60 Chronic Liver Disease Overview

Hep E

• Hep E can very rarely have a chronic course in profoundly immunosuppressed individuals

Hereditary Haemochromatosis

• Hereditary Haemochromatosis is a cause of chronic liver disease

Wilsons disease

• Wilsons disease is a cause of chronic liver disease

Autoimmune Liver Disease

• Primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis are causes of chronic liver disease

Non Alcoholic Fatty Liver Disease (NAFLD)

• High calorie intake, high fructose intake, saturated fat intake and sedentary behaviour are associated with NAFLD
• Western diet and lifestyle is associated with weight gain, obesity, and NAFLD
• NAFLD is alcohol-like liver disease in individuals who do not consume excessive alcohol
• NAFLD can progress through a histologic spectrum of liver damage including NAFLD (steatosis), steatohepatitis (NASH), and cirrhosis
• NAFLD diagnosis is one of exclusion and is made by fatty liver on imaging (ultrasound) in the absence of alcohol excess and features of the metabolic syndrome

Viral Hepatitis

• Viral hepatitis is caused by HAV, HBV, HCV, HEV
• HAV is an RNA virus with an incubation period of 15-50 days
• HBV is a DNA virus with an incubation period of 50-180 days
• HCV is an RNA virus with an incubation period of 14-84 days
• HEV is an RNA virus with an incubation period of 15-60 days
• All four viruses can cause acute hepatitis
• HBV and HCV can cause chronic hepatitis
• HBV and HCV can cause cirrhosis and primary hepatocellular carcinoma
• Vaccines are available for HAV and HBV

Hepatitis A

• Hep A is spread through close personal contact via household or sexual contact and at day-care centres
• Hep A is spread through fecal-oral contamination of food or water
• Hep A is spread through blood-borne transmission in injecting drug users (rare)

Hepatitis C Risk Factors

• Hepatitis C risk factors include:
  • clotting factor treatment prior to 1987
  • blood transfusion or organ transplant prior to 1992
  • long-term hemodialysis
  • multiple sexual partners
  • injection drug use
  • mass injections and traditional practices
  • birth from an infected mother

Hepatitis C Disease Course

• 55-85% of individuals with acute hepatitis C develop chronic infection
• 70% of those with chronic infection develop chronic hepatitis
• 1-4% per year of those with chronic hepatitis develop cirrhosis
• 20% of those with chronic hepatitis develop hepatocellular carcinoma (HCC)
• 4-5% per year of those with cirrhosis experience decompensation

Hepatitis B Transmission

• Hepatitis B transmission routes include percutaneous and perimucosal
• Percutaneous transmission occurs through injection drug use, transfusion or transplant, occupational exposure, and parenteral practices
• Perimucosal transmission occurs through perinatal, sexual, and household transmission
• Investigate recent travel/previous residency in high-risk endemic countries such as Southeast Asia and Africa.

Autoimmune Liver Disease: Primary Biliary Cholangitis (PBC)

• PBC features a T-lymphocyte mediated attack on small intralobular bile ducts
• The continuous assault on bile duct epithelial cells leads to their gradual destruction and eventual disappearance
• PBC is associated with female gender (95%), Sjogren's syndrome, autoimmune thyroid disease, rheumatoid arthritis, celiac disease, and inflammatory bowel disease
• Approx 50% of individuals with PBC are asymptomatic at the time of diagnosis
• Symptoms of liver disease may present

Autoimmune Liver Disease: Primary Sclerosing Cholangitis (PSC)

• PSC is a chronic progressive disorder of unknown aetiology
• PSC is characterized by inflammation, fibrosis, and stricturing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree
• PSC is associated with ulcerative colitis

Autoimmune Liver Disease: Autoimmune Hepatitis (AH)

• AH is a chronic inflammatory disease of the liver
• AH is characterized by circulating autoantibodies and elevated serum globulin levels
• AH is associated with a female to male ratio of 4:1

History for Chronic Liver Disease and Cirrhosis

• Important history includes:
  • alcohol use
  • medication use
  • drug use, especially IV drug use
  • recent travel to endemic areas
  • skin pigmentation
  • obesity
  • family history

