Chronic Liver Disease Flashcards
What is cirrhosis of the liver?
Fibrosis of the sinusoids of the liver that induces nodular regeneration, causing a decline in liver function and portal hypertension with Haematemesis and Melena.
What is an indicator on diagnostic testing for autoimmune hepatitis?
ANA, ASMA, IGg and anti-LEMI
What diseases can cause parenchyma disease of the liver?
Alcohol, Autoimmune hepatitis, Hepatitis B, Hepatitis C, Hereditary haemochromatosis, Wilson’s disease, Alpha-1 antitrypsin disease, Non-alcoholic fatty liver disease.
What is Budd-Chiari syndrome?
Clotting in the circulation.
What is primary biliary cholangitis?
Intrahepatic duct inflammation, autoimmune inflammation involving AMA.
What does primary sclerosing cholangitis involve?
Both intrahepatic and extrahepatic duct inflammation, associated with ulcerative colitis.
What are the consequences of decompensated liver function?
Oesophageal varices due to portal hypertension, Porto-systemic shunt, hepatic encephalopathy.
What is the cause of high oestrogen?
High oestrogen causing testicular atrophy, reduced body hair and gynaecomastia and palmar erythema and spider angioma
What is an indicator of hepatocellular carcinoma??
Alpha feto-protein
What is the stigmata of chronic liver disease?
includes spider nevi, palmar erythema, gynecomastia, caput medusae, Dupuytren contractures, parotid gland enlargement, and testicular atrophy.
Palpable lymph nodes can also direct the clinician towards malignancy (left supraclavicular & periumbilical). Increased volume status of the patient evidenced by jugular venous distension can be a sign of right-sided heart failure, suggesting hepatic congestion.
What are the signs of end stage liver disease?
Temporal muscle wasting, cyanosis, icterus, enlarged parotid gland
Palmar erythema, asterixis, clubbing, Dupuytren contracture
Gynecomastia, small testes
* Fetor hepaticus: sweet rotting smell on breath
Ankle edema, spider nevi, petechiae, scant body hair
Caput medusae, paraumbilical hernia, hepatosplenomegaly
What are the investigations for liver cirrhosis?
FBC for LFT,s pT and INR and albumin
-> LFTs will show high AST/ALT and increased bilirubin and high PT and INR
-> Low albumin
-> low platelet count from low TPO production
U&Es for urine creatinine
High ALT with albumin/splenomegaly.Thrombocytopenia. High INR and high III Rubin indicates cirrhosis.
What does High ALP with Raised GGIT indicate?
gallbladder or bile duct stones
What does High ALP with Normal GGT indicate?
Vitmain D deficiency, bone disease, third trimester pregnancy but varies in adolescents that are rapidly growing
What does High bilirubin and Normal ALT, ALP, INR and albumin indicate?
Haemolysis if anaemia is present OR unconjugated bilirubin is high
What does High bilirubin and high unconjugated bilirubin indicate?
Gilbert’s syndrome
What is the treatment of cirrhosis?
Cirrhosis managed with sodium diet restriction and providing furosemide or spironolactone for mild ascites or for severe, rage volume paracentesis for over 5L of fluid and provide albumin. Consider transjgar intrahepatic portosystemic shunt to bypass from portray vein straight to the IVC
How can prognosis of liver cirrhosis be determined?
ABCDE
A=albumin, B=bilirubin, C= coagulopathy D=distented abdmone, E=encephalpathy
Indications for liver transplant
Which medications can cause chronic liver damage?
Methyldopa(Alzheimer’s), nitrofurantoin (antibacterial for UTI), isoniazid (TB) and ketoconnazole (antibacterial-fungal)can cause chronic liver damage, methotrexate and amiodarone can cause liver cirrhosis
What scoring is used to indicate need for transplant?
severity from 6 to 40 for transplant planning based on:
Bilirubin
INR
Sodium
What is ascites?
Most common complication of liver cirrhosis from Fluid accumulation in the abdominal cavity due to increased hydrostatic pressure that is poor in albumin.
How does ascites occur?
The portal hypertension in liver cirrhosis increases porta. pressure and causes vasodilation, with increase in RAAS hormones, decline in renal function from decmpensation of ascitic fluid.
Ascites can also be caused by the production of protein rich fluid by tumor cells in the peritoneum
What is the cause of transudative ascites?
Transudative ascites is poor in albumin, and typically arises from changes in pressure from sinusoidal obstruction portal venous hypertension with increased capillary permeability
Pre-sinusoids obstruction from portal vein thrombosis
Sinusoidal obstruction from cirrhosis
Post sinusoidal obstruction from Budd-chairi syndrome and right sided heart failure
How is ascites assessed?
