Chronic Liver Disease 2: Clinical Features PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Chronic Liver Disease 2: Clinical Features Department of Medicine LEARNING OUTCOMES Define chronic liver disease and cirrhosis Explain the pathophysiology of chronic liver disease and cirrhosis List the card...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Chronic Liver Disease 2: Clinical Features Department of Medicine LEARNING OUTCOMES Define chronic liver disease and cirrhosis Explain the pathophysiology of chronic liver disease and cirrhosis List the cardinal symptoms and signs of chronic liver disease and cirrhosis Explain how each symptom and sign is caused in chronic liver disease and cirrhosis Develop a differential diagnosis for chronic liver disease and cirrhosis Outline the overarching principles of investigations and management in chronic liver disease and cirrhosis LEARNING OUTCOME 1 Define chronic liver disease and cirrhosis CHRONIC LIVER DISEASE & CIRRHOSIS Chronic liver disease (CLD) is a progressive deterioration of liver functions for more than six months, which includes synthesis of clotting factors, other proteins, detoxification of harmful products of metabolism, and excretion of bile. It is a continuous process of inflammation, destruction, and regeneration of liver parenchyma, which leads to fibrosis and cirrhosis Cirrhosis is a final stage of chronic liver disease that results in disruption of liver architecture, the formation of widespread nodules, vascular reorganization, neo-angiogenesis, and deposition of an extracellular matrix LEARNING OUTCOME 2 Explain the pathophysiology of chronic liver disease and cirrhosis PATHOPHYSIOLOGY: CHRONIC LIVER DISEASE Chronic liver disease is a continuous and progressive process of hepatic fibrosis, liver tissue architectural distortion, and regeneration nodule formation. Fibrosis is the deposition of extracellular matrix (ECM) in response to chronic liver injury by any cause. Fibrosis is usually irreversible, but it can be reversible in the initial stage of development. The transition point to irreversible fibrosis is still not completely understood. The pathway is initiated by hepatic stellate cells (HSC), usually dormant cells found in space between sinusoids and hepatocytes. In response to chronic liver injury, HSC get transformed into fibroblasts and upregulate the expression of inflammatory receptors such as chemokine receptors. This pro-inflammatory phase makes the liver cells responsive to inflammatory cytokines, and leads to ongoing activation HSC cells, resulting in the accumulation of ECM and progressive fibrosis. https://basicmedicalkey.com/cirrhosis-and-portal-hypertension/ PATHOPHYSIOLOGY: CIRRHOSIS Cirrhosis is the end stage of the pathway described previously with irreversible fibrosis of the liver. In addition to fibrosis, cirrhosis is also characterised by portal hypertension (increased pressure in the portal vein) and hyperdynamic circulation (increased blood volume in the portal system) Sinusoidal endothelial cells (SECs), which line the hepatic sinusoids (specialised capillaries) produce nitric oxide (NO) vasodilator, and endothelin-1 (ET-1) vasoconstrictor. In cirrhosis, there's increased ET-1 and decreased NO inside the liver, leading to liver blood vessel constriction, initiating portal hypertension. In splanchnic (abdominal) circulation, there's an increase in NO leading to dilation of blood vessels, activating the renin-angiotensin-aldosterone system (RAAS), and resulting in water and sodium retention, increasing blood volume, creating a hyperdynamic circulation. Cirrhosis is a risk factor for developing Hepatocellular Carcinoma CIRRHOTIC LIVER PATHOPHYSIOLOGY: PORTAL HYPERTENSION Portal hypertension: As the resistance to blood flow increases within the portal circulation (in this case due to the upstream fibrosis), the pressure backs up and tries to find alternative routes around the obstruction. Due to the venous anatomy, this pressure can back up into: - Gastro-oesophageal veins: oesophageal varices. - Splenic vein: splenomegaly - Umbilical veins: caput medusae - Rectal veins: haemorrhoids DECOMPENSATION Common cause for GI acute medical admissions, complex medical needs, high risk of in hospital death. Def: Acute deterioration in liver function in a patient with cirrhosis, characterised by the development of one of the following complications: Jaundice (impaired excretion of bilirubin leading to accumulation in skin and mucous membranes) Ascites (most common complication of cirrhosis, accumulation of fluid in the abdomen due to portal hypertension) Hepatic Encephalopathy: a range of neurological symptoms, exact mechanism unknown but thought to be secondary to build up of toxins crossing the BBB, including ammonia Variceal Haemorrhage: High mortality LEARNING OUTCOME 3 List the cardinal symptoms and signs of chronic liver disease and cirrhosis CARDINAL SYMPTOMS Fatigue and weakness Nausea and vomiting Pruritis Jaundice Bleeding Weight gain Confusion Somnolence Fever/Abdominal pain Upper GI bleeding- Haematemesis WHAT DO YOU SEE? CARDINAL SIGNS Reduced GCS/Asterixis Jaundice Bruising/Petechiae Raised JVP Ascites Splenomegaly Peripheral Oedema LEARNING OUTCOME 4 Explain how each symptom and sign is caused in chronic liver disease and cirrhosis SYMPTOMS- CAUSES Symptom Cause Fatigue and weakness Catabolic state given inflammation, malnutrition, poor diet of ALD Nause and Vomiting Poor gastric emptying, increased acid production, ascites causing mechanical nausea Pruritis Excess bilirubin