Gastroenterology

Acute Liver Failure

Introduction

  • Rapid deterioration of hepatic function

Causes

  • Viral Hepatitis 40-70% : Hepatitis A, Hepatitis B, Hepatitis B + D , Hepatitis C - VERY RARE, Hepatitis E viruses.
  • Drug Induced/Poisoning 20% : Paracetamol ( much higher in UK), Halothane, Anti-TB therapy, Ecstasy, Herbal remedies - always check ALL drugs, Mushroom Amanita phyllodes, Carbon tetrachloride
  • Miscellaneous 10 %
  • Wilson's disease, Vascular, Budd-Chiari syndrome, Shock and Ischaemia
  • Acute fatty liver of pregnancy, HELLP syndrome - screen neonate for LCHAD
  • Infectious : Leptospirosis, Yellow fever, CMV, Severe Bacterial infections, Amoebic Infection
  • Reye's syndrome (aspirin induced)
  • Unknown 20-30% Viral ??

Clinical

  • Insufficient time to develop hepatosplenomegaly or ascites and portal hypertension [the exception is Budd-Chiari syndrome]
  • Encephalopathy - flapping tremor, poor concentration, reversal of day/night cycle
  • Jaundice
  • Bleeding and Coagulopathy - Measure prothrombin time or Factor V
  • Hypoglycaemia
  • Fetor hepaticus

Management

  • Patients are usually admitted to a HDU/ITU. This helps to deal with the issues which are
  • Coagulopathy - there are several problems, a lack of synthesis of clotting factors, defective fibrinogen and impaired platelet function. Vitamin K to reverse any deficiency. Haematology advice essential.
  • Hepatic encephalopathy - Avoid sedatives, diuretics, opiates and N-Saline. Lactulose + neomycin - 2-3 soft bowel movements/day.
  • Cerebral oedema - patients are positioned with 20 degree head up tilt mannitol and hyperventilate in some cases
  • Hypoglycaemia with frequent checking and 10% dextrose may be required
  • Monitor for Metabolic acidosis
  • Monitor and look for Infection
  • Renal/Multiorgan failure. Renal failure may require haemofiltration or hemodialysis.
  • N-acetylcysteine is now more commonly used even when Paracetamol is not involved in ALF.
  • Talk to local liver/transplant unit early
  • In Paracetamol poisoning liver transplantation may be considered for those with a pH < 7.3 at 24 hrs or a Prothrombin time > 100 seconds and encephalopathy. In reality you should have discussed the case with the local liver unit well before this stage is reached.
  • The Kings College criteria for Liver transplant In those with paracetamol induced liver failure
    • An Arterial pH < 7.3 at 24 hrs after ingestion
    • A prothrombin time > 100 seconds
    • A creatinine > 300 umoles/L
    • Grade III or IV hepatic encephalopathy For non Paracetamol induced liver failure
    • Prothrombin time > 100 seconds OR 3 of the following
    • Drug induced
    • Age < 10 or > 40
    • More than 1 week between jaundice and encephalopathy
    • Prothrombin time > 50 seconds
    • Bilirubin > 300 umoles/L
  • Hepatic Encephalopathy

    Introduction

    • Acute/Acute on chronic neuropsychiatric syndrome
    • A manifestation of advanced liver disease
    • May be precipitated or worsened by shunting e.g. TIPS

    Aetiology

    • Ammonia is the best characterised neurotoxin that precipitates HE
    • Loss of usual detoxification of gut derived psychoactive amines

    Clinical

    • Reversal of diurnal rhythm is an early sign
    • Disturbance in the diurnal sleep pattern (insomnia and hypersomnia) is common
    • Bradykinesia, asterixis (flapping motions of outstretched, dorsiflexed hands)
    • Hyperactive deep tendon reflexes, and, less commonly, transient decerebrate posturing.
    • Difficulty with some tests - drawing 5 pointed star
    • Inability to perform the number connection test and Constructional apraxia

    Investigations

    • Investigate cause of liver failure
    • Ammonia levels elevated
    • EEG - delta waves (rarely needed)
    • CT head to exclude other causes (occasionally needed)

