Chronic Liver Disease 1 (PDF)

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Chronic liver disease 1: Medical conditions causing CLD Department of Medicine LEARNING OUTCOMES 1. Define chronic liver disease and cirrhosis 2. List the causes of chronic liver disease and cirrhosis 3. Describe how ea...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Chronic liver disease 1: Medical conditions causing CLD Department of Medicine LEARNING OUTCOMES 1. Define chronic liver disease and cirrhosis 2. List the causes of chronic liver disease and cirrhosis 3. Describe how each cause leads to development of chronic liver disease and cirrhosis 4. Outline the common symptoms and signs in each cause of chronic liver disease and cirrhosis 5. Develop a differential diagnosis for what has caused cirrhosis in a patient 6. Outline the overarching principles of investigations and management in each cause of chronic liver disease and cirrhosis. LEARNING OUTCOME 1 Define chronic liver disease and cirrhosis DEFINE CHRONIC LIVER DISEASE AND CIRRHOSIS Liver failure is the inability of the liver to perform its normal synthetic and metabolic function in order to maintain normal physiology Chronic Liver Disease: Liver injury occurring over > 6 months Cirrhosis: Irreversible fibrosis with replacement of the normal liver architecture with nodules LEARNING OUTCOME 2 List the causes of chronic liver disease and cirrhosis LIST THE CAUSES OF CHRONIC LIVER DISEASE AND CIRRHOSIS Non-Alcoholic Fatty Liver Disease (NAFLD) Alcoholic Liver Disease Viral Hepatitis (Hepatitis B, C) – ** Hepatitis B and C can have a chronic course and potentially cause cirrhosis. – ** Hepatitis A & E usually have an acute course and can cause acute liver injury or rarely an acute fulminant liver failure. – ** Hep E can very rarely have a chronic course in profoundly immunosuppressed individuals Hereditary Haemochromatosis Wilsons disease Autoimmune liver disease (Primary biliary cholangitis, Primary sclerosing cholangitis, Autoimmune hepatitis) LEARNING OUTCOME 3 Describe how each cause leads to development of chronic liver disease and cirrhosis NON-ALCOHOLIC FATTY LIVER DISEASE High calorie intake High High fructose intake NAFLD saturated fat intake A Western diet and lifestyle has been associated with weight gain obesity and NAFLD Sedentary behaviour NON-ALCOHOLIC FATTY LIVER DISEASE Alcohol-like liver disease in individuals who do not consume excessive alcohol Histologic spectrum of liver damage - NAFL – fatty liver (steatosis) - NASH – fatty liver + increased hepatocyte death (steatohepatitis) - Cirrhosis – regenerative nodules + fibrosis Diagnosis of exclusion​: Fatty liver on imaging (ultrasound) in the absence of alcohol excess, and with features of the metabolic syndrome NON-ALCOHOLIC FATTY LIVER DISEASE VIRAL HEPATITIS HAV HBV HCV HEV Type RNA DNA RNA RNA Incubation period (days) 15-50 50-180 14-84 15-60 Can cause acute hepatitis Yes `Yes Yes Yes Can cause chronic hepatitis No Yes Yes No Can cause cirrhosis and primary No Yes Yes No hepatocellular carcinoma Vaccine available Yes Yes No No HEPATITIS A Close personal contact - Household or sexual contact - Day-care centres Faecal-oral contamination of food or water - Food handlers - Raw shellfish Blood-borne (rare) Injecting drug users (PWID) HEPATITIS C RISK FACTORS Clotting Factor Treatment Prior to 1987 Blood Transfusion Long-Term or Organ Transplant Hemodialysis Prior to 1992 Risk Factors Multiple for Hepatitis C Injection Sexual Partners Drug Use Mass Injections Birth from and Traditional Infected Mother Practices HEPATITIS C DISEASE COURSE Acute hepatitis C 55 - 85% Chronic infection 70% Chronic hepatitis 1 - 4%/yr 20% HCC Cirrhosis Decompensation Time 4 - 5%/yr (yr) 10 20 30 HEPATITIS B TRANSMISSION Percutaneous Injection drug use Transfusion or transplant Occupational exposure Parenteral practices Perimucosal Perinatal Sexual Household Consider if recent travel/previous residency in high risk endemic countries, south east asia, africa. HEPATITIS B DISEASE COURSE Recovery Acute Subclinical Hepatitis Fulminant Death Hepatitis Hepatitis Acute Infection Chronic Infection  Chronic HBV Infection Inactive Chronic Carrier State Hepatitis Cirrhosis HCC  HEREDITARY HAEMOCHROMATOSIS "BRONZED DIABETES" HH is a disorder in which increased intestinal iron absorption can lead to total-body iron overload. Hereditary haemochromatosis is most commonly due to homozygosity for the C282Y variant in the HFE gene. The HFE C282Y variant is quite common; however, not all individuals with this variant