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Cirrhosis of the Liver

Essentials

  • In cirrhosis the functional liver tissue is replaced by connective tissue.
  • Alcohol is the most common cause of liver cirrhosis, but other aetiologies should be excluded.
  • A patient with liver cirrhosis may be asymptomatic for a long period and the symptoms are often related to hepatic failure.
  • Proneness to developing an alcoholic liver disease is individual and not predictable.

Aetiology

Symptoms and signs

  • At an early stage cirrhosis is often asymptomatic. Fatigue, itching, jaundice, and abdominal swelling are late symptoms or are associated with the activity of the underlying disease.
  • Acute bleeding from oesophageal varices or acute jaundice may also be the first symptom of liver cirrhosis.
  • Possible findings (often the status is normal)
    • Small, indurated liver, with the edge possibly palpable in patients who have lost weight
    • Palpable spleen
    • Muscle wasting and weight loss
    • Spider naevi on the upper trunk and the face
    • Palmar erythema
    • Gynaecomastia and testicular atrophy
    • Dilated abdominal surface veins
    • Ascites
    • Jaundice

Laboratory investigations

  • The basic investigations when liver disease is suspected
    • ESR, basic blood count with platelet count, ALT, AST, alkaline phosphatase, GGT, bilirubin, prothrombin time or INR, albumin, prealbumin, potassium, sodium, creatinine and fasting plasma glucose
  • Investigations to determine the aetiology
    • HBsAg, HCV antibodies, smooth muscle antibodies, mitochondrial antibodies, antinuclear antibodies, transglutaminase antibodies, serum IgG, IgA, IgM, serum iron, transferrin saturation, ferritin, alpha-1-antitrypsin, ceruloplasmin, blood PEth, plasma ethanol.
  • Indicators of poor prognosis include
    • serum bilirubin above 300 µmol/l
    • serum albumin below 20 g/l
    • INR above 2.5.

Liver imaging

  • Upper abdominal ultrasonography
    • A "bright" liver indicates fatty transformation or cirrhosis, but is an unspecific finding.
    • Fatty transformation is not revealed by ultrasonography until it exceeds 30%.
    • Spleen enlargement, dilated vessels of the portal system, and visible collaterals suggest portal hypertension.
    • Even a small amount of ascites can be detected easily.
    • Retrograde flow or obstruction in the portal vein detected by Doppler ultrasonography is a sign of poor prognosis.
  • MRI or CT
    • May provide more indications of liver cirrhosis: structure of the liver, signs of portal hypertension, possible focal lesions.
  • Elastography (e.g. Fibroscan® )
    • Non-invasive investigation that can be used to evaluate the level of fibrosis in the liver
    • Associated with some sources of error.

Liver biopsy

  • Confirmation of cirrhosis
    • Stage of fibrosis (regenerative nodules, fibrous septa) may provide indications of the aetiology.
    • In advanced cirrhosis, biopsy does not always provide additional information to the aetiological investigations.
      • To be considered whether the biopsy has any influence from the therapeutic viewpoint.
  • Sources of error
    • False negative result, because even rather healthy tissue may be found between the cirrhotic areas
    • False positive resuls: biopsy along the capsule, poor sampling, etc.
  • Liver biopsy can be performed if INR is < 1.5 and platelet count is > 60.

Treatment of cirrhosis and its complications

  • Abstinence improves prognosis in alcoholic cirrhosis, but the risk of hepatocellular carcinoma Cancer of the Liver and the Biliary Tract nevertheless remains elevated. A diet rich in energy and protein is needed, because cirrhosis is often associated with malnutrition. Due to catabolism, the patient may even be advised to eat before going to bed.
  • No antifibrotic medication is available, but the treament of the underlying liver disease may halt the progression of cirrhosis.
  • The development of liver failure in a patient with liver cirrhosis often results from some complication (bleeding, infection, hypovolaemia for other reasons, etc.), the detection and treatment of which is important, in addition to treating the specific symptoms of liver failure.
  • Grading of cirrhosis enables the assessment of the severity of the liver damage and its influence on the patient's prognosis. Child-Pugh classification http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality/ is the most commonly used. It takes into account liver function (INR, albumin), cholestasis (bilirubin) and symptoms (encephalopathy, ascites).

