Acute and Chronic Hepatitis(A,B,C,D,E ,)

It is a presentation on acute hepatitis like A,B,C,D,E and chronic hepatitis like B,C and other causes

1. Acute and Chronic Hepatitis DR ASAD ULLAH Senior Registrar Endocrinology and Diabetes

2. Acute Hepatitis Acute hepatitis occurs when the liver suffers an injury resulting in an inflammatory reaction Clinical presentation Patients often present with fever, abdominal pain, and jaundice. Multiple serum lab values are often elevated, including AST, ALT, and GGT. ETIOLOGY : Hepatotropic viruses (e.g. HAV, HBV, HCV,HDV,HEV) non- hepatotropic viruses (e.g. EBV, CMV, HSV, etc.) other infections (e.g. parasites) drug/toxin-induced hepatitis (e.g. acetaminophen toxicity, alcohol) autoimmune hepatitis, acute fatty liver of pregnancy,HELLP syndrome metabolic disease (e.g. nonalcoholic fatty liver disease, Wilson disease, hemochromatosis) ischemic (e.g. systemic shock, Budd-Chiari syndrome)

3. ACUTE HEPATITIS A VIRUS Hepatis A virus(HAV) is a 27 nm RNA virus, which causes epidemics and sporadic cases. Globally over 1.5 million people are infected annually. The virus is transmitted by fecal-oral route by either person to person contact or ingestion of contaminated food or water. Common source outbreak resulting from contaminated food, untreated ground water from wells. The incubation period averages 30 days.HAV is excreted in faces for up to 2 weeks before clinical illness but rarely after the first week of illness. There is no chronic carrier state.

4. Clinical Presentation of HAV Malaise,myalgias,arthralgias,easy fatigability,anorexia,nausea,vomiting Jaundice occurs 5-10 days after symptoms The acute illness usually subsides over 2-3 weeks with complete clinical and laboratory recovery by 9 weeks. LABORATORY Findings ALT and AST levels are strikingly high followed by elevations of bilirubin. Anti body to hepatitis A(Anti-HAV) appears early in the course of the illness. Both IgM and IgG anti HAV are detectable in serum soon after the onset. PREVENTION Unvaccinated persons who are exposed to HAV are advised to receive post exposure prophylaxis with a single dose of HAV vaccine or immune globulin or both.

5. Vaccination for HAV Vaccination with one of the two effective inactivated hepatitis A vaccines are available. Vaccination is recommended for persons living in or travelling to endemic areas, persons aged above 40,Persons with HIV,animal handlers, injection drug users,incarcerated,homelesness,. For travelers, a single dose of vaccine at any time before departure can provide adequate protection. Treatment Symptomatic(anti emetics, dextrose)

6. Acute Hepatitis B Hepatitis B is DNA virus HBV is usually transmitted by inoculation of infected blood or blood products or by sexual contact and it is present in saliva,semen,and vaginal secretion,HBsAg positive mothers may transmit HBV at delivery. HBV is prevalent in homosexual people and those who inject drugs, but the greatest number of cases result from heterosexual transmission. Other groups at risk are physicians,dentists,nurses,laboratory technicians Incubation period is 6 weeks to 6 months. Symptoms and signs Similar to Hepatitis A Laboratory Findings HBsAg . First evidence of infection, persistence for more than 6 months signifies chronic hepatitis B. Anti-HBs . appears in most individuals after clearance of HBsAg and after successful vaccination, Disappearance of HBsAg and appearance of Anti-HBs signal recovery.

7. Anti- HBc -IgM anti- HBc appears shortly after HBsAg is detected. It indicates a diagnosis of acute hepatitis B. HBeAg .IT indicates viral replication and infectivity HBV DNA. It is a more sensitive and precise marker of viral replication and infectivity. Treatment of acute HBV Same as acute HAV.

8. ACUTE HEPATITIS C HCV is RNA virus, seven major genotypes of HCV have been identified. Transmitted by blood transfusion, injection drug use, body piercing,tattoos,hemodialysis.Risk of sexual and maternal-neonatal is low Symptoms and signs Incubation period 6-7 weeks, usually asymptomatic Laboratory Diagnosis. Enzyme immunoassay(EIA) that detects antibodies to HCV. Treatment. A 6 Week course of ledipasvir and sofosbuvir has been shown to prevent chronic hepatitis in patients with acute genotype 1 hepatitis C and lack of spontaneous clearance after 3 months. .

9. HEPATITIS D HDV is RNA virus that causes hepatitis only in association with HBV infection HDV may coinfect with HBV or may superinfect a person with chronic hepatitis B.in chronic hepatitis Superinfection by HDV appears to carry a worse short term prognosis often resulting in acute liver failure. Diagnosis is by detection of antibody to hepatitis D antigen(anti-HDV) or HDV RNA in serum.

10. HEPATITIS E HEV is RNA virus Transmission is by feco -oral route Most common in central and southeast Asia. 3 month course of Ribavirin has been reported to induce sustained clearance of HEV RNA infection.

11. CHRONIC VIRAL HEPATITIS It is defined as chronic necroinflammation of the liver of more than 3-6 months duration,demonstrated by persistently elevated serum aminotransferase level or characteristic histologic findings often in the absence of symptoms. Causes of chronic hepatitis is include viruses(HBV,HCV,HDV),Autoimmune hepatitis, alcohol associated and non alcoholic steatohepatitis, certain medications such as isoniazid,nitrofurantoin,Wilson disease,alpha-1 antitrypsin deficiency, Haemochromatosis and rarely coeliac disease. Chronic Hepatitis B and chronic hepatitis D Chronic HBV afflicts 316 million people worldwide. Five phases of chronic hepatitis B infection are recognized 1.Immune tolerant phase (HBeAg positive chronic HBV infection)HBeAg and HBV DNA are present in serum and are indicative of active viral replication, and serum aminotransferase level are normal with little necroinflammation in the liver, This phase is common in infants and young children whose immune system fails to mount an immune response to HBV.

