplantation is the only curative measure.
Autoimmune Hepatitis - Definition
Chronic hepatitis of unknown aetiology, characterized by autoimmune features, hyperglobulinaemia and the presence of circulating autoantibodies.
Autoimmune Hepatitis - Aetiology
A E T I O L O G Y In a genetically predisposed individual, an environmental agent (e.g. viruses or drugs) may lead to hepatocyte expression of HLA antigens which then become the focus of a principally T-cell-mediated autoimmune attack. The raised titres of ANA, ASM and anti-liver/kidney microsomes (anti-LKM) are not thought to directly injure the liver. The chronic inflammatory changes are similar to those seen in chronic viral hepatitis with lymphoid infiltration of the portal tracts and hepatocyte necrosis, leading to fibrosis and, eventually, cirrhosis. Two major forms: Type I (classic): ANA, anti-smooth muscle antibodies (ASMA), anti-actin antibodies (AAA), anti-soluble liver antigen (anti-SLA). Type 2: Antibodies to liver/kidney microsomes (ALKM-1, directed at an epitope of CYP2D6), antibodies to a liver cytosol antigen (ALC-1). Patients with variant forms of autoimmune hepatitis have clinical and serologic findings of autoimmune hepatitis plus features of PBC or PSC.
Autoimmune Hepatitis - History
May be asymptomatic and discovered incidentally by abnormal LFT. Insidious onset: Malaise, fatigue, anorexia, weight loss, nausea, jaundice, amenorrhoea,
epistaxis.
Acute hepatitis (25%): Fever, anorexia, jaundice, nausea, vomiting, diarrhoea, RUQ pain.
Some may also present with serum sickness (e.g. arthralgia, polyarthritis, maculopapular
rash).
May be associated with keratoconjuctivitis sicca.
Personal or family history of autoimmune disease, e.g. type 1 diabetes mellitus and vitiligo.
It is important to take a full history to rule out other potential causes of liver disease (e.g. alcohol, drugs).
Autoimmune Hepatitis - Examination
Stigmata of chronic liver disease, e.g. spider naevi (see Cirrhosis). Ascites, oedema and encephalopathy are late features.
Cushingoid features (e.g. rounded face, cutaneous striae, acne, hirsuitism) may be present
even before the administration of steroids.
Autoimmune Hepatitis - Investigations
Blood: LFT: very high AST and ALT, very high GGT, high AlkPhos, high bilirubin, low albumin in severe disease. Clotting: high PT in severe disease. FBC: Mild low Hb, also low platelets and WCC from hypersplenism if portal hypertension present. Hypergammaglobulinaemia is typical (polyclonal gammopathy) with the presence of ANA, ASMA or anti-LKM autoantibodies. Liver biopsy: Needed to establish the diagnosis. Shows interface hepatitis or cirrhosis. Other investigations: To rule out other causes of liver disease, e.g. viral serology (hepatitis B and C) caeruloplasmin and urinary copper (Wilsons disease), ferritin and transferrin saturation (haemochromatosis), a1-antitrypsin (a1-antitrypsin deficiency) and antimito- chondrial antibodies (PBC). Ultrasound, CT or MRI of liver and abdomen: To visualize structural lesions. ERCP: To rule out PSC.