    Criteria

    • Grade I : Subtle loss of awareness, reduced attention, impaired addition or subtraction
    • Grade II: Apathy, disorientated in time or place, behavioural change
    • Grade III: Somnolence by responds to stimulus. Confusion, Gross disorientation
    • Grade IV : Coma

    Management

    Look for and treat precipitants - many of which increase arterial ammonia levels

    • Gastrointestinal bleeding
    • Increased protein intake
    • Hypokalemic alkalosis - hypokalaemia increases renal ammonia production
    • Infection e.g. chest, urine, spontaneous bacterial peritonitis
    • Constipation
    • Hypoxia or hypoglycaemia
    • Use of sedatives and tranquillisers including benzodiazepines
    • Vascular occlusion (hepatic vein or portal vein thrombosis)
    • Alcohol intake

    In addition

    • Oral lactulose improves gut transit and alters colonic pH
    • Antibiotics given orally e.g. metronidazole to decrease gut organisms
    • Nutrition with initial protein restriction for 48 hours
    • Prognosis reflects underlying aetiology

    Chronic liver disease

    Introduction

    • Chronic liver disease is disease occurring over at least 6 months.

    Aetiology

    • There is a gradual loss of hepatic synthetic function and a slightly different clinical picture to acute liver failure.
    • Loss of liver function
      • prolonged prothrombin time (consider excluding Vitamin K deficiency)
      • Low albumin
      • Encephalopathy
    • There is jaundice and time to develop portal hypertension.
    • Removal of the cause (abstinence from alcohol) may lead to stabilisation of the disease hopefully leaving sufficient hepatic function for life.
    • Chronic liver disease often comes up in the exam as the examination and signs are fairly classical and need to be known well.

    Clinical

    • Leukonychia
    • Spider naevi (telangiectasia) > 3 in distribution of SVC
    • Palmar erythema
    • Finger Clubbing
    • Dupuytren's contracture
    • Loss of secondary sexual characteristics
    • Testicular atrophy
    • Ascites
    • Swollen parotid salivary glands
    • Fetor hepaticus
    • Splenomegaly
    • Caput Medusae
    • Palmar erythema
    • Paper money skin
    • Dupuytren's contracture
    • Tattoos (may hint to aetiology)
    • Anaemia (bleeding/chronic disease)
    • Jaundice
    • Gynaecomastia (alcohol)(spironolactone)
    • Parotid enlargement (alcohol)

    Chronic liver disease allows time to develop portal hypertension with oesophageal varices and a big spleen. There may be hepatomegaly typically with alcoholic (micronodular) cirrhosis and haemochromatosis. As disease progresses the liver does get smaller especially with viral hepatitis and autoimmune disease.

      Cirrhosis

      Introduction

      • Cirrhosis is defined as the presence of fibrous bands that divide the liver into regenerative nodules.
      • Cirrhosis represents a late stage of progressive hepatic fibrosis
      • Risk of developing Hepatocellular Carcinoma

      Pathology

      • It is a histological diagnosis and can be classified into micro and macronodular by the size of mm.
        • Macronodular > 3 mm
          • Chronic Viral Infection - HBV HCV
          • Wilson's disease
          • a-1 antitrypsin deficiency
        • Micronodular < 3 mm
          • Alcohol
          • Haemochromatosis
          • NASH
      • Alcohol and liver
        • Steatosis - is reversible with alcohol abstention
        • Alcoholic hepatitis - Mallory body
        • Alcoholic cirrhosis - hobnail appearance

      Causes

      • Chronic Hepatitis C infection (anti-HCV and HCV RNA)
      • Alcoholic liver disease (AST>ALT Elevated GGT)
      • Chronic Hepatitis B infection (HBsAg HBeAg/HBV-DNA)
      • Autoimmune liver disease (Raised Ig and Autoantibodies)
      • Primary Sclerosing cholangitis (pANCA MRCP/ERCP)
      • Primary Biliary cirrhosis (Anti Mitochondrial Ab)
      • Hereditary Haemochromatosis (Ferritin high Transferrin saturation high, Genetics)
      • Wilson's disease (Young, low Ceruloplasmin raised Urine copper, KF rings)
      • Budd-Chiari syndrome (USS caudate lobe)
      • Drugs - amiodarone, methotrexate, methyldopa
      • Cystic fibrosis (genetics + sweat Cl)
      • Alpha-1 antitrypsin (Young emphysema low serum AAT)
      • Idiopathic - unknown

