1. The seminar covered autoimmune hepatitis and hepatitis B. For autoimmune hepatitis, the goals were to define it, understand its immune pathogenesis, know its clinical features, disease course, lab findings, diagnostic criteria, differential diagnosis, and treatment. 2. For hepatitis B, the goals were to list the different types of viral hepatitis and discuss hepatitis B in detail, including its structure, serology, pathogenesis, pathology, clinical and lab findings, prognosis, complications, sequelae, treatment, and prophylaxis. 3. Key points about hepatitis B included that it is not directly cytopathic but causes liver damage through immune-mediated mechanisms, with cytolytic T cells attacking infected hepatocytes. Chronic

1. NUR FARRA NAJWA
082015100035

2. NUR FARRA NAJWA
082015100035

3. At the end of seminar, students should be able to
 Define autoimmune hepatitis
 Understand the immune-pathogenesis
 Know the clinical features, diseases course , lab findings
 Know the diagnostic criteria
 Able to give differential diagnosis
 Know the treatment

4.  Autoimmune hepatitis is a chronic disorder characterized by continuing
hepatocellular necrosis and inflammation, usually with fibrosis, which can progress to
cirrhosis and liver failure.
 The prominence of extra-hepatic features of autoimmunity and sero-immunologic
abnormalities in this disorder supports an autoimmune process in its pathogenesis.
 This concept is reflected in the prior labels lupoid and plasma cell hepatitis.
-The broader categories of “idiopathic” or cryptogenic chronic hepatitis, many, perhaps
the majority, are probably autoimmune in origin.

5.  Cell-mediated immunologic attack directed against liver cells.
 Autoimmunity predisposition
 Inherited
 Environmental (Chemical, drug, viral) factors.

7. 1. Liver histopathologic lesions are composed predominantly of cytotoxic t cells and
plasma cells
2. Circulating autoantibodies (nuclear, smooth muscle, thyroid) ,
rheumatoid factor, hyperglobulinemia
3. Other autoimmune disorders- occur with increased frequency in patients and in their
relatives who have autoimmune hepatitis
4. Histocompatibility haplotypes associated with autoimmune diseases- (HLA-
B1, -B8, -DR3, and -DR4)
5. This type of chronic hepatitis is responsive to glucocorticoid/immunosuppressive
therapy.

8.  Similar to those described for chronic viral hepatitis.
 Onset : insidious or abrupt
 Initially same and be confused = acute viral hepatitis;
 History : recurrent bouts of what had been labeled acute hepatitis
 Sometimes diagnosis is made in the absence of symptoms, based on abnormal liver
laboratory tests.
 A subset of patients with autoimmune hepatitis has distinct features.
 predominantly young to middle-aged women with marked hyperglobulinemia and
high-titer circulating ANAS.
 Positive lupus erythematosus (le) = (initially labeled “lupoid “ hepatitis)

9.  Fatigue, malaise, anorexia, amenorrhea, acne, arthralgias, and jaundice are common.
 Sometimes, arthritis, maculopapular eruptions, erythema nodosum, colitis, pleurisy,
pericarditis, anemia, azotemia, and sicca syndrome (keratoconjunctivitis, xerostomia)
occur.
 In some patients, complications of cirrhosis bring the patient to initial medical attention.

10.  VARIABLE.
 Mild disease or limited histologic lesions = piecemeal necrosis without bridging
 Progression to cirrhosis is limited,
 But clinical monitoring is important to identify progression
 In those with severe symptomatic autoimmune hepatitis
= aminotransferase levels >10 times normal, = Marked hyperglobulinemia,
= “aggressive” histologic —bridging necrosis/multilobular collapse, = cirrhosis
 The 6-month mortality without therapy
 Death may result from hepatic failure, hepatic coma, other complications of cirrhosis, and intercurrent
infection.
 In patients with established cirrhosis, hcc may be a late complication but less frequently than in cirrhosis due
to viral hepatitis

13.  Same to chronic viral hepatitis.
 Most patients have normal serum bilirubin, alkaline phosphatase, and globulin levels with only minimal
aminotransferase elevations.
 Serum bilirubin level is moderately elevated (51−171 μmol/l [3−10 mg/dl]), in severe cases
 Serum AST and ALT levels are increased and fluctuate in the range of 100−1000 units.
 Serum alkaline phosphatase levels may be moderately elevated or near normal.
 The prothrombin time is often prolonged, particularly late in the disease or during active phases.
 As noted above, circulating autoantibodies are also prevalent, most characteristically ANAs in a
homogeneous staining pattern.
 Very active or advanced disease has hypoalbuminemia occurs
 Hypergammaglobulinemia (>2.5 g/dl) is common in autoimmune hepatitis, as is the presence of rheumatoid
factor.

