Cirrhosis_L1707-1.pdf

Liver cirrhosis Dr haider abd alridha baqer  General characteristics Cirrhosis is a chronic liver disease characterized by fibrosis, disruption of the liver architecture, and widespread nodules in the liver. The fibrous tissue replaces damaged or dead hepatocyte. Cirrhosis is generally...

Liver cirrhosis Dr haider abd alridha baqer  General characteristics Cirrhosis is a chronic liver disease characterized by fibrosis, disruption of the liver architecture, and widespread nodules in the liver. The fibrous tissue replaces damaged or dead hepatocyte. Cirrhosis is generally irreversible when advanced. In early stages, specific treatment of the cause of cirrhosis may improve or reverse the condition. The point at which the disease becomes irreversible is not clear. General characteristics The distortion of liver anatomy causes two major events; Decreased blood flow through the liver with subsequent hypertension in portal circulation (portal hypertension)—this has widespread manifestations, including ascites, peripheral edema, splenomegaly, and varicosity of veins “back stream” in the circulation (e.g., gastric/esophageal varices, hemorrhoids). Hepatocellular failure that leads to impairment of biochemical functions, such as decreased albumin synthesis and decreased clotting factor synthesis.  General characteristics It can occur at any age, has significant morbidity and is an important cause of premature death. Worldwide, the most common causes are chronic viral hepatitis, prolonged excessive alcohol consumption and NAFLD, but any condition leading to persistent or recurrent hepatocyte injury may lead to cirrhosis. Liver biopsy is the gold standard for diagnosis of cirrhosis.  What are the causes of cirrhosis? 1. Alcoholic liver disease—most common cause; Fifteen percent to 20% of heavy drinkers develop alcoholic cirrhosis 2. Chronic hepatitis B and C infections—next most common causes 3. Non-alcoholic fatty liver disease 4. Immune: Primary sclerosing cholangitis Autoimmune liver disease  What are the causes of cirrhosis? 5. Biliary: Primary biliary cholangitis Secondary biliary cirrhosis Cystic fibrosis 6. Genetic: Haemochromatosis Wilson’s disease Alpha-1-antitrypsin deficiency  What are the causes of cirrhosis? 7. Cryptogenic (unknown – 15%) 8. Chronic venous outflow obstruction 9. Cardiac hepatopathy with chronic hepatic congestion 10. Drugs (e.g., methotrexate) Clinical features (symptoms) The clinical presentation is highly variable. Some patients are asymptomatic, and the diagnosis is made incidentally at ultrasound or at surgery. When symptoms are present, they are often non-specific and include weakness, fatigue, muscle cramps, weight loss, anorexia, nausea and upper abdominal discomfort. Cirrhosis will occasionally present because of shortness of breath due to a large right pleural effusion, or with hepatopulmonary syndrome. Clinical features (signs) 1) Signs of cirrhosis; Spider naevi Palmar erythema Leuconychia Bruising (low platelets) Loss of body hair (increased oestrogens) Gynaecomastia (increased oestrogens) Clinical features (signs) 2) Signs of portal Splenomegaly hypertension; Dilated abdominal wall veins Jaundice 3) Signs of Ascites/peripheral oedema decompensation; Flapping tremor (encephalopathy) Clinical features (signs) 4) Signs Dupuytren’s contracture (alcohol) related to specific Parotid swelling (alcohol) aetiologies; Intoxication/withdrawal (alcohol) Xanthelasma (PBC, NAFLD) Scratch marks (cholestatic liver disease) Clubbing (hepatopulmonary syndrome) Signs of liver cirrhosis Important Notes Hepatomegaly is common when the cirrhosis is due to alcoholic liver disease or haemochromatosis. One or two small spider telangiectasias may be present in up to 15% of young healthy adults and may occur transiently in greater numbers in the third trimester of pregnancy, but otherwise multiple spider telangiectasias are a strong indicator of liver disease. Florid spider telangiectasia and gynaecomastia are most common in alcohol- related cirrhosis, possibly related to phyto-oestrogens in alcoholic drinks. Pigmentation is most striking in haemochromatosis and in any cirrhosis associated with prolonged cholestasis. Important Notes Clubbing of the fingers and toes is not a sign of cirrhosis but is seen in combination with hypoxia in hepatopulmonary syndrome. Endocrine changes are noticed more readily in men, who show loss of male hair distribution and testicular atrophy. Gynaecomastia is common and can be due to drugs such as spironolactone. Jaundice, ascites, encephalopathy and variceal bleeding signify advanced disease, and are associated with a worse prognosis. The term ‘hepatic decompensation’ or ‘decompensated liver disease’ is often