Hepatology lecture 1. · 2021. 5. 13. · Hepatology lecture 1. Tomas Koller, ... significant...
Transcript of Hepatology lecture 1. · 2021. 5. 13. · Hepatology lecture 1. Tomas Koller, ... significant...
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Hepatology lecture 1. Tomas Koller, Doc. MUDr. PhD.
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Liver anatomy
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Liver histology
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Clinical manifestation of liver disease
❖ fatigue
❖ right upper quadrant tenderness
❖ petechiae and bleeding
❖ increase in abdominal circumference
❖ edema
❖ pruritus
❖ hematemesis
❖ melena
❖ jaundice
❖ dark urine
❖ caput medusae
❖ palmar erythema
❖ spider angiomas
❖ ascites
❖ flapping
❖ malnutrition
❖ sarcopenia
❖ fever
LATE !
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Clinical syndromes in liver disease
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Acute hepatitis
❖ fatigue
❖ right upper quadrant tenderness
❖ petechiae and bleeding
❖ increase in abdominal circumference
❖ edema
❖ pruritus
❖ hematemesis
❖ melena
❖ jaundice
❖ dark urine
❖ caput medusae
❖ palmar erythema
❖ spider angiomas
❖ ascites
❖ flapping
❖ malnutrition
❖ sarcopenia
❖ fever
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Hepatic insufficiency
❖ fatigue
❖ right upper quadrant tenderness
❖ petechiae and bleeding
❖ increase in abdominal circumference
❖ edema
❖ pruritus
❖ hematemesis
❖ melena
❖ jaundice
❖ dark urine
❖ caput medusae
❖ palmar erythema
❖ spider angiomas
❖ ascites
❖ flapping
❖ malnutrition
❖ sarcopenia
❖ fever
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Cholestasis impairmant of bile formation or transport
❖ fatigue
❖ right upper quadrant tenderness
❖ petechiae and bleeding
❖ increase in abdominal circumference
❖ edema
❖ pruritus
❖ hematemesis
❖ melena
❖ jaundice
❖ dark urine
❖ caput medusae
❖ palmar erythema
❖ spider angiomas
❖ ascites
❖ flapping
❖ malnutrition
❖ sarcopenia
❖ fever
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Portal hypertension increased blood pressure in the portal and corresponding veins
❖ fatigue
❖ right upper quadrant tenderness
❖ petechiae and bleeding
❖ increase in abdominal circumference
❖ edema
❖ pruritus
❖ hematemesis
❖ melena
❖ jaundice
❖ dark urine
❖ caput medusae
❖ palmar erythema
❖ spider angiomas
❖ ascites
❖ flapping
❖ malnutrition
❖ sarcopenia
❖ fever
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Acute liver injury
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Acute liver injury
❖ Asymptomatic liver test elevation
❖ Acute hepatitis (>5-8x) upper limit of normal
❖ cytolytic (AST, ALT)
❖ cholestatic (ALP)
❖ mixed (both ALP and ALT)
❖ Acute severe hepatitis (PT<50%)
❖ Acute liver failure (PT<30% and HE)
❖ =fulminant
❖ Death
❖ Asymptomatic liver test elevation
❖ Acute hepatitis (>5-8x) upper limit of normal
❖ cytolytic (AST, ALT)
❖ cholestatic (ALP)
❖ mixed (both ALP and ALT)
❖ Acute severe hepatitis (PT<50%)
❖ Acute liver failure (PT<30% and HE)
❖ =fulminant
❖ Death
Liver function
%
Prevalence
%
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Acute liver injury common causes
❖ Viral hepatitis A, B, C, E
❖ Drug induced idiosyncratic (autoimmune) injury
❖ Dose unrelated
❖ Toxic hepatitis (Amanita poisoning, paracetamol, isoniazid, methylprednisolone)
❖ Dose related
❖ Wison’s disease
❖ Ischemic hepatitis (low cardiac output)
❖ Hepatic vein thrombosis (Bud-Chiari syndrome)
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Acute hepatitis
Right upper quadrant dyscomfort
ALT, ALT
Hepatomegaly
Cause of ALD ALT
AST
time
upper limit of normal
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Acute hepatitis management
Viral hepatitis A, B, C, E no therapy, HBV antivirals
Drug induced idiosyncratic reaction (antibiotics, NSA, hormones...) drug withdrawal
Toxic hepatitis (Amanita, paracetamol, isoniazid, methylprednisolone) drug withdrawal+antidotes*
Wison’s disease penicillamin
Ischemic hepatitis (low cardiac output) increase cardiac output
Hepatic vein thrombosis anticoagulants
*Antidotes:
Amanita poisoning: G-PNC iv, or silymarin iv
Paracetamol and other drugs: N-acetyl cystein iv
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Acute severe hepatitis management (PT<50%)
❖ Transfer to the liver unit 🚑
❖ Liver support systems
❖ MARS, Prometheus, Bioartificial liver🐷
❖ Bridging to LT
❖ Urgent liver transplantation
❖ PT<30% and hepatic encefalopathy
❖ No other contraindications
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Chronic liver injury
