Chronic liver diseases

Portal Hypertension
• Portal hypertension is defined as a pathological
increase in the pressure of the portal venous system

• PH results from increased vascular resistance in the

portal venous system: the commonest cause is
vascular obstruction in the portal venous system
(Pressure measurements are usually made by using a
balloon catheter inserted using the transjugular route:
PHN is defined as a portal venous pressure above 7
mmHg (clinical symptoms develop at >12 mmHg)
 Portal Hypertension: Etiology
• The commonest cause of PH is liver cirrhosis
In fact, all the other causes are referred to as
Non- Cirrhotic causes of PH
• PH is Classified according to the site of
vascular obstruction:
1. Prehepatic
2. Intrahepatic
3. Post hepatic
 Portal Hypertension: Etiology
Prehepatic:
Portal vein thrombosis
Splenic vein thombosis
Splenomegaly (lymphoma, Gaucher's disease
etc)
 Portal Hypertension: Etiology
Intrahepatic
Cirrhosis, Malignancies
Schistosomiasis ( commonest after liver cirrhosis)
Idiopathic portal hypertension
Primary biliary cirrhosis(PBC)
Sclerosing cholangitis (SC)
Sarcoidosis
 Portal Hypertension: Etiology
Posthepatic
Budd-Chiari syndrome (hepatic vein thrombosis)
IVC obstruction
Cardiac disease (constrictive pericarditis,
restrictive cardiomyopathy)
 Portal Hypertension: pathophysiology

- Increased portal vascular resistance leads to a

gradual reduction in the flow of portal blood
to the liver
development of collateral vessels
Portal Systemic Shunting: portal blood
bypasses the liver and enter the systemic
circulation directly
 hepatic encephalopathy
 Portal Hypertension: clinical
• The clinical features of portal hypertension result
from these mechanisms:
1. Splenomegally
2. Collateral vessels:
-on the abd wall: when several vessels radiate from
the umbilicus: caput medusae
-In the oesophagus, stomach, Rectal: Variceal bleeding
-Sometimes, a large umbilical collateral vessel : can be
ascultated: Cruveilhier-Baumgarten syndrome
 Portal Hypertension: clinical
4. Fetor hepaticus: results from PSS: mercaptans to pass
directly to the lungs

5. Ascites:
Elevated portal pressures lead to splanchinic vasodilation
Pooling of blood in splanchnic circulation
reduced renal blood flow
leads to:
Renal vasoconstriction
Sodium and water retention: main pathophysiologic
mechanism in the development of ascites
 Complications of portal hypertension
1. Variceal bleeding: oesophageal, gastric,rectal
2. Ascites : Sponteneuos bacterial peritonitis
3. Hypersplenism ( splenic sequestration
pancytopenia)
4. Congestive gastropathy
5. Hepatic encephalopathy
6. Iron deficiency anaemia ( chronic GIT blood loss)
7. Renal failure
 Portal Hypertension: RX
• Mainly to management of the complications:

Variceal hemorrhage:
- Focus is primary prevention of variceal bleeding:
Reduction of the portal pressure using non selective
Beta blockers: propranolol 80-160 mg/day,
Atenolol 50-100mg/day
- If this is ineffective in preventing complications, a
TIPSS procedure can be undertaken (Trans jugular
intrahepatic portal systemic shunting)
 Portal Hypertension : RX
Ascites:
- Dietary sodium restriction
- Fluid restriction
- Fluid removal: paracentecis, diuretics
Paracentesis:
Removal of less than 5 liters of fluid does not appear to have
hemodynamic consequeces
Removal of > 5L/d can lead to a fall in IV volume leading to
ARF:
In Large paracentesis albumin can be administered to prevent
this complication
 Portal Hypertension : RX
Ascites ctnd:
NB: Paracentesis can precipitate/worsen HE: avoid
paracentecis in pts with HE
Diuretics:
Recommended Regimen: a combination
spironolactone (100mg - 400 mg/d) and
furosemide (40mg-160mg/d): to maintain
normokalemia: in the morning
( ratio; 100:40)
 Portal HTN: RX
Spontaneous bacterial peritonitis:
commonly caused by G-VE bact from ythe gut: E. coli,
Klebsiella. But often multiple microbes

