Chronic Liver Disease

Possible scenarios: Jaundice, fatigue, abdominal swelling, abdominal discomfort.
Assessing for chronic liver disease: You should be asking yourself four questions: 

1. What features of chronic liver disease are present? 
   • Features of reduced oestrogen breakdown – palmar erythema, spider naevi (5 or more), gynaecomastia, reduced axillary and genital hair, testicular atrophy.
   • Features of reduced liver synthetic function – cachexia, leukonychia, bruising.
   • Features of portal hypertension – caput medusae, splenomegaly.
2. What features of decompensation are present? Look for hepatic encephalopathy (liver flap, drowsiness, confusion), ascites (shifting dullness, fluid thrill, drain/tap marks, tazocin), easy bleeding (bruising), and jaundice. If there is decompensation, what is the patients fluid status? basing the latter on peripheral perfusion, pulse, mucous membranes, JVP, peripheral oedema.
3. What features of malignancy are present? Cervical lymphadenopathy, nodular lesions when palpating the liver, bruit on auscultation over the liver.
4. What do I think the underlying cause is? See below.

Classic cases:

1. Alcoholic liver disease: Dupytrens contracture, enlarged parotids.
2. Hepatitis B/C: Tattoos, track marks.
3. Hereditary haemochromatosis: finger prick marks from BM testing, arthropathy, bronze pigmentation.
4. Primary biliary cirrhosis: Middle aged female, xanthelasma, excoriation marks, easy bruising (due to CLD and impaired absorption of fat soluble vitamins), hepatosplenomegaly.
5. Autoimmune hepatitis: Vitiligo, scar from previous thyroidectomy.

Differential diagnosis: 

• Toxic: Alcohol, methotrexate, amiodarone, isoniazid.
• Metabolic: Non-alcoholic steatohepatitis (NASH).
• Infective: Hepatitis B and C.
• Autoimmune: Primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis, sarcoidosis.
• Hereditary: Hereditary haemochromatosis, alpha-1-anti-trypsin deficiency, Wilson’s disease, glycogen storage disorders.

Further investigations:

• Bedside tests: Urine dip (leukocytes and nitrates; pregnancy test if young female),  ascitic tap (fluid cell count and differential, protein, albumin, culture in aerobic/anaerobic blood culture bottles).
• Bloods: FBC (anaemia, thrombocytopaenia, leukopenia), clotting (due to reduced production of clotting factors, and prior to taps or drain insertion), U&Es (deranged electrolytes as a risk for decompensation, monitoring therapy if on diuretics, risk of hepatorenal syndrome), LFTs (albumin for synthetic function and SAAG, pattern of enzyme derangement if hepatic or post-hepatic), glucose (risk of hypoglycaemia, HH associated with diabetes).
• Imaging: USS abdomen (to assess liver and spleen size; look for cirrhosis, liver masses, ascites; assess portal pressures; once cirrhosis confirmed, an annual USS should be arranged to monitor for HCC), MRCP (could be done prior to ERCP, if features of obstruction on USS).
• Special tests: If cirrhotic a liver screen including – HBV/HCV, autoimmune screen including ANA and anti-mitochrondrial antibodies, immunoglobulins, caeruloplasmin, ferritin, alpha-1-anti-trypsin, oesophageao-gastro-duodenoscopy (surveillance for varices), also an  then consider liver biopsy and/or ERCP.

Referral:
Probably hepatology, may require admission to hospital or day unit for tap or drainage, or assessment for acute decompensation.
Management:

• Non-pharmacological: Dietician input, alcohol cessation, vaccinations (hepatitis, pneumococcoal, and annual influenza), avoid hepatotoxic agents (including NSAIDs and herbal remedies so educate the patient).
• Medical: Colestyramine (pruritus), laxatives (avoid constipation), adcal D3 (risk of osteoporosis), propanolol (if has varices), quinolone antibiotics (levofloxicin etc for SBP prophylaxis if previous episode), spironolactone +/- furosemide (if ascites), chlordiazepoxide+pabrinex (if current alcohol excess).
• Surgical/procedural: Serial therapeutic paracenteses, transjugular intrahepatic portosystemic shunt (TIPS), liver transplantation.

