Liver and Biliary Diseases

Liver cirrhosis

Cirrhosis is irreversible chronic injury to hepatic parenchyma that includes extensive fibrosis with the formation of regenerative nodules due to hepatocyte necrosis ,collapse of surrounding reticulate network with subsequent tissue deposition, distortion of vascular bed and nodular regeneration of remaining liver parenchyma.

Causes of cirrhosis

any cause of chronic hepatitis (post-necrotic) e.g. chronic hepatitis B,C and D.
Alcoholic liver diseases.
Primary biliary cirrhosis.
Primary sclerosing cholengitis.
Secondary biliary cirrhosis(stones, strictures...).
Hemochromatosis.
Wilson's disease.
α-1 antitrypsin deficiency.
Cystic fibrosis.

Classification of cirrhosis

Histological liver cirrhosis classification into:-
Micronodular cirrhosis.
Most common in alcoholic cirrhosis characterized by regular connective tissue septa, regenerative nodules approximating in size to the original lobules(1mm in diameter).

Macronodular cirrhosis
Common in post-infective cause, in which the connective tissue septa vary in thickness and the nodules show marked differences in size with large one containing normal lobule.
Mixed type ( micro. & Macronodular)

Clinical features

1.may be asymptomatic.
Found incidentally at surgery or at autopsy or in patient with isolated hepatomegaly.
2.nonspecific symptoms.
Include weakness, , muscle cramps, weight loss, anorexia, nausea, vomiting, upper abdominal discomfort and gaseous abdominal distension.
3.Hepatomegaly is common but progressive hepatocyte destruction and fibrosis gradually reduce liver size as disease progress. the liver is often hard, irregular and painless.
4.Jaundice (usually mild jaundice).
5.Endocrine changes.
Loss of libido, hair loss.
Men: gynecomastia, testicular atrophy, impotence.
Women: breast atrophy , irregular menses, amenorrhea

6_circulatory changes

Palmer erythema.
Cyanosis: due to portal HT and pul. A-V shunt
Spider telangiectasia (naevi) seen in upper chest.
7 .Hemorrhagic tendency: lead to:-
Bruises ,purpura, epistaxis and menoerrhagia.
8.portal hypertension: it cause Splenomagly .Collateral vessels (e.g in abd. Capus medusa) Variceal bleeding ( oesophageal varies , haemorrhoid).
Fetor hepaticus (foul odor from mouth due to toxin that cross from portal vein to systemic circulation to reach the lung.
9.ascites: due to combination of liver failure and portal HT. And Ascites indicated advance liver disease.
10. hepatic encephalopathy: occur due to shunting of toxin from portal vein to the systemic circulation that reach the brain.
11-nonspecific features : Skin pigmentation, clubbing, low grad fever.

Management of cirrhosis

Treatment of known cause.
Maintenance of nutrition.
Treatment of the complications of cirrhosis (G.I.T bleeding, infection , liver failure)
Liver transplantation.
Commonly done in:
Cholestatic form of cirrhosis :e.g. PBC , alcoholic cirrhosis ,cirrhosis due to hepatitis C virus.
Metabolic diseases: α-1 antitrypsin deficiency and hemochromatosis.

Signs of liver failure pointing to the need for transplantation include:

1.sustained or increased jaundice (bilirubin >100umol /l in cholestatic disease)
2.ascites or hepatic encephalopathy not responding to medical therapy.
3.hypoalbumina ( s. Albumin <30 g/l)
4.fatigue and lethargy affecting the quality of life.
5.intractable itching in cholestatic disease.
6.recurrent Variceal bleeding.
Contraindication
1)-sepsis.
2)-AIDs
3)-extrahepatic malignancy
4)-active alcoholic abuse
5)-marked cardio-respiratory and renal dysfunction

Prognosis

The overall prognosis is poor. Only 25% of patients survive 5 years from the diagnosis but when liver function test is good 50% survive 5 years and 25% survive 10 years.
The bad prognostic signs
Increased total S.bilirubin.
Decreased plasma albumin 30g/l.
Hyponatermia when S. Na < 120 umol/l.
Prolonged Prothrombin time(PT).
5)Advance Ascites and encephalopathy