SAAG is serum albumin ascites gradient which is based on serum albumin - ascites albumin. Value greater than 1.1 indicates transudative ascites due to low albumin in ascites
What causes a low SAAG?
SAAG will be less than 1.1 because ascites albumin will be higher than serum albumin, cancer of peritoneum, metastatic disease, pancreatitis, tuberculosis, hypoalbuminaemia.
What is the cause of exudative ascites?
Exudative ascites is poor in albumin
Hypoalbuminaemia in serum due to nephrotic syndrome
Capillary leakage from malignancy due to peritoneal carcionomatosis due to cancers seeding to the peritoneum producing protein rich fluid
Ifnfections such a s TB
Inflammation from pancreatitis
What does a high serum ascites albumin gradient (SAAG) indicate?
Over 1.1 poor in protein due to Portal hypertension related to:
cirrhosis, perciarditis, Budd-Chiari syndrome or heart failure
What does low SAAG indicate?
less than 1.1 indicates peritoneal caricnoma to sis, peritoneal tuberculosis, pancreatitis, serous it is and nephrotic syndrome
where ascitic fluid total protein over 2.5 indicates PVT, Right heart fialure or budd-chairi. Less than 2.5 indicates cirrhosis
What is the treatment of ascites?
Treatment of ascites is first line spironolactone with furosemide
for fluids over 5L it is large volume paracentesis
a long lasting chest drain or for recurrent ascites, transjugualr intrahepatic portosysteic shunt.
What is the aetiology of ascites?
Ascites can be caused by chronic alcohol use, IV drug use, obesity, hypercholesterolaemia, type 2 diabetes, nephrotic syndrome, severe malnutrition, Pancreatic ascites and Ovarian lesions
How does ascites present?
Ascites may present with progressive abdominal distention, early satiety, SOB, dyspnoea and increased abdominal pressure.
What are the clinical signs of ascites?
Clinical examination may show flank dullness, positive fluid wave, pleural effusion and stigmata of cirrhosis like spider angioma, palmar erythema, and abdominal wall collaterals. For advanced liver disease, muscle wasting, leukaemia.
What are the symptoms of spontaneous bacterial peritonitis (SBP)?
Abdominal pain, fever.
What is the treatment of spontaneous bacterial peritonitis?
Treatment of spontaneous bacterial periontitis is intravenous piperacillin-tazobactam. Prophylaxis antibiotic 1st line is ciprofloxacin
What is the treatment for hepatic encephalopathy?
Lactulose or rifaximin.
What is the Child-Pugh classification used for?
Assessing severity of cirrhosis.
What are the components of the Child-Pugh classification?
- Bilirubin over 3
- Albumin over 28
- INR over 2.3
- Ascites
- Encephalopathy
What does a serum albumin ascites gradient (SAAG) greater than 1.1 indicate?
Transudative ascites due to portal hypertension.
What are the key signs of hepatocellular carcinoma?
- Alpha-feto protein
- Spider nevi
- Palmar erythema
- Gynecomastia
- Caput medusae
- Dupuytren contractures
- Testicular atrophy
What is spontaneous bacterial peritonitis?
Spontaneous bacterial peritonitis is where bacteria in the peironteal fluid causes infection, which is further complicated by fluid leakage from portal hypertension causes bacteria to spread from mesenteric lymph nodes to abdominal cavity.
What is the cause of spontaneous bacterial peritonitis?
Commonly caused by gram negative aerobic organisms, like E.Coli, kiebsella pneumonia, streptococcus pneumonia. This is because ascitic fluid has a high oxygen tension so anaerobic organisms will not commonly be seen. The organisms arise from the intestinal lumen via translocation from the mesenteric lymph nodes
What is the presentation of spontaneous bacterial peritonitis?
SBP is characterised by cirrhosis with new onset ascites. Fever, abdominal tenderness and confusion may be seen with some guarding
How is spontaneous bacterial peritonitis diagnosed?
Perionteal fluid analysis is achieved through paracentesis (needle into perionteal cavity) a predictor of SBP is polymorphonuclear leukocytes in ascitic fluid.
Which patients are at high risk for SBP?
Patients with gastrointestinal bleed and cirrhosis.
* Patients who already had SBP one or more times in the past.
* Cirrhotic patients with ascites in which ascitic fluid protein is < 1.5 g/dl along with renal failure (creatinine > 1.2 mg/dl).
* Cirrhotic patients hospitalized for a cause other than SBP have an ascitic protein concentration of < 1 g/dl (10 g/L).