      Drugs that should be avoided in Cirrhosis

      • These would include NSAIDs with their effects on kidneys and gastric mucosa.
      • ACE inhibitors may be involved in hepatorenal syndrome and are best stopped.
      • Codeine, Narcotics, Benzodiazepines and anxiolytics can all precipitate or worsen hepatic encephalopathy

      Complications

      • Portal hypertension
      • Liver failure
      • Portosystemic Encephalopathy - always look for flap and assess mental state
      • Variceal Bleeding formed from left gastric and short gastric veins to the oesophagus
      • Ascites
      • Spontaneous bacterial peritonitis
      • Hepatorenal syndrome
      • Osteoporosis
      • Hepatocellular carcinoma Investigations
      • U&E LFT's (low Na common)
      • Prothrombin time and Albumin reflect liver synthetic function
      • See above
      • Alpha fetoprotein suggests Hepatocellular carcinoma
      • Liver USS Prognosis in cirrhosis - see Child-Pugh score below Prognosis may be estimated through the Child-Pugh score
      Encephalopathy none mild marked
      Bilirubin* <34 34-50 > 50
      Albumin >35 28-35 < 28
      PTT or INR < 4s 4-6s >6s
      Ascites none mild marked
      In Primary Biliary Cirrhosis or Sclerosing cholangitis a higher range for bilirubin is used

        Ascites

        Introduction

        • Ascites is due to the collection of free fluid in the peritoneal space. Commonly associated with liver cirrhosis.

        Aetiology

        • Hypoalbuminaemia
        • Activation of Renin angiotensin aldosterone system causing Na/H2O retention
        • Portal hypertension

        Clinical

        • Abdomen is distended and there is central resonance due to bowel loops floating in the fluid and lateral dullness with fullness in flanks
        • If the patient rolls on onto their from the supine position the gas filled bowel loops again float on top of the fluid and the area that was dull and at the highest point becomes resonant.
        • Ascites may be seen with any intra-abdominal pathology

        Investigations

        • Protein levels : a useful test is to measure the difference in the protein level in Ascitic fluid compared with plasma.
        • Gram stain and culture for Bacteria and TB in selected cases
        • Cell count : Causes of a neutrophil count > 250 /ml is diagnostic of spontaneous bacterial peritonitis
        • Glucose : A low glucose is seen with TB/Malignancy and a high amylase with pancreatitis.
        • Cytology : Malignant cells
        • Amylase : suggests related to pancreatitis

        A gradient (Plasma albumin - Ascitic albumin) of > 11 g/l (TRANSUDATE)

        • Portal hypertension
        • Cirrhosis
        • Hepatocellular carcinoma
        • Budd-Chiari syndrome
        • RV failure
        • Constrictive pericarditis
        • Meig's syndrome (ovarian tumour, ascites, hydrothorax)

        A gradient (Plasma albumin - Ascitic albumin) of < 11 g/ (EXUDATE)

        • Malignancy
        • Hepatic vein thrombosis
        • Tuberculosis
        • Pancreatitis
        • Budd-Chiari syndrome* (can be either)
        • Hypothyroidism
        • Nephrotic syndrome

        Management

        • Tense ascites ? paracentesis 4-6 L. Removal of less than 5 litres of fluid does not appear to have haemodynamic or hormonal consequences. Post-paracentesis colloid infusion does not appear to be necessary. For larger paracentesis, albumin (8 g/L of fluid removed) can be administered, although this does not appear to be mandatory based upon the available data. The main concern is hypotension.
        • Sodium restriction to 2 g/day
        • Spironolactone 50-400 mg /day
        • Furosemide 20-160 mg /day
        • TIPS / Transplant
        • Patients with ascites and previous SBP should be on prophylactic antibiotics e.g. norfloxacin or ciprofloxacin

        Alcoholic steatohepatitis

        Introduction

        • Fever jaundice and tender hepatomegaly in a known drinker
        • There are many similarities with NASH

        Aetiology

        • There is liver inflammation
        • Alcohol is hepatotoxic but most alcoholics do not get cirrhosis
        • Raised TNF-alpha
        • The limited rise in ALT with alcoholic hepatitis is due to a deficiency of pyridoxal 5' phosphate seen in alcoholics.

