Liver Flashcards
How is hepatocellular injury diagnosed?
Disproportionate elevation of AST and ALT levels compared to ALP level
What does disproportionate elevation of AST and ALT levels compared to ALP level mean?
hepatocellular injury
How is cholestatic injury diagnosed?
- Disproportionate elevation in ALP compared to AST and ALT levels
- Elevated serum gamma-glutamyl transpeptidase(GGT)
How is isolated hyperbilirubinemia diagnosed?
Elevation of bilirubin with normal ALP and AST/ALT levels
Sx of viral hepatitis
fever, malaise
nausea, vomiting, anorexia
hepatomegaly
inflammation, pain (right hypochondrial pain)
incr ALT > inc AST
incr atypical lymphocytes (lymphocytosis)
jaundice
dark urine(inc. conjugated Bilirubin and Urobilinogen (UBG) )
pale stools (bile obstruction)
if >6m –> chronic
Labs to look out for in viral hepatitis
Temp
Elevated ALT(higher) and AST
Raised GGT
Inc atypical lymphocytes (lymphoctyosis)
Leukopenia
antibodies for diff hepatitis types?
A/D/E:
Anti- HAV IgM(active infection) –> acute
Anti- HAV IgG(prior exposure/vaccination)
B:
HBsAg + (current infection)
HBeAg +/- (current infection)
Anti-HBc IgM +
HBV DNA PCR +
C:
Anti-HCV IgG + –> check RNA
HCV RNA (+ : current active infection; - : at risk of reinfection upon re-exposure)
Treatment goals for HBV
HBV suppresion, prevent progression cirrhosis, Hepatocellular carcinoma (HCC)
Eligibility for HBV treatment
- HBV DNA >2000IU/mL
- ALT 2xULN and/or cirrhosis
- if below, consider: age, FHx of HCC, extrahepatic HBV
Rx for HBV
Immune-mediating agents: (Injectables)
Pegylated interferon(IFN-a) and INF-a;
SE: bone marrow suppression, flu-like symptoms, GI, neuropsychiatric disorders; Given for pre-defines durations
Nucleoside Agents (NAs):(Oral)
Entacavir, tenofovir disoproxil, tenofovir alafenamide, Lamivudine, telbivudine, and adefovir; Given till specific endpt rched
What is Pegylated interferon(IFN-a) and INF-a for
HBV suppression?
SE of Pegylated interferon(IFN-a) and INF-a
SE: bone marrow suppression, flu-like symptoms, GI, neuropsychiatric disorders
What are oral Nucleoside Agents (NAs) for and examples?
For HBV suppression
Entacavir, tenofovir disoproxil, tenofovir alafenamide, Lamivudine, telbivudine, and adefovir; Given till specific endpt rched
What are to be done before HCV trx?
◦ Perform quantitative HCV testing and genotyping
◦ Assess for underlying liver disease(tx options/drn)
◦ Screen for hepatitis B
What are HCV trx?
Direct-acting antiviral (DAA) therapy:
N3/4A protease inhibitors (e.g. grazoprevir)
NS5A inhibitors (e.g. ledipasvir)
NS5B polymerase inhibitors (e.g. sofosbuvir)
Used in combination with at least 2 drugs acting
on different targets for 8-12 weeks
Significant DDIs
◦ Anti-HCV Nucleoside Agent (NA)
Ribavirin ; Given in combination with DAA
SE: Haemolytic anaemia, Fatigue, Teratogenic
◦ Peg-INF-a
Non-Rx for HBV or HCV?
B: - Prevention of diseas transmission
- no alcohol, smoking
C: Patient counselling and non-pharmacologic therapy:
◦ Prevention of Hepatitis C transmission
◦ Vaccination against Hepatitis A and B
◦ Lifestyle modification including reducing/stopping alcohol use and weight loss
How are the different hepatitis virus transmitted?
