This document provides an overview of chronic liver disease (CLD) including:
- CLD results from long-term inflammation and damage to the liver that can progress to cirrhosis over 6 months. Common causes include alcohol, viral hepatitis, fatty liver disease, and genetic/autoimmune conditions.
- Clinical manifestations range from asymptomatic to jaundice, abdominal pain/swelling, bleeding, confusion and liver failure. Complications include portal hypertension, ascites, hepatic encephalopathy and liver cancer.
- Investigations include blood tests of liver function and damage, imaging like ultrasound/CT, and biopsy. Prognosis is assessed using Child-Pugh or MELD scores. Management focuses on treating the underlying
4. 1. INTRODUCTION
Chronic liver disease (CLD) is a progressive deterioration of liver functions for more
than 6 months, which includes synthesis of clotting factors other proteins,
detoxification of harmful products of metabolism, and excretion of bile.
CLD is a continuous process of inflammation, destruction, and regeneration of liver
parenchyma, → fibrosis and cirrhosis.
Cirrhosis is a final stage of chronic liver disease that results in disruption of liver architecture,
the formation of widespread nodules, vascular reorganization, neo-angiogenesis, and
deposition of an extracellular matrix.
6. 2. AETIOLOGY (1)
1 Alcoholic Liver
Disease
➔ A spectrum of disease which includes alcoholic fatty liver with/ without hepatitis, alcohol
hepatitis → cirrhosis.
➔ Alcohol use disorder is the most frequent cause of CLD
2 Non-alcoholic Fatty
Liver Disease
(NAFLD/NASH)
➔ NAFLD has an association with metabolic syndrome (obesity, hyperlipidemia, DM)
➔ Some of these patients develop non-alcoholic steatohepatitis → liver fibrosis
3 Chronic Viral
Hepatitis
➔ Chronic hepatitis B,C and D infections are the most common causes of chronic liver
disease in East Asia and Sub-Saharan Africa
4 Genetic causes Alpha-1 antitrypsin
deficiency
➔ The most common genetic cause of CLD among children
Hereditary
hemochromatosis
➔ Autosomal recessive disorder of iron absorption
➔ Mutation involving HFE gene that regulates the iron absorption
from the intestine → excessive iron is absorbed from the GI
tract → pathological increase in ferritin and hemosiderin →
generation of hydroxyl free radicals → organ fibrosis
Wilson disease ➔ Autosomal recessive disorder leading to copper accumulation
7. 2. AETIOLOGY (2)
5 Autoimmune
Causes
Primary biliary
cirrhosis (PBC)
➔ An autoimmune and progressive disease of liver
➔ There is a destruction of intrahepatic biliary channel and portal
inflammation and scarring → cholestatic jaundice and fibrosis
of liver parenchyma
➔ Common in middle aged women
Primary sclerosing
cholangitis (PSC)
➔ Commonly associated with ulcerative colitis
➔ Characterized by a decrease in the size of intrahepatic and
extrahepatic bile ducts due to inflammation and fibrosis
Autoimmune
hepatitis (AIH)
➔ A form of chronic inflammatory hepatitis
➔ Women > men
➔ Characterized by elevated autoantibodies such as antinuclear
antibodies, anti - smooth muscle antibodies and
hypergammaglobulinemia
6 Other Causes Of
CLD
➔ Drugs: amiodarone, isoniazid, methotrexate, phenytoin, nitrofurantoin
➔ Vascular: Budd-Chiari syndrome
➔ Idiopathic/ cryptogenic around 15%
9. Kumar and Clark Clinical Medicine 8th ed.
LET’S GET TO KNOW..
10. Hepatotoxicity Cholestatic injury
Chronic injury to hepatocytes
Released of cytokines and RO
intermediates
INFLAMMATION
Stellate cells activated
Upregulation of receptors
E.g. PDGF
, TGF-B
Hepatocyte death
Myofibroblast
Normal matrix is replaced by
collagen
Increase resistance to portal flow
PORTAL HYPERTENSION
Endothelial barrier disruption
LIVER FUNCTION IMPAIRED
Kumar and Clark Clinical Medicine 8th ed.
