Hepatitis (PDF)

HEPATITIS By Usama M Abdelaal, PhD, MD Professor of Internal Medicine Faculty of Medicine Sohag University  HEPATITIS Infection with inflammation of hepatocyte Classified according: ❖ Etiology: ✓ Viral: - Viral hepatitis (Hepatitis A, B,...

HEPATITIS By Usama M Abdelaal, PhD, MD Professor of Internal Medicine Faculty of Medicine Sohag University  HEPATITIS Infection with inflammation of hepatocyte Classified according: ❖ Etiology: ✓ Viral: - Viral hepatitis (Hepatitis A, B, C, D and E virus). - Non A-E viruses. ✓Non-viral hepatitis. ❖ Clinical presentation; ✓Acute ✓Chronic  1- Acute Hepatitis Etiology: Viral infections: Viral hepatitis, Non A-E viruses e.g. Epstein-Barr virus, Cytomegalovirus, and Yellow fever virus. Non-viral infections (Toxoplasma gondii, Leptospira icterohaemorrhagiae, Coxiella burnetii (Q fever) Acute fatty liver degeneration of pregnancy. Circulatory insufficiency. Wilson’s disease. Poisons e.g. Amanita phalloides (mushrooms), Aflatoxin and Carbon tetrachloride Drugs e.g. Paracetamol, methyldopa, isoniazid, and ketoconazole. Alchol.  1- Acute Hepatitis Clinical features: Prodromal phase (Pre-icteric): ✓ Usually precedes 1-2 weeks before development of jaundice. ✓ Common symptoms are fever, chills, headache, malaise, anorexia, nausea, vomiting, distaste for smoking, fatigue, photophobia, cough. ✓ Physical signs are: Enlarged tender liver , splenomegaly may present particularly in children and cervical lymphadenopathy (10-20%) patient.  1- Acute Hepatitis Clinical features: 2. Acute icteric phase: ✓ Usually persist for 10-15 days. ✓ Constitutional symptoms usually diminish. ✓ Physical signs are: J aundice, dark color urine, stool gradually turns paler, and liver is easily palpable. Splenomegaly, cervical lymphadenopathy and spider angioma are present in 10-20%. 3. Recovery phase: ✓ Usually starts 1-2 weeks after the onset of icteric phase but may be delayed from 6 weeks to 6 months and persists usually for 2-12 weeks. ✓ Complete clinical and biochemical recovery is expected in 1-2 months in all cases of HAV, and HEV without any comorbid medical disorder and 3-4 months after onset of jaundice in about 75% of uncomplicated HBV and HCV infection.  1- Acute Hepatitis Investigations: Liver function tests: ✓ Rise of Liver enzymes (Aminotransferases); ALT and AST starts during early prodromal phase of acute viral hepatitis and precede the rise of serum bilirubin. The level of these enzyme donot coerelate well with the severity of liver cell damage. ✓ Rise in bilirubin level is an early finding and starts in the late prodromal phase and continue up to convalescent period. ✓ Prothrombin time gradually rise and unusual prolongation of P- time is an indicator of severe liver damage. ✓ Serum-alkaline phosphatase rarely exceeds 200 U/L unless marked cholestasis develops.  1- Acute Hepatitis Course and prognosis: ▪ Hepatitis A: Virtually, all healthy patients recover completely with no clinical sequelae. ▪ HBV: 95-99% of healthy people recover completely. ▪ HCV: The likelihood of developing chronic hepatitis is 85-90% with HCV infection, only 15% patient recover spontaneously. ▪ HBV and HDV: Simultaneous infection do not necessarily experience a higher mortality (5%) than with acute hepatitis B alone. However, HDV superi nfection on hepatitis B carrier state has a high mortality of 20%. ▪ HEV: Case fatality is 1-2% in normal subject but may be up to 20% in pregnant women.  1- Acute Hepatitis Differential diagnosis of viral hepatitis: ▪ Infectious mononucleosis, Cytomegalovirus, Herpes simplex virus, Coxsackievirus and toxoplasmosis may share certain clinical features of acute viral hepatitis. ▪ Certain anesthetics agent can produce picture of acute hepatitis or cholestasis. ▪ Acute cholecystitis, stone in CBD and ascending cholangitis may mimic acute viral hepatitis. ▪ HELLP syndrome (hemolysis, elevated liver enzyme, low platelet count) acute fatty liver of pregnancy and cholestasis of pregnancy can be confused with viral hepatitis during pregnancy.  