GIT

LIVER DISEASES

Anatomy

Physiology

Bilirubin metabolism:


• Cholic acid
• Chenodeoxycholic acid

Investigations:

Bilirubin
Enzymes- ALT (SGPT)
AST(SGOT)
ALP
ᴕ-gt
5’-nucleotidase
enzyme combinations
Plasma proteins Immunoglobulins
Coagulation factors
α-feto protein
copper ceruloplasmin
ferretin Fe & IBC
Serology- ANA ALKMA
ASMA SLP-PA AMA

Imaging:

• U/S
• Radiography
• CT + MRI + MRCP
• Radionucleotide imaging – TC99
• ERCP
• Cholangiography
• Arteriography
• Venography
• -Portal venography
• (Portal pressure = free hepatic vein pressure- wedged hepatic vein pressure = 3-5 mmHg)
• Endoscopy
• Ascitic fluid studies
• Liver biopsy & FNA
• Laproscopy


Jaundice

• > 3 mg/dl

• 1. Hemolytic
• 2. Hepatocellular
• 3. Obstructive [Cholestatic]
• - Intrahepatic- canalicular (hepatocyte)
• - Biliary Obstruction
- Extra hepatic
Clinical features
•
•
• Cholestasis of pregnancy
Benign recurrent intrahepatic cholestasis

Congenital Hperbilirubinemia

Unconjugated- Gilbert’s Syndrome (Dominant)
Criggler-Najar- (I) recessive
(II) dominant
Conjugated- Dubin-Johnson (recessive)
Rotor (dominant)


Portal hypertension
Causes: (I) Pre-hepatic
- Portal vein obstructions 50% ?
- splenic vein thrombosis
- massive splenomegaly ( Banti’s Syndrome)
(II) Hepatic
- Pre sinosoidal
- Sinusoidal
• Cirrhosis
• Myoproliferative diseases
• Drugs
• Sarcoid
- Post-sinosoidal
• (III) Post-hepatic
- Budd-Chiari
- Cardiac causes

Clinical features:

- Splenomegally
- Hypersplenisim
- Collateral vessels
- Fetor hepaticus


Complications:
- Bleeding
- Hypersplenisim

Contributary factor in:

Ascites
Encephalopathy
Hepato renal syndrome
Hepatopulmonary syndrome

VARICEAL BLEEDING

Recurrent
Risk factors

Other sites

Management:
- Supportive
- Confirm
1. reduction of portal pressure
2. Local measures
3. Prevention of recurrent bleeding


Primary prophylaxis:

Ascites

• Increased hydrostatic pressure
• Decreased oncotic pressure
• Increased portal pressure
• Inflammation
• Malignancy

Causes:

Investigations:

Ascites in chronic liver disease

• Poor prognostic sign
• Commonly with leg edema
• 10% right pleural effusion
• Ascites in CLD doesn’t exclude other causes (HCCA or PUTH…)
• Exudative ascites – infection, malignancy, H-V obstruction.


Management:
• Decrease Na & water by restriction
• Increase urine output
• Removal of ascetic fluid if necessary
• TIPSS

Spontanous bacterial peritonitis

Recurrent

Hepatorenal syndrome

Hepatopulmonary syndrome

Hepatic encephalopathy
• Definition
• Causes- Liver cell failure
- P-S shunting
• Features
• Precipitating factors
• Differential diagnosis
• Management


Fulminant hepatic failure
- Definition – Acute - absence of CLD
- Causes
- Pathology
- Presentation
- Investigations
- Complications
- Management
- Prognosis

Acute Hepatitis

• Pathology
• Causes: - Viral - Non-viral infections
- Drug - Immune Hepatitis
- Post-viral - Metabolic- Wilson
• - α1-antitrypsin deficiency
• - Pregnancy
• -Ischemic- Shock
• - Tamponade- severe heart failures
• - Budd-Chiari syndrome
• Clinical features
• Frequently anicteric or asymptomatic
• Investigations - Management
• Complications - Prognosis