Child-Pugh classification of prognosis in cirrhosis

Score
1
2
3
Encephalopathy
None
Mild
Marked
Bilirubin (μmol/L)*
PBC/sclerosing cholangitis
Other causes of cirrhosis

< 68

< 34
68-170
34-50
> 170
> 50
Albumin (g/L)
> 35
28-35
< 28
Prothrombin time (seconds prolonged)
< 4
4-6
> 6
Ascites
None
Mild
Marked
Add the individual scores: < 7 = Child's A, 7-9 = Child's B, > 9 = Child'sC


Child-Pugh classification of prognosis in cirrhosis

Survival (%)

Child-Pugh grade
1 year
5 years
10 years
Hepatic deaths (%)
A
82
45
25
43
B
62
20
7
72
C
42
10
0
85

Biliary cirrhosis

A)-primary biliary cirrhosis
Affect middle aged female.
Aetiology and pathology
The cause of PBC is unknown ,immunological reaction is suspected because, there is impaired cellular immunity with association of special Abs and other autoimmune disease.
The pathological lesion is chronic granulomatous inflammation damaging and destroying the interlobular bile ducts, progressive inflammatory damage with fibrosis eventually lead to cirrhosis.

Clinical features

Nonspecific symptoms are : anorexia , ill health and fatigue.
Pruritis: is the most common initial complaint pointing to the hepatobiliary disease. It may precede the jaundice by months or years.
Jaundice : it is occasionally as a presenting feature
Fever, abdominal discomfort and rigor.
Maabsorption: diarrhoea , bone pain and bone fractures due to Osteomalacia and osteoporosis,
Weight loss, xanthomata (cholesterol deposit around the eyes , hand creases and elbows.
6.hepatomegaly and splenomagly due to portal HT.
7.featurs of liver cirrhosis and it's complications.
8.associated diseases: sicca syndrome , celiac disease, Thyroid disease

Investigations

Liver function test : cholestatic pattern.
Hypercholesterolemia .
Ant-mitochondrial Abs positive in more than 95%.
ERCP and liver biopsy is required in Abs negative patients.
U/S of liver to exclude secondary biliary cirrhosis.

Management

-Nonspecific treatment is available.
- Ursodeoxy cholic acid 13-15 mg/kg/day
Improve the biochemical markers of cholestasis and jaundice.
3)-treatment of the complications
Pruritis : cholestyramine 4-16 g/day orally , Rifampicin , U/V light.
Maabsorption: decreased fat intake, monthly injection of vit. K and supplement of vit. D and calcium.






B)-Secondary biliary cirrhosis
This developed after prolonged duct biliary obstruction due to gallstones , bile duct strictures or sclerosing cholengitis. There is chronic cholestasis with episodes of ascending cholengitis or even liver abscess. Digital clubbing is common and xanthomata and bone pain may develop, cirrhosis, portal HT are a late features. Cholengitis required treatment with ant_ biotic which can be given continuously if attacks occur frequently.

Primary sclerosing cholengitis

In this disease there is fibrotic obliteration of the intra and/or extra hepatic bile duct system. the cause is unknown but associated with other auto-immune diseases like ulcerative colitis ,retroperitoneal fibrosis.

Clinical feature
The patient present with jaundice which may be fluctuated, intermittent fever, pruritis and right upper abdominal pain.
Secondary biliary cirrhosis may result. There is a strong associated with cholengiocarcinoma and progressive jaundice. Anorexia and weight loss are suggestive of this complication.

Investigation

1)-ERCP :which typically shows narrowed irregular obstruction (beading) of extra and intra hepatic duct.
2)-liver biopsy : appearance of fibrosis around the bile duct. And laparotomy may be need to exclude cholengiocarcinoma.
Management
There is no specific treatment.
Antibiotic for cholangitis.
Liver transplantation for advanced disease