        Clinical

        • Malaise anorexia weakness
        • Fever < 40 C + Jaundice + Sudden onset tender hepatomegaly
        • Known alcohol abuse and drinking heavily
        • Look for encephalopathy and ascites
        • RUQ pain
        • Signs of chronic disease Encephalopathy
        • Foetor hepaticus
        • Liver flap (asterixis)
        • Decreased level of consciousness
        • Unable to copy five pointed star

        Differential

        • Liver failure and hepatic encephalopathy
        • Cholecystitis
        • Acute Hepatitis A or B infection

        Investigations

        • FBC - Raised MCV, Low platelets
        • ALT is elevated but less than 300 iu/L and The AST/ALT ratio is usually >2-3
        • A much higher ALT - look for another cause
        • Elevated GGT is common
        • Raised IgG and IgA
        • Low Phosphate and Magnesium
        • Increased prothrombin time which does not respond to vitamin K
        • Increased ammonia
        • Reduced albumin
        • Check coexisting viral hepatitis HBV HCV
        • USS - fatty liver
        • Pathology
          • Hepatocellular ballooning which contain Mallory bodies, fibrosis.
          • Bridging hepatic fibrosis suggests progression to cirrhosis. Assessment
        • The discriminant function is useful and is also known as Maddrey's score
        • Maddrey's score = 4.6 x (Increase in Prothrombin time) + Bilirubin (mg/dl)
        • A value over 32 implies a poor prognosis and one should consider steroids

        Management

        • Steroids avoided if Sepsis, Bleeding, Pancreatitis and Renal failure
        • Patients may develop a hepatic encephalopathy and a coagulopathy over the first 1-3 weeks in hospital. Management
        • Stop alcohol
        • Thiamine, multivitamins (Pabrinex) + nutrition
        • Fluid balance - avoid dehydration and maintain diuresis
        • Monitor and replace K/Mg/Phosphate/Glucose
        • Encephalopathy - phosphate enemas, lactulose
        • Ascites - spironolactone
        • Prednisolone 40 mg od for 4 weeks reduces mortality (see above)
        • Pentoxifylline 400 mg tds for 4 weeks po reduces mortality

        Hereditary Haemochromatosis (HH)

        Introduction

        • Autosomal recessive inherited disease
        • Most commonly due to mutation on the gene for the HFE protein on Chromosome 6
        • Patients are homozygous for the C282Y mutation or C282Y/H63D compound heterozygote mutation.
        • Homozygous frequency of 1:200 and a heterozygous frequency of 1:8 in Northern Europeans

        Aetiology

        • HFE codes for a MHC class I like molecule which interacts with Beta2 microglobulin
        • This leads to increased iron uptake by the divalent metal iron transporter
        • Liver iron uptake increases leading to cell injury and necrosis.
        • There is increased fibrosis and cirrhosis develops.
        • Less than 10% of those homozygous for the gene mutation go on to develop liver disease
        • Leading to excess deposition of iron - Body iron rises from 4g to 40 g and induces Liver fibrosis.
        • Mutations in the HFE gene cause increased intestinal iron absorption.
        • Female protection by menstruation

        Clinical

        • Fatigue , malaise, apathy, weight loss
        • Abdominal pain - hepatomegaly
        • Secondary diabetes (pancreas deposition)
        • Hypogonadism is seen due to pituitary disease
        • Heart failure and arrhythmias - dilated cardiomyopathy
        • Increased melanin deposition in skin giving greyish or bronzed look
        • Arthritis - chondrocalcinosis
        • Testicular atrophy