Symptoms of Chronic Liver Disease and Cirrhosis

• Non-specific symptoms include fatigue, anorexia, and weight loss
• Decreased Glasgow Coma Scale indicates hepatic encephalopathy
• Jaundice is a symptom
• Itch (bile salt deposition in the skin) is a symptom
• Abdominal distension (ascites secondary to portal hypertension) is a symptom
• Weight gain (fluid accumulation - ascites) is a symptom
• Malaena or haematemesis (variceal bleeding) is a symptom
• Infertility (CLD leads to infertility) is a symptom
• Irregular menstrual bleeding is a symptom

Signs of Chronic Liver Disease and Cirrhosis

• General inspection:
  • Decreased GCS indicates hepatic encephalopathy
  • Confabulation indicates Korsakoff's
  • Jaundice indicates increased bilirubin
  • Grey pigmentation/tanned indicates haemochromatosis
• Arms:
  • Bruising
  • Scratch marks
  • Tattoos
  • Proximal muscle wasting
  • Needle track marks
• Head and Neck:
  • Scleral icterus
  • Fetor hepaticus
  • Conjunctival pallor
  • Angular stomatitis
  • Raised Jugular Venous Pressure (JVP)
  • Spider naevi
  • Gynaecomastia and reduced body hair
• Hands:
  • Clubbing
  • Palmer erythema indicates alcohol excess
  • Dupuytrens contracture
  • Asterixis indicates grade 2 hepatic encephalopathy
• Abdomen:
  • Hepatomegaly
  • Splenomegaly
  • Ascites
  • Caput medusa
• Other:
  • Lower limb pitting oedema
  • DRE -> Haemorrhoids

Differential Diagnosis for Cirrhosis

• Alcohol related liver disease
• Non-alcoholic fatty liver disease
• Viral Hepatitis - Hepatitis B, C
• Autoimmune Hepatitis
• Primary Sclerosing Cholangitis
• Primary Biliary Cholangitis
• Medication related:
  • Methotrexate, Amiodarone
• Hereditary:
  • Haemochromatosis, Wilson's Disease, Alpha 1 Antitrypsin Deficiency
• Toxins:
  • Alcohol: leading cause in Ireland
  • Paracetamol causes ACUTE liver failure
  • Other drugs: Methotrexate, Amiodarone
• Deposition:
  • Fat - NAFLD
  • Iron - Haemochromatosis
  • Wilsons - Copper
• Viral:
  • Hep A, B, C, E. B and C are predominantly viral
• Autoimmune:
  • AI hepatitis, PSC, PBC
• Genetic:
  • Alpha 1 anti-trypsin, haemochromatosis, wilsons

Liver Blood Tests

• Liver enzymes (damage to different parts of the liver):
  • ALT
  • AST
  • ALP
  • gGT
• Liver function (the liver is doing what it should be doing):
  • Bilirubin
  • Albumin
  • Prothrombin time
  • Platelets

LFT Patterns

• Hepatocellular/parenchymal damage: raised transaminases: ALT/AST
• Cholestatic/obstructive: raised ALK PHOS/GGT
• Bilirubin can be raised in either of these patterns
• Alcoholic hepatitis: AST>ALT ratio is >2:1
• Measure of function is critical:
  • Albumin, INR, APTT

Non Alcoholic Fatty Liver Disease (NAFLD) Management

• Weight loss
• Abstain from alcohol
• Immunization (Hep A, Hep B, Pneumococcal)
• Exclusion of significant alcohol consumption
• Exclusion of other causes of hepatic steatosis
• Absence of coexisting chronic liver disease

Hepatitis C Investigations

• Hepatitis C antibody test
• Hepatitis C antigen test
• Quantitative HCV RNA tests
• Genotyping
• Fibroscan
• Liver biopsy

Hepatitis C Treatment

• All treatment-naïve and treatment-experienced patients with recently acquired or chronic HCV infection must be offered treatment without delay.
• Hep C Treatment is prioritized in patients with:
  • significant fibrosis or cirrhosis
  • HIV/HBV coinfection
  • pre/post liver transplantation
  • autoantibodies can be supportive

