2.  Cc:weakness  PI:A 41 y/o female patient with elevated of liver enzyme in lab data and weakness since one year ago Nausea & vomiting(-)/Hx of icter(-) /Artheralgia(-)/Hx of Abdominal pain(-) /Dark urine(-)  PMH (-)  DH: (-)  SH: Smoking(-) Hx of tatto five years ago No Hx of Hospital addmision & transfusion

3.  23/6/1393 WBC:5500 Hb:12.3 MCV:80.5 PLT:180000 ESR:10 AST:132.7 ALT:136.9 ALP:143 Bill(T):0.69 Bill(D):0.16 LDH:637 INR:1.3 ANA(-) Anti ds DNA(-) HBS Ag(-) Anti HAV Ab(IgM) (-) Anti HCV Ab (+) ceruloplasmin level(normal)

4. Mild Hepatomegaly with Liver span 150 mm/Fatty liver G1/Spleen size upper limited of normal /portal vein 9 mm/NO Ascitis

5. 10/7/1393 335 Copies/ml 83.7 IU/ml HCV genotyping 1a

6. Metavir score :F4(Cirrhosis) Steatosis percent :6%

7. Section show liver tissue with distorted architecture.sever infiltration of inflamatory cells in seen septal tracts with diffuse interface hepatitis.one to four foci of focal necrosis is present in liver lobules.steatosis not identified.reticulin stain shows regenerative pattern.trichrome stain shows nodule formation.  CHRONIC HEPATITIS C

8. CANDIDATE FOR TREATMENT OF CHRONIC HEPATITIS C (Weight based)RIBAVIRIN + PEG IFN alpha-2b (48 weeks)

10. NASH OR AUTOIMMUNE HEPATITIS??

11.  Cirrhosis  Inflammatory cells of fibrous septa are mostly lymphocytes with a good number of plasma cells and few eosinophils.lymphoid nodules are formed in some areas.no granuloma is seen.no cholestasis is seen.the remaining bile ducts are intact.  Considering the extensive interface hepatitis and presence of good number of plasma cell contributing in the inflammatory infiltrate of fibrous septa the possibility of coexistent autoimmune liver disease should also be considered.

12. Prednisolone 50 mg /daily AND Azathioprine initialy step THEN LIVER BIOCHEMICAL TEST AST:42 ALT:65 AST:32 ALT:43 AST:38 ALT:37 AST:24 ALT:16

13. HEPATITIS C

14.  HCV is a member of flavivirus family  HCV genome is a single stranded positive-sense RNA and contain 9.4 kb  HCV genome may be divided into many types and subtypes(6 genotype)  Diagnostic test: Serologic assays that detect antibodies to hepatitis c Molecular assays that detect or quantify HCV RNA

15.  Transfusion or transplant from infected donor  Injecting drug use  Hemodialysis(yrs on treatment)  Accidental injuries with needles/sharp  Sexual/household exposure to anti-HCV positive contact  Multiple sex partners  Birth to HCV-infected mother  Hx of tatto and piercing

16. Incubation period: Average 6-7 wks Range 2-26 wks Clinical illness(jaundice): 30-40%(20-30%) Chronic hepatitis : 70% Persistent infection: 85-100% Immunity: No protective antibody

17.  Bile ductal injury  Lymphoid aggregate in portal tract

18.  Genotype 1a:Daily daclatasvir(60mg) and sofosbuvir(400mg)for 12 weeks(no cirrhosis) or 24 weeks with or without weight-based RBV (1000mg{ 75 kg})(cirrhosis)  Viral loads checked at baseline and at weeks 4,12,and 24 of therapy to assess for a treatment response and to make decisions about continuing treatment or possibly altering the duration of treatment

19.  Rapid virologic response(RVR):HCV RNA negative after four weeks of treatment if HCV RNA remains negative at 12 weeks it is known as an extended rapid virologic response(eRVR)

20.  Early virologic response(EVR):at least a 2 log 10 reduction in HCV RNA(a partial EVR)or HCV RNA negativity(a complete EVR) by week 12 of treatment  Delayed virologic response :HCV RNA negativity at week 24 in patients who fail to achieve a complete EVR (such patients are also known as”slow responders”)  End of treatment response(EOT):HCV RNA negativity at the end of treatment

21.  Relapse:reappearence of HCV RNA in patients who HCV RNA negative at the end of treatment  Sustained virologic response(SVR):absence of HCV RNA by polymerase chain reaction six months after stopping treatment

22. AUTOIMMUNE HEPATITIS

23.  Autoimmune hepatitis (AIH) is a generally unresolving inflammation of the liver of unknown cause  A failure of immune tolerance mechanisms, and a genetic predisposition collaborate to induce a T cell–mediated immune attack upon liver antigens, leading to a progressive necroinflammatory and fibrotic process in the liver  Women are affected more frequently than men (sex ratio, 3.6:1)

26.  Drugs such as minocycline, diclofenac, Infliximab, Propylthiouracil,Atorvastatin, Nitrofurantoin,Methyl dopa,and Isoniazid can cause a syndrome that resembles AIH replete with autoantibodies that generally disappear after discontinuation of the drug.

29.  Interface hepatitis is the histological hallmark, and plasma cell infiltration is typical  Eosinophils, lobular inflammation, bridging necrosis, and multiacinar necrosis may be.  The portal lesions generally spare the bile ducts. In all but the mildest forms, fibrosis is present and, with advanced disease, bridging fibrosis or cirrhosis is seen

30.  A probable diagnosis of autoimmune hepatitis is made if the total point are six,while a definite diagnosis is made if the total points are >=seven  Differential diagnosis:

32.  Prednisolone or Prednisone (60 mg)alone OR  Lower dose Prednisone (30 mg)in combination with Azathioprine(50 mg daily is used most commonly in the United States,while in Europe it is often given as 1 to 2 mg/kg body weight)  During treatment,serum ALT,total bilirubin,and gamma glubuline levels should be checked  Patient should be vaccinated against hepatitis A and B if not already immune,before immunosuppression

33.  The hepatitis C-Autoimmune hepatitis overlap syndrome is an uncommon condition  Scandinavian Journal Gastroenterology. 2013; Diagnostic difficulties, therapeutic strategies, and performance of scoring systems in patients with autoimmune hepatitis and concurrent hepatitis B/C

34.  This large case series describes concurrent AIH and chronic viral hepatitis. The revised scoring system for AIH had a better performance than the simplified scoring system. However, neither scoring system is optimal for diagnosing AIH alone. In these patients, a definitive diagnosis of AIH should be based on a combination of serological profiles, histological findings, scoring systems, treatment response, and outcomes

35. Lymphoplasmocytic portal interface and Acinar hepatitis 81%specificity in AIH versus Bile duct damage,Bile duct loss,Steatosis and lymphoid cell follicule with portal tract in Hepatitis C

36.  The Result of the following Article (Result of steroid-based therapy for the hepatitis C autoimmune hepatitis overlap syndrom 2001) Corticosteroids are beneficial as a first line therapy for some patients with the hepatitis c-autoimmune overlap syndrome,resulting in appreciable biochemical and histological response but without viral eradication