29 - Chr.hepatitis And Cirrhosis

Chronic Hepatitis. Liver Cirrhosis. 1

Liver function

2

Liver function

3

International classification of disorders… -10 - about liver diseases

К

70: Alcoholic liver disease  К 71: Тoxic liver disprders  К 72: Hepatic failure and acute hepatitis  К 73: Chronic hepatitis  К 74: Liver fibrosis and cirrhosis 4

Chronic hepatitis a

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 cirrhosis 5

History  1937

– J.M.Findlay, F.O.McCallum – first investigation of “serum” hepatitis

 1956

- F.O.McCallum - first finding about viral hepatitis A and B and its transmission mechanisms 6

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

Classification by Cause Aetiology chronic viral hepatitis, caused by hepatitis B, hepatitis B plus D, hepatitis C, or other viruses autoimmune

hepatitis drug-associated chronic hepatitis cryptogenic chronic (idiopathic) hepatitis 8

Classification By Grade  histologic

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

- mild, moderate, or severe degree of CH 9

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 Ishak 14

Classification By Stage 0

= no fibrosis

1

= mild fibrosis

2

= moderate fibrosis

3

= severe fibrosis, including bridging fibrosis

4

= cirrhosis 15

Pathogenesis  Liver

tissue damage by aetiologic factor

 Cellular

and humoral immune response

 Autoimmunoaggression  Progression

of chronic liver tissue inflammation 16

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 term 17

Examination  Jaundice

(желтуха)  Paleness (anemia)  “Vascular stars” =spider naevi (сосудистые звездочки)  “Hepatic palms of the hand” (печеночные ладони) = palmar erythema  Stratches due to Pruritus (расчесы)  Bruises and petechieae (синяки и петехии)  Xanthomas and xanthelasmas (deposits of cholesterol)  Gynaecomastia  Loss of body hair in men or hirsutism in women 18

Hepatic marks

19

Examination  Liver

enlargement  Low liver margin rounding (закругление нижнего края печени)

 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 cancer 22

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 НBV  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 time 25

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

TREATMENT Chronic 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 treatment 

27

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) factors 31

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 disorders 4.

33

Clinical features  Many

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

34

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

35

Liver Cirrhosis 36

Liver Cirrhosis chronic

injury of the hepatic parenchyma include extensive fibrosis in association with the formation of regenerative nodules 37

Aetiology and Classification  Alcoholic  Postnecrotic

(Cryptogenic and

Postviral)  Biliary  Cardiac  Metabolic  Inherited  Drug-related  Miscellaneous

38

Classification  Micronodular  Macronodular  Mixed  PRIMARY

BILIARY CIRRHOSIS

39

Pathogenesis hepatocyte

necrosis collapse of the supporting reticulin network with subsequent connective tissue deposition distortion of the vascular bed nodular regeneration of remaining liver parenchyma 40

41

Clinical features derive

from the morphologic alterations and often reflect the severity of hepatic damage rather than the etiology of the underlying liver disease 42

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 hypertension 43

Clinical features Are

similar to chronic hepatitis + portal hypertension signs

44

Portal hypertension signs Ascites  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

Examination data

 Jaundice  Palmar

erythema  Spider angiomas (“vascular stars”)  Parotid and lacrimal gland enlargement,  Clubbing of fingers  Splenomegaly  Muscle wasting  Ascites with or without peripheral edema 48

 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 irregularities 

49

Examination data A

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

(esophageal varices) (

 CT,

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 transplantation 58