What is the haemochromatosis?
Autosomal recessive condition with a mutation of the HFE gene.
What is the pathophysiology of haemochromatosis?
Reduced production of hepcidin, found in Northern Europeans . Hepcidin regulates/inhibits levels of ferroportin which is responsible for regulating iron transport and results in high levels of iron absorption, causing increased release of iron from stores in the macrophages and the spleen.
How does haemochromatosis affect the liver?
Liver within the parenchyma cells causing hepatotoxicity and liver cirrhosis. The only exception to this is in secondary haemochromatosis where iron will be deposited in the reticuloendothelial cells the excess iron is deposited as haemosiderin causing cell death and fibrosis.
Which Extrahepatic systems are affected in haemochromatosis?
Heart causing restrictive cardiomyopathy and results in myocardial fibrosis
Pancreas deposition occurs at the islets of langerhaan causing type 1 diabetes
Gonads causing sexual dysfunction
Pituitary gland casing hypo organism and infertility
Hypothyroidism
Calcium deposits in the joints causing arthritis
What is type 1 haemochromatosis?
homozygous loss of function of HFE which disproportionately affects males
What is type 2. haemochromatosis?
juvenile, onset is adolescents or early adulthood with decreased sex hormone production by age 20 with risk of fatal heart disease in the 30s
What is type 3 haemochromatosis?
autosomal recessive with onset around 30 to 40 years old from a mutation in the transferrin-receptor gene on chromosome 7
What is type 4 haemochromatosis?
autosomal dominant caused by mutations in ferroportin transport protein, with a highly variable age of onset
What is the cause of secondary haemochromatosis?
erythropoeisis
Recurrent blood transfusion
How is haemochromatosis diagnosed?
Diagnosis is through serum ferritin (also an acute phase reactant) and transferrin saturation) and genetic testing to confirm diagnosis.
CT scan can reveal attenuation of the liver. Fasting glucose should be performed
What are the clinical features of haemochromatosis?
- Bronze skin
- Type 2 diabetes
- Fatigue
- Joint pain as arthropathy may occur with calcium pyrophosphate
- Liver cirrhosis
- hair loss
- Adrenal insufficiency
Women typically present later due to menstruation eliminating iron.
How is haemochromatosis managed?
*Management is with phlebotomy 1-2 x a week which improves insulin sensitivity, skin pigmentation and fatigue but there may be no cirrhosis, hypogonadism and Arthropathy.
*Patients should not drink alcohol at all because of risk of accelerating liver and pancreatic toxicity
*The use of an iron-chelating desferroxamin which removes excess iron build up in the body.
What is the risk with untreated haemochromatosis?
It can cause progressive liver damage and cirrhosis and develop compications like diabetes, heart failure, hypogonadism and osteoporosis.
What is Wilson’s disease caused by?
Mutation in the ATP7B protein responsible for copper. apoceruloplasmin which will convert -> ceruloplasmin. This condition results in high levels of copper in the hepatocytes and apoceruloplasm.
What is the pathophysiology of Wilson’s disease?
Copper is typically excreted in the liver but it will accumulate in the liver and will move into the bloodstream and deposit into the Desmond’s membrane in the cornea causing Kayser fleischer rings around the eyes.
Liver will have more free radical reactions causing inflammation and cirrhosis and release copper as ceruloplasmin
Basal ganglia deposition will be affected and cause movement disorder like bird wing tremor or dystonia (random contractions of muscle or limbs) and Parkinsonism
CNS deposition in the basal ganglia causing dysarthria, dystonia and loss of coordination
Haemolytic anaemia may occur
What are the key clinical features of Wilson’s disease?
- Hepatitis
- Asterixis
- Chorea
- Dementia
- Parkinsonism
- Kayser-Fleischer rings
*abdoman pain jaundice and weakness - hemiballismus due to CNS involvement
What is the main treatment for spontaneous bacterial peritonitis?
Intravenous piperacillin-tazobactam.
What is the significance of a positive fluid wave test?
Indicates the presence of ascites.
What is the first-line treatment for ascites?
Spironolactone with furosemide.
What are the risk factors for spontaneous bacterial peritonitis?
- Gastrointestinal bleed and cirrhosis
- Previous episodes of SBP
- Ascitic fluid protein < 1.5 g/dl with renal failure
What is the role of paracentesis in ascites diagnosis?
To analyze fluid for SAAG.
What is the most common complication of liver cirrhosis?
Ascites.
What is the significance of Kayser-Fleischer rings?
