Cirrhosis, CLD complication, fatty liver disease Flashcards
List causes of cirrhosis
- Alcoholic liver disease
- Nonalcoholic fatty liver disease (fatty liver)
- Hepatitis B
- Hepatitis C
- Drugs
- Ethanol **
- Fatty liver
- Genetic: copper, alpha-1 antitrypsin deficiency
- Haemochromatosis
- Immune: AIH (Autoimmune Hepatitis), PBC (Primary Biliary Cholangitis), PSC (Primary Sclerosing Cholangitis)
DESCRIBE CLiiical featurs of cirrhosis
- spider naevi
- palmar erythema
- ascites
- white nails/leuconychia
Hepatic damage–>insufficiency:
- coma
- jaundice
- liver damage
- anaemia
- haemorrhage
- oedema
- ascites –also portal hypertension
- note hepatic damage also results in hyperestrinism, causing spider naevi, gynaecomastia, pectoral alopecia, altered hair distribution, palmar erythema and testicular atrophy
- portal hypertension
- oeso varices
- splenomegaly
- caput medusae
- ascites
- ankle oedema
- hyperspenism–> bone marrow changes
Routes to mortality from liver disease
- Bleed (varices)
- Infection (spontaneous bacterial peritonitis)
- Cancer (HCC - Hepatocellular Carcinoma)
- Coma (encephalopathy)
- Renal failure
Describe ascites, relationship to liver disease, and how to determine if ascites, infection, neoplastic process involved
- 85% (cirrhotic)
-
15% (non-cirrhotic)
- Renal
- Cardiac
- Peritoneal metastasis
Ascites: Questions to Ponder
- Is it cirrhotic ascites?
- SAAG (Serum albumin - ascites albumin gradient) > 11 g/L indicates portal hypertension
- Is there infection?
- Neutrophils > 250/cu.mm
- Is there cancer?
- Cytology
Describe pathophysiology of ascites
see also [[Gastroenterology - Lecture 5]]
- renal retention of sodium
- reduced effective arterial blood volume (due to stiffliver)
- activates RAAS, SNS, ADH
- Na, H2O retention and increased plasmavolume
- compartmentalisation of fluid to peritoneal cavity
- increased hydrostatic pressure due to stiff liver, lymphatic flow
—-> ascites
Describe management of ascites
- Salt restriction (2 g/day)
-
Diuretics:
- Start with spironolactone - due to high aldo conc
- Add frusemide
- Monitor weight, U&E, urine sodium to prevent complications from diurtic use
- No need to restrict fluid (unless Na+ below 120)
describe treatment of diuretic-resistant ascites
- Definition: Ascites not responding to max doses or adverse effects develop/not tolerated
-
Large volume paracentesis with albumin (supplement Albumin 8-10 g/litre fluid removed)
- To prevent postparacentesis circulatory dysfunction
Describe sbp
- Signs: Often none, nonspecific; diagnosis by ascitic fluid test - WCC >250–> antibiotics
- Treatment: IV antibiotics (e.g., ceftriaxone) for 5 days
- Prevention: Prophylactic oral antibiotics if there is a history of SBP; in patients with GI bleed
Descrieb hepatic encephalopathy
- Impaired neuropsychiatric syndrome due to acute or chronic liver disease
- Hepatic encephalopathy in essence: ammonia intoxication as a result of portal shunting to brain, altering mental state
- ammonia end-product of protein metabolism in intestine, due to bacteria
- shunted to liver, normal de-toxxed to urea and excreted
-
Grades I (mild confusion, non-specific, poor sleep, ‘night watchman- awake at night, asleep in day’) to IV (coma)
- FLAP/Asterixis - more prominent in GII/III - unlikely in GI
- neuropsychiatric symptoms worsens in III
-
STROOP TEST/psychometric number connection tests (timed test)
- can be used to check response to treatment
-
Remember!
- There are other causes of confusion: SDH, sedating drugs and meds, hyponatremia, hypoglycaemia, withdrawal delirium from alcohol or Wernicke’s
Describe hepatic encephalopathy management
- Treat precipitating factors (infection, drugs, constipation, hypokalaemia, GI bleeding) -> helps improve encephalopathy
-
Lactulose (MAIN STAY)
- How does it work?
