Hepatitis includes all parenchymal liver damage with a subsequent inflammatory reaction caused by infectious, toxic or other agents. Acute hepatitis differs from chronic hepatitis in the duration of histological and biochemical changes. The change limit is 6 months.
Acute viral hepatitis = diffuse hepatitis caused by various viruses. There is no cross-immunity between different forms of hepatitis. We distinguish 6 types of viral hepatitis. They are indicated by capital letters A to G. These cause up to 95 % of all viral hepatitis. But some other viruses are also occasionally hepatotropic and responsible for liver damage. These are mainly: cytomegalovirus, Ebstein-Barr virus, rubella virus, coxsackie, herpesvirus viruses and many exotic viruses - yellow fever virus, Lassa virus, Ebola virus, Dengue virus fever.
Transmission: Hepatitis A - by the faecal-oral route, especially in poor hygiene and often in facilities where several people live together. The incubation period is 15 to 45 days. Hepatitis B - blood and blood products, sexual secretions, saliva and perinatal - from mother to child. Incubation period - 30 to 180 days. Hepatitis C - as in hepatitis B + in 45 % unknown origin. Up to 90 % of acute hepatitis C is asymptomatic. Incubation period - 50 to 180 days. Hepatitis D - transmission and incubation period as in hepatitis B. Hepatitis D infection is most common as a superinfection in HBsAg carrier with HDV. This condition often becomes chronic. It can also be co-infected with HBV + HDV. It is less common, but healing occurs up to 90 %. Hepatitis E - by the faecal-oral route with an incubation period of 10 to 60 days. It occurs mainly in third world countries, it can be imported to rest of the world. Hepatitis G - parenteral transmission, similar to HB and HC, is associated with transfusions.
Clinical picture: does not differ significantly between viral hepatitis. We distinguish 2 basic stages: prodromal and the stage of manifestation of liver damage. Up to 2/3 of cases are asymptomatic. The prodromal stage lasts about 2 to 7 days (longer in hepatitis B). Flu symptoms appear: subfebrile and fatigue. GIT symptoms: anorexia, nausea, palpable pain in the right hypochondria, diarrhea may be present. In hepatitis B, there is also joint pain and a volatile rash from the storage of immunocomplexes. Stage 2 - the stage of manifestation of liver damage lasts 4 to 8 weeks (shortest in hepatitis A) - 1/3 is icteric: urine is darkly colored + stool hypocholic, sclera and skin are yellow with a rise in bile acids in the serum leading to pruritus - 2/3 of cases of acute viral hepatitis, it occurs anicterically - enlargement of the liver may be present (with a change in consistency and palpable pain) and in 20 % mild splenomegaly with enlargement of the lymph nodes.
Laboratory tests: Increased transaminases - increased serum bilirubin and urobilinogen + bilirubin in urine - increased GMT and ALP levels (especially in cholestatic course). May be present: increased serum iron levels, increased gamma globulins in electrophoresis, lymphocytosis, increased sedimentation, increased CRP - during severe course with the development of liver insufficiency - reduced Quick time, decreased albumin in the serum. Serological examination: IgM antibodies against individual viral markers, IgG after overcoming infection. If hepatitis B is suspected (before clinical symptoms occur), we find a surface antigen in the serum - HBsAg, nuclear HBcAg, in addition to these also HBV-DNA, HBeAg and anti-HBcIgM and anti-HBcIgG. In hepatitis C, HCV-RNA is determined. Anti-HCV antibodies are not present until 1 to 5 months after infection.
Complications of acute viral hepatitis: Cholestatic course (5 %) - significantly increased bilirubin and cholestatic enzymes: ALP and GMT. The prognosis is usually good. Prolonged and recurrent hepatitis - elevated transaminases either constantly or intermittently for more than 3 but less than 6 months. Fulminant hepatitis - severe especially in hepatitis E virus infection in pregnant women (up to 20 % of cases), in other types of hepatitis the incidence is only 1 to 2 %. Multiple necrosis occurs, then the liver shrinks, severe jaundice, ascites, hemorrhagic diathesis appear, and liver coma develops. Fulminant hepatitis is a valid indication for liver transplantation. Extrahepatic manifestation - arthralgia and rash. Persistence of the virus (carrier) - in hepatitis B - 5-10 %, hepatitis C – 80 %, hepatitis A, E – 0 %. We distinguish 3 forms of carriers - a healthy, asymptomatic individual - carriers with low inflammatory activity - carriers with high inflammatory activity, where there is a risk of developing liver cirrhosis and hepatocellular carcinoma (especially in HB and HC).