Portal hypertension

  • Gastroscopy should be performed on all patients with liver cirrhosis to detect possible oesophageal varices.
  • If the patient has had a variceal bleeding, a recurrence can be prevented
    • by ablating the varices by rubber band ligation
    • by lowering portal pressure with a non-selective beta blocker (propranolol 10-40 mg 2-3 times daily; the heart rate is titrated 25% lower).
    • in profuse acute bleeding by endoscopic procedures, by somatostatin or its analogue octreotide, by Sengstaken-Blakemore tube
    • sometimes by transjugular intrahepatic portosystemic shunt (TIPS) or shunt surgery if the forementioned methods fail .
  • If clear oesophageal varices are detected but the patient has not had variceal bleeding, the first bleeding can be prevented by using a beta blocker (propranolol ).

Ascites

  • Salt restriction (1-3 g of sodium daily; 1 g of sodium is equal to 2.5 g of table salt)
  • Spironolactone 50-400 (-600) mg daily
  • If necessary, spironolactone can be combined with a loop diuretic (e.g. furosemide 20-80 mg daily).
  • Usually no water restriction; sometimes recommended in severe hyponatraemia
  • Excessively rapid weight loss should be avoided (> 0.5 kg daily if there is no peripheral swelling).
  • Prostaglandin inhibitors (non-steroidal anti-inflammatory drugs) may impair renal function.
  • In therapy-resistant ascites even a large paracentesis (5-10 litres during 6-8 hours) is safe if 6-8 g of albumin is infused intravenously for every removed litre of ascites. The ascites puncture (video Removal of Ascites) may be performed with a needle for percutaneous cystostomy or also with Seldinger's technique.
  • Coagulation factors need not be corrected in association with the puncture, at least if thrombocyte count is > 50 × 109 /l. Diuretics are paused for 2 days after the puncture.
  • Complications include spontaneous peritonitis, hyponatraemia and hepatorenal syndrome (control sodium, potassium, diuresis, body weight).
    • Spontaneous peritonitis is often asymptomatic; the ascitic fluid sample is tested for the following: cell count, glucose, albumin, bacterial stain and culture, sometimes tuberculosis samples.
  • If the ascites does not respond to therapy consult a surgeon or a radiologist: shunt, TIPS .
  • Refractory ascites may be an indication for liver transplantation.

Hepatorenal syndrome Terlipressin for Hepatorenal Syndrome

  • In hepatorenal syndrome (HRS), renal failure develops in a patient with severe acute or chronic liver disease.
  • Exclusion of other renal diseases and assessment of predisposing factors
    • Stop medications with renal toxicity.
    • Adequate fluid therapy, correction of hypovolaemia and electrolyte disturbances
  • The condition is regarded as HRS when ascites formation refractory to treatment has led to the impairment of renal function so that no response is anymore obtained even if hypovolaemia were corrected with albumin infusion.
    • HRS 1: rapid development of renal failure, associated with acute hepatic failure (also in cirrhosis); the prognosis is poor, only some weeks, mortality rate 80-100%
    • HRS 2: renal failure develops in a slower pace in a patient with hepatic failure; without liver transplantation, 75% of the patients will die within one year.
  • Treatment
    • Correction of hypovolaemia, fluid therapy, intravenous albumin, drainage of ascites
    • Terlipressin and albumin intravenously
    • Sometimes renal replacement therapies

Hepatic encephalopathy Probiotics for Patients with Hepatic Encephalopathy

  • Generally no protein restriction
  • Lactulose should be given 15-30 ml 2-3 times daily aiming at 2-3 loose stools per day. It can also be used prophylactically. Lactitol can be used instead of lactulose.
  • Antimicrobials
  • Treatment of factors that worsen liver function (bleeding, infections)
  • Flumazenil relieves the symptoms of encephalopathy but has no effect on the patient's prognosis Flumazenil for Hepatic Encephalopathy.
  • Consider liver transplantation in end-stage cirrhosis.

Monitoring of patient with liver cirrhosis

  • Treatment according to aetiology
    • Cessation of alcohol use
  • Is there evidence of liver failure, complications of cirrhosis, liver cancer?
  • Follow-up investigations depending on the case
    • Laboratory tests
      • Basic blood count with platelet count, sodium, potassium, creatinine, liver enzyme values (ALT, ALP), liver function tests (INR, albumin) at intervals of 3-6 months
      • Alpha fetoprotein at ½-1-year intervals
    • Ultrasonography at ½-1-year intervals (screening for liver cancer, portal vein circulation, ascites, etc.)
    • Gastroscopy at intervals of 1-3 years
  • Follow-up often takes place in primary health care; specialized care is consulted as needed.
  • Liver transplantation should be considered, if there are signs of liver failure and no contraindications.