Deposits of copper in the cornea associated with Wilson’s disease. They can also occur with primary biliary cholangitis, multiple myeloma, chronic cholestasis, neonatal cholestasis, autoimmune hepatitis
What are the potential complications of untreated haemochromatosis?
- Progressive liver damage
- Cirrhosis
- Diabetes
- Heart failure
- Hypogonadism
- Osteoporosis
What is a key clinical feature of Wilson’s disease?
Key clinical features include hepatitis, asterixis, chorea, dementia, Parkinsonism, and Kayser-Fleischer rings.
What are the common presentations of Wilson’s disease in children and adults?
Children generally present with liver disease and adults commonly present with neurological disease.
What diagnostic test is used to confirm Wilson’s disease?
Diagnosis is made with high serum caeruloplasmin, low serum copper, and raised urinary copper levels.
ECG may show ventiruclar hypertrophy, arrythmias and changes in T waves and ST segments. 24 hour urine collection for urinary copper excretion and genetic analysis of ATP7B gene
What is the treatment for Wilson’s disease?
Treatment involves trientine, a chelating agent that binds to copper to form a complex to be more easily excreted in the kindeys.
D-penicillamine, and zinc salts.
What is the management of Wilson’s disease?
Management of WIlson’s is avoiding foods high in copper such as chocolate, nuts and liver, chelators like D-penicillamine and trientine. Zinc salts to promote negative copper balance.
What is the main cause of Alpha 1 antitrypsin disease?
It is caused by mutation of the PiS gene leading to accumulation of alpha-1 antitrypsin in the liver causes cirrhosis and hepatotoxicity. neutrophils are now hyperactive from deficiency and can result in panacinar emphysema in the lungs. It presents with neonatal jaundice, COPD.
Management can invovle liver transplantation and smoking cessation
What is Gilbert syndrome?
Autosomal recessive condition involving benign recurrent episodes of pre-haptic jaundice with sclera icterus with buildup of unconjugated hyperbilirubinaemia due to mutation in UGT gene that causes a mild decrease in activity of UDP-glucoronyltransferase which is import at for Glucoronidation of bilirubin.
What are the common symptoms of Gilbert syndrome?
triggered by fasting, dehydration, stress, menstruation and illness. Onset of symptoms occur during puberty and primary symptom is ictus sclerus , with nausea and vomiting and abdominal pain being less common.
Symptoms include benign recurrent episodes of pre-hepatic jaundice and scleral icterus.
How is Gilbert syndrome diagnosed?
measuring the levels of unconjugated hyperbilirubinaemia at several intermittent measurements and liver function will be normal
What triggers episodes in Gilbert syndrome?
Triggers include fasting, dehydration, stress, menstruation, and illness.
What are the phases of hepatitis infection?
- Phase 1: Incubation/Viral Replication Phase where patients are asymptomatic
- Phase 2: Prodromal Phase
- Phase 3: Icteric Phase
- Phase 4: Convalescent Phase
How do patinets present in Phase 2 of hepatitis?
Patients in this phase may present with anorexia, nausea, vomiting, malaise, pruritus, urticaria, arthralgias, and fatigue. These patients are often diagnosed as having gastroenteritis or other viral infections.
How do patients present in phase 3 of hepatitis?
Patients in this phase present with dark-colored urine and pale-colored stool. Some patients develop jaundice and right upper quadrant pain coupled with liver enlargement. Liver enzymes will be elevated.
How does Phase 4 Of hepatitis present?
Patients typically start noticing the resolution of symptoms, and laboratory studies show liver enzymes returning to normal levels.
What is the main transmission route for Hepatitis A?
RNA virus Commonly transmitted through the fecal-oral route via contaminated food or close contact.
What is the incubation period for Hepatitis A?
The incubation period is 2-6 weeks.
What are the symptoms of Hepatitis A?
Self limiting illness and Symptoms include nausea, vomiting, abdominal pain, fatigue, malaise, poor appetite, and fever.
Symptoms usually start after the approximately 4-week incubation period, with 1-3 weeks in the icteric phase and they resolve spontaneously in most patients. Recovery is a month in younger people.
What are the diagnostic findings for hepatitis A?
ALT will be highest, with bilirubin levels increasing later. Anti-HAV IgM antibodies are produced, positive for 4-7 months. Anti-HAV IgG is present for a ifetime.
Antibodies can be tested through reverse transcription genetic testing. There may be a cholestasis variant of hepatitis A infection, where ALP and GGT are highest
What is hepatitis B?
double stranded DNA virus fund in the serum, semen, vaginal mucus, saliva, and tears. It can be transmitted parenterally and sexually, with high risk groups being healthcare workers, IV drug users, gay men, people wh require multiple blood transfusions and endemic areas. It can be transmitted parenterally to infants that can develop a chronic infection. It typically causes acute hepatitis and has an incubation period of 60-90 days.
