The document outlines chronic liver disease (CLD), detailing its definition, causes, symptoms, investigations, management, complications, and prognosis. It highlights the significance of liver function tests, imaging, and specific laboratory tests for diagnosis, while emphasizing the management strategies for conditions such as cirrhosis and portal hypertension. The prognosis for CLD depends on factors such as etiology, severity, and potential for liver transplantation.

1. Azong Abdul-Wahid Akanlug-Ba
Chronic Liver Disease

2. OUTLINE
• DEFINITION
• BRIEF ANATOMY AND PHYSIOLOGY OF THE LIVER
• AETIOLOGY
• CLINICAL BREAKDOWN
• INVESTIGATIONS
• APPROACH
• COMPLICATIONS
• MANAGEMENT
• PROGNOSIS
• CASE SCENARIO

3. DEFINITION
• Definition: persistent liver disease for more than 8 weeks
• Persistent hepatic injury, with or without clinical
symptoms, resulting in progressive histological alterations
• Chronic liver disease in the clinical context is a disease
process of the liver that involves a process of progressive
destruction and regeneration of the liver parenchyma
leading to fibrosis and cirrhosis.

4. CIRRHOSIS
• Definition: histological presence of bands of fibrous tissue
that link central and portal areas and form parenchymal
nodules, is a potential end stage of any acute or chronic
liver dx
• Aetiological type
Posthepatitic – after acute or chronic hepatitis
Postnecrotic – after toxic injury
May follow chronic biliary obstruction – biliary cirrhosis

5. CIRRHOSIS
• Morphological type
Macronodular – nodules of various sizes up to 5cm
separated by broad septa
Micronodular – with nodules of uniform size <1cm
separated by fine septa

6. BREIF ANATOMY AND PHYSIOLOGY OF THE LIVER

8. AETIOLOGY
 Major congenital disorders ;
Biliary atresia, Idiopathic neonatal hepatitis,Tyrosinaemia ,Untreated
galactosaemia, ETC
Toxic :Alcohol ,Glucocorticoids,Amiodarone ,Tamoxifen,
Antiretroviral agents,Tetracyline, Herbal preparations
Autoimmune Hepatitis (AIH) ,Clinically
indistinguishable .
Infectious : Hepatitis A-E , EBV, CMV,Yellow Fever, Lues,
Typhoid, Leptosp
Others:Wilson disease, Cystic fibrosis, Non-alcoholic fatty liver
disease

9. CLINICAL PRESENTATION
• Common signs and symptoms may stem from decreased hepatic synthetic
function eg, coagulopathy, portal hypertension, hepatic encephalopathy.
• Jaundice
• Clubbing
• Itchiness
• Fatigue
• confusion
• Oedema
• Bleeding disorders such as epistaxis
• Palmer erythema
• Leuconychia
• Spider naevae
• Growth failure
• Infections
• Gynecomastia

10. CLINICAL PRESENTATION
• Portal hypertension causes may be
Prehepatic eg. Portal vein thrombosis, splenic vein
thrombosis
Intrahepatic eg. Schistosomiasis, Cirrhosis, Veno-
occlusive disease
Posthepatic eg. Budd-Chiari syndrome (hepatomegaly,
abdominal pain, ascites)

11. CLINICAL PRESENTATION
• Ascites is suggested by the following findings on physical
examination:
Abdominal distention
Bulging flanks
Shifting dullness
Fluid thrill

12. INVESTIGATION
• These will depend to a considerable extent upon clinical
suspicion of the aetiology.
• FBC: occult bleeding may produce anaemia;
hypersplenism may cause thrombocytopenia
• LFTs: Aspartate transaminase (AST), alanine
transaminase (ALT), alkaline phosphatase (ALP), bilirubin,
gamma-glutamyltransferase (gamma-GT), bilirubin,
albumin, Coagulation profile

13. INVESTIGATION
• Renal function tests and electrolytes
• Ferritin: low ferritin may indicate iron deficiency from diet
or blood loss; ferritin is raised in haemochromatosis.
• Viral antibody screen: to look for evidence of hepatitis B or
C infection.
• Fasting glucose/insulin/triglycerides and uric acid levels:
these should be measured if non-alcoholic steatohepatitis
(NASH) is suspected.

