Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
1 |World Health Organization
Western Pacific Region
Standard modules for hepatitisStandard modules for hepatitis
2 |World Health Organization
Western Pacific Region
Standard Module 1Liver anatomy and physiology
Standard Module 1Liver anatomy and physiology
3 |World Health Organization
Western Pacific Region
Located in right upper abdomen
Protected by the right rib cage
Measures: 12‐15 cm in vertical direction
Weight: ~1500 grams
Two lobes Right: Extends till near the right costal margin
(the lower edge of the rib cage) Left: Extends midway between xiphisternum
and umbilicus
Position of liverPosition of liver
Midline
Umbilical line
Left upperRight upper
Left lowerRight lower
4 |World Health Organization
Western Pacific Region
Several functions, including some of the following
Glucose metabolism During the feeding phase Move glucose into glycogen stores (liver)
During fasting Move sugar from stores (liver) to the blood
Excretory function (detoxication) Bile pigments (bilirubin)
Bile salts Important for absorption of fats
Other harmful substances
Synthetic function Albumin
Coagulation factors
Functions of the liverFunctions of the liver
5 |World Health Organization
Western Pacific Region
Blood supply of liverBlood supply of liver
Blood flow ~ 1500 ml/min
~ 25% of cardiac output (what the heart pumps)
Dual blood supply
Hepatic artery 1/3rd
Venous blood (portal vein) 2/3rdfrom the intestine
6 |World Health Organization
Western Pacific Region
Normal circulationNormal circulationBlood from all the tissues reaches the right heart
and then goes to lungs
Left HeartRight Heart
Arteries
Capillaries
Veins
Lung capillaries
7 |World Health Organization
Western Pacific Region
Portal circulationPortal circulationVenous blood goes to another organ instead of to the right heart
Left HeartRight Heart
Arteries
Capillaries
Veins
Lung capillaries
Another organ
10 |World Health Organization
Western Pacific Region
Liver: Microscopic anatomyLiver: Microscopic anatomy
Organized as hepatic lobules
Lobules are penta‐ to hexagonal structures, located closely together
11 |World Health Organization
Western Pacific Region
Liver: Microscopic anatomyLiver: Microscopic anatomy
Portal tract
Organized as hepatic lobules
Lobules are penta‐ to hexagonal structures, with portal tracts at each corner and central vein in the middle
12 |World Health Organization
Western Pacific Region
Microscopy anatomy of liverMicroscopy anatomy of liver
13 |World Health Organization
Western Pacific Region
Portal tract
Direction of flow of bloodDirection of flow of blood
Organized as hepatic lobules
Lobules are penta‐ to hexagonal structures, with portal tracts at each corner and central vein in the middle
14 |World Health Organization
Western Pacific Region
Direction of flow of bileDirection of flow of bile
Organized as hepatic lobules
Lobules are penta‐ to hexagonal structures, with portal tracts at each corner and central vein in the middle
Portal tract
15 |World Health Organization
Western Pacific Region
Standard Module 2Laboratory test in liver diseases
Standard Module 2Laboratory test in liver diseases
16 |World Health Organization
Western Pacific Region
Common tests of liver functionCommon tests of liver function
Test Normal values Purpose
Total bilirubin mg/dL <2.0 Conjugation, excretion
Conjug. Bilirubin mg/dL <15% of total bilirubin
ALT/SGPT IU/L <40 Enzymes released by liver cell injury/death
AST/SGOT IU/L <40
Alk.phosphatase Varies by method Enzymes released by biliaryinjury or obstruction
GGT IU/L <35
Albumin g/dL 3.5‐5.5 Synthetic function
Prothrombin time INR 0.9‐1.2
The reference ranges for these tests may vary slightly between laboratories and populations
17 |World Health Organization
Western Pacific Region
Assessing the liver disease severityAssessing the liver disease severity
Chronic hepatitis Liver cirrhosis(compensated)
Liver cirrhosis(decompensated)
Liver failure
18 |World Health Organization
Western Pacific Region
Fibroscan®(http.myliverexam.com/en/lexamen‐fibroscan.html)
AST; aspartate aminotransferase ALT; alanine aminotransferaseAPRI; aspartate aminotransferase‐to‐platelet ratio indexFIB‐4; fibrosis‐4 score
