Autoimmune Hepatic Disorders

 

• Autoimmune hepatitis (AIH)

  Pathophysiology

  • Autoimmune hepatocyte damage.
  • A minority of cases are triggered by drugs e.g. minocycline.
  • Can overlap with PSC.

  Clinical features

  • 25% present acutely, with signs of acute liver injury and systemic autoimmune symptoms such as fever, polyarthritis, malaise, and urticaria.
  • Otherwise, presents in usual way for chronic liver disease, including as an incidental finding.
  • History of previous episodes.
  • Past or family history of autoimmune disease.
  • Amenorrhea

  Investigations

  • Bloods: ↑anti-nuclear Ab (ANA), ↑anti-smooth muscle Ab (ASMA), ↑IgG (indicator of disease activity too).
  • Biopsy is always needed.

  Management

  • Prednisolone ± azathioprine. 2nd-line is MMF.
  • Continue treatment until LFTs normalize then maintain on ↓dose.

  Prognosis

  Aggressive disease, but with treatment 10 year survival is 95%.

• Primary biliary cholangitis (PBC)

  Formerly known as primary biliary cirrhosis.

  Pathophysiology

  • Small intra-hepatic bile duct destruction.
  • Resulting cholestasis causes hepatocyte damage, fibrosis, and, eventually, cirrhosis.

  Epidemiology and risk factors

  Commonest autoimmune liver disease in UK: 1/3000 prevalence.

  Risk factors:

  • 10 x commoner in women.
  • Mean onset is around age 50.
  • Past or family history of autoimmune disease

  Signs and symptoms

  BILE EXCESS:

  • Bone disease (30%): osteoporosis. Possibly due to fat malabsorption leading to impaired uptake of fat soluble vitamins including vitamin D.
  • Itch (50%).
  • Lethargy (80%).
  • Eyes yellow: jaundice. Late sign.
  • Eyes dry: Sicca.
  • Xanthelasma due to...
  • ↑Cholesterol, due to ↑synthesis and ↓biliary clearance.
  • Enlarged liver: hepatomegaly (25%) ± splenomegaly. RUQ discomfort in 10%.
  • Skin pigmentation, due to ↑melanin deposition.
  • Steatorrhea due to fat malabsorption.

  25% are incidentally found, usually due to altered LFTs.

  Investigations

  • Bloods: ↑anti-mitochondrial Ab (AMA), ↑IgM, ↑total cholesterol (but no ↑CVD risk due to ↑HDL).
  • Cholestatic LFTs, especially ↑alk phos. BR rises later.
  • Abdo US to exclude focal lesion obstructing duct.
  • Liver biopsy not usually needed as AMA is highly sensitive and specific.

  Management

  Lifestyle and preventative:

  • Reduce alcohol intake, especially in cirrhosis
  • Fat-soluble vitamins (ADEK) if deficient.
  • Monitor LFTs, PT, albumin.
  • Osteoporosis: screen (DEXA) and treat (bisphosphonates, Ca2+, vit D).

  Medical:

  • Ursodeoxycholic acid (UDCA), a non-toxic bile acid which protects against toxic hydrophobic bile acids. Add bezafibrate if persistent ↑ALP/AST/BR.
  • Cholestyramine (bile acid sequestrant) for itch.
  • Consider prednisolone if there is an inflammatory component.

  Surgical:

  • Transplantation

  Complications and prognosis

  • Prognosis is highly variable and with treatment many never become cirrhotic.
  • 50% 10 year survival.
  • Poor prognostic signs: poor response to UDCA, jaundice.

• Primary sclerosing cholangitis (PSC)

  Pathophysiology and epidemiology

  • Inflammation of intra and extra-hepatic medium and large bile ducts. Leads to strictures, blockage, and fibrosis, which in turn leads to hepatocyte damage and fibrosis.
  • IBD is present in 75%, usually ulcerative colitis.
  • Epidemiology: 2 x commoner in men, and mean onset is 40 years.
  • Can overlap with AIH.

  Signs and symptoms

  • Hepatic: RUQ pain, itch, jaundice, hepato ± splenomegaly.
  • Systemic: fatigue, weight loss, and fevers.
  • May be incidental finding in asymptomatic patient.

  Investigations

  • ↑p-ANCA. Not very specific.
  • Cholestatic LFTs, especially alk phos. BR rises later.
  • Abdo US may show bile duct changes and rule out other causes.
  • MRCP or ERCP usually make the diagnosis, showing biliary strictures. ERCP has more complications, but allows biopsy to check for cholangiocarcinoma, and stone clearance if needed.
  • Liver biopsy not usually useful as it rarely changes management.

  Management

  Lifestyle and preventative:

  • Reduce alcohol to reduce cholangiocarcinoma risk.
  • Fat-soluble vitamins (ADEK) if deficient.
  • Monitor LFTs, PT, albumin.
  • Cholangiocarcinoma screening: annual CA19-9 and abdo US.
  • Osteoporosis: screen (DEXA) and treat (bisphosphonates, Ca2+, vit D).

  Medical:

  • Cholestyramine for itch.
  • Evidence of benefits from UDCA is unclear.

  Interventional:

  • Balloon dilation of biliary stricture with ERCP if acutely unwell with a dominant biliary stricture.
  • Transplantation

  Complications and prognosis

  Complications:

  • Cholangiocarcinoma (10%).
  • Bacterial cholangitis.
  • CRC if there is UC.

  Prognosis:

  • Median survival to death or liver transplantation: 15 years.
  • 1/3 will need transplantation. 70% 10 year survival after transplantation.