14. INVESTIGATION
• Autoantibody screen: ANA, SMA, anti-LK microsomal,
soluble liver
• Alpha-1-antitrypsin level: to assess for alpha-1-antitrypsin
deficiency
• Ceruloplasmin and urinary copper: to look for Wilson's
disease.
• Fasting transferrin saturation and HFE
(haemochromatosis C282Y) mutation: along with a raised
ferritin, these tests can screen for haemochromatosis.
• Urine for reducing sugars to look for Galactosaemia. If
galactose positive check blood for GALT deficiency
• Fat soluble Vitamin levels in the blood

15. INVESTIGATION
• USG with doppler
• CT Scan
• MRI
• Liver biopsy
Histology is usually needed for the definitive diagnosis of
cirrhosis and liver biopsy is the gold standard.
It may also give a clue to the underlying cause.
If there are clear signs of cirrhosis, such as ascites,
coagulopathy, and a shrunken nodular-appearing liver,
then confirmation of diagnosis by biopsy may not be
necessary.

16. Approach to the Patient
• Stepwise
• Assess for alcohol use
• Identify medications and supplements that can cause
elevation of the LFT
• Test for viral hepatitis B and C
• Test for fatty liver

17. Prognosis in Cirrhosis
• Fibrosis
• Reversible in initial stages
• Cirrhosis
• Irreversible
• High susceptibility for complications
• Life expectancy markedly reduced
• Quality of life impaired

18. Child-Pugh Score
A=5-6 (2 yr survival 85%)
B=7-9 (2 yr survival 57%)
C=10-15 (2 yr survival 35%)
1 2 3
Bilirubin <2 2-3 >3
Albumin >3.5 3.5-2.8 <2.8
INR <1.7 1.7-2.3 >2.3
Ascites Absent Mild-Moderate Severe /
Refractory
Encephalopathy Absent Mild (I-II) Severe (III-IV)

19. COMPLICATIONS OF CLD
• Definition: complications of CLD and cirrhosis are a
consequence of the impaired metabolic and synthetic
function and structural alterations of the parenchyma
leading to elevated portal pressure.

20. COMPLICATIONS
• Growth faltering and malnutrition
• Hepatic encephalopathy
• Coagulopathy
• Hepatopulmonary syndrome
• Portal hypertension and variceal bleeding
• Ascites
• Spontaneous bacterial peritonitis
• Hepatorenal syndrome
• Hepatocellular carcinoma
• Endocrine dysfunction

21. MANAGEMENT OF CLD
• SUPPORTIVE
 Preventive therapy
Malnutrition
Fat soluble vitamin deficiency
Variceal bleeding and coagulopathy
Ascites
Sepsis
 Nutritional support
 Psychosocial – both child and parents

22. NUTRITIONAL SUPPORT
• Modular feed
High protein/CHO
Balanced MCT/LCT
Low salt
150% RDA
Fat soluble vitamins A, D, E, K
• Route of feeding
 Oral
 Nasogastric
 Parenteral

23. Hepatic Encephalopathy
• 0 - Normal mental status,
asterixis absent
• 1 – mild confusion,
asterixis might be detected
• 2 - lethargy with
inappropriate behaviour.
Obvious asterixis
• 3 - Somnolent with
incomprehensible speech and
marked confusion
• 4 - coma
• HE is reversible!
• Treatment of precipitating
causes (GIB, infection,
dehydration, sedatives…)
• Lactulose (45-90g/dly)
• Enemas
• Protein restriction
0,8g/kg/day??
• Antibiotics
• Liver Transplant

24. MANAGEMENT OF CLF – FLUID MGT
• Management of ascites
Diagnosis: fluid thrill/shifting dullness, USG and
abdominal paracentesis
 Fluid restriction
Nutritional support

25. ASCITES AND FLUID RETENTION
• Fluid and salt restriction
(2/3 maintenance)
Diuretics: Spironolactone 2-3mg/kg/d up to 7mg/kg/d
Furosemide 1-2 mg/kg or hydrochlorothiazide
If resistant consider 5ml/kg 20% albumin infusion over 4-
6h with furosemide
• Therapeutic paracentesis if ascites is resistant esp if
compromising respiratory function
• Shunt – peritoneal-jugular or TIPSS
• Haemofiltration/Dialysis

26. MGT OF PRURITUS
• Enzyme inducers
 Phenobarbitone (5-15 mg/kg)
 Rifampicin (3 mg/kg)
• Bile diversion or Choleretics
 Ursodeoxycholic acid (20 mg/kg)
Cholestyramine (1-4g/d)
Biliary diversion
• Central
Naloxone
Ondansetron

27. MGT OF COAGULOPATHY
• Coagulopathy:
Vitamin K 1mg/year to maximum of 5mg-10mg
Fresh frozen plasma 10 ml/kg
Cryoprecipitate
Platelets
Factor VII infusions or desmopressin
Treat associated sepsis
• Anaemia:
Oral iron
Blood transfusion

28. SPECIFIC MGT
• Immunosuppression for Autoimmune hepatitis
• Penicillamine , Zinc, trientine for Wilsons
• Ursodeoxycholic acid for Cystic Fibrosis
• Anti-viral therapy for Hep B and C
• Diet
• Liver Transplantation

29. Treatment of alcoholic liver disease
• Abstinence
• Single most predictive factor for progression
• Can achieve improvement in fibrosis, reduction or
normalisation of portal pressure, resolution of ascites.