HEPATITIS A VIRUS
• Incubation 2-4 wks

• Diagnosis

• No chronic carrier

• Vaccine

• Immune serum globulin

HEPATITIS E VIRUS

• Incubation 4-8 wks
• Water borne epidemics – fecal -oral
• High mortality in pregnant woman
HEPATITIS B VIRUS
• Incubation 4-20 wks
• Not cultured
• Only man-man
• Carrier
• Vaccine
• hyperimmune serum globilin
• HBsAg - HBe Ag
• Anti HBs Ab - Anti-HBeAb
• Anti- HBcAb IgM
• IgG


Chronic HBV infection
Activity Increased enzymes
HBsAg Anti-HBcAb
HBeAg
Anti HBeAb
Viral load (PCR)

HD virus

Incomplete RNA
Incubation 6-8 wks

HC virus

• Incubate 2-26 wks

• Chronic carrier > 50%

• Anti-HCV Ab ?


• PCR HCV-RNA in blood

CHRONIC HEPATIC + CIRRHOSIS

• 6/12
• Causes
• Viral
• Drugs and alcohol
• Metabolic
• Wilson
• Hemochromatosis
• α1 anti-trypsin deficiency
• Immune
• Nutritional (intestinal bypass)
• Biliary obstruction-
• Primary biliary cirrhosis
• Sclerosing cholangitis
• Secondary biliary cirrhosis
• Hepatic congestion-
• Budd-Chieri
• Veno-occlusive disease
• Cardiac failure
• NAFLD
• Cryptogenic


• Symptomatology

• Assessment & investigations

• Is there active liver disease ?
•
• Liver functions
•
• Staging of liver disease- clinical

• Decompensated liver disease

• Bleeding
• Ascites
• Encephalopathy
•
• Complications
• Infections
• Portal hypertension
• Ascites
• Hepatic encephalopathy
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Hepatoma
•
• Management

Immune hepatitis

• Presentation
• Associated features

• Investigations

• ANA AMA A-LKmA
•
• ASMA SLA


• Wilson disease
• ATP7B gene Ch13
• Presentation
• Investigations
• Management
Hemochromatosis
HFE gene Ch6
C282Y

Presentation

Investigation

Management

Secondary Hemochromatosis

• α1-antitrypsin deficiency

• PiM
• PiS
• PiZ
•
• Primary biliary cirrhosis
• Pathology
• Presentation
• Associated auto immune disease
• Investigations
• Management
• Pruritis
• Malabsorption
• Lipids

Secondary biliary cirrhosis


Alcoholic liver disease
• Dose – Duration - Genetics – Sex
• Mechanism

• Pathology

• Fatty liver
• Alcoholic hepatitis – Mallory’s hyaline
• Central hyaline sclerosis
• CAH
• Cirrhosis
• Hepatoma

• Clinical

• Asymptomatic
• Gradual
• Cholestasis and abdominal pain
• Alcoholic hepatitis

• Investigations

• Establish alcohol abuse
• Exclude other causes of liver disease
• Establish severity
• AST/ALT> 2/1


• Management

• Drugs and the liver

Liver metabolism conversion of fat-soluble (non-polar)

Water soluble (polar) MFO (P450) on SER

Genetics, nutritional, hepatic blood flow, plasma protein binding, combination of drugs
Induction and inhibition of enzymes

Hepatotoxicity of drug:

All forms of liver disease
Acute hepatic injury - Dose dependent – paracetamol, CCl4
- Idiosyncratic
- Cholestasis
- Fatty liver
- Chronic hepatitis
- Granulomas
- Fibrosis
- Vascular
- Tumors
- Toxins


Hepatic vein obstruction
• Anywhere from the small central hepatic veins heart
• Veno-occlusive disease
• Heart failure, tamponade
• Budd- Chiari syndrome- thrombogenic disease
• PRV
• PNH
• AT III deficiency
• Anti-phospholipid syndrome
• Protein C & S deficiency
• Vena Caval obstruction
• Webs
• Tumors
• Clinical features
• SPEED
• Management

• Hepatic Tumors