deposited in skin Jaundice Hepatocyte damage, reducing conjugation of bilirubin. Bleeding Reduced clotting factors produced, platelets consumed due to splenomegaly Weight gain Fluid retention and third spacing, given hyperdynamic state, reduced albumin production Confusion Encephalopathy due to reduced ammonia excretion, B12 deficiency due to alcohol Wernicke's Fever/ Abdominal pain Subacute bacterial peritonitis due to ascites Upper GI Bleed: Haematemesis, malaena Oesophageal Varices due to portal hypertension SIGNS- CAUSES Signs Causes Reduced GCS/Asterixis Hepatic Encephalopathy due to reduced excretion of ammonia Jaundice Hepatocyte damage reducing conjugation of bilirubin Bruising/Petechiae Reduced clotting factor synthesis, consumptive thrombocytopaenia Ascites Due to portal hypertension, reduced oncotic pressure sue to reduced albumin synthesis Splenomegaly/Caput medusae Portal hypertension Peripheral oedema Reduced albumin production Pallor Anaemia of chronic disease, B12 deficiency, iron deficiency LEARNING OUTCOME 5 Develop a differential diagnosis for chronic liver disease and cirrhosis DIFFERENTIAL DIAGNOSIS 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 CHF/Nephrotic syndrome (for oedema) LEARNING OUTCOME 6 Outline the overarching principles of investigations and management in chronic liver disease and cirrhosis INVESTIGATIONS Bloods Explanation LFTs Raised ALT/AST hepatocyte damage, raised GGT/ALP biliary tree injury Raised bilirubin: Jaundice Coagulation profile Raised INR, reduced coagulation factor production –measure of liver synthetic function Albumin Reduced- measure of synthetic function FBC Low platelets Anaemia Viral Hepatitis Screen Hep A, B, C, EBV, CMV, VZV, HIV Autoantibody screen Anti Liver Kidney Ab- AIH Anti Smooth muscle Ab- PSC Anti Mitochondrial Ab-PBC Iron studies and ferritin Raised Ferritin, Fe, and T sat, low TIBC- HFE Caeruloplasmin and serum copper Reduced in Wilson's Serum A1AT Level Reduced A1AT deficiency INVESTIGATIONS Imaging Explanation Liver Ultrasound Evaluate liver morphology for nodularity or coarse texture of cirrhosis, evaluate for ascites, hepatomegaly/splenomegaly, HCC MRI Liver/ MRCP MRI Liver- higher quality image evaluate for liver tumour/morphology MRCP to evaluate the biliary tree- PSC/PBC OGD To screen/surveillance of oesophageal varices Special Tests Liver elastography Can give a score to evaluate for hepatic steatosis and fibrosis Liver Biopsy Gold standard but invasive, may not be required if other investigations suggest CLD/Cirrhosis MANAGEMENT Prevention: Alcohol cessation, avoid hepatotoxic medications e.g paracetamol/NSAIDS, weight loss and diet management, DM optimisation for hepatic steatosis, Hep A and B vaccination Pharmacological: B Blockers for varices, Lactulose for encephalopathy (increases bacterial uptake of ammonia), Rifaxamin for encephalopathy, Diuretics and low salt diet for ascites and oedema management. Procedures: Paracentesis to drain ascitic fluid, OGD banding of varices, Trans-jugular Intrahepatic Portosystemic Shunt Surgical: Liver transplant definitive management Palliative care: can be involved early for optimisation of symptoms and advanced care planning Paracentesis  1 2 3 4 5 6 7 8 Case Presentation: 3 A 65 year old gentleman presents to the emergency department with acute confusion PLANNING MANAGEMENT and behavioural disturbance. His past medical history includes haemochromatosis and chronic liver disease. Physical examination demonstrates asterixis, distended abdomen with shifting dullness, caput medusae. Which of the following is an appropriate treatment to address this gentleman's confusion? a. Cefotaxime b. Lactulose c. Lorazepam d. Rifampacin e. Senna  1 2 3 4 5 6 7 8 Case Presentation: A 65 year old gentleman presents to the emergency department with acute confusion and 3 PLANNING behavioural disturbance. His past medical history includes chronic liver disease. Physical MANAGEMENT examination demonstrates asterixis, distended abdomen with shifting dullness, caput medusae. Which of the following is an appropriate treatment to address this gentleman's confusion? a. Cefotaxime b. Lactulose c. Lorazepam d. Rifampacin e. Senna ANSWER: B Lactulose lowers ammonia levels and therefore is indicated for the treatment of hepatic encephalopathy, aim for 3 bowel motions per day. Rifaxamin (not rifampacin) is also indicated, in addition to lactulose. Senna is a stimulant laxative and has no role in ammonia reduction. Lorazepam sedation will not address the underlying cause. Cefotaxime is an antibiotic used for treatment of spontaneous bacterial peritonitis. KEY POINTS / SUMMARY Chronic liver disease (CLD) is a progressive deterioration of liver functions for more than six months Cirrhosis is the final stage of chronic liver disease The pathway is initiated by hepatic stellate cells (HSC) in response to chronic liver injury, which are transformed into fibroblasts, causing progressive fibrosis. Fibrosis can result in portal hypertension and it's sequalae Management is based on prevention, reversing underlying cause where possible, and addressing features of decompensation. INSERT FURTHER READING / REFERENCES https://www.uptodate.com/contents/portal-hypertension- in- adults?search=portal%20hypertension&source=search_r esult&selectedTitle=1~150&usage_type=default&display _rank=1 https://www.uptodate.com/contents/cirrhosis-in-adults- overview-of-complications-general-management-and- prognosis?search=portal%20hypertension&source=sear ch_result&selectedTitle=3~150&usage_type=default&dis play_rank=3