What is the first serum marker to appear in acute Hepatitis B infection?
HBsAg (hepatitis B surface antigen) indicates current infection.
What indicates a chronic Hepatitis B infection?
If HBsAg is present for more than 6 months.
What does HBeAg indicate?
HBeAg-positive patients are most infectious, loss of HBeAg and conversion to anti-HbeAg is an indicator of seroconversion and clinical remission of disease.
What does anti-HbsAg mean?
immunity to Hep B
What does anti-HbE indicate?
Anti-HBe (hepatitis B antibody indicates lower ifnectivitiy from clearance of HBeAg from plasma
What does HBcab mean?
HBcAb (hepatitis B core antibody) where IgM is acute infection and IgG indicates past infections.
How does Hep B infection present?
incubation period of approximately 12 weeks and have symptoms of anorexia, malaise, and fatigue, which are the most common initial clinical symptoms. Some patients may experience right upper quadrant pain
Jaundice and painful hepatomegaly, dark-colored urine, and pale-colored stools.
What is the most common blood borne pathogen?
Hep C transmitted mainly through IV drug use and blood transfusions but can be transmitted parenterally, perinatally. There are seven genotypes which makes developing curative treatment difficult. Genotype 1 i the most common worldwide.’
Sexual transmission is rare.
What is the pathophysiology of hepatitis C?
Enters hepatocytes via endocyotisis and induces viral replication, detectable 1-4 weeks after exposure. It peaks in the first 8-12 weeks of infection.
Hepatitis C is not cytoplasmic as a chronic infection but can result in a local inflammatory response which triggers fibrogenesis.
What is the presentation of Hep C?
Presentation is usually asymptomatic but may include malaise, nausea, and right upper quadrant pain, followed by dark urine and jaundice. Chronic infection can result in liver decompensation with portal hypertension, esophageal varices, ascites, coagulopathy, encephalopathy, or hepatocellular carcinoma.
What does Hep C increase the risk of?
fatty liver disease by 50%
What is the marker for HCV?
HCV exposure can bedetected with antibodies to theHCV (anti-HCV). These assays can detect antibodies within 4 to 10 weeks of infection.
anti-HCV can remain negative for a few months after an acuteHCV infection.
What is the treatment for chronic Hepatitis C infection?
It is treated with pegylated interferon and ribavirin.
What is the marker for hepatitis D?
Hepatitis D infection is diagnosed by checking for Anti-HDV antibodies for IgM and IgG, but IgM to anti-HBc must be checked for coinfection
What is Hepatitis E infection?
self-imitng acute hepatitis and a non-enveloped single stranded RNA virus, transmitted via the faecal-oral route. Though self-limiting, it can be severe in pregnant patients or those with chronic liver disease as they will be at risk of fulminant liver failure.
What is the presentation of Hep E?
Eelvated bilirubin, ALT and AST
It has an incubation period of 28 to 40 days, which is absorbed from the gastrointestinal mucosa into portal circulation. Patients with acuteHEV infection develop an acute self-limited illness similar to HAV infection. Genotype 1 and 2 is strongly associated with pregnancy.
What is the key characteristic of Hepatitis D infection?
RNA virus which requires co-infection with Hepatitis B virus to replicate.
What is the main management approach for Hepatitis E?
Supportive care, especially in severe cases.
What is a common complication of Hepatitis E in pregnant patients?
Higher mortality rate and risk of fulminant liver failure.
How does pegylated interferon act?
first line for hepatitis which acts by acting on human type 1 interferon receptors to dimerise and increase expression of genes involved in the innate antiviral response via the JAK/STAT pathway
Which hepatitis types have vaccine available?
Hepatitis A
Hepatitis B
Hep C has no vaccine
How does alcohol affect the liver?
Alcohol is converted by alcohol dehydrogenase -> acetaldehyde,facilitated by the conversion of NAD+ -> NADH and the acetaldehyde -> acetate by ALDH.
Acetaldehyde can bind to hepatocytes and induce immune mediated damage from hepatocytes. Lipopolysaccharide will be translocated from intestines to hepatocytes and hepatic Kuppfer cells
What is the typical progression of alcoholic liver disease?
- Alcoholic fatty liver
- Alcoholic hepatitis
- Cirrhosis
What are the symptoms of alcoholic hepatitis?