        Investigations

        • High Ferritin levels > 500 ug/L
        • Fasting Serum transferrin saturation (serum iron/(TIBC or Transferrin) x 100%) > 50% and often > 90%
        • LFT's may be normal or elevated
        • Total iron binding capacity - Reduced
        • Serum Iron - elevated
        • Gentotyping by PCR for HFE mutations
        • Liver biopsy is less needed with genetic testing - periportal iron deposition
        • Testosterone low as FSH and LH low
        • MRI - T2 Gradient return echo (GRE) shows Iron overload in liver and pancreas
        • Check Negative HCV or HBV if risks

        Management

        • Venesection is the main therapy twice weekly for first 2 years limited only by anaemia
        • This is followed by life long monthly or quarterly venesection
        • Continue until transferrin saturation < 50% and ferritin level < 50 ng/ml
        • Screen all first degree relatives with Iron and transferrin saturation
        • Screening of family members should be with HFE gene if the index case is C282Y/C282Y or H63D/C282Y.

        Complications

        • Cirrhosis
        • Hepatocellular carcinoma

        Autoimmune Hepatitis

        Introduction

        • Liver inflammation with autoantibodies
        • Type 1 and Type 2

        Clinical

        • Most commonly found in young and middle aged women
        • Signs of fatigue and mild to moderate jaundice and chronic liver disease.
        • Hepatosplenomegaly.
        • Some have Hashimoto's, RTA, RA.

        Investigations

        • Anaemia low WCC, low platelets, Elevated ESR
        • Elevated AST & ALT. Mild elevated ALP and Bilirubin
        • Antibodies as below. Raised IgG.
        • Prolonged Prothrombin time
        • Biopsy - interface hepatitis, There is periportal piecemeal and bridging necrosis on liver biopsy

        Classification

        • Type 1
          • older females with +ve anti smooth muscle (Anti-Actin Antibodies AAA)
          • +ve antinuclear antibody and anti-dsDNA and even +ve ANCA
          • +ve anti smooth muscle (Anti-Actin Antibodies AAA)
          • +ve Soluble liver antigen antibodies (SLP)
          • Strong association with other autoimmune diseases.
        • Type 2
          • +ve Anti Liver Kidney Microsomal (Anti-LKM1)
          • Main target is Cytochrome P4502D6 on liver plasma membranes

        Management

        • Prednisolone 30 mg for 2 weeks then slow reducing dose
        • Azathioprine improves prognosis (Test for Thiopurine methyltransferase activity first)
        • Ursodeoxycholic acid
        • Liver transplantation in end stage liver disease

        Primary Biliary Cirrhosis

        Introduction

        • Progressive autoimmune destruction of the small and medium sized bile ducts
        • There is cholestasis and eventual cirrhosis
        • Positive Anti-mitochondrial antibody in 95%

        Background

        • PBC is a chronic progressive granulomatous inflammation of the liver
        • Eventually leading to cholestasis, fibrosis and eventually cirrhosis.
        • It is much more common in females and typically presents in middle aged females.
        • There is an association with other autoimmune disease e.g. hypothyroidism.

        Clinical

        • Middle aged females classically
        • Subclinical for years until it presents with signs of liver disease
        • May be picked up incidentally on a blood test with a raised ALP
        • Most commonly presents with lethargy and itch.
        • Progressions with skin pigmentation, xanthoma, xanthelasma
        • Jaundice is late and then hepatomegaly and splenomegaly can occur.
        • There is malabsorption of ADEK fat soluble vitamins

        Investigations

        • Raised Alkaline phosphatase (>1000) and GGT
        • Raised Bilirubin and jaundice are elevated late
        • Prolonged PTT - fat and Vitamin K malabsorption and a low albumin
        • Non specific Raised IgM
        • AST and ALT mildly elevated
        • Hyperlipidaemia - not associated with increased risk of IHD **
        • 98% have a Positive Anti-mitochondrial antibody (AMA) (E2 fragment of Pyruvate dehydrogenase complex found on the inner mitochondrial membrane)
        • USS shows no extrahepatic obstruction (Gallstones are common in this age and the population in general but in this case are likely irrelevant)
        • Histology of liver biopsy : Not needed for diagnosis but useful to exclude other causes. Granulomas are found around the proliferating bile ductules with liver fibrosis and cirrhosis but poor prognostic value

