Liver Disease Flashcards
what are the causes of NAFLD?
- Unknown
- Associated with metabolic syndromes
- Associated factors: obesity, hyperlipidaemia, type 2 diabetes, jejunoileal bypass, sudden weight loss/starvation
what are the clinical features of NAFLD?
• Usually asymptomatic • Hepatomegally o Steatosis = greasy, yellow, soft o Cirrhosis = bumpy • ALT is usually greater AST • Inceased echogenicity on US
what is the management of NAFLD?
lifestyle
what is the spectrum of disease in NAFLD?
o Steatosis = fat in liver
o Steatohepatitis = fat with inflammation
o Progress to fibrosis + liver cirrhosis
what is the “first step” in NAFLD?
steatosis
how does steatosis occur?
o Insulin resistance causes increased fat storage and decreased fatty acid oxidation
o = decreased secretion of fatty acids into bloodsteream, increased synthesis and uptake of free fatty acids from blood
o Causes fat droplets to form + grow in heaptocytes, some of which become large enough for hepatocytes to swell + nuclei
what is the second hit in NAFLD?
STEATOHEPATITIS
how does steatohepatitis occur?
o Oxidative stress + lipid peroxidation – unsaturated fatty acids react with hydroxyl radical forming water and a fatty acid radical – reacts with non radicals
o Process causes damage of lipid membrane = cell death
o Proinflam cytokine release = TNFa, TGFb, 17B-estradiol
o Presence of Mallory denk bodies = intermediate filaments
what is liver cirrhosis?
• consequence of chronic hepatic injury with healing by regeneration and fibrosis
what are the toxin related causes of liver cirrhosis?
alcohol
what are the infectious causes of liver cirrhosis?
hepatitis B, hepatitis C
what are the autoimmune causes of liver cirrhosis?
o Autoimmune chronic acute liver disease
o Primary biliary cirrhosis
o Primary sclerosing cholangitis
what are the metabolic causes of liver cirrhosis?
o Non alcoholic fatty liver disease
o Iron overload – haemochromatosis
o Copper overload – Wilson’s disease
o A1-antitrypsin associated liver disease
what are the hepatic venous outflow obstructive causes of liver cirrhosis?
o Budd-Chiari syndrome
o Sebere chronic congestive cardiac failure
what are the other causes of liver cirrhosis?
o Secondary to prolonged biliary obstruction
o Cystic fibrosis
o Cryptogenic
o Parental nutrition related
what are the consequences of liver cirrhosis?
- Hepatocellular failure
- Portal hypertension
- Ascites due to portal hypertension
- Malignant change: hepatocellular carcinoma
what are the features of hepatocellular failure in liver cirrhosi
o Impaired protein synthesis: prolonged prothrombin time and low albumin
o Impaired metabolism of toxins: encephalopathy
o Impaired bilirubin metabolism: jaundice
what are examples of benign liver neoplasms?
- Haemangioma
- Adenoma
- Focal Nodular Hyperplasia
what are examples of primary malignant liver neoplasms?
o Hepatocellular carcinoma
o Fibrolamellar carcinoma
o Cholangiocarcinoma
what are examples of secondary malignant liver neoplasms?
o Portal spread
o Systemic blood spread
o Direct spread (from gallbladder, stomach, and hepatic flexure of colon)
what is the cause of liver hemangiomas?
congenital
what is the pathophysiology of haemangioma?
hypervascular tumour of hepatic endothelial cells of blood vessels
what are the clinical features of haemangiomas?
usually asymptomatic, small lesions <1.5xn
how are haemangiomas diagnosed?
US, CT, MRI
what is the treatment of haemangioma?
no need for treatment
what are the causes of focal nodule hyperplasia?
congenital arteriovenous malformation, vascular injury
o Associated with osler-weber-rindu + haemangioma)
what is the macroscopic features of focal nodular hyperplasia?
o Classically – central scar, containing large artery radiating branches to periphery – hyperplastic abnormal response to blood flow
what is the pathophysiology of focal nodular hyperplasia?
o Benign nodule formation of normal tissue
o All normal liver constituents – including RES and bile ducts
what are the clinical features of focal nodular hyperplasia?
usually asymptomatic, may cause minimal pain
what imaging can be done for focal nodular hyperplasia?
US – vary echogenicity, CT, MRI, FNA
how is focal nodular hyperplasia managed?
none required
what are the causes of hepatic adenoma?
o Associated with estrogen
Oral contraceptives and anabolic
Estrogen binds to estrogen receptors on hepatocytes converting them into hepatocellular adenoma cell
o Genetic disposistion
o Glycogen storing disorders – von gherkes disease (multiple adenomas)
what is the pathophysiology of hepatic adenomas?
o Benign neoplasm composed of normal hepatocytes, no portal tract, central veins or bile ducts
o Non-functional cells that contain more glycogen and lipids than normal
o Tissue around highly vascularised
what are the clinical features of hepatic adenomas?
o Usually asymptomatic
o May have RUQ pain
o May present with rupture , haemorrhage or malignant transformation
o Usually in right lobe
what are the investigations for hepatic adenomas?
o US – filling defect
o CT – diffuse arterial enhancement
o MRI – hypo or hyper intense lesion
o FNA – may be needed
what is the management of hepatic adenoma?
o Stop hormones, weight loss o Males = surgical excision o Females – image after 6 months <5cm or reducing = annual MRI >5cm or increased in size = surgery
what are the causes of hepatocellular carcinoma?
Liver cirrhosis – secondary to o Hep B and hep C o Alcohol o NAFLD o Haemochromatosis o PBC
what are the risk factors of hepatocellular carcinoma?
Alpha-1 antitrypsin deficiency, hereditary tyrosinosis, glycogen storage disease, aflatoxin, drugs – oral contraceptive, anabolic steroids, poryphyria cutanea tarda, male, diabetes
what are the types of hepatocellular carcinoma?
fibromellar (presents in younger (5-35), non cirrhosis, normal AFP), pseudo glandular, giant cell, clear cell
what are the macroscopic appearances of hepatocellular carcinoma?
nodular or infiltrate
what is the pathophysiology of hepatocellular carcinoma?
• Hepatocytes develop mutations that cause them to replicate at uncontrolled rates and/or avoid apoptosis
what are the clinical features of hepatocellular carcinoma?
- Present late (masked by cirrhosis)
- Weight loss and RUQ pain
- Asymptomatic
- Worsening or pre-exisiting chronic liver disease
- Acute liver failure
- Hard enlarged RUQ mass
- Liver bruit
what are the investigations for hepatocellular carcinoma?
- Serum AFP (Alfa-fetoprotein) – may be raised
- US
- Triphasic CT Scan
- MRI
- Biopsy
what is the treatment of hepatocellular carcinoma?
- Liver transplantation
- Resection
- Local ablation (ethanol injection, radiofrequency)
- Chemoembolisation = TACR
- Sorafenib – inhibits vase endothelial receptor