1- Acute Hepatitis Treatment of acute viral hepatitis: ▪ Is mainly supportive. Only severely affected patients require hospital care. ▪ Nutritious diet, if vomiting is severe - Intravenous glucose may be given. - Antiemetic like—Domperidone, metoclopramide ondansetron can be used. ▪ Forced and prolonged bed rest is not essential for full recovery but many patients will feel better with restricted physical activity. ▪ If severe pruritus is present; Bile salt sequestering agent cholestyramine can be used. ▪ All hepatotoxic, cholestatic, sedative, hypnotic, alcohol and oral contraceptive are strictly contraindicated. ▪ All HAV and 99% of HEV require no specific antiviral therapy as they undergo spontaneous remission.  1- Acute Hepatitis Specific Therapy in Severe HBV and HCV Hepatitis: ▪ For HBV in acute viral hepatitis entecavir and tenofovir (most potent and least resistant prone) oral therapy to be continued for 3 months after HBsAg seroconversion and 6 month after HBeAg seroconversion. ▪ Many authority recommend oral brief duration, low resistance antiviral regimen telaprevir and boceprevir to decrease the number of patient that become chronic carrier following acute HCV infection  1- Acute Hepatitis Prophylaxis of viral hepatitis: ▪ HAV: Both active and passive immunization is available; ✓ Active immunization is done with formaldehyde inactivated killed virus containing vaccine which gives life-long immunity after two doses of vaccination 6-12 months apart. ✓ Passive immunization is done with immunoglobulin containing anti-HAV 0.02 ml/kg given prior to exposure or at least 14 days within exposure (within the incubation period). ✓ Combined active and passive immunization can be given to an appropriate patient simultaneously at two different sites.  1- Acute Hepatitis Prophylaxis of viral hepatitis: ▪ HBV: ✓ Active immunization is done with three intramuscular (deltoid not gluteal) injection of HBV vaccine at 0, 1 and 6th months. Pregnancy is not a contraindication for vaccination. ✓ Passive immunization is done with a single intramuscular injection of HBIG 0.06 ml/kg administered as soon as possible after exposure and is to be followed by a complete course of hepatitis B vaccine to be started within 1 week. ✓ Infection with HDV can be prevented by vaccinating with HBV vaccine. ✓ No prophylactic measures (active and passive immunization) is available for HCV infection.  2- Chronic Hepatitis Definition: ▪ Chronic hepatitis is a liver disorder of varying etiology in which hepatic inflammation and necrosis continue for more than 6 months. ▪ The clinical and pathological spectrum of disease varies from mild asymptomatic chronic hepatitis with mild or non-progressive form of chronic hepatitis to more severe form of hepatitis leading to cirrhosis associated with scarring and architectural reorganization.  2- Chronic Hepatitis ETIOLOGY: ▪ Chronic viral hepatitis. ✓ HBV infection S HBV+ HDV co-infection. ✓ HCV infection. ▪ Autoimmune hepatitis. ▪ Drug-associated chronic hepatitis. ▪ Cryptogenic chronic hepatitis.  Chronic Viral Hepatitis Chronic hepatitis occurs as a sequele of acute viral hepatitis B alone or superimposed with hepatitis D and acute viral hepatitis C. Enterically transmitted form of viral hepatitis HAV and HEV are self-limited and do not develop chronic hepatitis.  CHRONIC HEPATITIS B Overall 1–2% of patients infected with acute HBV develop chronic viral hepatitis. The likelihood of chronicity after acute hepatitis B varies with age. Infection at birth is associated with clinically silent acute infection but 90% patient develop chronic viral hepatitis whereas in young immunocompetent persons, the risk of developing chronic hepatitis following acute HBV is approximately 1%.  CHRONIC HEPATITIS B Clinical features: Usually, they are asymptomatic but may be associated with fatigue, malaise and anorexia. Persistent jaundice with intermittent deepening or intermittent jaundice often coinciding with evidence of viral reactivation. Features of cirrhosis, e.g. ascites, edema, bleeding, varices, coagulopathy, and hepatic encephalopathy develop at the end stage of chronic hepatitis. Extra-hepatic complications: Arthritis and arthralgias, purpura, polyarteritis nodosa, and glomerulonephritis.  CHRONIC HEPATITIS B Laboratory Features: Serological markers for HBV infection consist of HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc IgM and IgG. The identification of serological markers allows: to identify patients with HBV infection; to assess the clinical phases of infection; and to monitor antiviral therapy. HBsAg is the serological hallmark of HBV infection. After an acute exposure to HBV, HBsAg appears in serum within 1 to 10 weeks. Persistence of this marker for more than 6 months implies chronic HBV infection.  