Primary Sclerosing Cholangitis (PSC) Management

• Trial UDCA
• No proven medical therapy
• Screening for complications:
  • Cholangiocarcinoma (Lifetime risk 7-15%)

Autoimmune Hepatitis

• Presents in middle-aged (or teenage) woman, a non-drinker with no viral hepatitis
• Symptoms include: fatigue, arthralgias/myalgias, oligomenorrhea, jaundice
• Liver function tests show increased ALT, AST, IgG globulins
• Positive ANA and SMA antibodies
• Interface hepatitis with lymphoplasmacytic infiltrate on biopsy
• Responds to corticosteroids

Autoimmune Hepatitis Treatment

• Prednisone is the initial treatment
• Azathioprine is used for long-term maintenance therapy
• Monitor bone protection, gastric protection, hypotension, diabetes risk, and risk of stopping steroids suddenly.

Case Presentation: Section 4

• This patient presents with symptoms of chronic liver disease and is diagnosed with autoimmune hepatitis
• Patients with AIH should be counselled about the risks and benefits of long-term steroid use.
• Long-term prednisolone use can cause complications such as osteoporosis, diabetes, hypertension, and peptic ulcer disease.

Hepatits E

• Profoundly immunosuppressed individuals can have a chronic course of Hepatitis E

Hereditary Haemochromatosis (HH)

• An inherited disorder where increased intestinal iron absorption leads to iron overload
• Most commonly caused by the C282Y variant in the HFE gene
• Not all individuals with the C282Y variant will develop iron overload
• Diagnosis requires genetic testing and monitoring iron levels in tissues
• Can affect the liver, heart, pancreas, pituitary and other organs
• Symptoms include bronze-colored skin, diabetes, joint pain, fatigue, impotence in males, cirrhosis, and abnormal ECG results

Wilson's Disease

• An inherited disorder affecting copper metabolism
• Caused by mutations in the ATP7B gene affecting a copper transporter
• Leads to copper accumulation in the liver, brain and cornea
• Can cause liver cirrhosis and neurological symptoms like difficulty speaking, Parkinsonism, ataxia, dystonia and tremor

Non-Alcoholic Fatty Liver Disease (NAFLD)

• Refers to liver disease in individuals who do not consume excessive alcohol
• Can progress from fatty liver (steatosis) to steatohepatitis and cirrhosis
• Often associated with a Western diet and lifestyle factors, including high calorie intake, high fructose intake, high saturated fat intake, and sedentary behavior
• Diagnosis involves demonstrating fatty liver on imaging and ruling out other causes like excessive alcohol consumption

Viral Hepatitis

• Hepatits A, B, C and E are categorized by the type of virus (RNA or DNA) and their incubation periods
• All can cause acute hepatitis
• Hepatitis B and C can lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma
• Vaccines are available for Hepatitis A and B

Hepatitis A

• Transmission occurs through close personal contact, fecally contaminated food and water, and rarely through blood
• Can be transmitted through household or sexual contact and in day-care centers
• Food handlers and people handling raw shellfish are at risk of spreading the virus
• Injecting drug users are also at risk

Hepatitis C

• Primarily transmitted through blood
• Risk factors include blood transfusions or organ transplants before 1992, long-term hemodialysis, multiple sexual partners, injection drug use, mass injections, and birth from an infected mother

Hepatitis C Disease Course

• About 70% of people infected with Hepatitis C develop chronic infection
• Chronic hepatitis can progress to cirrhosis in 20% of cases
• Cirrhosis carries a high risk of developing hepatocellular carcinoma (HCC)
• Decompensation of cirrhosis occurs over a 4-5 year period

Hepatitis B Transmission

• Transmission can be percutaneous (through the skin), including through injection drug use, transfusions or transplants, occupational exposure, and parenteral practices
• Perimucosal transmission occurs through perinatal (mother to child), sexual, and household routes.
• Recent travel to endemic countries like Southeast Asia or Africa may increase the risk of infection

Hepatitis B Disease Course

• Most infections result in recovery
• Acute hepatitis can progress to chronic infection or fulminant (rapidly progressing) hepatitis, leading to death in some cases