Painful hepatomegaly, jaundice, inflammation, fever, and fatigue. Occurs within 60 days of heavy alcohol consumption for a minimum of 6 months. There will be steatosis and hepatocellular necrosis with inflammation. Serum bilirubin will be elevated and raised AST to ALT ratio.
What is the pathophysiology of alcoholic fatty liver?
first stage where accumulation of fat in liver causes hepatomegaly but is asymptomatic and reversible. Women are more susceptible and obesity and a high fat diet increases the risk.
High levels of NADH formation causes glycerol phosphate to be created which combines with fatty acids to form triglycerides which accumulate in the liver and impaired lipolysis from alcohol consutmpion worsens this. The fat cells accumulate around the venules and progresses to the portal tracts, with ballooning of the hepatocytes, neutrophil infiltration.
What is the unit consumption for alcoholic liver disease?
in men is more than 3 units per day or 21 units per week. For women, it is 2 units per day or 14 units per week. Hepatitis C can result in a younger age of disease susceptibility and progression.
What laboratory finding is typical in alcoholic hepatitis?
Elevated serum bilirubin and raised AST to ALT ratio.
What is the role of alcohol dehydrogenase in alcohol metabolism?
It converts alcohol to acetaldehyde.
Fill in the blank: The mutation in Gilbert syndrome affects the _______ gene.
UGT
True or False: Hepatitis A can lead to chronic infection.
False
What is the main method for diagnosing Hepatitis C?
HCV RNA testing and antibodies to HCV (anti-HCV).
What is the significance of anti-HBs antibodies?
Indicates clearance of HBV and immunity from subsequent exposure.
What is the treatment for acute Hepatitis B infection with liver failure?
Nucleoside analogues.
What is the minimum duration of alcohol consumption associated with alcoholic liver disease?
6 months
What are the typical histological features of alcoholic liver disease?
Steatosis and hepatocellular necrosis with inflammation
What laboratory findings are expected in alcoholic liver disease?
Elevated serum bilirubin and raised AST to ALT ratio
PT and INR increased
Metabolic profile will show low potassium, magnesium a dn phosphorus
What is cirrhosis?
Hepatic tissue is replaced with scar tissue resulting in portal hypertension
What age group is typically affected by alcoholic liver disease?
40 to 60 years old
What is the alcohol consumption threshold for men that increases the risk of alcoholic liver disease?
More than 3 units per day or 21 units per week
What is the alcohol consumption threshold for women that increases the risk of alcoholic liver disease?
2 units per day or 14 units per week
What are common physical examination findings in a patient with alcoholic liver disease?
- Jaundice
- Hepatomegaly
- Splenomegaly
- Spider telangiectasias
- Dupuytren contractures
- Testicular atrophy
- Decreased libido
- Parotid and lacrimal gland enlargement
- White nails
- Muecke lines
- Asterixis
- Ascites
- Pedal edema
- Encephalopathy
- Caput-medusae
What is the management strategy for alcoholic liver disease?
- Alcohol abstinence
- Nutritional support
- Monitoring for hepatocellular carcinoma
- Reducing acetaminophen dose
What short-term treatment can be used for alcoholic hepatitis?
Oral prednisolone
What condition should be treated immediately with parenteral thiamine?
Wernicke’s encephalopathy
What does the FRAMES principle stand for in patient advice?
- Feedback
- Responsibility for change
- Advise
- Menu for change
- Empathy
- Self-efficacy
What are the features of alcohol withdrawal?
- Agitation
- Tremor
- Nausea
- Vomiting
- Sweating
- HLA urination
When do mild withdrawal symptoms typically occur after alcohol abstinence?
24-48 hours
What is the first-line treatment for alcohol withdrawal?
Chlordiazepoxide
What is Budd-Chiari syndrome?
Post-hepatic obstruction of blood flow
What are the two main types of causes for Budd-Chiari syndrome?
- Hepatic vein thrombosis
- Secondary compression from a tumor
What are common conditions predisposing to hepatic vein thrombosis?
- Virchow’s triad of hypercoagulability, endothelial injury and haemostasis
*Myeloproliferative disorders - Oral contraceptive pill
- Pregnancy
- Lupus anticoagulant
- Liver cancer
What causes compression leading to Budd-chairi syndorme
hepatocellular carcinoma followed by adrenal gland, renal cell carcinoma, Wilm’s tumor and myxoma.
Lesions of the liver can cause compression of the vasculature like hepatic cysts, adenomas and aortic aneurysm. Inflammatory conditions like Behçet’s disease and tuberculosis
What is the clinical triad associated with Budd-Chiari syndrome?