        Management

        • Patients are treated with ursodeoxycholic acid which helps itch and possibly prognosis
        • No role for immunosuppression (steroids, colchicine, azathioprine and methotrexate all failed)
        • Patients are given vitamin replacement and nutrition is optimised.
        • The onset of jaundice is a poor prognostic sign suggesting a prognosis of less than 2 years.
        • Liver transplantation is an option and excellent results are seen.
        • The complications are, portal hypertension and varices and eventual liver failure and hepatic encephalopathy Poorer prognosis
        • Raised bilirubin
        • Low albumin
        • Prolonged prothrombin time
        • Oedema

        Budd-Chiari syndrome

        Introduction

        • A cause of acute liver failure which should always be considered
        • Look for a prothrombotic cause and get an USS

        Aetiology

        • Thrombosis of one or more hepatic veins
        • There is centrilobular congestion and necrosis (zone 3) of the liver lobule
        • Extravasation of RBC's into the space of Disse and liver cell plate.
        • Acute liver failure ensues

        Clinical

        • Abdominal pain, ascites and hepatomegaly.
        • The ascites is an exudate initially and the protein falls to be a transudate
        • The syndrome may come on acutely, sub acutely or chronically
        • Chronic disease may result in cirrhosis.
        • The caudate lobe may hypertrophy as it has a separate venous drainage into the IVC

        Causes

        • Myeloproliferative disorders - polycythaemia vera, essential thrombocythemia
        • Cancer - renal cell cancer, hepatocellular carcinoma
        • Prothrombotic states - Factor V Leiden mutation, pregnancy, oral contraceptive, Protein C and S deficiency, Paroxysmal nocturnal haemoglobinuria

        Investigations

        • FBC and Blood film
        • Liver enzymes
        • Prothrombin time
        • Renal function
        • Tap Ascites (exudate ? transudate)
        • Investigate hepatic vein thrombosis with a routine technetium Tc 99m colloid scan of the liver and spleen. This often reveals diminished function in all portions of the liver except the caudate lobe, which is spared because it is drained by the inferior vena cava rather than the hepatic vein.
        • MRI or ultrasound can demonstrate the cessation of flow through the hepatic vein or by venography and injecting or using a dye to demonstrate thrombus in the vein.
        • Thrombophilia screen

        Management

        • Manage as for liver failure
        • Treat any underlying disorder and considered catheter delivered thrombolysis in selected cases
        • Dilatation and stenting of the hepatic vein and portosystemic shunts e.g. porto caval
        • Liver transplantation - in those with Protein C and S deficiency the thrombophilia is also treated to as these are produced by the donor liver (assuming the donor does not have Protein C and S deficiency !)

        Acute fatty liver of Pregnancy

        Introduction

        • Potential fatal liver failure in pregnancy
        • late 2nd and during 3rd trimester commonest between 31 and 38 weeks
        • Acute fatty liver of pregnancy is commonest in twin and first pregnancies.
        • Role for long-chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHAD)

        Clinical

        • There is vomiting jaundice and abdominal pain.
        • Liver failure may rapidly occur with jaundice
        • There is coagulopathy and encephalopathy and hypoglycaemia.
        • There is a defect in the mitochondrial Beta oxidation of fats.
        • The differential is preeclampsia and HELLP syndrome.

        Investigations

        • AST and ALT ranging from modest values up to 1000 IU/L
        • Hypoglycaemia and high uric acid
        • Coagulopathy
        • Liver biopsy is diagnostic, showing the characteristic picture which is the micro vesicular fatty infiltration of the hepatocytes

        Management

        • Treatment is with early recognition and delivery of the fetus.
        • The mother and neonate should be screened for LCHAD HELLP syndrome is the differential and is a form of pre-eclampsia with
        • HELLP syndrome : Haemolysis - ELevated Liver enzymes - Low Platelets.