14. A MORE SIMPLIFIED,
MORE SPECIFIC
SCORING SYSTEM
RELIES ON FOUR
VARIABLES:
 Autoantibodies
 Serum IgG level
 Typical or
compatible
histologic features,
 And absence of
viral hepatitis
markers.
FACTOR WEIGH IN FAVOUR FOR
DIAGNOSIS
• Female gender
• Predominant aminotransferase
elevation
• Presence and level of globulin
elevation
• Presence of nuclear, smooth
muscle, LKM1, and other
autoantibodies
• Concurrent other autoimmune
diseases
• Characteristic histologic features
FACTOR WEIGH AGAINST
DIAGNOSIS
• Predominant alkaline phosphatas
elevation,
• Mitochondrial antibodies,
• Markers of viral hepatitis,
• History of hepatotoxic drugs or
excessive alcohol,
• Histologic evidence of bile duct
injury,
• Or such atypical histologic features
as fatty infiltration, iron overload,
and viral inclusions.

15.  May resemble typical acute viral hepatitis.
 Without histologic assessment, severe chronic hepatitis cannot be readily distinguished from mild chronic
hepatitis.
 In adolescence, Wilson’s disease may present with features of chronic hepatitis long before neurologic
manifestations and before the formation of kayser-fleischer rings
 serum ceruloplasmin and serum and urinary copper determinations plus measurement of liver copper
levels establish the correct diagnosis.
 Postnecrotic/cryptogenic cirrhosis/primary biliary cirrhosis and both alcoholic hepatitis and nonalcoholic
steatohepatitis may present with many same features
The distinction between autoimmune and chronic viral hepatitis is not always straightforward,
especially when viral antibodies occur in patients with autoimmune disease or when autoantibodies
occur in patients with viral disease.

16.  The presence of extrahepatic features such as arthritis, cutaneous vasculitis, or the presence of
circulating autoantibodies
 Cause confusion with rheumatologic disorders and systemic lupus erythematosus.
 The existence of clinical and biochemical features of progressive necroinflammatory liver disease
distinguishes chronic hepatitis from these other disorders
 Occasionally, features of autoimmune hepatitis overlap with features of autoimmune biliary
disorders. Such overlap syndromes are difficult to categorize, and response to therapy may be
the distinguishing factor that establishes the diagnosis.

17.  Mainstay management = glucocorticoid therapy
 A therapeutic response can be expected in up to 80% of patients.
 But has not been shown in clinical trials to prevent ultimate progression to cirrhosis -
- however, reversal of fibrosis and cirrhosis have been reported in patients responding
to treatment,
--- and rapid treatment responses within 1 year do translate into a reduction in
progression to cirrhosis.
 The use of prednisone is just as effective as prednisolone and is favored by most
authorities.

18. Therapy may be initiated at
20 mg/d, but a popular
regimen in the United
States relies on an initiation
dose of 60 mg/d.
This high dose is tapered
successively over the course
of a month down to a
maintenance level of 20
mg/d.
An alternative, but equally
effective, approach is to
begin with half the
prednisone dose (
30 mg/d) along with az
athioprine (50 mg/d).
With
azathioprine maintained
at 50 mg/d, the pre
dnisone dose is tape
ered over the course of a
month down to a
maintenance level of 10
mg/d.

19.  Continue therapy for 12−18 months.
 After tapering and cessation of therapy, relapse is at least 50%, even if post-
treatment histology improved
 Majority of patients require therapy at maintenance doses indefinitely.

20.  Medically refractory cases,
 Attempt to intensify treatment with high-dose glucocorticoid monotherapy (60 mg
daily) or
 Combination glucocorticoid (30 mg daily) plus high-dose azathioprine (150 mg
daily) therapy.
 After a month
 Doses of prednisone can be reduced by 10 mg a month,
 And doses of azathioprine can be reduced by 50 mg a month

21.  Liver transplantation is the only recourse if
 Therapy fails
 Progresses to cirrhosis
 Associated with liver failure
 Failure of the bilirubin to improve after 2 weeks of
 Patients with autoimmune hepatitis should be vaccinated against hepatitis A and B,
ideally before immunosuppressive therapy is begun, if practical.

22. NUR FARRA NAJWA
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23. At the end of seminar student should
be able to
1. List different viral hepatitis
2. Discuss the hepatitis B in details
 Structure
 Serology
 Pathogenesis
 Pathology
 Clinical findings
 Laboratory findings
 Prognosis
 Complication and squelae
 Treatment
 Prophylaxis

30.  None of the hepatitis viruses is known to be directly cytopathic to hepatocytes.
 Clinical manifestations and outcomes after acute liver injury associated with viral hepatitis are
determined by the immunologic responses of the host.
 Hepatitis B , the existence of inactive hepatitis b carriers with normal liver histology and
function suggests that the virus is not directly cytopathic.
 The fact that patients with defects in cellular immune competence are more likely to remain
chronically infected rather than to clear HBV
 The model that has the most experimental support involves cytolytic Y cells sensitized
specifically to recognize host and hepatitis B viral antigens on the liver cell surface.
 Nucleocapsid proteins (HBcAG and possibly HBeAG), present on the cell membrane in
minute quantities, are the viral target antigens that, with host antigens, invite cytolytic T
cells to destroy HBV-infected hepatocytes.