- Abdominal pain
- Ascites
- Painful hepatomegaly
What are the common diagnostic findings in Budd-Chiari syndrome?
- Raised AST and ALT
- Increased PT
Which imaging modality confirms Budd-Chiari syndorme?
Ultrasound pulse and Doppler ultrasonography is ideal. There will be IVC webs and thrombi, decreased IVC diameter, presence of hepatic venous thrombosis, presence of ascites.
What is the pathophysiology of budd-chairs syndorme?
thrombosis will cause back pressure and lead to centrilobular necrosis, resulting in ischaemia and peripheral fatty changes. Congestion of portal vein can result in splenomegaly, ascites and oesophageal varices and hepatorenal syndrome. The most common lobe affected is the caudate lobe because blood is directly shunted into the inferior vena cava.
What are the acute manifestations of budd-chairs syndorme?
Acute manifestation develops rapidly over a few weeks with hepatic necrosis and intractable ascites, and abscence of venous collaterals
What are the subacute manifestations of budd-chairi syndrome?
stasis ulceration (venous ulcer)
Subacute has insidious onset with venous collaterals taking up to 3 months to developChronic development has patients presentin with complications of cirrhosis and venous collaterals are present.
What are the treatment options for Budd-Chiari syndrome?
- Anticoagulants initially with LMW heparin and then transition to warfarin
*dietary salt restriction to manage ascites
Alternatives include:
* Thrombolysis
* Stenting
* Transjugular intrahepatic portosystemic shunt
What condition is characterized by increased portal venous pressure and dilation of the portal vein?
Hepatorenal syndrome
in response through nitric oxide release, causing vasodilation in splanchnic circulation however cardiac output will increase and reduced circulatory volume, reducing blood flow to kidneys. There will be RAAS activation to worsen cardiac output. This can result in peripheral oedema and ascites
vWhat precipitates hepatorenal syndrome?
- Bacterial infection
- Large volume paracentesis
- Gastrointestinal bleeding
What is the most common cause of hepatorenal syndrome worldwide?
viral hepatitis
What is the most common cause of hepatorenal syndorme in the UK?
medications like acetaminophen, chronic alcoholism or drugs that induce cytochrome p450 or non-alcoholic steatohepatitis.
What are the two types of hepatorenal syndrome?
- Type 1: Rapid and progressive decline in renal function
- Type 2: Ascites resistant to diuretics
What management strategies are used for hepatorenal syndrome?
- Achieving euvolemia
- Administering vasoconstrictors
- Transjugular intrahepatic shunt
- Liver transplant and dialysis
What laboratory finding is typical in chronic liver disease associated with hepatorenal syndrome?
Rise in serum creatinine
What is hepatorenal syndrome treated with?
Ocreotide or midodrine, splanchnic vasoconstrictors
What are the components of the Child-Pugh classification for cirrhosis?
- Bilirubin over 3
- Albumin over 28
- INR over 2.3
- Ascites
- Encephalopathy
What characterizes non-alcoholic fatty liver disease (NAFLD)?
Most common cause of chronic liver disease where there is Indolent fat storage driven by insulin resistance
What are common associated conditions with NAFLD?
- Hypertension
- Type 2 diabetes
- Hypercholesterolemia
What is the primary source of hepatic fat accumulation in NAFLD?
Circulating free fatty acids from adipose tissue lipolysis due to insulin resistance
Which endocrine conditions contribute to NAFLD?
- Hypothyroidism
- Underactive pituitary gland
- Rapid weight loss
- Jejunum bypass surgery
- Obstructive sleep apnea
- PCOS
- Post menopause
What hormones are involved in satiety and how do they respond in NAFLD?
- GLP-1 response reduced
- Ghrelin response increased
What happens to leptin and adiponectin levels in NAFLD?
- Leptin is lowered
- Adiponectin is low
How does insulin function in the liver regarding gluconeogenesis?
Inhibits gluconeogenesis, lipogenesis, and glycogenesis
In NAFLD, increased lipolysis and FFA and glycogenolysis storage and increase gluconeogenesis.
What are the stages of NAFLD?
- Steatosis
- NASH
- Cirrhosis
What defines steatosis in NAFLD?
Fatty liver with fat accumulation in hepatocytes, asymptomatic and reversible
What occurs during NASH?
Inflammation and hepatocellular injury with fat accumulation leading to fibrosis
What is the threshold for alcohol consumption in NAFLD?
Less than 2.5 units a day for women and 3.75 units for men
What is the main diagnostic approach for NAFLD?