WHO Guidelines, 2015
Assessing the degree of liver fibrosisAssessing the degree of liver fibrosis Non‐invasive tests
Components Requirements Cost
APRI AST, platelets Simple serum andhematology test +
FIB‐4 Age, AST, ALT, Platelets
FibroTest gGT, haptoglobin, bilirubin,A1apoprotein, α2‐macroglobulin
Specialized tests atdesigned laboratories ++
Fibroscan ® Transient elastography Dedicated equipment +++
19 |World Health Organization
Western Pacific RegionWHO Guidelines, 2015
Assessing the degree of liver fibrosis
APRI = [ (AST(IU/L)/ AST_ULN(IU/L)) x 100 ] / platelet count (109/L)ULN signifies the upper limit of normal for AST in the laboratory where these investigations were undertaken
FIB‐4 = age(yr) x AST(IU/L)/platelet count(109/L) x [ALT(IU/L)1/2]
Fibrosis stages
assessed
Cut off values for the detection of fibrosis
Cirrhosis(METAVIR F4)
Significant fibrosis(METAVIR ≧F2)
APRI ≧F2, F4 High cut‐off 2.0 High cut‐off 1.5FIB‐4 ≧F3 High cut‐off 3.25
FibroTest ≧F2, F3, F4 0.32‐0.48 0.58‐0.75
Fibroscan® ≧F2, F3, F4 >11‐14 kPa >7‐8.5 kPa
20 |World Health Organization
Western Pacific Region
The Child‐Turcotte‐Pugh Classification systemPoints 1 2 3
Encephalopathy None Minimal(grade1 or 2)
Advanced(grade 3 or 4)
Ascites Absent Controlled Refractory
Total bilirubin(μmol/L)(mg/dL)
<34 (<2) 34‐51 (2‐3) >51 (>3)
Albumin(g/dL) >3.5 2.8‐3.5 <2.8
Prothrombin time (seconds) or PT‐INR*
<4 or <1.7 4‐6 or 1.7‐2.3 >6 or >2.3
Child‐Pugh Class A: 5‐6 pointsChild‐Pugh Class B: 7‐9 pointsChild‐Pugh Class C: 10‐15 points
*PT‐INR ; prothrombin time international normalized ratio
21 |World Health Organization
Western Pacific Region
Standard Module 3Symptoms and Signs of liver disease
Standard Module 3Symptoms and Signs of liver disease
22 |World Health Organization
Western Pacific Region
Features of liver failureFeatures of liver failure Glycogenesis & Gluconeogenesis
Poor glycogen store > hypoglycemia
> hyperglycemia
Poor gluconeogenesis > hypoglycemia
Excretory function
Bile pigment
Impaired excretion > Jaundice
Synthetic function
Albumin > Hypoalbuminemia > edema/ascites
Coagulation factors > Prolonged prothrombin time (INR)
23 |World Health Organization
Western Pacific Region
Other signsOther signs
Dark skin pigmentation
Palmar erythema
Vascular spider
Xanthoma
Subcutaneous bleed
Gynecomastia
Palmar erythema
Spider angiomas
24 |World Health Organization
Western Pacific Region
Standard Module 4Introduction of viral hepatitis
Standard Module 4Introduction of viral hepatitis
25 |World Health Organization
Western Pacific Region
Definitions
Hepatitis: Inflammation of liver
• Acute hepatitis: Hepatitis usually recovered < 3 months
• Chronic hepatitis: Hepatitis continuing for > 6 months
What is hepatitis ?What is hepatitis ?
26 |World Health Organization
Western Pacific Region
Cause of hepatitis
Hepatitis viruses infection (HAV, HBV, HCV, HDV, HEV)
Other infections
• Viruses other than hepatitis viruses (e.g. CMV, EBV, …)
• Parasites (e.g. malaria)
• Bacteria (e.g. typhoid)
Toxic substances (Alcohol, Aflatoxin, …)
Autoimmune disease
Ischemia (reduced blood supply)
27 |World Health Organization
Western Pacific Region
Hepatitis A virus(HAV)
Chronic infectionLiver cirrhosisLiver cancer
Hepatitis E virus(HEV)
Hepatitis C virus(HCV)
Hepatitis B virus(HBV)
Hepatitis D virus(HDV)
Main hepatitis viruses
28 |World Health Organization
Western Pacific Region
HAV HBV HCV HDV HEVAcute hepatitis
Case fatality increases with age
Case fatality increases with age
Uncommon Superinfection in HBV may lead to fulminant disease
Higher case fatality in pregnant women
Chronic infection
No 5% (adults)90% (children)
55‐85%Complicates hepatitis B
Very rare
HCC* No Yes Yes NoRoute of transmission
WaterborneFoodbornePerson‐to person
PerinatalBloodborneSexual
BloodbornePerinatalSexual
Bloodborne WaterborneFoodborne
Vaccine Yes Yes No HBV vaccine NoTreatment options
None Available Available Modified treatment of
HBV
None
Main hepatitis viruses
*HCC; hepatocellular carcinoma
29 |World Health Organization
Western Pacific Region
Acute hepatitis and chronic hepatitisAcute hepatitis Chronic hepatitis
Definition Usually recovered <3months Continuing for > 6monthsEtiology HBV, HEV, HAV, … HBV, HCV, Alcohol, …
