Viral Hepatitis Presentation PDF

‫بسم اهلل‬ ‫الرحمن‬ ‫الرحیم‬ VIRAL HEPATITIS A, B, C, D, and E  VIRAL HEPATITIS All OF viruses are RNA viruses except for hepatitis B, which is a DNA virus  molecular and antigenic properties, all types of viral hepatitis produce clinically similar illnesses. Blood borne...

‫بسم اهلل‬ ‫الرحمن‬ ‫الرحیم‬ VIRAL HEPATITIS A, B, C, D, and E  VIRAL HEPATITIS All OF viruses are RNA viruses except for hepatitis B, which is a DNA virus  molecular and antigenic properties, all types of viral hepatitis produce clinically similar illnesses. Blood borne types (HBV, HCV, and HDV)  Viral hepatitis  morphologic lesions of all types of viral hepatitis are similar and consist of panlobular infiltration with mononuclear cells,  hepatic cell necrosis, hyperplasia of Kupffer cells, and variable degrees of cholestasis  Hepatitis A AGENT  nonenveloped RNA virus member of the picornavirus hepatotropic Hepatovirus  heat-, acid-, and ether- resistant  Inactivation of by boiling for 1 min by contact with formaldehyde and chlorine by ultraviolet irradiation. No HAV carrier state  HAV  incubation period of 3--4 weeks  Replication to the liver  present in the liver, bile, stools, and blood  fecal-oral route  Person-to-person spread of HAV is enhanced by poor personal hygiene and overcrowding  occur in late fall and early winter. rarely bloodborne  Several outbreaks recognized in recipients of clotting- factor concentrates  transmission from pregnant women  HAV  Genotype I is most prevalent worldwide  Infectivity of stools was demonstrated from 21 days before to 8 days after onset of jaundice  Peak infectivity (risk of transmission) occurs during the 2 weeks before the onset of symptoms  HAV  Excretion in older children and adults was demonstrated 1 to 3 months after clinical illness HAV may be detected in saliva in infected human, saliva transmission by saliva has not been demonstrated. children and adults with hepatitis A can be assumed to be non infectious 1 week after jaundice appears  HAV MANIFESTATION  1 to 7 days before the onset of dark urine  (bilirubinuria) and jaundice prodromal symtoms  Flulike symtoms: fever, chill, mild headache, malaise, and fatigue. Loss of appetite, nausea, vomiting, and weight loss are common.  Occasionally, children may experience atypical symptoms such as diarrhea, cough, coryza, and arthralgia  HAV MANIFESTATION  Icteric phase : dark urine pale or clay-colored feces jaundice scleral icterus Pruritus in less than 50% of patients  hepatomegaly is common and usually associated with tenderness to palpation  Palpable splenomegaly in 5% to 15% of patients  skin rashes and arthralgias  Return of color to the stool occurs 2 or 3 weeks after the onset of illness and is an indication of resolution of disease  HAV  third week most patients feel better and normal or nearly normal levels of (ALT) (AST).  clinical course and histologic findings do not differ in pregnancy  HAV infection in persons with chronic liver disease is more severe and more likely to result in fulminant hepatitis A  HAV COMPLICATION  clinical course of hepatitis A is usually benign  cholestasis and acalculous cholecystitis  hemolysis, prolonged and relapsing disease, fulminant hepatitis,  autoimmune hepatitis, pancreatitis  Fulminant hepatic failure requiring transplantation and death  HAV  cardiac involvement : bradycardia and electrocardiograms may show prolongation of the PR interval and some mild T-wave depression  Less common: post viral encephalitis, Guillain-Barré syndrome, cholecystitis, acute pancreatitis,  acute renal failure secondary to interstitial nephritis, aplastic or hemolytic anemia, agranulocytosis, thrombocytopenic purpura, and pancytopenia. arthritis, vasculitis, and cryoglobulinemia depression  fulminant hepatic failure HAV  severe acute liver disease  excitability, irritability, insomnia, confusion, and severe vomiting  Prolonged Pt or INR  histologic picture of almost complete destruction of the hepatic parenchyma  HAV  hepatitis A can be more severe in older patients and in patients with other comorbidities or hepatitis B or C  Spontaneous survival from  fulminant hepatitis A occurs more commonly than from fulminant hepatitis of other causes  LAB TEST  serum levels of ALT and AST ↑  Alkaline phosphatase levels only mildly elevated  Peak bilirubin levels can exceed 30 mg/Dl  atypical mononuclear cells serologic assays: IgM –HAV  PCR highly sensitive test  THERAPY HAV  no specific therapy available for hepatitis A, and management is supportive  rare event of fulminant hepatitis