        Portal Hypertension

        Introduction

        • Normal Portal Pressure is about 2-5 mmHg and in Portal Hypertension this rises to 12 mmHg and above. Anatomy
        • The causes of can be separated anatomically. If one remembers the portal system is made up by the venous drainage from the GI tract. If you remember your anatomy you will recall that the inferior mesenteric vein joins the splenic vein. The splenic vein then joins with the superior mesenteric vein to from the portal vein. The portal vein enters the liver and feeds into the liver sinusoids. From this the venous blood supply then passes to the IVC through the hepatic vein. The usual gradient across the liver venous outflow from portal vein to hepatic vein is usually 3 mmHg. This is the wedged hepatic venous pressure. Portal hypertension leading to bleeding occurs when the pressure is > 12 mmHg

        Causes

        • Pre sinusoidal Extrahepatic usually due to Portal vein thrombosis, Sepsis, Surgery, Procoagulopathy, Abdominal trauma/surgery, Malignancy, Pancreatitis , Congenital
        • Intrahepatic pre sinusoidal : Schistosomiasis, Sarcoidosis, Congenital hepatic fibrosis, Vinyl chloride, Drugs
        • Sinusoidal : Cirrhosis, Malignancy, Cystic disease
        • Intrahepatic post sinusoidal : Veno-occlusive disease
        • Extrahepatic post sinusoidal : Budd-Chiari syndrome Aetiology
        As with any system of flow the Portal pressure is proportional to flow x resistance. The causes are shown below
        • The main component in Portal hypertension is increased resistance.
        • There is compensatory portosystemic circulation set up so that most of the portal blood supply goes directly into the systemic circulation.
        • Across the world the main cause is schistosomiasis which causes Portal hypertension but without liver failure

        Clinical

        • Splenomegaly is the classic finding of portal hypertension and would be very unusual not to be present. Splenomegaly can be diagnosed clinically and confirmed by USS.
        • Cruveilhier-Baumgarten disease where there is a patent umbilical vein that acts as a portosystemic shunt in a patient with underlying cirrhosis causing a venous hum over the liver or at the xiphisternum.
        • The venous hum is known as the Cruveilhier-Baumgarten sign. Interestingly allegedly ascites does not occur in the classical syndrome. In Portal Hypertension varices occur in the lower oesophagus and also at the anus and may be mistaken for haemorrhoids.

        Investigations

        • Hypersplenism with reduced platelet counts of about 50-100 x10^9/L.
        • There may also be some mild leucopenia.

        Primary sclerosing cholangitis

        Introduction

        • Progressive fibrosis and inflammation and destruction of the intrahepatic and extrahepatic bile ducts
        • Cholangiocarcinoma develops in 10 to 15% of patients.
        • Ulcerative colitis seen in 75%
        • Median survival is 12 years

        Aetiology

        • There is an association with inflammatory bowel disease in over 50% of cases
        • Can be classified as primary and secondary due to another disease

        Clinical

        • Progressive jaundice possibly in a patient with IBD
        • Malaise, Itch , weight loss
        • Episodes of cholangitis - fever, jaundice, RUQ pain

        Investigations

        • Isolated raised Alkaline phosphatase at first
        • Mildly elevated AST and ALT
        • Raised Bilirubin (normal initially) and cholestatis
        • +ve ANA and anti smooth muscle
        • +Ve Anti Mitochondrial suggests PBC
        • Positive pANCA is common but non specific
        • Raised gamma globulins
        • USS - exclude gallstones and other causes of cholestasis
        • MRCP is the imaging of choice and shows strictures with intervening normal areas. "Beaded appearance"
        • Histology - classical onion skin of bile ductules

        Staging

        • Stage I : Inflammation in portal tracts
        • Stage II : Hepatitis and portal fibrosis
        • Stage III: Bridging fibrosis
        • Stage IV: Biliary cirrhosis and nodules

        Management

        • No treatment slows progression
        • Stenting for strictures and balloon dilatation
        • Immunosuppressives ineffective
        • Treat with cholestyramine for itch.
        • Ursodeoxycholic acid improves Bilirubin, ALP and Albumin but not survivial
        • Liver transplant with Choledochojejunostomy
        • Transplanted patients need annual colonoscopy for colonic cancer