SymptomAlmost no symptom or
jaundice, dark urine, general fatigue, abdominal pain, …
Almost no symptom orascites, edema, jaundice, …
(decompensated liver cirrhosis)
Sequela Acute liver failure
Liver cirrhosis→Chronic liver failure
Hepatocellular carcinomaEsophageal varices
Findings
30 |World Health Organization
Western Pacific Region
Progression of liver fibrosis
Metavir fibrosis stages: F0‐F4
Cirrhosis: An advanced stage of liver fibrosis characterized by – Extensive fibrosis– Nodular regeneration– Distortion of liver architecture = F4 fibrosis
31 |World Health Organization
Western Pacific Region
Chronic hepatitis
Ascites, edema, variceal hemorrhage,encephalopathy, jaundice, …
Liver cirrhosis and hepatocellular carcinoma Liver cirrhosis is an advanced stage of chronic hepatitis
Liver cirrhosis(compensated)
Liver cirrhosis(decompensated)
death
Hepatocellular carcinoma
Liver failure
32 |World Health Organization
Western Pacific Region
Effect of cirrhosis on liver circulationEffect of cirrhosis on liver circulation
Decreased blood flowthrough the liver leads to
high pressure in the portal venous system
or Portal hypertension
33 |World Health Organization
Western Pacific Region
Features of portal hypertensionFeatures of portal hypertension
Ascites
Esophageal Vx Gastric Vx Splenomegaly
34 |World Health Organization
Western Pacific Region
Liver disease: Effect on blood circulationLiver disease: Effect on blood circulation
Obstruction of blood flow through the hepatic lobules leads to increased pressure in portal vein
Portal hypertension = increased pressure in portal vein
Manifestations Development of collateral veins Abnormally enlarged veins
(varices) Exudation of fluid into abdomen Ascites Congestion of venous system Splenomegaly > pancytopenia
35 |World Health Organization
Western Pacific Region
Standard Module 5Burden of viral hepatitis
Standard Module 5Burden of viral hepatitis
36 |World Health Organization
Western Pacific Region
Hepatitis mortality is increasingHepatitis mortality is increasing 1.34 million deaths from viral hepatitis in 2015
7th leading cause of death among all cause mortality
Sources – WHO Global hepatitis report 2017
96% hepatitis deaths from HBV and HCV (cirrhosis and hepatocellular carcinoma)
0
0.5
1
1.5
2
2000 2005 2010 2015
Millions of d
eaths
Year
Hepatitis
Tuberculosis
HIV
Malaria
1.34 milliondeaths in 2015
37 |World Health Organization
Western Pacific Region
WHO Global health sector strategy on viral hepatitis 2016‐2021
Regional distribution of hepatitis deathsRegional distribution of hepatitis deaths
38 |World Health Organization
Western Pacific Region
GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age‐sex specific all‐cause and cause‐specific mortality for 240 causes of death, 1990‐2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Jan 10;385(9963):117‐71.
Comparison of global and Western Pacific mortality
39 |World Health Organization
Western Pacific Region
(2015)
Hepatitis deaths in Western Pacific RegionHepatitis deaths in Western Pacific Region
Liver cancer is second most common cause of deaths.
78% of liver cancer are due to HBV or HCV.
40 |World Health Organization
Western Pacific Region
Guidelines for the prevention, care and treatment of personswith chronic hepatitis B infection. WHO: 2015(http://www.who.int/hepatitis/publications/hepatitis‐b‐guidelines/en/)
Global epidemiology of Hepatitis B infection 240 million people around the world infected with HBV
680,000 die every year due to hepatitis B
Children 5‐9 years, 2005 Adults 19‐49 years, 2005
41 |World Health Organization
Western Pacific Region
WHO Global health sector strategy on viral hepatitis 2016‐2021
240 million of adults 19‐49 years of age living with HBV infection (HBsAg) worldwide, 2005
Sources – Ott J et al, Vaccine, 2012
42 |World Health Organization
Western Pacific Region
Guidelines for the screening, care and treatment of persons with chronic hepatitis C infection. Updated version, April 2016. WHO; 2016 (http://www.who.int/hepatitis/publications/hepatitis‐c‐guidelines‐2016/en/)
Global epidemiology of Hepatitis C infection 80 million people around the world infected with HCV
700,000 die every year due to hepatitis C