- Acidifies gut (reduces ammonia)
- Inhibits ammonia-forming bacteria
- Acts as a laxative
- How does it work?
-
Antibiotics: Sterilize gut - if not responsive to lactulose
- Rifaximin
- Metronidazole
- Neomycin (historical)
- combination of lactulose and antibiotics may be useful, eg if lactulose poorly tolerated ie patient becomes bloating
What are other consequences of cirrhosis?
- Kidneys: Hepatorenal syndrome (decreased blood flow)
- Lungs: Hepatopulmonary syndrome (rare), portopulmonary hypertension
-
Grading of cirrhosis severity
- CHILD-PUGH score, MELD score -
Describe varices and their significance
- back flow of blood into portal vein tributaries
- eg stiff liver —> left gastric and oesophageals anastomoses at GEJ; rectal anastomoses and haemorrhoids
Varices - Why Are They Important?
- Most (80%) cirrhotics will develop varices.
- Main cause of upper GI bleeding in cirrhosis (peptic ulcer, other causes less often).
- High mortality from bleed and rebleed (SCREEN ALL CIRRHOTICS).
- use platelet count, liver stiffness measurements i.e. fibroscan to screen
Describe management of varices
- Prevent: Prevent bleeding through banding or drugs that lower portal pressure (propranolol, carvedilol - beta blocker with alpha blocking action, may be useful in liver specifically). ^[avoid non-selective drugs in asthmatics]
- Bleeding: Treat bleeding with banding + drugs that lower portal pressure (octreotide IV/infusion - somatostatin analog).
- Prevent Re-Bleeding: Prevent re-bleeding through banding.
Descrieb managing acute bleeding from varices
- Bleeding can be SEVERE.
- Protect airway e.g. intubation, aim for Hb 80 g/L.
- Administer antibiotics and lactulose.
- SBP (Spontaneous Bacterial Peritonitis) and encephalopathy are common after a bleed.
- Antibiotics also reduce rebleeding risk.
- Start octreotide (reduces splanchnic flow).
- Endoscopy
##### Endoscopic Variceal Ligation (EVL) - EVL is 90% effective for control of acute bleeding.- done monthly until all variceal columns targeted
List alternatives to endoscopy
- If endoscopy fails:
- Balloon Tamponade: Sengstaken-Blakemore tube – OCCLUDE varices.
- Transjugular Intrahepatic Portosystemic Shunt (TIPS): DIVERT BLOOD.
- Surgery: Very rare now.
Sengstaken-Blakemore Tube (Balloon Tamponade)
- compress haemorrhaging vessels to occlude
#### Transjugular Intrahepatic Portosystemic Shunt (TIPS)
- DIVERT BLOOD.
Describe HCC, its relatinshup to cirrhosis and howearly tumours and detected
Hepatocellular Carcinoma (HCC)
- Cirrhosis of any cause (especially alcohol, hepatitis B and C) but can occur in absence of cirrhosis eg HepB, fatty liver
- usually ID’d by imaging eg U/S, CT
- Suspect HCC when there is weight loss, abdominal pain/mass, jaundice, or ascites.- but do not wait for these as these are signs of advanced disease
How to Detect Early Tumours
- Imaging: Ultrasound first, CT or MRI later, every 6 months.
- Tumour Marker: Alpha feto-protein (AFP).
Liver Imaging
- eg ultrasound, CT, in conjunction with AFP
- AFP (Alpha Feto-Protein)
- Produced by the fetal liver.
- Increased in 60% of cases.- absence does not exclude cancer
- Can be increased in other disorders (testicular tumours, (viral) hepatitis because it is a marker of liver regeneration).
Describe course of fatty lvier disease and increased susceptibility factors to liver injury from alcohol
- from fatty liver to alcoholic hepatitis to cirrhosis, alternatively straight to cirrhosis
- all heavy drinkers will have fat in liver
- fewer develop hepatitis, even fewer progress to cirrhosis
- Increased susceptibility to liver injury from alcohol:
- Women
- Other liver disorders (e.g., Hepatitis C)
- Metabolic syndrome: obesity, diabetes
- Genetic factors: genes involved in immune response, cytokines
Discuss sex differences in alcohol threshold for liver injury
- Men: 60-80 g/day x 5 years
- Women: 20 g/day
- Less than 20% of men who ingest 2 six-packs/day for 10 years end up with cirrhosis.