12. Persons in the immune tolerant phase and those who acquire HBV later in life may enter an immune active phase (HBeAg positive chronic HBV)in which aminotransferase and HBV DNA levels are elevated and necroinflammation is present in the liver with a risk of progression to cirrhosis and HCC;Low level IgM Anti-HBC is present in serum in about 70%. Patents enter the inactive HBs carrier state (HBeAg negative chronic HBV infection) when biochemical improvement follows immune clearance, This improvement coincides with the disappearance of HBeAg and reduced HBV DNA levels(less the 10 5 copies/ml or less than 20,000 iu /ml in serum, appearance of anti Hbe and integration of the HBV genome into the host genome in infected hepatocytes. Patients in this phase are at low risk of cirrhosis. The reactivated chronic hepatitis B phase (HBeAg negative chronic hepatitis B)may result from infection by a pre core mutant of HBV or from spontaneous mutation of the pre core or core promoter region of the HBV genome during the course of chronic hepatitis caused by wild type HBV.HBeAg negative chronic hepatitis B accounts for less than 10% of cases of chronic HBV . In reactivated chronic HBV,there is rise in serum HBV DNA levels and possible progression to cirrhosis. Only 1% of treated and untreated patients per year reach the HBsAg negative phase ,in which anti-Hbe may remain detectable ,serum ALT are normal and HBV DNA is undetectable in serum but remains present in liver. This is called Functional cure.

13. TREATMENT Patients with active viral replication (HBeAg and HDV DNA [10 5 copies/ml or more or 20,000 iu /ml or more in serum and elevated aminotransferase levels may be treated with a nucleoside or nucleotide analogs or with PEGylated interferons. For patients who are HBeAg negative, the threshold for treatment is serum HBV DNA level of10 4 copies/ml or 2000 iu/ml the threshold HBV DNA levels for treatment is met but the serum ALT levels is normal, treatment may still be considered in patients over age 3-40 if liver biopsy or a noninvasive assessment of liver fibrosis demonstrates a fibrosis stage of 2 of 4(moderate or higher. AIMS (Reducing and maintaining HBV DNA to the lowest level, normalization of ALT,IN HBeAg positive patients seroconversion to ant-Hbe and clearance of HBsAg. Therapy should continue for 6-12 months after HBeAg to anti- Hbe seroconversion. Preferred first line oral agents are entecavir and tenofovir.

14. CHRONIC HEPATITIS C Chronic hepatitis c develops in 85% of patients with acute hepatitis c. Worldwide,8 million people are infected with HCV.It is diagnosed by Anti- HCV.In rare cases of suspected HCV but a negative EIA,HCV RNA is detected by PCR testing. TREATMENT Sofosbuvir- Velpatasvir ( Hilvel,Epclusa ) 1 tablet daily for 12 weeks Glecapriver-Pibrentasvir 3 tablets daily for 8 weeks

15. AUTOIMMUNE HEPATITIS Usually seen in young women Symptoms and signs Insidious,25% with acute severe hepatitis Exacerbation may occur postpartum, amenorrhea may be the presenting feature Laboratory findings Aminotransferase levels may be greater then 1000u/l and total bilirubin is usually increased. It has classified as type ɪ or type ɪɪ . In type ɪ ,ANA or smooth muscle antibodies are usually detected. Anti bodies to soluble liver antigen (anti-SLA) characterize a variant of type that is marked by severe disease ,high relapse rate after treatment and absence of ANA,ASMA Type ɪɪ is seen more often in girls under age 14 is characterized by Liver kidney micro some type ɪ (anti-LKM1) TREATMENT (Prednisolone with or without azathioprine)..cilosporin,tacrolimus,methotrexate,Mycophenoalte mofetil

16. OTHER CAUSES OF CHRONIC HEPATITIS Alcohol associated liver disease Excessive alcohol intake can lead to fatty liver,hepatitis and cirrhosis. Frequency is 10-15% among persons ho consume over 0gm of alcohol(4 oz of 100-proof whiskey,1 oz of wines, or four 12 oz cans of beer daily for more than 10 years. Symptoms and signs From hepatomegaly to acute liver failure Laboratory Anemia(macrocytic),AST is usually elevated than ALT by a factor of 2 or more. Liver biopsy ;macro vesicular fat,polymorphonuclear infiltration with hepatic necrosis, Mallory bodies,pervenular and per sinusoidal fibrosis. Treatment Abstinance,naltrexone,topiramate,gabapentin,methyprednisolone

17. NON ALCOHOLIC FATTY LIVER DISEASE Mostly asymptomatic, hepatomegaly present in 75% of patients Laboratory Mild elevated aminotransferses,ALP The ratio of ALT to AST is almost always greater then 1.0 in NALD. Imaging Steatosis may be demonstrated on USG,CT or MRI. Liver Biopsy and risk scores Percutaneous liver biopsy is the gold standard. Treatment Lifestyles changes( wt loss,exercise,fructose restriction,dietry fiber DRUGS(vitamin E,Thioolidinediones,obeticholic acid,semaglutide,liraglutide) Bariatric surgery, Liver transplantation