- Early recognition and treatment with broad spectrum

antibiotics: IV cefotaxime, ceftriaxone
- Prophylactic antibiotics in patients who have had any
episode of SBP, is recommended:
with ciprofloxacin 500mg OD, norfloxacin 400mgOD, or
septrin(one double-strength tablet OD):
Duration: indefinite
 Portal HTN: RX
Hepatic encephalopathy : monitor for even the
subtle symptoms of HE: if present, inititiate
RX: restriction, lactulose and antibiotics as
discussed in acute liver failure
 Liver Cirrhosis
• Liver Cirrhosis is defined as progressive hepatic fibrosis
characterized by distortion of the hepatic architecture
and the formation of regenerative nodules.
• It is a histological diagnosis: characterised by diffuse
hepatic fibrosis and nodule formation
• It is generally considered to be irreversible in its
advanced stages
• However, reversal has been reported in a few cases
where the underlying liver disease was treated during the
early stages of cirrhosis
 Liver Cirrhosis
• Liver Cirrhosis can be classified histologically
into two types:
Micronodular cirrhosis: small nodules about 1
mm in diameter and seen in alcoholic cirrhosis
Macronodular cirrhosis: larger nodules of
various sizes and areas with large fibrous scars
 Liver cirrhosis: Etiology
Any condition that cause persistent or recurrent hepatocyte death
can lead to cirrhosis:

1. Toxins: chronic Alcohol use

2. Infections: Chronic viral hepatitis (B or C)
3. Non-alcoholic fatty liver disease
4. Autoimmune liver disease
5. Biliary tree diseases
- Primary sclerosing cholangitis (Chronic immune mediated ds characterized
by inflammation, fibrosis, and stricturing of ducts in the intrahepatic and
extrahepatic biliary tree
- Primary /Secondary biliary cirrhosis( PBC- immune mediated ds
characterised by destruction of bile ducts)
 Liver cirrhosis: Etiology
6. Genetic liver diseases
- Haemochromatosis( inherited disorder –characterised
by increased intestinal iron absorption and deposition
of the excess iron in tissues))
- Wilson's disease ( copper deposition)
- Alpha-1 antitrypsin (AAT) deficiency : autosomal
recessive disorder which can cause cirrhosis
7. Chronic venous outflow obstruction e.g Budd-
Chiari syndrome
8. Cryptogenic (unknown-15%)
 Liver Cirrhosis: pathophysiology
Insult  Liver injury
Kupffer cells and hepatocytes death/injury
Production of cytokines
Activation and transformation of the stellate cells into a
myofibroblast-like cell
Produce collagen and pro-inflammatory cytokines and other
mediators
which promote further hepatocyte damage and cause fibrosis
Formation of regeneration nodules
Destruction of the liver architecture and loss of the normal
hepatic vasculature
CIRRHOSIS
 Liver Cirrhosis: clinical
• May be assymptomatic: incidental finding on U/S
Non-specific symptoms: weakness, fatigue, muscle cramps,
weight loss, anorexia, nausea, vomiting and upper
abdominal discomfort
Signs: physical findings:
1. Liver:
- Hepatomegaly ( in early disease with nodules, alcoholic liver
disease and haemochromatosis)
- Small liver: late disease, often in Viral hepatitis, AIH
- Usually hard, Irregular and non-tender liver
2. Jaundice
 Liver Cirrhosis: clinical
3. Features of Portal hypertension:
- Splenomegaly
-Collateral vessels ( caput medusae)
- Ascites, edema, rt sided pleural effusions
- Variceal bleeding
4. Circulatory changes
- hyperdynamic circulation: palmar erythema
- Arterial venous shunting: cyanosis
- Spider telangiectasia on skin ( a central arteriole from
which small vessels radiate)
 Liver Cirrhosis: clinical
5. Endocrine changes: altered sex hormone metabolism
- Loss of libido, hair loss
-Men: gynaecomastia, testicular atrophy, impotence
-Women: breast atrophy, irregular menses, amenorrhoea
6. Coagulopathy/Haemorrhagic tendency: Bruises,
epistaxis
7. Hepatic encephalopathy (portosystemic shunting)
 Liver Cirrhosis: clinical
8. Other features
-Pigmentation (haemochromatosis, cholestasis)
- Digital clubbing (hypoxia)
- Dupuytren's contracture (Results from the thickening and
shortening of the palmar fascia, which causes flexion
deformities of the fingers)
- parotid enlargement: ( chronic alcohol rather than
cirrhosis)
- Renal failure
- Diabetes mellitus is seen in 15 -30 % of patients with
cirrhosis
 Liver Cirrhosis: clinical
- Fetor hepaticus ( A sweet, pungent smell to the
breath - PSS)
- Asterixis (Flapping tremors)
- Hypoalbuminaemia
- Nail changes
Muehrcke's nails are paired horizontal white bands
separated by normal color
Terry's nails: The proximal two-thirds of the nail
plate appears white whereas the distal one-third is
red
 Liver Cirrhosis: clinical
Eventually Chronic liver failure develops: The
term 'hepatic decompensation' or
'decompensated cirrhocis
 Liver Cirrhosis: clinical
Complications:
1. Portal hypertension: Variceal hemorrhage,
Ascites, Hepatic encephalopathy, Spontaneous
bacterial peritonitis
2. Hepatocellular carcinoma
 Liver Cirrhosis: RX
1. Slowing (or reversing) the progression of liver
disease :
- Treatment of the underlying disease( hep B, C, AIH)
- Abstinence from alcohol
2. Preventing superimposed insults:
- Avoid hepatotoxins/drugs
- Vaccination against hepatitis A and B
(Pneumococcal vaccine and influenza vaccination
should also be considered)
 Liver Cirrhosis: RX
Hepatocellular carcinoma screening: some
authorities recommend screening patients
with cirrhosis: serum AFP and liver U/S every
six months
 Liver Cirrhosis: Definitive RX
Chronic liver failure/ Decompensated liver ds
develops:
liver transplantation is the only effective RX
( liver cirrhosis accounts for about 75% of all
liver transplants)
 Liver Cirrhosis: prognosis
• Depends on the severity as assed using the
child Pugh Grade: (Encephalopathy, Bilirubin,
Albumin, Prothrombin time, Ascites)