requiring liver transplantation admission to the hospital is not indicated  bed rest or restriction of physical activity HAVE NOT INDICATION  Abstaining from alcohol  Infection Prevention and Control  hand washing  restriction of activities of workers  avoid uncooked vegetables and shellfish  Private rooms, gowns, and masks are not necessary  Active immunization with hepatitis A vaccines  HBV  small DNA virus doubl estranded DNA  Bloodborne virus  HBV is now divided into 10 genotypes (A–J)  genotypes A in North America, Europe, and parts of Africa; genotypes B and C in Asia  genotype D in India, the Middle East, the Mediterranean region, and parts ofAfrica  genotype E in Africa  genotype F in Central and South America;  genotype G in France, Germany, and North America  Genotype H is found in Central America  Genotype J in japan  HBV  Genotypes G and C are associated with more severe liver disease and higher HCC risk.  Genotype C also has slower HBeAg seroconversion compared with genotype B  Genotypes A and B are more responsive to pegylated interferon-α (PEG IFN-α) therapy than are genotypes  C and D  HBV ANTIGEN:  HBsAg  HBcAg  HBeAg  HBsAg-positive mothers who are HBeAg-positive (>90%) transmit hepatitis B infection to their offspring  HBsAg-positive mothers with anti-Hbe rarely (10–15%) infect their offspring  EPIDEMIOLOGYAND NATURAL HISTORY  HBV is acquired in adulthood, ~95% i recovery and production of protective antibodies (anti-HBs)  5% to 10% of perinatally acquired infection RECOVERY 3.6% of the world’s population is chronically infected with HBV  EPIDEMIOLOGYAND HBV  HBV is found in semen, saliva,cervical secretions, and tears, and can survive up to 7 days on environmental surfaces  HBV is not found in urine, sweat, or stools  Percutaneous  Perinatal  Sexual  100 times more efficient transmission  of HBV compared with HIV after needlestick exposure  Virology markers  After 8-12weeks first marker HBsAg  HBsAg precedes elevations of serum aminotransferase activity and clinical symptoms by 2–6 weeks  HBsAg becomes undetectable 1–2 months after the onset of jaundice HBcAg in the serum, sequestered within an HBsAg coat HBcAg is not detectable routinely in the serum  Virology marker  anti-HBc beginning within the first 1–2 weeks after the appearance of HBsAg and preceding detectable levels of anti-HBs by weeks to months  HBeAg, appears concurrently with or shortly after HBsAg HBeAg undetectable shortly after peak elevations in aminotransferase activity, before the disappearance of HBsAg, and anti-HBe then becomes detectable  PATHOLOGY  panlobular infiltration with mononuclear cells,  hepatic cell necrosis, hyperplasia of Kupffer cells, and variable degrees of cholestasis. small lymphocytes, plasma cells and eosinophils  pathology Liver cell damage consists of hepatic cell degeneration and necrosis, cell dropout, ballooning of cells, and acidophilic degenerationof hepatocytes  Large hepatocytes with a ground-glass appearance IN HBV  CLINICAL FEATURES  incubation period of 30 to 180 days (mean, 8–12 weeks)  flulike syndrome : malaise, fatigue, anorexia, nausea, vomiting, MYALGIAS ,headache ,pharyngitis , photophobia and right upper quadrant discomfort , precede the onset of jaundice by 1—2 weeks  Clinical features  Dark urine and clay-colored stools may be noticed by the patient from 1–5 days before the onset of clinical jaundice  onset of clinical jaundice, the constitutional prodromal symptoms usually diminish  Hepatomegaly,RUQtenderness ,spenomegaly, cervical adenopathy(10-20%)  Clinic features  Complete clinical and biochemical recovery is 3–4 months after the onset of jaundice in three- quarters cases of hepatitis B diagnosis of anicteric hepatitis is based on clinical features and on aminotransferase elevations  EXTRAHEPATIC MANIFESTATIONS  Immune complex–mediated tissue damage serum sickness–like syndrome:  Glomerulonephritis with the nephrotic syndrome polyarteritis nodosa essential mixed cryoglobulinemia (EMC):arthritis, cutaneous vasculitis (palpable purpura), glomerulonephriti  Serum sickness–like syndrome characterized by arthralgia or arthritis, rash, angioedema, and, rarely, hematuria and proteinuria  Laboratory Features  AST,ALT increase during the prodromal phase of and precede the rise in bilirubin level with ALT being higher than AST Jaundice PHASE:  serum bilirubin may continue to rise despite falling serum aminotransferase levels  Neutropenia and lymphopenia followed relative lymphocytosis  Lab features  Atypical lymphocytes (varying between 2 and 20%) are common during the acute phase PT prolong may reflect severe hepatic, extensive hepatocellular necrosis, and worse prognosis  hypoglycemia  Labra. features  mild and transient steatorrhea  slight microscopic hematuria and minimal proteinuria.  