CHRONIC HEPATITIS B Laboratory Features: HBV DNA using quantitative HCV-DNA PCR. The aminotransferase level. Non-invasive methods for the diagnosis of fibrosis such as serum markers and elastography can replace the need for biopsy in many cases and are useful in follow-up  CHRONIC HEPATITIS B Treatment: ▪ Management of chronic HBV infection is directed at suppression of viral replication. ▪ Aminotransferase level, HBV DNA level and fibrosis assessment are three factors determing initiarion and duration of treatment. ▪ Suppression of viral replication is done with: ✓ Injectable interferon α (INF α) /pegylated interferon. ✓ Oral agent (Neucleoside analog): Lamivudine, adefovir dipivoxil, entecavir, telbivudine and tenofovir. ✓ Tenofovir can be used safely during pregnancy. ✓ Optimal duration of antiviral therapy standard clinical end point is reached which are as follow; suppression of HBV DNA to undetectable and/ or normalization of ALT. ▪ For patient with end-stage chronic hepatitis B liver transplant is the only potential life-saving measure.  CHRONIC HEPATITIS D Although, HDV coinfection increases the severity of acute hepatitis B, it does not increase the likelihood of progression to chronic hepatitis B. Except for severity HBV + HDV has similar clinical and laboratory features to those seen in chronic hepatitis B alone. Treatment INF or PEG-INF is recommended at present for chronic HDV infection for 48 weeks and extend the therapy until HDV RNA or HBeAg clear. None of the neucleoside analog antiviral for HBV is effective in HDV infection. No antiviral is satisfactory. Liver transplant is effective and superior to antiviral in chronic hepatitis D.  CHRONIC HEPATITIS C Chronic hepatitis C tends to be very slowly and insidiously progressive in vast majority of patients. Overall in chronic hepatitis C (78%) patient progression of the disease is very slow whereas in 25% patient of chronic hepatitis C the HCV infection progress eventually to end stage liver disease Decompensation takes place at the rate of 4–5%/ year. Development of hepatocellular carcinoma occurs at the rate of 1–4%/year.  CHRONIC HEPATITIS C Clinical features: Fatigue—Most commonly present. Jaundice is rare. Extra-hepatic complication of chronic hepatitis C are less common than HBV but can evolve into B-cell lymphoma, mixed cryoglobulinemia, Lichen planus, and porphyria cutanea tarda.  CHRONIC HEPATITIS C Laboratory Features: This is made by finding HCV antibody in the serum using ELISA-3 tests. HCV RNA using quantitative HCV-RNA PCR.. The HCV genotype should be characterized in patients who are to be given treatment. Non-invasive methods for the diagnosis of fibrosis such as serum markers and elastography can replace the need for biopsy in many cases and are useful in follow-up.  CHRONIC HEPATITIS C Treatment: The aim of treatment is to eliminate the HCV RNA from the serum in order to; stop the progression of active liver disease and prevent the development of HCC. Treatment is appropriate for patients with chronic hepatitis on liver histology (Fibroscan) and/or who have HCV RNA in their serum whether or not serum aminotransferases are raised. The presence of cirrhosis is not a contraindication, but therapeutic responses are less likely. Patients with decompensated cirrhosis should be considered for transplantation.  CHRONIC HEPATITIS C Treatment: Current treatment; Direct-acting antiviral agents (DAAs) with different mode of actions. HCV is curable with many DAAs available that specifically target the HCV virus replication cycle to inhibit replication (NS3 protease inhibitors, nucleoside/nucleotide analogues and non-nucleoside inhibitors of the RNA-dependent RNA polymerase and NS5A inhibitors). (daclatasvir; DSV, dasabuvir; EBV, elbasvir; GLE, glecaprevir; GRZ, grazoprevir; LDV, ledipasvir; OMV, ombitasvir; PIB, pibrentasvir; PTV, paritaprevir; RTV, ritonavir; SMV, simeprevir; SOF, sofosbuvir; VEL, velpatasvir) CHRONIC HEPATITIS CHRONIC HEPATITIS  AUTOIMMUNE HEPATITIS It occurs most frequently in women. The cause is unknown but presence of serologic abnormality supports autoimmune pathogenesis. Types: Type I AIH: Type II AIH: ▪ Often seen in children more ▪ Occurs in young women common in Mediterranean associated ANA. there is an population (not associated with association with other ANA) but with anti-LKM-1 autoimmune diseases (e.g. antibody. pernicious anaemia, thyroiditis, ▪ Associated with other autoimmune coeliac disease and Coombs’- disorders like thyroiditis, autoimmune hemolytic anemia, positive haemolytic anaemia). ulcerative colitis, and type-I DM.  