11. Pellicoro, A., Ramachandran, P., Iredale, J. et al. Liver fibrosis and repair: immune regulation of
wound healing in a solid organ. Nat Rev Immunol 14, 181–194 (2014).
https://doi.org/10.1038/nri3623
13. History taking
SPECIFIC SYMPTOMS
● Right hypochondrial pain: liver distension
● Abdominal distension: ascites
● Ankle swelling: fluid retention
● Haematemesis and melaena: GI hemorrhage
● Pruritus: cholestasis
● Gynaecomastia, loss of libido, amenorrhea:
endocrine dysfunction
● Confusion and drowsiness: portosystemic
encephalopathy
May be asymptomatic
Non-specific : Fatigue
17. Portal hypertension ● Elevated pressure in the portal venous system
● Increased resistance of blood flow
● Gastrointestinal bleeding, splenomegaly and
ascites. Often asymptomatic
Variceal bleed ● dilated veins in distal esophagus or proximal
stomach cause by elevated pressure in the
portal venous system.
● Sudden, painless, upper GI bleeding,
Hematemesis,melena, or hematochezia.
18. Ascites ● Cause: portal hypertension
● Clinical features: abdominal distension, loss of appetite,
shortness of breath and weight gain
● Examination: shifting dullness and fluid thrills can be elicited
Spontaneous bacterial
peritonitis
● Infection of abdominal fluid
● Clinical features: fever, malaise, and symptoms of ascites and
worsening hepatic failure. Present of peritoneal sign (eg.
abdominal tenderness and rebound tenderness).
● Diagnose by: diagnostic paracentesis
19. Hepatic encephalopathy ● Reversible brain dysfunction caused by liver
insufficiency and portosystemic shunts.
● Clinical features: wide spectrum of neurological
and psychiatric abnormalities.
● Precipitants: gastrointestinal bleeding,
constipation, infection, dehydration and
portosystemic shunts
Hepatorenal syndrome ● Occurs in advanced liver disease and is a
diagnosis of exclusion
● Pathophysiology: vasoconstriction of a renal
vessels from RAAS activation leading to renal
hypoperfusion
20. Hepatocellular carcinoma ● The risk is higher in chronic liver disease
such as cirrhosis caused by hepatitis B or C
infection
● Clinical features: abdominal pain, weight
loss, early satiety, right upper quadrant mass
and jaundice
● Diagnosis: alpha-fetoprotein measurement
or imaging (CT or MRI)
21. Overall, the 5-year survival rate is approximately 50%.
This is variable and depends on the aetiology and presence of complications.
The severity and prognosis of liver disease can be graded according to the
- modified Child–Pugh classification
Or
- MELD score (modification of end-stage liver disease)
PROGNOSIS
23. MELD SCORE (MODIFICATION OF
END STAGE LIVER DISEASE)
To convert:
• bilirubin from umol/L to mg/dL divide by 17
• creatinine from umol/L to mg/dL divide by 88.4
[ 3.8 x LN (bilirubin in mg/dL)] + [ 9.6 x LN
(creatinine in mg/dL) ] + [ 11.2 x LN (INR) ] + 6.4
25. LAB FINDINGS
1.FULL BLOOD COUNT
● Anaemia
● Leukopenia
● Thrombocytopenia
● Prolonged prothrombin
time (PT) and partial
thromboplastin time
(aPTT)
● Elevated internalized
normalized ratio (INR)
● Liver enzymes elevated
(AST, ALT, ALP, GGT)
● Hyperbilirubinemia
● Hypoalbuminemia
● Hyponatremia (Na+)
● Elevated Urea
● Elevated creatinine
2. LIVER FUNCTION
TEST
3. COAGULATION
PROFILE
4. RENAL PROFILE
5. BIOMARKERS
● Serum
alpha-fetoprotein
> 200mg/ml
● Enhanced liver
fibrosis test
- < 7.7: None to mild
- 7.7 - 9.8: Moderate
- > 9.8: Severe
26. 6. LIVER BIOPSY
Performed percutaneously with a Trucut or Menghini needle, usually through an
intercostal space under local anaesthesia or radiologically using a transjugular
approach. Wisely not done if coagulation profile is deranged due to risk of
bleeding.