IOW titers of rheumatoid factor ANA+  HBeAg indicator of relative infectivity indicator of HBV replication: HBeAg ,HBV DNA  evaluation of cases of acute viral hepatitis  Four serologic tests: HBsAg IgM anti-HAV IgM anti-HBc anti-HCV  prolonged PT, low serum albumin level, hypoglycemia, and very high serum bilirubin values suggest severe hepatocellular disease.  COMPLICATIONS HBV  fulminant hepatitis: is seen primarily in hepatitis B, D, and E hepatitis E can be complicated by fatal fulminant hepatitis in 1–2% of all cases and in up to 20% of cases in pregnant women  Signe and symtoms fulminant hepatitis  Encephalopathy that may evolve to deep coma.  The liver is usually small and the PT excessively prolonged.  The combination of rapidly shrinking liver size, rapidly rising bilirubin level, and marked prolongation of the PT, aminotransferase levels fall, together with clinical signs of confusion, disorientation, somnolence, ascites, and edema ,,seen primarily in hepatitis B, D, and E liver transplantation may be lifesaving  likelihood of remaining chronically infected after acute HBV infection is especially high among neonates, persons with Down’s syndrome, chronically hemodialyzed patients, and immunosuppressed patients, including persons with HIV infection.  Chronic hepatitis is an important late complication of acute hepatitis B clinical and laboratory features suggest progression of acute hepatitis to chronic  (1) lack of complete resolution of clinical symptoms of anorexia, weight loss, fatigue, and the persistence of hepatomegaly  (2) the presence of bridging/interface or multilobular hepatic necrosis on liver biopsy during protracted, severe acute viral hepatitis  (3) failure of the serum aminotransferase, bilirubin, and globulin levels to return to normal within 6–12 months after the acute  (4) the persistence of HBeAg for >3 months or HBsAg for >6 months after acute hepatitis  TREATMENT HBV  recovery occurs in ~99% IN HEALTHY ADULT  antiviral therapy is not required Recommend antiviral therapy with entecavir or tenofovir, the most potent and least resistance-prone agents) for severe, but not mild-moderate, acute hepatitis B.  Treatment should continue until 3 months after HBsAg seroconversion or 6 months after HBeAg seroconversion.  PROPHYLAXIS  passive immunoprophylaxis:HBIG  active immunization:VACCINATION END HBV  Hepatitis C  Enveloped , single-stranded RNA  Important NS proteins involved in virus replication include : the NS3 helicase  NS3-4A serine protease  the multifunctional membrane-associated phosphoprotein NS5A  HCV  most sensitive indicator of HCV infection is the presence of HCV RNA  HCV RNA can be detected within a few days of exposure to HCV WITH PCR  EPIDEMIOLOGY HCV  most often transmitted through percutaneous exposure to blood  Transmitted sexually  perinatally(frequency range from 0% to 4%)  Fatalities are rare  PATHOGENESIS  After exposure to HCV , resulting in the elaboration of interferons and other cytokines that result in activation of innate and adaptive immune responses  Genotype 1 is the most widely dispersed worldwide Genotype 2 is widely dispersed in central and west Africa Genotype 3 is the second most prevalent globally (25%) and diverse in Asia but has been linked in other geographic regions, including North America, to illicit drug use. Genotype 4 infections are most prevalent in northern Africa and the Middle East Types 5 and 6 have been reported in South Africa and Southeast Asia  PATHOLOGY  HCV infection leads to hepatic inflammation and steatosis,  the major consequence of persistent HCV infection is the development of hepatic fibrosis,  Risk factors associated more rapid progression  in persons infected after the age of 40 years  Immunosuppression from HIV  organ transplantation  Agammaglobulinemia  HBV coinfection, diabetes,  insulin resistance, obesity  excessive alcohol consumption  Hepatic steatosis  CLINICAL MANIFESTATIONS Acute Hepatitis C Incubation period from 15 to 160 days (mean, 7 weeks) clinical symptoms (present in 15%–30%) within 5 to 12 weeks of the HCV exposure  prodromal symptoms: anorexia, nausea and vomiting, fatigue, malaise, arthralgias, myalgias, headache, photophobia, pharyngitis, cough, and coryza  Dark urine and clay-colored stools may be noticed by the patient from 1–5 days before the onset of clinical