Definition: end-stage of chronic irreversible liver damage with impairment of function. Histologically, there is a loss of normal hepatic architecture with bridging fibrosis & nodular regeneration. Decompensation occurs when there are complications such as ascites, jaundice, encephalopathy or GI bleeding.
-Develops in response to chronic liver injury from any cause.
-Most often, chronic alcohol abuse (1st UK), HBV or HCV infection (1st worldwide).
-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. 80% of alcoholic hepatitis progresses to cirrhosis (final stage).
- Genetic disorders– Haemochromatosis, α1-antitrypsin deficiency, Wilson’s disease, galactosaemia, cystic fibrosis
- Hepatic vein events- Budd-Chiari (hepatic vein occlusion, hepatic venous congestion)
- Autoimmune– Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, autoimmune hepatitis
- Drugs– amiodarone, methyldopa, methotrexate
- Cryptogenic (5-10%)
-Decompensation may be precipitated by: dehydration, constipation, covert alcohol use, infection (SBP), opiate over-use, occult GI bleed, high protein meal, electrolyte imbalances, tumour development, portal vein thrombosis
-among the top 10 leading causes of deaths worldwide
-Lifetime prevalence of alcoholism is ~10% (~4% in women)
-10-35% of heavy drinkers develop alcoholic hepatitis
-80% of those with alcoholic hepatitis progress to cirrhosis
May have no signs or symptoms (apart from ↑LFTs), or may present with decompensated end stage liver disease, often presenting with one of the complications of cirrhosis.
-Early non-specific symptoms: anorexia, nausea, fatigue, weakness, weight loss
-Easy bruising, abdominal swelling, ankle oedema = decreased synthetic function
-Jaundice, personality change, altered sleep pattern, amenorrhoea = reduced detoxification (inc bilirubin, ammonia and oestrogen)
-Abdominal swelling, haematemesis, PR bleeding or melaena = portal hypertension
-Usually have signs of chronic liver disease, with clinical features secondary to portal hypertension and liver cell failure).
-Leukonychia (due to low albumin)
-Terry’s nails = white proximally but distal 1/3 reddened by telangiectasia
-Palmar erythema (reddened palms)
-Gynaecomastia (enlarged male breasts)
-Xanthelasma (fatty deposits around eyes)
-Loss of body hair
-Parotid enlargement (enlargement of the parotid salivary gland)
-Asterixis (a.k.a hepatic flap- large flapping tremor of hands when wrists are extended = sign of hepatic encephalopathy = decompensated liver disease)
-Scratch marks (from pruritus)
-Ascites (fluid in peritoneal cavity = fluid thrill, shifting dullness)
-Caput medusa (due to portal hypertension)
-Splenomegaly (due to portal hypertension)
-Hepatomegaly, or small liver in later disease
Signs of decompensation = jaundice, encephalopathy, ascites or variceal haemorrhage
–LFTs: normal or raised bilirubin, raised AST and ALT, raised alk phosph and GGT.
later with loss of synthetic function- decreased albumin
–Coagulation: +/- raised PT/INR (along with Albumin = best indicators of liver function)
–FBC: decreased WCC and platelets- indicates hypersplenism, anaemia develops later
–U&E: low Na indicates severe liver disease 2ry to impaired free water clearance or excess diuretic therapy. ↑Cr = worse prognosis
–AFP: increased in chronic liver disease, but high levels may suggest HCC (alpha-fetoprotein)
-U/S + duplex: may show small liver of hepatomegaly, splenomegaly, focal liver lesions (e.g HCC), hepatic vein thrombus (if Budd Chiari), reversed flow in the portal vein or ascites. Exclude biliary obstruction. – Also CT or MRI
–MRI: increased caudate lobe size, smaller islands of regenerating nodules, and the presence of the right posterior hepatic notch are more frequent in alcoholic cirrhosis than in virus induced. MRI scoring systems of severity available. MRCP if PSC suspected.
–Ascitic tap: send fluid for MC+S. Neutrophils > 250/mm3 indicates SBP (spontaneous bacterial peritonitis). Biochemistry- protein, albumin, glucose, amylase. Cytology.
–Liver biopsy: confirms diagnosis- loss of normal hepatic architecture with bridging fibrosis & nodular regeneration. Periportal fibrosis.
To investigate cause:
-ferritin, iron/ total iron-binding capacity (haemochromatosis)
-hepatitis serology (HBsAg, HBsAb, HCV Ab)
-Immunoglobulins & Auto-Antibodies- ANA, ANCA (PSC), AMA (PBC), SMA (autoimmune hepatitis)
-α-fetoprotein- (may rise in chronic liver disease, > 200ng/mL suggestive of HCC = tumour marker)
-caeruloplasmin (low in Wilson’s disease)
-may do endoscopy to seek esophageal varices
-Cirrhosis is irreversible and frequently progresses. Management is of complications as they arise. Correcting underlying cause may arrest progression
-Alcohol abstinence (may require Chlordiazepoxide for withdrawal symptoms)
-Avoid NSAIDs, sedatives & opiates (because they affect liver)
–Cholestyramine helps pruritus (bile acid sequestrant)
-Consider U/S +/- α-fetoprotein every 3-6M to screen for HCC
-Offer influenza immunisation
-Specific treatment for viral hepatitis induced cirrhosis (anti-virals)
-High dose ursodeoxycholic acid in PBC may normalise LFTs but may have no effect on disease progression
–Penicillamine for Wilson’s disease (copper chelating agent)
-fluid restriction (<1.5L/d)
-low salt diet, avoid alcohol and NSAIDs
-chart daily weight, aim for loss of < 0.5 kg/d
-add furosemide if response poor (loop diuretic)
-monitor U&Es, keeping an eye on Na
-may try therapeutic paracentesis with concomitant albumin infusion (6-8g/L removed)
Spontaneous Bacterial Peritonitis:
-Must consider in any patient with ascites that deteriorates suddenly (may be asymptomatic)
-Common organisms: E.coli, Klebsiella, Streps
-ABx: e.g. cefotaxime or tazocin for 5d or until sensitivities known + metronidazole if recent instrumentation to ascites
-Give prophylactic ABx for high risk patients (low albumin, low ascetic albumin, high PT/INR) or those who have had a previous episode, until death/ transplant/resolution of ascites (e.g. norfloxacin)
-exclude GI bleed
–lactulose, phosphate enemas
⇒Liver transplant is the only definitive treatment. Increases 5yr survival from ~20% in end-stage disease to ~70%.
–Portal hypertension: ascites, splenomegaly, porto-systemic shunt including oesophageal varices (+/- life threatening upper GI bleed), caput medusa
–Hepatic failure: coagulopathy, encephalopathy (asterixis + confusion/ coma), hypoalbuminaemia (oedema, leuconychia), sepsis (pneumonia, septicaemia), spontaneous bacterial peritonitis, hypoglycaemia
-Spontaneous bacterial peritonitis
–Renal failure (AKI/hepato-renal syndrome)- in cirrhosis, decreased hepatic clearance of immune complexes leads to their trapping in the kidney = IgA nephropathy +/- hepatic glomerulosclerosis.
–Hepato-pulmonary syndrome– pulmonary hypertension
-Increased risk of hepatocellular carcinoma
-Bacteremia, infection, malnutrition, osteoporosis
-In alcoholic liver disease, 5yr survival is 48% if drinking continues (if not, 77%)
-So, overall 5yr survival is ~50% (2yr 50% if ascites)
-Poor prognostic indicators: encephalopathy, Na < 110/mmol/L, serum albumin < 25g/L, ↑INR