Chronic Hepatitis Classification viral hepatitis Clinical features and Treatment

Chronic Hepatitis

• Chronic hepatitis is a liver disorder with inflam­mation and necrosis persisting for more than 6 months.
• Chronic hepatitis may be mild, non-progressive, or severe, or may lead to cirrhosis.

Chronic hepatitis may be of three types:

• · Chronic viral hepatitis
• · Chronic drug-induced hepatitis
• · Autoimmune chronic hepatitis.

Other presentations of chronic hepatitis may be

• · Wilson’s disease
• · Alcoho’lic hepatitis.

Classification of Chronic Hepatitis Classification by extent of liver injury

• 1. Chronic persistent hepatitis
• 2. Chronic lobular hepatitis
• 3. Chronic active hepatitis.

Classification of Chronic hepatitis by Cause

• · Hepatitis B
• · Hepatitis B plus D
• · Hepatitis C
• · Autoimmune hepatitis type I, II and III based on serology
• · Drug-associated chronic hepatitis
• · Cryptogenic chronic hepatitis.

Classification of Chronic hepatitis by Grade

• 1. Periportal necrosis
• a. Piecemeal necrosis or interface hepatitis
• b. Bridging necrosis
• 2. Intralobular necrosis
• 3. Portal inflammation
• 4. Fibrosis.

Chronic viral hepatitis generally follows:

• Viral hepatitis B
• Viral hepatitis C
• Viral hepatitis Band C with superimposed hepa­titis D.
• Hepatitis A and E are self-limited and do not progress to chronic hepatitis.

Chronic Hepatitis B

• Hepatitis B infection at birth may be silent but there
• is a 90% chance of chronic infection. •
• In young adults there is overt symptomatic acute hepatitis but progression to chronic hepatitis is rare.
• Chronic hepatitis may be asymptomatic, mild or se­vere.
• Chronic hepatitis B may progress to severe form, cir­rhosis, and liver failure in about a quarter of the cases.

Hepatitis B virus replication (HBV)

• Replicative phase is identified by the presence of se­rum markers – HBeAg (Hepatitis B e antigen) and HBV DNA, presence of intrahepatocyte antigens ­HBcAg (Hepatitis B core antigen) and liver injury.
• Non-replicative phase is characterized by absence of HBeAg and HBV DNA, and minimal liver injury.
• Chronic HBV infection at birth and in early childhood leads to hepatocellular carcinoma in a majority of, cases.

Clinical features of Chronic hepatitis B

• · Asymptomatic infection
• · Deblitating disease
• · Progresses to end-stage hepatic failure
• · Onset may be insidious (slow), or chronic disease may follow acute hepatitis B.
• · Fatigue
• · Persistent or intermittent jaundice
• · Malaise, anorexia, leading to slow hepatic dec­ompensation
• · Cirrhosis of liver – ascites, edema, bleeding gas­troesophageal varices, hepatic encephalopathy, coagulopathy and hypersplenism.
• Extrahepatic manifestations – arthralgias, arthritis, purpuric lesions due to vasculitis, polyarteritis nodosa.

Laboratory features

• · Amino transferase elevation may be from 100 to 1000 units.
• · ALT (Alanine amino transferase) is elevated more
• than AST (aspartate amino transferase).
• · In cirrhosis AST may be more than A LT.
• · Alkaline phosphatase may be normal.
• · Serum bilirubin may be moderately raised – 3 to 10 mg/dL.
• · Hypoalbuminemia may be present.
• · Prothrombin time increased.

Chronic hepatitis B Treatment

• Progression of disease occurs in patients with active HBV replication.
• Patients with high level HBV replication are at risk of hepatocellular carcinoma.
• Antiviral therapy should be given to all patients of chronic hepatitis B. The drugs for chronic hepa­titis B are injectable interferon alpha IFNa, oral lamivudine, oral adefovir dipivoxil.
• Antiviral therapy should be given to patients with detectable· markers of HBV replication, in patients with incr~ased ALT twice the upper limit of nor­mal, all immunocompromised individuals, pa­tients of compensated or uncompensated disease. “,
• Dose of interferon – IFN 5 million units subcutaneous daily for 16 weeks or 10 million units 3 times a week.
• Dose of Lamivudine – Daily oral dose of 100 mg for 12 months.
• Dose of Adefovir – Oral daily dose of 10 mg for 48 weeks (1 year).

Chronic Hepatitis D

• Chronic hepatitis D may follow acute infection with hepatitis B virus.
• HDV infection can increase the severity of acute hepa­titis B but progression to chronic hepatitis mayor may not occur.
• If HDV infection occurs in chronic hepatitis B then there is deterioration of liver function resulting in se­vere liver disease.
• The clinical features of hepatitis D over hepatitis B are same as for chronic hepatitis B alone.
• In chronic hepatitis D, anti-LKM i.e. antibodies to liver­kidney microsomes is an important serological fea­ture. This anti-LKM is called anti LKM3 (anti LKM1 is seen in patients with chronic hepatitis C and autoim­mune hepatitis).

Chronic Hepatitis D Treatment

• IFN-ex in high doses – 9 million units 3 times a week for 12 months.
• Liver transplantation.

. Chronic hepatitis C

• Acute hepatitis C virus infection may lead to chronic hepatitis C in more than half the cases.
• In chronic transfusion-associated hepatitis there is progression to cirrhosis in l/S^th of cases.
• Even in asymptomatic patients who go for blood do­nation, hepatitis C may be detected.
• The source of HCV infection may be percutaneous exposure in the past.
• ALT may be normal.
• In patients with normal ALT the disease may not be serious and may not progress to failure and cirrhosis.
• In chronic hepatitis C, progression to liver failure is common with old age, longer duration of infection, histological changes, alcoholic liver disease, chronic hepatitis B, HIV infection, a antitrypsin deficiency.
• Chronic hepatitis C may also convert to hepatocellu­lar carcinoma.

Clinical features

• · Fatigue
• · Jaundice – rarely
• · Sjogren’s syndrome
• · Lichen planus
• · Porphyria cutanea tarda.

Laboratory features

• · ALT may be raised
• · Autoantibodies in serum
• · Anti-LKM.

Chronic hepatitis C Treatment

• IFN ex subcutaneous – 3 times a week for 6 months.
• IFN ex plus Ribavirin daily.
• Pegylated IFNs – Long acting IFN bound to poly­ethylene glycol (PEG) – have a longer half life with once weekly dose.

Chronic Autoimmune Hepatitis

• It is a chronic hepatitis with continued hepatocellular necrosis with fibrosis progressing to cirrhosis and liver failure.
• Mortality is high.
• Clinical features are similar to chronic viral hepatitis. Onset may be insidious or abrupt.
• Common in young or middle-aged women.
• There is high titer of circulating ANA
• There is fatigue, malaise, anorexia, amenorrhoea, acne, arthralgias, jaundice, arthritis, colitis, pericardi­tis, anaemia, sicca syndrome, cirrhosis.
• Course is variable. There may be hepatocellular car­cinoma as a late complication.

Laboratory features

• · Serum AST 100 to 1000 units
• · Serum bilirubin normal to 10 mgjdL
• · Prothrombin time prolonged
• · Hypergammaglobulinemia >2.5 gjdL
• · ANA positive
• · Smooth- muscle antibodies
• · Anti-LKM 1 antibody.

Autoimmune Hepatitis Treatment

• Glucocorticoid therapy Cyclosporine Tacrolimus.