- sex difference alcohol threshold for injury; lower alcohol can still precipitate cirrhosis in men
Describe clinical presentation fo fatty lvier
alc
- Asymptomatic
- Enlarged, soft liver (fatty liver)
- Fever, jaundice, leukocytosis (hepatitis – will distinguish from eg HepB, see also [[Gastroenterology - Lecture 11]])
- Features of cirrhosis: jaundice, ascites, GI bleeding, encephalopathy
List relevant investigations in fatty liver disease
- Clinical suspicion important (CAGE)
- FBC/LFT: Anaemia, high MCV (direct effect of alcohol + B12+ folate), AST > ALT, GGT
- Other signs of advanced liver disease:
- Bilirubin, low albumin, coagulopathy, low platelets
escribe principles of treatment for fatty liver disease
alcohol
- No alcohol.
- Nutritional supplements: thiamine, B12, folate
- Corticosteroids (in severe alcoholic hepatitis).- only s-term, first 4 weeks therapy. Long-term does not improve outcomes
- Managing cirrhosis complications (AFP, liver ultrasound, endoscopy- looking for varices).
- Liver transplant (abstinence > 6 months, good social support demonstrated).
Describe relationship between alcohol and lvier disease
- Safe limits important but liver risk variable.
- Clinical spectrum: asymptomatic, big liver, “hepatitis”, cirrhosis/liver failure.
- Suspicion important: MCV, AST > ALT.
- Fatty liver reversible, hepatitis can progress, cirrhosis can progress.
- Treatment: stop drinking, supplements, steroids, rarely liver transplant.
Describe the specteum of MAFLD
Spectrum
- Healthy liver
- Fatty liver (Steatosis) >5% vol - at this stage, <1d/d women, <2 in men
- Steatohepatitis (N/MASH)
- Cirrhosis - irreversible step
- HCC either from MASH, or cirrhosis
- Alcohol-like liver histology in persons who don’t drink significant amounts of alcohol.
Fatty Liver - Spectrum
- Lobular inflammation
- Ballooning degeneration
- Perivenular fibrosis
What is the significance of MAFLD?
- 30%
- Advanced liver disease in a subgroup [age >45, obesity, diabetes].- screen
- Co-factor for other liver diseases.
- Increased cardiovascular risk^[significant contributor to mortality], diabetes mellitus.
- HCC risk.
DESCRIBE MAFLD pathogenesis
- Main underlying mechanism: insulin resistance.
- mAFLD is the hepatic manifestation of the metabolic syndrome.
- Other important processes: lipotoxicity, oxidative stress, adipocytokines, mitochondrial defects, genetic factors.
Describe MAFLD clinical presentation
- Asymptomatic
- Abnormal ultrasound, liver tests
- ALT > AST
- Enlarged, soft liver
- Advanced liver disease not common
- Look for metabolic syndrome: hypertension, type 2 diabetes, central obesity
Descrieb MAFLD natural history
- Overall, 5% of mAFLD develop cirrhosis, 1.7% die of cirrhosis complications (mean follow-up 7 years).
- Simple steatosis: benign outcome.
- mASH: One-third will progress (fibrosis).
- Cirrhosis 5%-10% over 5 years.
- Poor outcome of mASH-related cirrhosis.
Describe MAFLD principles of treatment
- lifestyle modification- aerobic and resistance exercise, eg Med diet; engaging personal trainer/dietitian/family support
- targeting MetS components
- liver-directed pharmacotherapy- only one recent drug, not mainstay
- managing complications of cirrhosis
-
Impact of Weight Loss on Improving Fatty Liver
- steatosis 35-100 - w/ weight loss >=103
- ballooning/inflammation 41-100 - w/ weight loss >=5
- NASH resolution in 64-90% - w/ weight loss >=7
- fibrosis in 45% - w/ weight loss >=10
List other MAFLD treatments
- bariatric sg when done for other metabolic disease
- semaglutide no effect on fibrosis, steatosis; only in context of diabetes
- other drugs not licensed except resmeritrom (thyroid hormone b-receptor), pioglitazone, vitamin E
