Chronic Hepatitis. Liver Cirrhosis.1

Liver function

2

Liver function

3

International classification of disorders -10 - about liverdiseases

70: Alcoholic liver disease 71: oxic liver disprders 72: Hepatic failure and acute hepatitis 73: Chronic hepatitis 74: Liver fibrosis and cirrhosis4

Chronic hepatitisa

series of liver disorders of varying causes and severity in which hepatic inflammation and necrosis continue for at least 6 months the end of the process liver cirrhosis5

History 1937

J.M.Findlay, F.O.McCallum first investigation of serum hepatitis - F.O.McCallum - first finding about viral hepatitis A and B and its transmission mechanisms6

1956

ClassificationNow By Cause (aetiology) By Grade (activity) By Stage Late Histologic Classification (chronic active, lobular and persistent hepatitis)7

Classification by Cause Aetiologychronic viral hepatitis, caused by hepatitis B, hepatitis B plus D, hepatitis C, or other viruses autoimmune

hepatitis drug-associated chronic hepatitis cryptogenic chronic (idiopathic) hepatitis8

Classification By Grade histologic

assessment of necroinflammatory activity is based upon examination of the liver biopsy Clinically

- mild, moderate, or severe degree of CH9

Normal picture of the liver tissue

10

Hepatitis

11

Liver cirrhosis

12

Hepatitic steatosis

13

Classification By Grade: degree of periportal

necrosis bridging necrosis hepatocyte degeneration focal necrosis within the lobule portal inflammation numerical

histologic activity index (HAI), based on the work of Knodell and Ishak14

Classification By Stage0 1 2 3

= no fibrosis = mild fibrosis = moderate fibrosis

= severe fibrosis, including bridging fibrosis = cirrhosis15

4

Pathogenesis Liver

tissue damage by aetiologic factor and humoral immune response

Cellular

Autoimmunoaggression Progression

of chronic liver tissue inflammation16

Clinical syndromes>

70% - without complaints, symptomless Not acute onset Asthenic s. (weakness, fatigue,) Dyspeptic s. Aching s. Inflammatory s. Haemorrhagic s. Fever Also - See the lecture of previous term17

Examination Jaundice

() Paleness (anemia) Vascular stars =spider naevi ( ) Hepatic palms of the hand ( ) = palmar erythema Stratches due to Pruritus () Bruises and petechieae ( ) Xanthomas and xanthelasmas (deposits of cholesterol) Gynaecomastia Loss of body hair in men or hirsutism in women18

Hepatic marks

19

Examination Liver

enlargement Low liver margin rounding ( )

Tenderness

area

with palpation of liver

20

Chronic Viral Hepatitis

21

Chronic Viral Hepatitis hepatitis

A and E, are self-limited and do not cause chronic hepatitis the entire clinicopathologic spectrum of chronic viral hepatitis occurs in patients with chronic B and C as well as in patients with chronic hepatitis D superimposed on chronic hepatitis B HBV may leads to liver cancer22

Particularity of clinical features ranging

from asymptomatic infection to fatal hepatic failure Fatigue is a common symptom persistent or intermittent jaundice is a common feature in severe or advanced cases Appetite loss Arthralgia and arthritis Skin rash

23

Particularity of chronic HBV Replicative

phase : very contagious - in the serum - markers of HBV replication (hepatitis B e antigen (HBeAg)and HBV DNA) - in the liver - detectable intrahepatocyte nucleocapsid antigens - primarily hepatitis B core antigen (HBcAg) Nonreplicative (latent) phase : not contagious - absence of HBeAg and HBV DNA - presens of anti-HBe (antibodies)

24

Particularity of chr. HBV In

young age after acute hepatitis in 1% Majority of adults never had acute BV Spontaneous remission in 30% All depend on immunity! AsAT

increased: from 100 to 1000 units Moderate elevations in serum bilirubin (51.3 to 171 umol/L) (3 to 10 mg/dL) Hypoalbuminemia Prolongation of the prothrombin time25

Particularity of chronic HCV chronic

hepatitis follows acute hepatitis C in 50 to 70 % of cases almost 60 % of patients are asymptomatic in 25 % of patients hepatitis C will progress eventually to end-stage cirrhosis Clinical features of chronic hepatitis C are similar to chronic hepatitis B aminotransferase levels tend to fluctuate more and to be lower, especially in patients with long-standing disease compare with HBV

26

TREATMENTChronic Hepatitis B and C: - Interferon - alpha : A 4-month course of subcutaneous injections, daily at a dose of 5 million units or 3 times a week at a dose of 10 million units Chronic Hepatitis D (Delta Hepatitis) management is not well defined Symptomatic treatment27

Prevention of chronic hepatitis Vaccination

against HBV

28

Chronic AUTOIMMUNE HEPATITIS

29

Chronic AUTOIMMUNE HEPATITIS is

a chronic disorder characterized by continuing hepatocellular necrosis and inflammation, usually with fibrosis, which tends to progress to cirrhosis and liver failure.