Therapy for acute viral hepatitis
Predominantly non-pharmacological - bed rest (for better liver circulation) - strict ban on alcohol and all potentially hepatotoxic drugs (including estrogens and corticosteroids) - patient isolation - mandatory reporting of illness and death. Pharmacological treatment has proven successful in hepatitis C and the fulminant course of other hepatitis. Interferon-alpha is used in combination with the antiviral agent ribavirin.
Prognosis: Healing in HA is 100 %, HB 90 %, HC in pharmacological therapy more than 50 %, HD - in co-infection as in HB, in superinfection, there is only a small probability of cure, in HE 98 % (but in pregnant women it is only in 20 % in fulminant course)
Profylaxis: - hepatitis A, E - compliance of hygienic principles (disinfection, protection of drinking water and food) - hepatitis B, C, D, G - screening of blood donors for viral markers and avoidance of promiscuity - active immunization. In HA - vaccine inactivated by formaldehyde HB. HD - vaccine containing surface Ag - HBsAg. Vaccination affects the following people: healthcare professionals, dialysis patients and those who often take blood derivatives, patients with chronic liver disease and people who are in close contact with the hepatitis carrier. HC vaccine is not available - passive immunization: HA - administration of immunoglobulin within 10 days after contact with HA + person, protection for three months HB. HD - specific immunoglobulin administered within 48 hours (optimally within 6 hours) after contact with infection neonatal HBsAg+ mothers are given mixed active-passive immunization
Chronic hepatitis
Chronic inflammatory process affecting the liver, with various etiopathogenesis and prognosis, characterized mainly by an increase in aminotransferases and histological changes that last for more than 6 months.
Etiology:
1. Viral chronic hepatitis
2. Autoimmune chronic hepatitis
3. Diseases that can occur under the picture of chronic hepatitis
Histological findings are expressed in 3 aspects:
1. Etiology
2. Degree of inflammatory activity - inflammatory infiltration, degree of necrosis,
3. Degree of fibrotic changes - from a slight increase of connective tissue in the portal areas, through the transfer of connective tissue to the environment to the formation of multiple septa with a transition to cirrhosis.
Clinical symptoms: 1. Fatigue - the most common symptom of liver disease. 2. with low inflammatory activity - decreased performance. 3. with increased inflammatory activity further - anorexia - palpable liver pain - arthralgia - dark urinary jaundice (exacerbation) - enlarged liver with stiffer consistency - hypersplenism with thrombocytopenia - skin marks - smooth red tongue - palmar and plantar erythema - cobweb nevi - pruritus and excoriation due to scratching - skin atrophy with telangiectasias - Dupuytren's contracture. Women - menstrual disorders including secondary amenorrhea. Men – reduction of body hair, testicles atrophy. Gynecomastia causes: low testosterone and high estrogen levels. Complications: liver cirrhosis, hepatocellular carcinoma.
Diagnosis: history and clinical findings. Laboratory evidence of viral markers and autoantibodies. Liver morphological changes (sonography, or CT, MR, laparoscopy). Liver biopsy and histological examination.
Chronic viral hepatitis (CVH)
Chronic hepatitis B (CHB)
The course of HBV infection is determined by the state of cellular immunity - mainly cytotoxic T cells and interferon-alpha 5-10 % of the infected (90 % for perinatal infection) are unable to eliminate the virus and become carriers of HBsAg. These carriers are either healthy or have CHB. HBsAg carrier has 3 phases: 1. Early phase of viral replication. Production of complete HBV - increased transaminases and histological signs of inflammation. Markers of serum replication - HBV DNA, HBeAg - high infectivity. 2. Late phase of replication. Mostly only HBsAg production. Transition from early to late phase, 10 % of patients spontaneously during the year, 50 % in IFN-alpha treatment. Exacerbations and subsequent normalizations often occur - HBeAg disappears from the serum. Anti-HBe-HBV DNA production can be detected by PCR, low infectivity 3. Definitive healing - loss of HBsAg, formation of anti-HBs, disappearance of HBV DNA - spontaneously only rarely, in IFN-alpha therapy in 10 %.