30. SCHISTOSOMIASIS
• Caused by the deposition of Schistosoma oocytes in
presinusoidal portal venules
• Development of granulomata and portal fibrosis.
Schistosomiasis is the most common noncirrhotic cause
of variceal bleeding worldwide
• Schistosoma mansoni infection is described in Puerto
Rico, Central and South America, the Middle East, and
Africa.
• S japonicum is described in the Far East.
• S hematobium, observed in the Middle East and Africa,
can produce portal fibrosis but more commonly is
associated with urinary tract deposition of eggs.

31. PORTAL HYPERTENSION
• Results in
Varices – oesophageal, gastric, rectal
Portal gastropathy
Hypersplenism
• Implications for a normal life
 School
Contact sports

32. MGT OF PORTAL HYPERTENSION
• Medical Therapy
UGI endoscopy - diagnostic and therapeutic
Drug therapy – somatostatin analogues, Vasopressin
propranolol
• Transjugular Intrahepatic Porto-systemic Shunt
stent shunt (TIPS)
• Prophylaxis - propanolol

33. MGT OF ACUTE VARICEAL BLEEDING
• Resuscitation
 ABC
IV access
site of bleeding
Stabilization
• Octreotide infusion
• Endoscopic – banding or sclerotherapy
• Baloon tamponade with Sengstaken-Blakemore tube if
above unsuccessful
• Portosystemic shunt - TIPSS
• Liver transplantation

34. HEPATORENAL SYNDROME
• Definition: Functional renal failure in patients with severe
liver disease
• Two types: I and II
• Pathophysiology –intense renal vasoconstriction with co-
existent systemic vasodilation thereby reducing renal
blood flow
• Diagnosis: by exclusion, rule out
Hypovolaemic shock, nephrotoxic drugs or kidney dx
Hereditary tyrosinaemia, Alagilles and polycystic kidney dx
GFR is markedly reduced
• Treatment – heamofiltration, liver transplantation

35. ENDOCRINE DYSFUNCTION
• Regulation and function of multiple endocrine systems is
affected in CLD
• Increased growth hormone resistance due to reduced
synthesis IGF-1 and IGF-3
• Feminization and hypogonadism in males – reduced
testosterone and relative increase in oesterone and
oestradiol
• Hypothyroidism – reduced T3 and T4

36. SPONTANEOUS BACTERIAL PERITONITIS
• Bacterial infection of ascitic fluid in the absence of
secondary causes such as bowel perforation or intra-
abdominal abscess
• Presentation – subtle with fever and irritability
• Diagnosis
high index of suspicion
Non-specific deterioration in condition
Ascitic fluid for microscopy, culture (monomicrobial)
PMN >250/mm cube is diagnostic
• Treat with antibiotics for 5-7days

37. PROGNOSIS OF CLD
• Depends on
Aetiology
Severity
Progression to cirrhosis
Portal hypertension
Access to liver transplantation

38. CLIP Score
Prospective validation of the CLIP score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000; 31:840
Child-Pugh
A 0
B 1
C 2
Tumor morphology
Uninodular and extension 50% 0
Multinodular and extension 50% 1
Massive or extension >50% 2
AFP
<400 0
>400 1
Portal Vein Thrombosis
No 0
Yes 1

39. Survival curves based on the CLIP score
Farinati, F, Rinaldi, M, Gianni, S, Naccarato. Cancer 2000; 89:2266.

40. INDICATIONS FOR TRANSPLANT
• Laboratory Indices
Serum cholesterol <2.6 mmol/l (100 mg/dl)
Indirect bilirubin >100 mmol/l (6mg/dl)
Serum albumin <35 g/l (3.5 mg/dl)
Prothrombin ratio (INR) >1.4
Portal vein reverse flow on ultrasonography

41. INDICATIONS FOR TRANSPLANT
• Clinical
Severe portal hypertension
Recurrent variceal bleeding
Refractory ascites
Intractable pruritus
Growth retardation
Unacceptable quality of life

42. REFERRAL OF CLD
• Early referral and recognition of liver disease
• Referral to Specialist Centre
Early diagnosis
Consideration of Treatment
Improve outcomes for children

43. Case Senario
• 75 year old woman who
• HBsAg (+)
• HBeAg (+)
• ALT of 50 IU/L
• HBV DNA is 8000 copies/mL.
• She has ascites and known esophageal varices..
• Is she a Candidate for Liver Transplant??

44. THANK YOU