30

Chronic AUTOIMMUNE HEPATITIS 80

% of patients women < 30 y.o. and > 50 y.o idiopathic/autoimmune hepatitis is the result of a cell-mediated immunologic attack directed against liver cells predisposition to autoimmunity is inherited, while the liver specificity of this injury is triggered by environmental (e.g., chemical or viral) factors31

Evidence to support an autoimmune pathogenesis includes the following:1. 2.

3.

In the liver - cytotoxic T cells and plasma cells Circulating autoantibodies (nuclear, smooth muscle, thyroid, etc.), rheumatoid factor, and hyperglobulinemia are common In patients and in their relatives - other autoimmune disorders (thyroiditis, rheumatoid arthritis, autoimmune hemolytic anemia, ulcerative colitis, proliferative glomerulonephritis, juvenile diabetes mellitus, and Sjogren's syndrome)32

Evidence to support an autoimmune pathogenesis includes the following:

Histocompatibility haplotypes associated with autoimmune diseases, such as HLA-B1, -B8, -DRw3, and -DRw4, are common 5. This type of chronic hepatitis is responsive to glucocorticoid/immunosuppressive therapy, effective in a variety of autoimmune disorders4.33

Clinical features Many

of the clinical features of autoimmune hepatitis are similar to chronic viral hepatitis

34

Treatmentis glucocorticoid therapy - 12 18 month and - with azathioprine Symptomatic treatment Unfortunately, therapy has not been shown to prevent ultimate progression to cirrhosis

35

Liver Cirrhosis36

Liver Cirrhosischronic

injury of the hepatic parenchyma include extensive fibrosis in association with the formation of regenerative nodules37

Aetiology and Classification Alcoholic Postnecrotic

(Cryptogenic and

Postviral) Biliary Cardiac Metabolic Inherited Drug-related Miscellaneous

38

Classification Micronodular Macronodular Mixed PRIMARY

BILIARY CIRRHOSIS

39

Pathogenesishepatocyte

necrosis collapse of the supporting reticulin network with subsequent connective tissue deposition distortion of the vascular bed nodular regeneration of remaining liver parenchyma40

41

Clinical featuresderive

from the morphologic alterations and often reflect the severity of hepatic damage rather than the etiology of the underlying liver disease42

Clinical features Loss

of functioning hepatocellular mass lead to jaundice, edema, coagulopathy, and a variety of metabolic abnormalities fibrosis and distorted vasculature lead to portal hypertension and its sequelae, including gastroesophageal varices and splenomegaly Ascites and hepatic encephalopathy result from both hepatocellular insufficiency and portal hypertension43

Clinical featuresAre

similar to chronic hepatitis + portal hypertension signs

44

Portal hypertension signsAscites Splenomegalia Bleeding esophageal varices and hemorrhoid

45

Pathogenesis

ascites

of

46

Complaints Appetite

loss, Anorexia Weight loss Reduction in skeletal muscle mass Easy bruising Increasing weakness and fatigue

47

Jaundice Palmar

Examination data

erythema Spider angiomas (vascular stars) Parotid and lacrimal gland enlargement, Clubbing of fingers Splenomegaly Muscle wasting Ascites with or without peripheral edema48

Men:

Examination data

- decreased body hair - gynecomastia - testicular atrophy (result from disturbances in hormonal metabolism, including increased peripheral formation of estrogren due to diminished hepatic clearance of the precursor androstenedione) Women: - signs of virilization - menstrual irregularities49

Examination dataA

firm, nodular liver may be an early sign of disease deep palpation

50

51

jaundice, telangiectasis and gynaecomastia

52

53

54

55

Laboratory Findings Elevations

of AST, alkaline phosphatase and bilirubin levels Hypoproteinemia Anemia, low WBC and thombocytes, incr. ESR

56

Instrumental methods Sonography Endoscopy CT,

(esophageal varices) (

MRI Laparoscopy Biopsy of the liver

57

Treatment of Liver Cirrhosis Diet

5 Glucocorticoids Beta-blockers Spironolactone and furosemide Ursodiol Cholestyramine Oral bile salt-sequestering resin Liver transplantation58