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Chronic liver injury
❖Chronic mild liver test elevation +++ (<2xULN)
❖Most common
❖ Chronic hepatitis (liver test elevation >2xULN/4-6 months)
❖ Cytolytic (dominant ALT elevation)
❖ Cholestatic (dominant ALP elevation)
❖ Vascular liver lesions
❖ Bud-Chiari syndrome, portal vein occlusion, venooclusive dis., regenerative nodular hyperplasia
❖ Focal liver lesions
❖ Benign (cysts, hemangioma, focal nodular hyperplasia)
❖ Malignant (metastasis, primary liver cancer)
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Chronic liver injury common causes
Alcoholic liver disease
Non-alcoholic fatty liver disease
Chronic viral hepatitis B, C, D, (E)
Primary biliary cholangitis
Autoimmune hepatitis
Primary sclerosing cholangitis
Wilson’s disease
Hereditary hemochromatosis
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Liver lobulus
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Chronic liver disease progression Regardless of the cause
❖ Increase in liver fibrosis
❖ Increase in liver stiffness*
❖ Increase in hepatic venous
pressure gradient (HVPG)**
❖ Abnormal laboratory findings
❖ AST>ALT
❖ Low platelets
**
*
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Chronic liver injury Fibrosis progression stages
Stage F1, mild fibrosis Stage F2, significant fibrosis Stage F3, advanced fibrosis Stage F4. cirrhosis
Liv
er
his
tolo
gy
Ela
sto
gra
phy
<7.5 kPa >7.5 kPa >13 kPa >13 kPa
HV
PG
<5 mmHg <5 mmHg 5-9 mmHg >10 mmHg
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Alcoholic liver disease
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The risk of liver disease after the1st. drink
Alcohol GBD, Drug Use C. The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of
Disease Study 2016. Lancet Psychiatry. 2018;5(12):987-1012.
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Alcoholic liver disease (ALD)
Risk factors for alcohol-induced liver damage:
• Amount of alcohol/day or per setting
>20g/day, or 4-5 (binge) drinks in few hours
• Time of exposure
• Females
• Genetic background (PNPLA3 polymorphism)
• Other toxins – trace elements in home-made a.
• Other liver diseases – steatosis, viral …..
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Alcoholic liver disease Patterns of progression
Driving force: alcohol consumption, obesity, viral hepatitis
abstinenc
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Alcoholic liver disease
Clinical: asymptomatic+++, portal hypertension a
late manifestation
Laboratory: AST>ALT, ↑ ↑ ↑ GGT, >MCV,
carbohydrate def. transferin, urine
ethynil glucuronide
Diagnosis: clinical history, objective history, AUDIT
C questionaire
Treatment: abstinence, psychological support
Prognosis: very good in case of abstinence, if
not - cirrhosis 30-40%/10-15
years
Audit C questionnaire
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Alcoholic hepatitis
❖ Clinical: jaundice+++, fever, abstinence syndrome, hepatomegaly ++
❖ Laboratory: AST>>>ALT, >MCV, high conjug. Bilirubin, elevated WBC, CRP
❖ Diagnosis: laboratory pattern, exclusion of biliary obstruction (US), (histology)
❖ Severity: Mild or Severe (Maddrey score, Lille model)
❖ Treatment: abstinence, severe: steroids
❖ Prognosis: mild: good, severe: mortality 30-50%, refractory to steroids>50%
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Non alcoholic fatty liver disease (NAFLD)
❖ Projected the most common chronic liver disease world-wide
❖ The fastest growing liver disease in terms of prevalence
❖ The second most common indication for LT in the USA
❖ Has recently been proposed to change its name to:
❖ “Metabolic associated fatty liver disease (MAFLD)”
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Non-alcoholic (metabolic) fatty liver disease Patterns of progression
Driving force: obesity, diabetes (insulin resistance)
Weight loss
TK1
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Snímka 34
TK1 Tomas Koller; 8. 5. 2021
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❖ Clinical: asymptomatic, obese, diabetic
❖ Laboratory: ALT>AST, ↑GGT, normal bilirubin, elevated ferritin
❖ Diagnosis: proof of liver fat (ultrasound or MRI), exclusion of significant alcohol intake, viral, AI and other etiologies, NASH – histology++
❖ Severity: depends on the fibrosis stage, histology or elastography
❖ Treatment: weight loss, exercise, control of diabetes, cholesterol, specific targeted drugs in the pipeline (liraglutide……)
❖ Prognosis: depends on the fibrosis stage, good up-to F2, bad in F3-4
Non-alcoholic (metabolic) fatty liver disease