28. RADIOLOGICAL FINDINGS
8. ABDOMINAL
ULTRASOUND
● Non-invasive, safe and
widely available
● Routinely used to
evaluate liver cirrhosis.
● To detect size and
echogenicity nodularity
of the liver cirrhosis.
● Used to measure the
diameter of portal vein.
● Assess the clot in
hepatic vein
29. RADIOLOGICAL FINDINGS
9. CT SCAN
● Not routinely used to
evaluate liver cirrhosis
● CT findings shows
hepatic nodularity,
atrophy of the right
lobe, hypertrophy of
caudate/left lobe,
ascites or varices.
● CT portal phase
imaging can
demonstrate the
patency of portal vein
and assess the
obstruction of biliary
channel.
31. Major goals of managing patients with CLD
31
● Prevent superimposed insults
to the liver
- Vaccinations
● To slow progression of
liver disease
● Avoid any complications
- Antiviral treatments for
hep C
- Alcohol abstinence
32. GENERAL MANAGEMENT
● Diet control
- reduce intake of red meat, eggs, cheese
- Sodium restriction
● Weight loss, control metabolic risk factors
- Glucose
- Blood pressure
- Cholesterol
● Avoid hepatotoxins
- Alcohol
- Hepatotoxic meds eg acetaminophen, azathioprine
- Herbal remedies
● Vaccinations
- Hep A & B vaccines
- Pneumococcal vaccines
- Influenza vaccines
33. SPECIFIC MANAGEMENT
Alcoholic liver disease
● Cessation of alcohol
consumption
● Alcohol abstinence (most
effective in preventing
progression of liver
disease)
● Alcohol rehabilitation
program
Non - alcoholic fatty liver disease (NAFLD)
Treatment of metabolic syndrome
● Metformin 1st line treatment in T2DM patient with NAFLD
● Thiazolidinediones such as pioglitazone could improve
inflammation and fibrosis in T2DM patient
● Weight loss
Viral hepatitis
● Continuous viral
suppression with
nucleoside and
nucleotide analogs
● Direct- acting antivirals
achieving hep C virus
eradication
● Interferon alpha
34. MANAGEMENT OF CIRRHOSIS COMPLICATIONS
Portal hypertension leads to :
1. Ascites
● Sodium & fluid retention
● Diuretics
- Spironolactone (mainstay)
- Frusemide
● Chart daily weight
● Large volume paracentesis (in massive ascites)
● Transjugular intrahepatic portosystemic shunts
(TIPS)
2. Variceal bleeding
● Resuscitate, stabilize patient
● Fluid, blood infusion
● IV somatostatin
● Antibiotic prophylaxis
● Acid suppression
- omeprazole, pantoprazole
● Emergency endoscopy
- diagnostic and therapeutic
- Esophageal varices : variceal ligation
- Gastric varices : injection with cyanoacrylate
glue
● Transjugular intrahepatic portosystemic shunts
(TIPS)
Spontaneous bacterial peritonitis
● Empirical antibiotics
- immediately after diagnosis
● 3rd gen cephalosporin (IV
cefotaxime)
- for 5 days or until
sensitivities is known
Hepatic encephalopathy
● Stop all meds that depress
CNS functions
- such as sedatives and
benzodiazepine
● Eliminate precipitating factors
- such as hypovolaemia,
hypokalemia, GI bleed,
constipation
● Lactulose
Hepatorenal syndrome
● Type 1 HRS
- Terlipressin + albumin
● Type 2 HRS
- TIPS
● Liver transplant is the treatment
of choice
Hepatocellular carcinoma
● Initial stage (single HCC lesion )
- resection and ablation
● Intermediate stage
- transarterial
chemoembolization and
radio-embolization
● Metastatic disease
- sorafenib