31.  Mainly due to immune complex mediated tissue damage
 Prodromal syndrome observed in acute hepatitis B related to the deposition in tissue
blood vessel walls of hbsag-anti-hbs circulating immune complexes, leading to activation of the
complement system and depressed serum complement levels.
 In patients with chronic hepatitis b, other types of immune-complex disease may be seen.
 Glomerulonephritis with the nephrotic syndrome
 Whereas generalized vasculitis (polyarteritis nodosa)
 Polyarteritis nodosa have hbsag in serum in these patients, the affected small- and medium-
size arterioles contain

32. Consist of panlobular
infiltration with mononuclear
cells, hepatic cell necrosis,
hyperplasia of kupffer cells,
and variable degrees of
cholestasis.
Hepatic cell regeneration is
present = numerous mitotic
figures, multinucleated cells,
and “rosette” or
“pseudoacinar” formation.
The mononuclear infiltration
consists primarily of small
lymphocytes, some plasma
cells and eosinophils present.
Hepatic cell degeneration
and necrosis, cell dropout,
ballooning of cells, and
acidophilic degeneration of
hepatocytes
Large hepatocytes with a
ground-glass appearance of
the cytoplasm may be seen
in chronic but not in acute
HBV infectionx.

33.  Incubation periods = 30–180 days (mean, 8–12 weeks)
 Constitutional symptoms of anorexia, nausea and vomiting, fatigue, malaise, arthralgias,
myalgias, headache, photophobia, pharyngitis, cough, and coryza may precede the
onset of jaundice by 1–2 weeks.
 A low-grade fever between 38° and 39°c (100°–102°f
 Dark urine and clay-colored stools may be noticed by the patient from 1–5 days
before the onset of clinical jaundice.

34.  With the onset of clinical jaundice
 The constitutional prodromal symptoms usually diminish
 Mild weight loss (2.5–5 kg)
 The liver becomes enlarged and tender (right upper quadrant pain and discomfort)
 Splenomegaly and cervical adenopathy
 Rarely, a few spider angiomas appear during the icteric phase and disappear during
convalescence.

35.  During the recovery phase
 Constitutional symptoms disappear
 Some liver enlargement and abnormalities in liver
biochemical tests are still evident.
 The duration of the posticteric phase is variable, ranging
from 2–12 weeks
 Complete clinical and biochemical recovery is to
be expected 3–4 months after the onset of jaundice
 Hep B with Hep D (the duration of HBV infection
determines the duration of HDV infection)

38.  Recover completely with no clinical sequelae.
 Patients of advanced age and with serious underlying medical disorders = have a
prolonged course and are more likely to experience severe hepatitis.
 Initial presenting features = ascites, peripheral edema, and symptoms of suggest a
poorer prognosis.
 Severe hepatocellular disease = prolonged pt, low serum albumin level, hypoglycemia,
and very high serum bilirubin values
 Advanced age and underlying debilitating disorders = increase fatality rate in hepatitis a
and b

39.  Rheumatologic diseases= often diagnosed during the prodromal phase of acute hepatitis B
 Fulminant cases of viral hepatitis = >50% of hepatitis B case
 Deep coma = usually present with signs and symptoms of encephalopathy
 Chronically hbsag-positive = hbsag-positive for >6 months after the onset of clinically apparent acute
hepatitis B
 Chronic hepatitis = late complication of acute hepatitis B
 Rare complications = pancreatitis, myocarditis, atypical pneumonia, aplastic anemia, transverse
myelitis, and peripheral neuropathy.
 Hepatocellular carcinoma = persons with chronic hepatitis b have an enhanced risk

40.  Recovery occurs in ~99%;
 A nucleoside analogue at oral doses used to treat chronic hepatitis B
 (entecavir or tenofovir)
 Treatment should continue until 3 months after HBsAg seroconversion or 6 months
after HBeAg seroconversion
 Restricted physical activity.
 A high-calorie diet is desirable
 Drugs capable of producing adverse reactions such as cholestasis and drugs
metabolized by the liver should be avoided.
 For severe pruritus is present, the use of cholestyramine is helpful.
 Emphasis should be placed on blood precautions

41.  In fulminant hepatitis, the goal of therapy is to support the patient by maintenance of
 Fluid balance,
 Support of circulation and respiration,
 Control of bleeding,
 Correction of hypoglycemia, and
 Treatment of other complications of the comatose
 Protein intake should be restricted, and oral lactulose or neomycin administered.
 Prophylactic antibiotic coverage is the one factor that does appear to improve
survival.
 Liver transplantation

43. At the end of seminar, students should be able to
 Define autoimmune hepatitis
 Understand the immune-pathogenesis
 Know the clinical features, diseases course , lab findings
 Know the diagnostic criteria
 Able to give differential diagnosis
 Know the treatment

44. At the end of seminar student should
be able to
1. List different viral hepatitis
2. Discuss the hepatitis B in details
 Structure
 Serology
 Pathogenesis
 Pathology
 Clinical findings
 Laboratory findings
 Prognosis
 Complication and squelae
 Treatment
 Prophylaxis