develop iron overload. Evaluation and diagnosis of HH requires integration of genetic information with other markers of tissue iron deposition. Manifests years later after significant iron deposition Can affect liver, heart, pancreas, pituitary and other organs Onset in premenopausal women can be delayed by menstrual loss of blood Symptoms: Bronze skin hyperpigmentation, diabetes, arthralgias, fatigue, impotence in males, cirrhosis, ECG abnormalities WILSONS DISEASE Wilsons disease (hepatolenticular degeneration) is a genetic disorder of copper metabolism with an autosomal recessive pattern of inheritance due to mutations that lead to impaired function of the intracellular copper transporter ATP7B Impaired biliary copper excretion leads to accumulation of copper in several organs, most notably the liver, brain, and cornea. Liver: – Over time, the liver is progressively damaged and eventually becomes cirrhotic. The rate at which this occurs varies between patients. A small percent of patients (approximately 5 percent) develop acute injury (without encephalopathy) that progresses to acute liver failure, most often in the setting of advanced fibrosis of the liver Neurological: Dysarthria, parkinsonism, cerebellar ataxia, dystonia, tremor etc. Psychiatric: mood disorders, psychosis, cognition Ocular: Kayser fleisher rings Other organs: Kidney, heart, joints, endocrine AUTOIMMUNE LIVER DISEASE - PBC Primary Biliary Cholangitis Characterized by a T-lymphocyte-mediated attack on small intralobular bile ducts. A continuous assault on the bile duct epithelial cells leads to their gradual destruction and eventual disappearance Associations: Female (95%) Sjogren's syndrome Autoimmune thyroid disease Rheumatoid arthritis Coeliac disease Inflammatory bowel disease Appox 50% asymptomatic at time of diagnosis, symptoms of liver disease AUTOIMMUNE LIVER DISEASE - PSC Primary sclerosing cholangitis A chronic progressive disorder of unknown aetiology that is characterized by inflammation, fibrosis, and stricturing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree Associations Ulcerative colitis AUTOIMMUNE LIVER DISEASE - AH Autoimmune Hepatitis A chronic, inflammatory disease of the liver that is characterized by circulating autoantibodies and elevated serum globulin levels Associations Female > Male (4:1) LEARNING OUTCOME 4 Outline the common symptoms and signs in each cause of chronic liver disease and cirrhosis HISTORY Alcohol use Medications Drug use, especially IV drug use Travel to endemic areas Skin pigmentation Obesity Family history SYMPTOMS Non- specific (fatigue, anorexia, weight loss) Decreased GCS (Hepatic encephalopathy) Jaundice Itch (bile salt deposition in skin) Abdominal distension (ascites secondary to portal hypertension) Weight gain (fluid accumulation – ascites) Malaena or haematemesis (variceal bleeding) Infertility (CLD leads to infertility) Irregular menstrual bleeding SIGNS General inspection: Arms: Decreased GCS -> Hepatic Bruising encephalopathy Scratch marks Confabulation -> Korsakoff's Tattoos Jaundice -> Increased bilirubin Proximal muscle wasting Grey pigmentation/tanned -> Needle track marks Haemochromatosis Head and neck: Hands: Scleral icterus Clubbing Fetor hepaticus Palmer erythema -> Alcohol excess Conjunctival pallor Dupytrens contracture Angular stomatitis Asterixis -> grade 2 hepatic Raised JVP encephalopathy Spider naevi Gynaecomastia and reduced body hair SIGNS Abdomen: Hepatomegaly Splenomegaly Ascites Caput medusa Other: Lower limb pitting oedema DRE -> Haemorrhoids WHAT DO YOU SEE? LEARNING OUTCOME 5 Develop a differential diagnosis for what has caused cirrhosis in a patient DIFFERENTIAL Alcohol related liver disease Toxins: ALCOHOL: leading cause in Ireland. Non-alcoholic fatty liver disease Paracetamol is a cause of ACUTE liver failure Other drugs: Methotrexate, Amiodarone Viral Hepatitis- Hepatitis B, C Deposition Autoimmune Hepatitis Fat: NAFLD Iron: Haemochromatosis Primary Sclerosing Cholangitis Wilsons: Copper Primary Biliary Cholangitis Viral Medication related: Hep A, B, C, E. B and C predominantly Methotrexate, amiodarone Autoimmune Hereditary: Haemochromatosis, AI hepatitis, PSC, PBC Wilson's Disease, Alpha 1 Antitrypsin Genetic Alpha 1 anti-trypsin, haemochromatosis, wilsons Deficiency LEARNING OUTCOME 6 Outline the overarching principles of investigations and management in each cause of chronic liver disease and cirrhosis WHAT ARE LIVER BLOOD TESTS? Liver enzymes (damage to different parts of the liver): ALT ALT/AST AST /gGT ALP gGT ALP/gGT