used when any of these are present. Anaemia is common and often multifactorial, due to a combination of chronic inflammation, bone marrow suppression, haemolysis or chronic blood loss  Once the diagnosis of cirrhosis is made, endoscopy should be considered to screen for oesophageal varices. As cirrhosis is associated with an Screening for increased risk of hepatocellular carcinoma, patients should be placed complications under regular surveillance for it. Cirrhosis is associated with an increased risk of osteoporosis and associated fractures, and bone mineral density measurement is recommended. Prognosis Cirrhosis can be categorized into two prognostic groups: compensated and decompensated. Decompensated cirrhosis is defined by the presence of complications, including ascites, variceal bleeding, jaundice and encephalopathy, which are the main determinants of patient survival. Compensated patients have a relatively good prognosis with median survival >12 years. However, in decompensated cirrhosis median survival is around 2 years, albeit with significant patient-to-patient variability. Prognosis Complications 1-Hepatic encephalopathy Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver disease that occurs in 30%–40% of patients with cirrhosis. It causes a spectrum of symptoms ranging from mild fluctuating cognitive impairment to coma. The degree of encephalopathy can be graded from 1 to 4, and this is useful in assessing progression or response to therapy. What are the grades of hepatic encephalopathy? Pathophysiology Hepatic encephalopathy is thought to be due to a disturbance of brain function provoked by circulating gut-derived neurotoxins that are normally metabolised by the liver and excluded from the systemic circulation. The ‘neurotoxins’ causing encephalopathy are unknown but are thought to be mainly nitrogenous substances produced in the gut, at least in part by bacterial action. Ammonia has traditionally been considered an important factor, but the correlation between serum ammonia levels and encephalopathy is poor. Clinical features The earliest features are very mild and easily overlooked, but as the condition becomes more severe, inability to concentrate, delirium, disorientation, drowsiness, slurring of speech and eventually coma develop. Seizures are rare. Fetor hepaticus, a sweet musty odour to the breath, is usually present but is more a sign of liver failure and portosystemic shunting than of hepatic encephalopathy. Hepatic encephalopathy rarely causes focal neurological signs; if these are present, other causes must be sought. Clinical features Examination usually shows; 1) Aa flapping tremor (asterixis) 2) inability to perform simple mental arithmetic tasks or to draw objects such as a star (constructional apraxia).  Factors precipitating hepatic encephalopathy Drugs (especially sedatives, antidepressants) Dehydration (including diuretics, paracentesis) Portosystemic shunting Infection Hypokalaemia Hyponatraemia Constipation ↑Protein load (including gastrointestinal bleeding)  Differential diagnosis of hepatic encephalopathy Intracranial bleed (subdural/extradural haematoma) Drug or alcohol intoxication Delirium tremens/alcohol withdrawal Wernicke’s encephalopathy Primary psychiatric disorders Hypoglycaemia Neurological Wilson’s disease Post-ictal state Investigations The diagnosis can usually be made clinically. When doubt exists, an electroencephalogram shows diffuse slowing of the normal alpha waves with eventual development of delta waves. The arterial ammonia is usually increased in patients with hepatic encephalopathy. Increased concentrations can, however, occur in the absence of clinical encephalopathy, rendering this investigation of little diagnostic value. Management The principles are to treat or remove precipitating causes and to suppress the production of neurotoxins by bacteria in the bowel.  Lactulose (15–30 mL 3 times daily) is increased gradually until the bowels are moving twice daily. It produces an osmotic laxative effect, reduces the pH of the colonic content, thereby limiting colonic ammonia absorption, and promotes the incorporation of nitrogen into bacteria. Phosphate enemas may be required in patients where the oral route is compromised or in patients with refractory constipation. Management Rifaximin (550 mg twice daily) is a well-tolerated, non-absorbed antibiotic that acts by reducing the bacterial content of the bowel and is effective in reducing episodes of recurrent hepatic encephalopathy. Dietary protein restriction is no longer recommended because it can lead to a worsening nutritional state in already malnourished patients. Chronic or refractory encephalopathy is one of the main indications for liver transplantation.