A: 1yr survival is 82%, 5yr S= 45%, 10yr S= 25%

deaths=43%
B 62 20 7 72
C 42 20 0 85
Evaluation of a patient with chronic liver
disease
 Chronic liver disease: Evaluation
1. Detailed history and physical examination
2. Imaging: Ultrasound: adequate: liver archtecture,
billiary tree, spleen, ascites
3. LFTs, coagulation profile, U/EC, CBC.
4. Ascitic fluid analysis( in general)
- Cell count and differential: detect infection
- Gram stain
- Bacterial cultures
- cytology
- Biochemistry:
 Chronic liver disease: Evaluation
Protein : determine whether the fliud is a transudate or
an exudate
an exudate: if total protein is 3 g/dL
a transudate if it is below this cut-off
Glucose: lower than serum glucose:
infection/malignancy
Lactate dehydrogenase:
The ascitic fluid/serum (AF/S) ratio of LDH is
approximately 0.4 : elevated LDH indicates
infection/malignancy
 Chronic liver disease: Evaluation
- Biochemistry cntnd:
Serum-to-ascites albumin gradient( SAAG) : Calculated by
subtracting the ascitic fluid albumin value from the serum
albumin value, (obtained on the same day)
The SAAG accurately identifies the presence of portal hypertension
It is more useful than the protein-based exudate/transudate
concept
- The presence of a gradient ≥1.1 g/dL (11 g/L) indicates that the
patient has portal hypertension
- A gradient <1.1 g/dL (<11 g/L) indicates that the patient does not
have portal hypertension
 Chronic liver disease: Evaluation
5. Evaluation to establish cause: Hepatitis
serologies, tests of auto immunity (AIH)
6. Liver biopsy: percuteneus under U/S or CT
guidance( liver cirrrhosis is a histological
diagnosis)
7. Complications: endoscopy: varices
 Upper GIT bleeding
• This is the most common gastrointestinal
emergency, accounting for 50-170 admissions
to hospital per 100 000 of the population each
year in the UK.
• The mortality of patients admitted to hospital
is about 10%
 causes
Esophagus:
Esophagitis- 10%
varices- 2-9%
mallory weiss tears-5%, cancer
Stomach:
PUD, H.pylori,=35-50%
NSAIDS/Alcohol: gastric erosions:
Cancer-1%,
vascular malformations-1%
 RX
1. Resccucitation
2. Endoscopy
3. PPI- IV
Varices:
ballon tamponade
Vassopressors: Vassopressin, terlipressin,
octreotide( somatostatin analogue: causes
splanchnic vasoconstriction)
Endoscopy: variceal banding, sclerotherapy
• PUD: endoscopy; injection of noradrenaline to
the ulcer, mettalic clips, sclerotherapy,
gastrectomy