Possible questions:

1. How do you diagnose Spontaneous Bacterial Peritonitis (SBP)? Ascitic tap – positive if neutrophil count >250 per ml.
2. What is the commonest cause of SBP? Escherchia coli.
3. If someone presented with abdominal swelling that is found to be ascites, what would be your differential diagnosis?
   • Cirrhosis: Any of the causes listed above – alcohol related, infectious, immune, iatrogenic (medications like methotrexate), or hereditary.
   • Malignancy: Primary or secondary, solid organ or haematological.
   • Heart failure, pancreatitis.
   • Hypoalbuminaemia: Nephrotic syndrome, malnutrition.
   • Infection: Tuberculosis.
   • Endocrine: Hypothyroidism.
4. How much fluid usually needs to be present to be clinically detectable as ascites? 1500mls though it can be less if very slim, and more if obese. An USS can detect smaller amounts of <500mls.
5. How would you manage ascites? Establish the cause and manage/treat that if possible. Refer to a dietician to educate on a salt restricted diet and maintaining adequate nutrition, and advise the patient to avoid alcohol and get vaccinated against hepatitis B. Medications wise, usually start with 100mg spironolactone and titrate up to 400mg a day, adding in frusemide if needed, and monitoring closely for side-effects including electrolyte disturbance and deteriorating renal function. If large volume, and causing respiratory distress, consider performing therapeutic paracentesis, with 20% HAS at the same time if large volumes are removed. If due to a malignant process and likely to be longstanding you can arrange insertion of a PleurX drain which remains in place and can be used for regular small volume draining in the community by district nurses. Surgical options include TIPS (transjugular intrahepatic portosystemic shunt) but this increases the risk of hepatic encephalopathy.
6. Which forms of chronic liver disease are prone to causing hepatosplenomegaly? Primary biliary cirrhosis, alcoholic liver disease, cirrhosis with hepatocellular carcinoma.
7. How would you manage a patient with primary biliary cirrhosis? Confirm the diagnosis with deranged liver function tests, positive anti-mitochrondrial antibody, raised IgG and high cholesterol; a liver biopsy demonstrates granulomas. If asymptomatic they have a good prognosis and near normal life expectancy. If symptomatic the prognosis is poor with a life expectancy of just a few years without transplant. Medical management involves replacing fat soluble vitamins, avoiding alcohol, ursodeoxycholic acid (improves LFTs), cholestyramine (for pruritus).
8. What is the cause of Wilson’s disease? Autosomal recessive defect in ATP7B on chromosome 13, which means that there is reduced excretion of copper into the bile and subsequent accumulation in other organs including the liver and brain. It results in low caeruloplasmin levels and high urinary copper levels. Kayser fleisher rings are seen on slit lamp, and a liver biopsy may be required. It is managed with dietary avoidance of high copper containing foods (shellfish, avocados etc) and other hepatotoxic agents like alcohol, in addition to copper chelation with penicillamine and zinc acetate. It can present with acute or chronic liver failure, haemolysis, and neurological involvement including movement disorders (asymmetrical tremor or choreiform movements) and psychiatric manifestations. Other complications include cardiomyopathy and Fanconi’s syndrome. Some will undergo liver transplant which will cure the underlying defect via a form of surgical gene therapy.

*Example presentation: This is an elderly male with chronic liver disease as suggested by the presence of palmar erythema, spider naevi, gynaecomastia, and reduced axillary hair. The liver is not palpable. There is evidence of decompensation with purpura, icterus and ascites; but no encephalopathy was elicited today. Their disease is complicated by portal hypertension with splenomegaly, ascites and caput medusae. The spleen is felt 3 finger breadths below the costal margin, and is firm and non-tender. Other notable findings on examination are the presence of a recent ascitic drain or tap mark and a tattoo on the right forearm. My differential diagnosis includes hepatitis B and C, alcoholic and non-alcoholic steatohepatitis, and a range of autoimmune and inherited diseases. To investigate the patient further I would like a full set of bedside observations, to review stool and fluid balance charts, and send an ascitic tap sample for cytology, microbiology and biochemistry. Blood tests should focus on assessing the liver synthetic function and enzyme profile and include a screen for the diseases listed previously. An abdominal ultrasound could confirm the presence of cirrhosis, focal liver lesions, splenomegaly and ascites; whilst an endoscopic examination could confirm varices. A liver biopsy may be required to confirm or stage the disease. Management would require education and counselling, advice to cease alcohol or drug abuse if relevant, vaccination against hepatitis A and B, and referral to a dietician to advise on low salt diet. If possible, the underlying disease should be treated, and long term complications managed such as diuretics and elective paracentesis for ascites, antibiotics as per local guidelines for SBP followed by antibiotic prophylaxis, laxatives aiming for 2 soft stools a day, beta blockers if varcies are present, and rifaximin if they’ve experienced encephalopathy. Surgical options include transjugular intrahepatic portosystemic shunt formation, although this increases the risk of encephalopathy; or liver transplant if they meet eligibility criteria.