Clinical history to assess alcohol consumption and metabolic risk factors
Indications of NAFLD is persist elevation of ALT 3 times above normal, greater than AST, high bilirubin, with absence of exces alcohol intake and increased echogenicitiy on ultrasound.
What symptoms can present in NAFLD?
Typically asymptomatic but may present with:
* Fatigue
* RUQ discomfort
* Hepatomegaly
* Jaundice
* Ascites
* Peripheral edema
* Hepatic encephalopathy
What complications can arise from NAFLD?
- Portal hypertension
- Variceal hemorrhage
- Liver failure
- Hepatocellular carcinoma
What investigations are included in the assessment of NAFLD?
- Physical examination stigmata of hypertriglyceridaemia including Xanthomas, palmar striae and milky plasma and hepatosplenomegaly. Assess weight, height, blood presssure and signs of advanced liver disease.
- Blood pressure
- FBC
- Liver function test
- Lipid panel
- Metabolic panel
- Imaging (ultrasound, CT)
- Fibroscan
- MRE
What is the gold standard for diagnosing NAFLD?
Liver biopsy
Fibroscan of the liver using transient elastography, a Non invasive ultrasound test which measures liver stiffness and correlates with the degree of fibrosis.
What scans can detect fibrosis in NAFLD?
Fibroscan
MRE which is a ultrasound and MRI imaging to create visual map of liver fibrosis and assesses the entire liver, detect fibrosis at an early stage and reduction risk of liver complications like ascites
What are the indications of NAFLD?
- Persistently elevated ALT 3 times above normal
- Greater than AST
- High bilirubin
- Absence of excessive alcohol intake
- Increased echogenicity on ultrasound
What tools assess fibrosis in NAFLD?
- FIB-4 score
- NAFLD fibrosis score
What does the FIB-4 test evaluate?
Age, AST, ALT, and platelet count
What does the ELF test assess?
enhanced liver fibrosis (elf) test for Risk of advanced liver fibrosis in NAFLD based on 3 fibrosis markers in blood: hyaluronic acid, pro collagen III amino-terminal peptide and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)
What are the management strategies for NAFLD?
- Lifestyle modification
- Optimal management of hypertension, hyperlipidemia, and type 2 diabetes
- Monitor for signs of advanced liver disease
- Annual cardiovascular disease risk assessment
- Liver fibrosis reassessment every 3 years
What is recommended for non-diabetic patients with NAFLD?
Vitamin E supplementation
What are off-label therapies for NAFLD?
- Pioglitazone
- Vitamin E
What are the definitive management options for NAFLD?
- Liver transplantation
- Bariatric surgery
What is acute porphyria?
A group of disorders caused by a defect in the haem biosynthesis pathway arising from the liver
What is the most common subtype of acute porphyria?
Acute intermittent porphyria
What are common triggers for acute porphyria attacks?
- Hormonal therapies
- Antibiotics
- Anaesthetics
- Barbiturates
- Sulphonamides
- Antifungal agents
What is the triad of symptoms for acute porphyria?
- Visceral abdominal pain
- Neurological dysfunction
- Psychiatric disturbances
What are symptoms of acute attacks in acute porphyria?
- Severe abdominal pain
- Nausea
- Constipation
- Palpitations
- Sweating
- Confusion
- Neurological manifestations
What triggers acute porphyria?
Hormonal therapies containing oestrogen and progesterone
Antibiotics like rifampicin and isoniazid and nitrofurantoin
Anaesthetics ketamin and etomidatie
Barbiturates
Sulphonamides
Antifungal agents
What is the diagnosis for acute porphyria based on?
Urgent fresh urine samples for urinary porphobilinogen levels
What is crucial for urine, plasma, and faecal samples in acute porphyria?
Keep out of sunlight to prevent breakdown
What is the management for acute porphyria?
- Manage precipitating factors
- IV infusion of saline and glucose
- Pain relief
- Definitive treatment with IV heme
What drugs are metabolized by P450?
- Clopidogrel
- Statins
- Warfarin
What is the mnemonic for P450 inhibitors?
SICKFACES.COM
What drugs are included in P450 inhibitors?
- Sodium valproate
- Isoniazid
- Cimetidine
- Ketoconazole
- Fluconazole
- Alcohol & Grapefruit juice
- Chloramphenicol
- Erythromycin
- Sulfonamides
- Ciprofloxacin
- Omeprazole
- Metronidazole
What is the mnemonic for P450 inducers?
CRAP GPS
What drugs are included in P450 inducers?
- Carbamazepines
- Rifampicin
- Alcohol
- Phenytoin
- Griseofulvin
- Phenobarbitone
- Sulphonylurea