Chronic Hepatitis B Infection

• Can progress to an inactive carrier state, chronic hepatitis, cirrhosis and HCC

Hereditary Haemochromatosis - Management

• Regular phlebotomy (blood removal)
• Ferritin target levels of 50-100 ug/L
• Phlebotomy performed every few months for life
• Screening of family members is essential

Primary Biliary Cholangitis

• Characterized by high levels of alkaline phosphatase and gamma-glutamyl transferase
• AST and ALT levels are usually low
• Bilirubin levels rise later in the disease course
• Cholesterol levels are elevated in 85% of cases
• Treatment involves ursodeoxycholic acid (UDCA), benzafibrate, obeticholic acid, and budesonide

Primary Sclerosing Cholangitis - Diagnosis

• Elevated alkaline phosphatase and gamma-glutamyl transferase
• History of inflammatory bowel disease
• Imaging: MRCP/ERCP is essential for diagnosis
• Characteristic findings include multifocal, short, annular strictures, resulting in a "beaded" appearance

Liver Blood Tests

• Liver enzymes (ALT, AST, ALP, GGT) indicate liver damage.
• Liver function tests (bilirubin, albumin, prothrombin time, platelets) assess the liver's ability to perform its functions

Liver Function Test Patterns

• Hepatocellular or parenchymal damage: Elevated transaminases (ALT, AST)
• Cholestatic or obstructive: Elevated alkaline phosphatase and gamma-glutamyl transferase
• Alcoholic hepatitis: AST > ALT ratio is >2:1
• Function tests (albumin, INR, APTT) are important for assessing liver function

Non-Alcoholic Fatty Liver Disease - Management

• Weight loss
• Abstinence from alcohol
• Immunization against Hepatitis A and B, and pneumococcal vaccine
• Exclusion of other causes of steatosis
• Management of co-existing chronic liver disease

Hepatitis C - Investigations

• Hepatitis C antibody test
• Hepatitis C antigen test
• Quantitative HCV RNA tests
• Genotyping
• Fibroscan
• Liver biopsy

Hepatitis C Treatment

• All treatment-naïve and treatment-experienced patients with chronic HCV infection should be offered treatment
• Treatment is prioritized in patients with significant fibrosis or cirrhosis, HIV/HBV coinfection, pre/post liver transplantation, and those with a high risk of transmitting the virus
• Antiviral therapies include glecaprevir/pibrentasvir and sofosbuvir/velpatasvir

Hepatitis B Serology

• HBsAg: Acute/Chronic infection
• Anti-HBc IgM: Acute infection
• HBeAg high infectivity
• Anti-HBe: Low infectivity
• Anti-HBs: Immunity
• Anti-HBc IgG and HBsAg: Chronic infection
• Anti-HBc IgG and anti-HBs: Resolved infection

Hepatitis B Management

• Antiviral treatment
• Prevention through vaccination

Hepatitis B Treatment

• Antiviral therapies: Pegylated Interferon, Lamivudine, Adefovir, Entecevir, Tenofovir
• Prevention: Hepatitis B vaccination is recommended for high-risk groups

Differential Diagnosis of Cirrhosis

• Alcohol related liver disease
• Non-alcoholic fatty liver disease
• Viral hepatitis (A, B, C, E)
• Autoimmune hepatitis
• Primary sclerosing cholangitis
• Primary biliary cholangitis
• Medication related (methotrexate, amiodarone)
• Hereditary (haemochromatosis, Wilson’s disease, Alpha1 antitrypsin deficiency)
• Toxins
• Paracetamol (overdose)
• Other drugs (methotrexate, amiodarone)
• Deposition
• Fat (NAFLD)
• Iron (Haemochromatosis)
• Copper (Wilson's Disease)
• Viral (Hepatitis A, B, C, E)
• Autoimmune
• AI hepatitis, PSC, PBC
• Genetic
• Alpha1 anti-trypsin, haemochromatosis, Wilson's disease.

This quiz covers various types of chronic liver diseases including Hep E, hereditary haemochromatosis, Wilson's disease, autoimmune liver disease, and non-alcoholic fatty liver disease (NAFLD). Test your understanding of the causes, progression, and implications of these conditions in this informative quiz.