A/E: Faecal-oral contamination
B/C: Blood and body fluids, parental and perinatal, sexual
D: coinfection w hep B
Clinical sequalae of chronic hepatitis B and C
Liver cirrhosis
Chronic active hepatitis
Hepatocellular carcinoma
Hep D superinfection w B
extrahepatitic manifestations (w hep C) –>cryoglobinemia (protein clump tgt at Temp<37 degC), vascolotiis, skin, worsening organ function (kidneys)
Vaccination is available for?
Hep A and B only
A: all travelers/susceptible persons travelling/working w hep A endemic
B: given to all newborn as part of childhood immunisation programme/ people at risk
Pathophysiology of liver cirrohosis
chronic damage to lungs causes damaged to normal liver tissues and results in development of regenerative nodulessurrounded by dende fibrotic material.
This impedes portal blood flow, interferes with hepatocyte perfusion and disrupts hepatic synthesis functions (eg. produce albumin)
Clinical sequelae of liver cirrhosis
portal hypertension, varices, variceal bleeding, ascites, infection, encephalopathy and HCC, cirrhotic cardiomyopathy, coagulation defects (dec protein C and S + incr factor VIII and vonWillebrand factor)
First clinical signs of liver cirrhosis
ascites, bleeding, encephalopathy, jaundice
What is ascites?
accumulation of excessive fluid in peritoneal cavity
formed due to portal hypertension, increasing hydrostatic pressure in portal circulation
intravascularoncotic pressure decreasedand underfillin g ofreduced aldosterone metabolisim, acitivating RAA system
Splanchnic vasodilation –> fluid shift out of portal circulation peritoneal cavity
***leads to varices in esophagus and stomach
Definition of portal hypertension?
gradient greater than 5 mmHg btwn portal and central venous pressures (eg. hepatic venous pressure gradient)
When may variceal bleeding occur?
HVPG of >10mmHg
Goal of liver cirrhosis
prevent bleeding
Sx of hepatic encephalopathy
altered mental state, lethargic, delirium, coma
What is hepatic encephalopathy
accumulation of nitrogenous substance (ammonia) in blood which may enter CNS
Types of HE
A: induced by acute liver failure
B: due to portal systemic bypass w/o associated liver disease
c: pt w cirrhosis
Sx of liver cirrhosis
- thrombocytopenia
- Pruritis
− Palmar erythema
− Spider angiomata
− Hyperpigmentation
− Metabolic complications including gynecomastia, testicular atrophy, and axillary hair loss (decr. estrogen)
Sx of liver cirrhosis
- ascites,
- bleeding,
- encephalopathy(confusion, inattention, personality change)
- jaundice
- weight loss, fatigue, appetite loss
- signs of decompensated liver cirrhosis
Liver cirrhosis:
- thrombocytopenia
- Pruritis
− Palmar erythema
− Spider angiomata
− Hyperpigmentation
− Metabolic complications including gynecomastia, testicular atrophy, and axillary hair loss (decr. estrogen)
Causes of liver cirrhosis
- Alcohol use
- Obesity + diabetes suggestive of NAFLD
- RF for Hep B/C
- Hx of autoimmune/hepatitic disease
- Medications
Labs for liver cirrhosis
Liver function tests
− Coagulation tests (PT, aPTT, INR)
− Complete blood count including platelet
(Cause)
- Serologic tests for viral causes(hep B/C)
− Antinuclear antibody titer to evaluate for the presence of autoimmune hepatitis
− Serum iron and transferrin saturation + genetic testing, to look for hemochromatosis
− Alpha1 antitrypsin level and genotyping to test for alpha1 antitripysin deficiency
ABCDE approach to liver cirrhosis
Portal hypertensin Rx