jaundice 0  CLINICAL MANIFESTATIONS Acute Hepatitis C  ICTERIC PHASE: liver becomes enlarged and tender, Splenomegaly and cervical adenopathy  Recovery phase: constitutional symptoms disappear, but liver enlargement and abnormalities in liver biochemical tests are still evident  The duration of the posticteric phase is variable, ranging from 2 to 12 weeks  Chronic Hepatitis C  have few symptoms (e.g., fatigue or malaise)  Serum ALT levels typically fluctuate  serum HCV RNA levels remain fairly constant  degree of inflammation present varies over time  Develop fibrosis, which typically begins in portal triads but can bridge between triads or central veins that progressing to nodularity and cirrhosis  Extrahepatic Manifestations  essential mixed cryoglobulinemia:  membranoproliferative glomerulonephritis  porphyria cutanea tarda  HCV is associated with aggressive diffuse large B cell NHL and follicular lymphoma  HCV infection has been associated with Mooren corneal ulcers, Sjِ gren syndrome, lichen planus, and idiopathic pulmonary fibrosis  Extrahepatic Manifestations  Thyroid autoantibodies, Hashimoto thyroiditis, and hypothyroidism  insulin resistance, type 2 diabetes mellitus, and atherosclerosis  Laboratory Features detect HCV antibody within 6 to 8 weeks of exposure  HCV RNA can be detected with RT- PCR(10– 50 IU/mL)  HCV RNA can be detected within 2 to 3 days after an exposure  LAB TEST OF HCV  Aminotransferase elevation is common anti-HCV can be detected in acute hepatitis C during the initial phase of elevate aminotransferase activity HCV RNA are the most sensitive tests for HCV infection and represent the “gold standard”  Liver Fibrosis Staging  liver biopsy  serum fibrosis markers:AST-to-platelet ratio index(APRI)  radiographic modalities (e.g., elastography)  the likelihood of remaining chronically  infected approaches 85–90% after acute HCV  Progression of chronic hepatitis C may be influenced by: advanced age of acquisition  long duration of infection, immunosuppression, coexisting excessive alcohol use  concomitant hepatic steatosis  other hepatitis virus infection,  HIV co-infection  HCV TREATMENT  acute hepatitis C, recovery is rare (~15–20%) Because spontaneous recovery can occur and because most cases of acute hepatitis C are not clinically severe or rapidly progressive, delaying antiviral therapy of acute hepatitis C for 3–6 months  HCV TREATMENT  pangenotypic regimens—sofosbuvir- velpatasvir and glecaprevir-pibrentasvir— can be used, for 8–12 weeks, mostly without ribavirin, in almost all treatment- naive, noncirrhotic and cirrhotic patients, including those with advanced renal failure and HCV-HIV co-infection  HDV  is a defective RNA virus that co-infects with  and requires the helper function of HBV for its replication and expression formalin-sensitive , hybrid structure  circular, single-strand RNA  HDV RNA requires host RNA polymerase II for its replication in the hepatocyte nucleus  HDV  HBV and HDV enter hepatocytes via the sodium taurocholate cotransporting polypeptide receptor  Complete hepatitis D virions and liver injury require the cooperative helper function of HBV  coinfection Superinfect  HDV  HDV relies absolutely on HBV, the duration of HDV infection is determined by the duration of HBV infection  Transmission HDV :Percutaneous Perinatal Sexual  HDV requires the envelope of HBV for viral assembly and transmission etiology of liver injury in HDV infection is unclear adaptive immune response plays an important role in control of HDV infection control of an HDV infection require Th1 CD4 and CD8 T-cell responses  EPIDEMIOLOGY HDV  where HBV is highly endemic, such as Asia and sub- Saharan Africa, as many as two-thirds of the HBV- infected population is infected with HDV  highest prevalence include:  Central and West Africa (33% in Mauritania, 67% in Gabon)  parts of the Amazon Basin (42%)  the Middle East (33%–47%), India,  Pakistan (24%–89%), and Northern Vietnam (15%– 43%).  