Forms of HBV infection 1. Asymptomatic carrier HBsAg - serological findings: positive HBsAg, anti-HBc and anti-HBe negative. Anti-HBs - liver functions and enzymes are normal - histology 80 % is normal. Low viremia, people are not infectious 2. Chronic HB with low inflammatory activity - low titer HBV DNA, slightly increased transaminases, unchanged histology 1 year apart, normal synthetic liver function (Quick time, albumin) 3. Chronic HB with increased inflammatory activity - increased HBV DNA titer, significantly increased transaminases, typical histology, limited synthetic liver function (Quick time, albumin). 4. Extrahepatic manifestations - polyarteritis nodosa, membranoproliferative glomerulonephritis
Therapy and prognosis:
The success rate of IFN-alpha therapy is 50 %. Without therapy, 50 % of patients develop cirrhosis after 10 years. Hepatocellular carcinoma occurs in 50 % of cirrhotic patients and in 5 % of patients with chronic active HB.
Chronic hepatitis B + D
Co-infection is similar to HBV itself (but more frequent fulminant course) - superinfection leads in 90 % to chronic B + D hepatitis diagnostics.
Clinical findings and serology (evidence of anti-HDV, HDV-RNA and HBsAg) + biopsy liver (HBV and HDV in hepatocytes).
Therapy and prognosis 3 times higher lethality than CHB, 20 % success rate of IFN-alpha treatment.
Chronic hepatitis C
The most common form of CVH, 90 % of HCV infections lead to chronic hepatitis in half of patients, have increased markers of cholestasis in addition to increased transaminases.
Complications: cirrhosis and liver failure, carcinoma in 5 % of cirrhotic patients.
Differential diagnosis:
common finding of autoantibodies ANA, anti-LKM - misdiagnosis of autoimmune hepatitis.
Diagnosis:
History + clinical finding.
Serology: anti-HCV evidence + verification HCV-RNA evidence = replication and infectivity HCV-RNA quantitative - treatment assessment. Normal liver transaminases does not exclude chronic HC. Therapy and prognosis:
IFN-alpha therapy is below 25 % successful. IFN-alpha and ribavirin is 50 % successful. Poor results in high viremia. In cholestasis, we administer ursodeoxycholic acid. Autoimmune hepatitis - progressive inflammation of the liver, immunological reaction against hepatocyte antigens.
Diagnosis
History: young women - weakness, exhaustion, loss of appetite, pain in the right thigh, arthralgia, menstrual disorders, other autoimmune diseases.
Biochemical examination:
Elevated ALT and AST Be up to 10 times higher, gamma globulins usually exceed 30 grams per liter. Immunological examination:
lupoid subtype 1: anti-nuclear antibodies (ANA), anti-actin antibodies (anti-SM). Subtype 2: antibodies against liver and kidney microsomes (anti-LKM). Subtype 3: antibodies against soluble liver antigen (anti-SLA). Liver biopsy: crucial in diagnosis and control of treatment.
Ultrasonography: increased echogenicity, hepato- and splenomegaly.
Therapy:
Non-pharmacological: when the process is active – bed rest, diet rich in proteins and vitamins, ban on alcohol and hepatotoxic drugs, removal of inflammatory foci.
Pharmacological: 1. Corticosteroids: prednisone dose with gradual reduction to maintenance dose. 2. Corticosteroids + azathioprine - reduction of side effects. 3. Immunosuppressants - cyclosporine at least 1 year, in case of cirrhosis 2 years, in case of relapse resume the treatment. 4. Hepatoprotectives - essential phospholipids. 5. Ursodeoxycholic acid in cholestatic form.