AUTOIMMUNE HEPATITIS Clinical Features: ▪ Onset may be insidious or abrupt. ▪ There are two peaks in presentation: ✓ In the peri and postmenopausal group, patients may be asymptomatic or present with chronic liver disease on routine examination. ✓ In the teens and early 20s, the disease (often type II) presents as an acute hepatitis with jaundice and very high aminotransferases, which do not improve with time.  AUTOIMMUNE HEPATITIS Clinical Features: ▪ There are rare overlap syndromes with primary biliary cirrhosis and primary sclerosing cholangitis, existing concomitantly or developing consecutively. ▪ Manifestation of other autoimmune disorders like thyroiditis, autoimmune hemolytic anemia, ulcerative colitis,and type-I DM. ▪ Extra-hepatic manifestation of autoimmune/idiopathic hepatitis are: Arthralgia and arthritis, cutaneous vasculitis, and glomerulonephritis.  AUTOIMMUNE HEPATITIS Laboratory Investigation: Liver biochemistry The serum aminotransferases are high, with lesser elevations in the ALP and bilirubin. The serum γ-globulins are high, particularly the IgG.The prothrombin time is often high. Autoantibodies: Two types of autoimmune hepatitis: Types: ❖ Type I with antibodies (titres >1 : 80) Type II with ✓ Anti-nuclear (ANA) antibodies: ✓ anti-smooth muscle (anti-actin) ✓ anti-liver/kidney ✓ Soluble liver antigen (anti SLA/LP): 10–30% microsomal (anti- of cases. LKM1).  AUTOIMMUNE HEPATITIS Liver biopsy: This shows interface hepatitis. Lymphoid follicles are less often seen than in hepatitis C, and plasma cell infiltration is frequent. Approximately one-third of patients have cirrhosis at presentation. Simplified diagnostic criterion of autoimmune hepatitis: ✓ Female patient. ✓ Presence of auto antibody. ✓ Raised serum IgG level. ✓ Histology—interface hepatitis and plasma cell rosette formation. ✓ Absence of marker of viral hepatitis.  AUTOIMMUNE HEPATITIS Treatment: ▪ Prednisolone/prednisone: 60 mg/day tapered over a month to 20 mg/day. ▪ Prednisolone—30 mg/day with azathioprine (2 mg/kg daily), as a steroid- sparing agent and in some patients as sole long-term maintenance therapy. Prognosis ▪ Steroid and azathioprine therapy induce remission in over 80% of cases. Treatment is lifelong in most cases. ▪ Those with initial cirrhosis are more likely to relapse following treatment withdrawal and require indefinite therapy. ▪ Liver transplantation is performed if treatment fails, although the disease may recur. Hepatocellular carcinoma occurs less frequently than with viral-induced cirrhosis.  DRUG INDUCED HEPATITIS ▪ Several drugs can cause a chronic hepatitis which clinically bears many similarities to autoimmune hepatitis. Patients are often female, present with jaundice and hepatomegaly, have raised serum aminotransferases and globulin levels. ▪ Improvement follows drug withdrawal but exacerbations can occur with drug reintroduction. ▪ Isoniazid, amiodarone and methotrexate can lead to chronic histological changes. With rare exceptions patients with pre-existing chronic liver disease are not more susceptible to drug injury  CHRONIC HEPATITIS OF UNKNOWN CAUSE (Cryptogenic) ▪ As more and more people are having routine blood tests, mild elevations in the serum aminotransferases and γ-GT are found. Many of these patients have no symptoms and no evidence of liver disease clinically. ▪ All known etiological agents should be excluded, and tests carried out to exclude primary biliary cirrhosis, primary sclerosing cholangitis, Wilson’s disease, haemochromatosis and α1- antitrypsin deficiency. ▪ Liver biopsy should be performed if the elevation in the aminotransferases continues for over a year, to confirm the presence of chronic hepatitis, but often nonspecific changes are found. THANK YOU FOR YOUR LISTENING