Clinical Manifestations HDV  Incubation period of 30–180, (mean 60–90)  Acute coinfection(first episode is due to hepatitis B replication and immune response, followed by that of hepatitis D)  acute self-limited hepatitis with complete recovery with only 4% to 5% progressing to chronic HBV and HDV coinfection  rare instances a severe or fulminant hepatitis can occur  Clinical Manifestations HDV  Superinfection of HDV in individuals with chronic hepatitis B generally results in acute severe hepatitis  Superinfection with HDV can be associated with fulminant hepatitis and chronic active hepatitis with cirrhosis  Fulminant hepatitis, a severe form of acute hepatitis, The prognosis with fulminant hepatitis is very poor. Massive liver necrosis can occur with mortality approaching 80% in the absence of liver transplantation Fulminant hepatitis prevalace 5---20% (5% in acute HBV/HDV co-infection; 20% in HDV superinfection of chronic HBV infection) Progression to chronicity common in HDV  Clinical Manifestations HDV  chronic HDV infection is established, the clinical course of hepatitis is accelerated compared with HBV monoinfection. Cirrhosis occurs in 60% to 80% of chronic hepatitis D patients within 5 to 10 years, and the risk of hepatocellular carcinoma (HCC) is about threefold higher than in HBV monoinfection  Splenomegaly along with elevated aminotransferases and high levels of viremia are common in chronic hepatitis D  Treatment HDV  current recommended treatment for chronic hepatitis D is weekly PEG IFN-α for a minimum of 48 weeks  Liver transplantation is reserved for patients with end-stage liver disease from HBV-HDV coinfection  Hepatitis E Virus  epidemic or enterically transmitted non-A, non-B hepatitis  causes clinically apparent hepatitis primarily in India, Asia, Africa, and Central America  HEV is the most common cause of acute hepatitis  heat-stable,  HAV-like virus  single-strand, positive-sense RNA  EPIDEMIOLOGY  most common forms of transmission are through fecal-oral contamination of drinking water, through zoonoses  20 million HEV infections annually occur worldwide  PATHOLOGY HEV  typical morphologic lesions of all types of viral hepatitis are similar and consist of panlobular infiltration with mononuclear cells, hepatic cell necrosis, hyperplasia of Kupffer cells, and variable degrees of cholestasis.  Liver cell damage consists of hepatic cell degeneration and necrosis, cell dropout, ballooning of cells, and acidophilic degeneration of hepatocytes  PATHOLOGY HEV  more severe histologic lesion, bridging hepatic necrosis, also termed subacute or confluent necrosis or interface hepatitis, is observed occasionally in acute hepatitis reveal a pattern of cholestatic injury  CLINICAL PRESENTATION  more common form of HEV infection is acute viral hepatitis. It is usually caused by genotypes 1 and 2  clinically resembles other forms of viral hepatitis  INCUBATION period 14–60, mean 40  prodromal phase: fever, anorexia, nausea, vomiting, abdominal pain, skin rash, and arthralgia. lasts from 1 to 7 days  Icteric phase: Organomegaly ,yellowesh color skin and scelera  abdominal tenderness,, lasting up to a few weeks  rarely result in severe, fulminant hepatitis  Progression to chronicity (NONE) EXCEPTION observed in immunosuppressed liver allograft recipients or other immunosuppressed hosts.  Carrier(NONE)  Cancer(NONE)  CLINICAL PRESENTATION  viremia was detected as early as 9 days after exposure, and  disease became apparent as early as 2 weeks after exposure  Histologic resolution lags behind and may take up to 6 months  Extrahepatic Manifestations: are seemingly rare,, but Neurologic manifestations: acute meningoencephalitis, acute transverse myelitis, brachial plexus neuritis, Bell palsy, and Guillain-Barré syndrome  Acute pancreatitis is rare,, membranous glomerulonephritis,, membranoproliferative glomerulonephritis  Thrombocytopenia  Pure red cell aplasia  Hemophagocytic syndrome  HEV  Fulminant hepatitis occurs more frequently with HEV infection in pregnancy  Mortality rates as high as 20% to 25% have been reported in women in the third trimester of pregnanc  increased risk of fetal loss  Mechanism by which HEV infection increases mortality in pregnancy is not clearly understood  Transmission of HEV infection via the transplanted organ is possible, but fortunately rare  DIAGNOSTIC EVALUATION of HEV  SEROLOGY: anti-HEV IgM antibodies occur in early phases of infection and usually last 4 to 5 months  IgG antibodies develop a few days after IgM antibodies and can remain positive up to several years  RT-PCR HEV  THERAPEUTIC OF HEV  Acute HEV infection most commonly has a self-limiting course  hepatic failure require admission to the intensive care unit, where measures to monitor for signs of cerebral edema can be used and evaluation for transplantation can be performed  Pregnant patients, require hospitalization with close monitoring  HEV genotype 3 infections response to ribavirin therapy  PREVENTION HEV  protecting water from fecal contamination  Chlorination and filtration are usually inadequate for cleaning a contaminated water supply  boiling water  avoiding undercooked meats