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Chronic viral hepatitis
❖ Clinical: asymptomatic, rare extrahepatic manisfestations, cryoglobulinemia, glomerulonephritis
❖ Risk factors: HCV (iv. drugs++, tatoo, piercing, recipient of blood products, invasive procedures), HBV (infection in mother, invasive procedures, Asian origin)
❖ Laboratory: ALT>ULN in 70%, ALT can be normal
❖ Diagnosis: screening (anti HCV, HBs Ag), proof (HCV RNA, HBV DNA)
❖ Severity: depends on the fibrosis stage, histology or elastography, HBV depends on viral load
❖ Treatment: HCV (oral direct acting antivirals 2-3 months, cure 100%), oral HBV antiviral therapy (tenofovir or entecavir) long-term, follow-up and monitoring HBV DNA, ALT, and liver fibrosis markers)
❖ Prognosis: good, depends on the fibrosis stage, and the risk of liver cancer – F3,4 – surveillance for liver cancer by liver ultrasound á 6 months needed, fibrosis and even cirrhosis can regress on treatement
❖ Prevention: HBV vaccination, HCV – testing for blood products, HCV and HBV ELIMINATION WHO goal by 2030
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Primary biliary cholangitis
❖ Pathogenesis: autoimmune destruction of lobular bile ducts, trigger unknown
❖ Clinical: asymptomatic, pruritus, sicca syndrome, fatigue
❖ Laboratory: chronic cholestasis (ALP>>>ULN)
❖ Diagnosis: antiM2 (mitochondrial) autoantibodies or ANA anti-gp210
❖ Severity: depends on the fibrosis stage, histology or elastography
❖ Treatment: ursodeoxycholic acid (UDCA) 13-15 mg/kg orally (>80% success), non-response (obeticholic acid or bezafibrate), tratment of pruritus: cholestyramin, rifampin, naloxon, LT
❖ Prognosis: very good in initial stages and in responders, worse in higher fibrosis stage, LT in case of decomp. cirrhosis
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Autoimmune hepatitis
❖ Pathogenesis autoimmune destruction of hepatocytes, female predominance
❖ Clinical: asymptomatic, jaundice in severe cases
❖ Laboratory: acute or chronic hepatitis, ALT>AST, ↑ bilirubin
❖ Diagnosis: high IgG, auoantibodies anti-nuclear, anti-smooth muscle, histology+++ (piece-meal necrosis, infiltration of plasma cells)
❖ Severity: depends on the fibrosis stage, synthetic liver function
❖ Treatment: steroids followed by azatioprin, 80-90% success
❖ Prognosis: good if effective therapy, depends on the fibrosis stage, monitor steroid side-effects
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Primary sclerosing cholangitis
❖ Pathogenesis periductal inflammation and stenosis of segmenteal bile ducts
❖ Clinical: jaundice, diarrhea (IBD), pruritus, fever (cholangitis)
❖ Laboratory: chronic cholestasis, high bilirubin
❖ Diagnosis: any 2 of the 4: 1. chronic cholestasis, 2. IBD, 3. “dead-tree” image of bile ducts on MRCP and 4. “onion skin” bile ducts patter in liver histology
❖ Severity: depends on the fibrosis stage, occurrence of cholangitis and/or cholangiocarcinoma
❖ Treatment: none approved, UDCA given to improve the quality of life, LT in case of cirrhosis, frequent cholangitis, jaundice, or splenomegaly, LT CI in cholangiocarcinoma
❖ Prognosis: depends on the fibrosis stage and complications
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Primary sclerosing cholangitis
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Wilson’s disease
❖ Pathog.: failure of copper excretion in the liver, oxidative stress, AR disease
❖ Clinical: acute (even fulminant) or chronic hepatitis, neurological syndrome, neuro-psychiatric syndrome, Kayser-Fleischer ring
❖ Laboratory: high ALT, renal impairment, low ceruloplasmin
❖ Diagnosis: proof of high liver copper on histology, low ceruloplasmin, KF ring, genetic profile, MRI (liver and brain)
❖ Severity: depends on the degree of hepatitis and liver failure, and fibrosis stage
❖ Treatment: penicillamin, or triamtarene, zinc
❖ Prognosis: depends on the liver damage and fibrosis stage, good up-to F2, bad in F3-4, acute liver failure – depends on the liver function and rapidity of therapy
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Wilson’s disease
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Hemochromatosis
❖ Clinical: asymptomatic, arthritis, diabetes, tanned skin, heart failure
❖ Laboratory: chronic mild hepatitis, elevated ferritin and transferin saturation
❖ Diagnosis: proof of iron overload, proof of genetic muation in HFE gene
(C282Y homozygote, C282Y heterzygote, H63D, S65C)
❖ Treatment: venepuncture, chelates (less effective)
❖ Prognosis: depends on the extent of multiorgan damage (heart, cancer risk)
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