Other Liver Diseases

Other Liver Diseases

·        Toxic: drugs, alcohol

·        Fatty Liver: obesity, diabetes, drugs, alcohol

·        Drugs: e.g. flucloxacillin (and other antibiotics) can cause intrahepatic cholestasis

Haemochromatosis

·        Bronzed diabetes: triad of micronodular cirrhosis, diabetes mellitus, and skin pigmentation (iron stimulates ­melanin)

·        Affects liver, pancreas, heart, gonads. Also causes osteoarthritis and diabetes

·        Primary/idiopathic/genetic:

o   Common autosomal recessive, usually males 40 – 60 years. Most common genetic disorder. Homozygotes: 65 – 100% will have iron overload. Heterozygotes have elevated ferritin but no disease 

o   Die from hepatocellular carcinoma, cardiac disease, liver failure 

o   Iron accumulates in the cytoplasm of liver cells (lots of black dots), also in pancreas, endocrine glands, skin, myocardium, joint linings 

o   Macroscopic appearance: micronodular, brown, cirrhotic liver. Atrophy and fibrosis of pancreas. Enlarged heart. Brown/grey skin

o   Microscopic appearance: Initially golden brown periportal ferritin deposits in hepatocytes.  Later

o   Kupffer cells become loaded.  Non-inflammatory cirrhosis.  Pearl stain: stains iron blue

o   Monitoring:

§  If transferrin > 45% or serum ferritin > 300 ng/ml then liver biopsy if > 39 years

§  Hepatic Iron Index = hepatic iron concentration/age.  Normal < 1.9 mmol/gm/yr

§  If cirrhosis for > 10 years then screen for hepatocellular carcinoma every 6 or 12 months. If picked up clinically then too late 

§  Screen for a-feta Protein (tumour marker), or inject lipiodol into hepatic artery ® preferentially taken up by HCC ® hypodense on CT 

§  Treatment of HCC: resection or liver transplantation.  Chemo ineffective

o   Treatment of haemochromatosis: if regular venesection before organ damage then normal life expectancy. Regular initial venesection to ¯¯iron load, then venesection very 3 – 6 months

·        Secondary:

o  Ineffective erythropoiesis (eg thalassaemia, liver disease, high iron intake)

o  Iron first in Kupffer cells, later in hepatocytes

o  Cirrhosis unusual

Diseases of Intrahepatic Bile Ducts

·        Ascending Cholangitis

o  Suppurative inflammation within the bile ducts with bile stasis

o  Caused by obstruction, treated with drainage

o  Common organisms are enteric: E Coli, Klebsiella, Enterobacilli

·        Primary Sclerosing Cholangitis

o  Autoimmune destruction of intra and extra hepatic bile ducts

o  In young males, associated with ulcerative colitis and HLA types

o  Cirrhosis and liver failure within 5 years

o  Microscopic appearance: onion skin fibrosis around intrahepatic ducts

·        Primary Biliary Cirrhosis:

o  Autoimmune destruction of intrahepatic ducts

o  F:M = 9:1, average age = 50

o  Antimitochondrial antibodies typical 

o  Focal inflammatory destruction of bile ducts, no primary inflammation in stroma ® ducts reduced in number ® green bile plugs in canaliculi ® bile infarct and portal-portal fibrosis ® cholestasis and cirrhosis

·        Secondary biliary cirrhosis: scarring following obstruction and ascending cholangitis

·        Disappearing bile ducts: Autoimmune, Graft vs. Host, Post transplant – all due to lymphocytic destruction of biliary epithelium

Vascular Disease of the Liver

·        Post hepatic disease:

o  Right sided heart failure:

§  Enlarged, tense, tender liver 

§  Marked centrilobular congestion and haemorrhagic necrosis: „nutmeg liver‟ – lacy pattern with dark and light areas

o  Cardiac Sclerosis:

§  Less common complication of heart failure

§  A peri-venular fibrosing reaction following long-standing congestion

§  Rarely causes ­portal pressure

o  Hepatic Vein Thrombosis (Budd Chiari Syndrome)

§  Hepatic congestion from obstruction to blood flow due to occlusion of hepatic veins or IVC 

§  Associated with anything causing hypercoagulability: polycythaemia vera, pregnancy, oral contraceptives, hepatocellular carcinoma

§  Appearance: swollen, red liver, congestion, veins containing thrombi

·        Intrahepatic Disease: Hepatic veno-occlusive disease. Subendothelial sclerosis of veins. Lumen of central vein occluded + collagen deposition in Space of Disse

·        Pre-hepatic disease: Portal vein obstruction due to cancer, peritoneal sepsis, pancreatitis, surgery, cirrhosis

Gilbert’s Syndrome

·        Normal variant in ?7% of the population

·        Raised indirect bilirubin due to „defective‟ uptake and conjugation of bilirubin by liver 

·        Exacerbated by low fat/low calorie diet (e.g. when gastroenteritis). Use this to test: fast and see if it increases. Also worse when ill due to other causes (may present as a red hearing)

·        Bilirubin rarely > 100 micromol/L

·        Is totally benign

Neonatal Liver Disease

·        Extrahepatic Biliary Atresia: destructive inflammation of bile ducts ® cirrhosis

·        Neonatal Hepatitis: non-specific idiopathic response to neonatal hepatic insult (eg virus). Giant cell transformation of hepatocytes, chronic inflammation around portal tracts, focal necrosis and lobular disarray

Wilson’s Disease

·        Rare autosomal recessive: accumulation of dietary copper in liver, brain, eye

·        Leads to non-inflammatory cirrhosis

·        Can look like alcoholic liver disease due to mallory hyaline and bile plugging

Alpha-1 Antitrypsin Deficiency

·        Autosomal co-dominant. 

·        ® Ineffective protease inhibitor enzymes

·        Genetics:

o   Only liver disease if < 10% normal function (ie ZZ allele).

o   Z is bad, M is normal, S is mildly impaired.  Only 10% of ZZ get chronic liver disease.

o   7 – 10% of the population have a variant associated with mild/moderate deficiency

·        Abnormal alpha-1AT accumulates in cells as cytoplasmic globules ® cell death ® fibrosis

·        Clinical: neonatal hepatitis, can present as macronodular in adult.  Suspect in premature emphysema