Liver function (the liver is doing what it should be doing): Bilirubin Albumin Prothrombin time Platelets  LFT PATTERNS LFT PATTERNS Pattern of LFT derangement: Hepatocellular/parenchymal damage: Raised transaminases: ALT/AST Cholestatic/obstructive: Raised ALK PHOS/GGT Bilirubin can be raised in either Alcoholic hepatitis: AST>ALT ratio is >2:1 (AST>ALT: Scotch is stronger than Limoncello) Measure of function is critical: – Albumin, INR, APTT NON ALCOHOLIC FATTY LIVER DISEASE Diagnosis Management Demonstration of hepatic Weight loss steatosis by imaging or biopsy Abstain from alcohol Exclusion of significant alcohol Immunization (Hep A, Hep, consumption pneumococcal) 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 prioritised in patients with: 1. Significant fibrosis or cirrhosis 2. HIV/HBV coinfection 3. Pre/post liver transplantation 4. At high risk of transmitting the virus Antiviral therapies: Glecaprevir (300 mg) / pibrentasvir (120 mg) to be taken with food for a duration of 8 weeks Sofosbuvir (400 mg) / velpatasvir (100 mg) for a duration of 12 weeks 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 HEPATITIS B TREATMENT Antiviral treatment: Pegylated Interferon Lamivudine Adefovir Entecevir Tenofovir Prevention: Vaccination – Hepatitis B vaccination should be offered to all high risk groups HEREDITARY HAEMOCHROMATOSIS – DIAGNOSIS AND MANAGEMENT Management: Weekly phlebotomy 1 unit venesected = 200- 250mg of iron Ferritin target 50- 100ug/L Maintenance phlebotomy every few months for life Screen family members! PRIMARY BILIARY CHOLANGITIS Diagnosis: Alkaline Phosphatase /GGT almost always elevated (generally 3-4x normal) AST, ALT < 200 U/L Bilirubin - usually rises late Cholesterol elevated in 85% IgM - commonly elevated AMA +++ Treatment UDCA Benzafibrate Obeticholic acid Budesonide PRIMARY SCLEROSING CHOLANGITIS – DIAGNOSIS Raised ALP and gGT History of IBD Imaging: MRCP/ERCP Characteristic features usually make diagnosis: Multifocal, short, annular strictures that alternate with normal or mildly dilated segments. This results in a "beaded" appearance of the bile duct. Long strictures may also be seen and are concerning for cholangiocarcinoma. Autoantibodies can be supportive PRIMARY SCLEROSING CHOLANGITIS – MANAGEMENT Trial UDCA No proven medical therapy Screening for complications - Cholangiocarcinoma (Lifetime risk 7-15%) AUTOIMMUNE HEPATITIS Middle-aged (or teenage) woman, non-drinker without viral hepatitis Fatigue, arthralgias/myalgias, oligomenorrhea, jaundice Increased ALT, AST, IgG globulins Positive ANA and SMA Interface hepatitis with lymphoplasmacytic infiltrate on biopsy Responds to corticosteroids  AUTOIMMUNE HEPATITIS TREATMENT 60 Placebo 40 % Treatment Azathioprine failures 20 Prednisone Pred + Aza 0 0 1 2 3 Years Adapted from Soloway, et al, Gastroenterology 1972; 63:828  1 2 3 4 5 6 7 8 Case Presentation: Section 4: A 55 year old lady is referred to the hepatology service with jaundice and Providing Information hepatocellular derangement of her liver function tests. She is a non drinker, with no metabolic risk factors, normal ferritin. Her AMA and SMA antibodies are positive. The hepatology team prescribes a prolonged tapering course of prednisolone. Select the most appropriate piece of information to discuss with the patient? a. Bone protection should be considered with prolonged steroid use b. Gastric protection is not required with prednisolone c. Patients are at risk of hypotension on steroid therapy d. Steroids do not increase the risk of diabetes e. There is no risk associated with stopping steroids suddenly  1 2 3 4 5 6 7 8 Case Presentation: Section 4: A 55 year old lady is referred to the hepatology service with jaundice and Providing Information hepatocellular derangement of her liver function tests. She is a non drinker, with no metabolic risk factors, normal ferritin. Her AMA and SMA antibodies are positive. The hepatology team prescribes a prolonged tapering course of prednisolone. Select the most appropriate piece of information to discuss with the patient? a. Bone protection should be considered with prolonged steroid use b. Gastric protection is not required with prednisolone c. Patients are at risk of hypotension on steroid therapy d. Steroids do not increase the risk of diabetes e. There is no risk associated with stopping steroids suddenly ANSWER: A The following are amongst the steroid risk: Osteoporosis, gastric ulceration, hypertension, diabetes, adrenal crisis with abrupt discontinuation of steroids. CHRONIC LIVER DISEASE – WORK UP