Non selective Beta-adrenagric blockers(NSBBs)
(HR of 55-60bpm)
- Propanol 20-40mg BD (max:320mg norm/160mg w ascites)
- Carvedilol (6.25mg OD; max: 12.5mg) +/- endoscopic variceal ligation(EVL)
MOA: decr. CO,(b1 blockage), decr. splanchnic blood flow (b2 blockage), vasodilation via NO release(anti-a)
SE: bradycardia, bronchospasm(b2)
CI: SBP<90mmHg, Refractory ascites, bleeding AKI
IF BLEEDING:
Vasoactive agents(3-5 days):
inhibit splanchnic vasodilation –> decr. flow to GIT
- Octreotide IVb 50mcg (repeated in first hr if ongoing bleeding) –> cont. IVf 50mcg/hr for 2-5d
- Vasopressin cont IVf 0.2-0.4 U/min (max 0.8) + IV nitroglycerin start dose 40mcg/min (max: 400mcg/min) for 24h
- Somatostatin IVb 250mcg(rpt in 1st hr if ongoing bleeding) –> cont IVf 250-500ug/h for 2-5d
- Terlipressin intial 48h: 2mg/4h IV until bleeding controlled; 1mg/4h IV to prevent bleeding for 2-5d
SE: hyperglycemia, HTN, bradycardia
Only one to be used
Antibiotic prophylaxis(5-7 days):
ceftriaxone, norfloxacine
If further bleeding: Transjugular intrahepatic portosystemic shunt(TIPS) / Balloon tamponade
What is used in primary/secondary prophylaxis?
Primary prophylaxis: NSBBs/Endoscopic Variaceal ligation )EVL every 2-8wks until eradication of varices
Secondary prophylaxis: NSBB + chronic EVL
Goals of liver cirrhosis
eliminate causes, prevent/stop bleeding, prevent complications(ascites, HE)
Primary prophylaxis recommended in?
small varices w red wale marks/ Child-Pugh C
medium/large varices
goals in ascites
control ascites, relieve sx (dyspnea, abdominal pain, distention), prevent life threatening complications (SBP, HRS)
Management of ascites?
Spironolactone 100mg + furosemide 40mg PO OM using 100:40mg ration for natriuresis + weight loss
(max: 400:160)
SE: AKI, hyponatremia, hypokalemia, HE, gynecomastia, muscle cramps
- Avoid NSAIDs, ARB, ACEI!!!
- Avoid alcohol
- Reduce sodium intake to <2000mg/day
- No fluid restr. unless Na < 125mmol/L
Goals for hepatic encephalopathy
reduce ammonia levels in blood
- diet: 1.2 -1.5g/kg/day from veg + dairy compared to meat + zinc
- Rifaximin 550mg BD +/- lactulose –> inhibit anaerobic bact w urease(converts urea to ammonia)
- Lactulose 20-30g BD-QDS(prevention); 20-30g every 1-2h to induce soft stools : lowers colonic pH (ammonia to ammonium for excretion) –> go to toilet 2-3 times a day + monitor electrolytes
Definition of nonalcoholic fatty liver disease
- hepatic steatosis by imaging/histology
- no secondary causes of hep fat accumulation(alc med)
- may have elavated serum ferritin and autoimmune ab
how to differentiate non alcoholic fatty liver disease and non-alcoholic steatohepatitis
NAFL: no evidence of hepatocellular injury + minimal risk of progression to cirrhosis/liver failure
NASH: with inflammation and hepatocellular injury, may progress to cirrhosis/liver failure
RF for NAFLD
Obesity, T2DM, dyslipidemia, Metabolic symdrome, polycystic ovary syndrome
management of NAFLD
Pioglitazone (for metabolic dysfunction NASH)
30 mg once daily for 2 months, then increase dose to 45 mg once daily (Ref). Consider limiting dose to ≤30 mg/day if CHF concern
SE: bladder cancer, fractures, HF/edema, acute hepatic failure, hypoglycemia, URTI
Vitamin E 800 units (360 mg dl-alpha tocopherol or 536 mg of d-alpha tocopherol) once daily
- statins for dyslipidemia (except decomp cirrhosis) –> modify CVS factors
what is the boxed warning for pioglitazone?
congestive heart failure: excessive, rapid weight gain, dyspnea, and/or edema
