ch44 part 1: Hepatitis

• Alteration in normal bilirubin metabolism (or) alteration in flow of bile into hepatic or biliary duct systems
• Occurs when bilirubin concentration is 3x normal levels (2-3 mg/dL)
• Three types of jaundice - hemolytic, hepatocellular, and obstructive.

Breakdown of hemoglobin (erythrocytes) by macrophages creates unconjugated bilirubin. In the liver, bilirubin conjugates with glucuronic acid to form conjugated (direct) bilirubin, which is excreted into the small intestine via the hepatic and biliary duct system. Feces brown color result of bilirubin breakdown.

Increased breakdown of red blood cells, increased amount of unconjugated bilirubin in the blood; liver unable to handle increased load. Causes include blood transfusion reaction, sickle cell crisis, and hemolytic anemia.

Liver's altered ability to take up bilirubin from the blood or conjugate or excrete it; damaged hepatocytes result in increase in both unconjoined and conjoined bilirubin in serum blood. Causes include hepatitis, cirrhosis, and hepatic carcinoma.

Decreased or obstructed flow of bile through the liver or biliary duct system; may be intrahepatic or extrahepatic. Intrahepatic obstructions due to swelling or fibrosis of the liver's canaliculi and bile ducts; causes include liver tumors, hepatitis, or cirrhosis. Extrahepatic obstructions within the bile duct include stones, biliary strictures, sclerosing cholangitis, or carcinoma of the pancreatic head. Decreased to no fecal bilirubin levels result, stool clay colored.

Inflammation of the liver caused from viral infection (Hep A, B, C, D, E, & G), drugs (e.g., alcohol), autoimmune liver disease, and rarely bacteria.

RNA virus, transmitted through fecal-oral route (contaminated food or drinking water). Incubation 15-50 days (avg. 28). HAV is found in feces 2+ weeks prior to symptoms and up to 1 week after onset of jaundice. IgM anti-HAV indicates acute hepatitis, IgG anti-HAV indicates past infection.

DNA virus, transmitted perinatally (mom-fetus), percutaneously (blood; needles, IV drug use), horizontally (mucosa, blood, body fluids). Incubation 45-180 days (avg. 56-96). 90% of infected neonates develop chronic Hep B. Serum surface antigen (HBsAg) that persists 6 to 12+ months after infection indicates carrier state. Serum surface antibodies (anti-HBs or HBsAB) indicate immunity from HBV vaccine or past HBV infection. With chronic HBV infection, liver enzymes may be normal, elevated with low-grade disease, or severe liver disease.

RNA virus, transmitted percutaneously (blood; needles, IV drug use) and perinatally. Incubation 14-180 days (avg. 56). Infectivity 1-2 weeks before symptoms appear, continues during clinical course; 75-85% develop chronic hepatitis.

Delta virus; defective single-stranded RNA virus, cannot survive on its own, requires helper function of HBV to replicate (must have HBV to contract HDV). Transmitted percutaneously (blood; needles, IV drug use). Incubation 2-26 weeks. No vaccine, but HBV vaccine reduces risk. HBV-HDV co-infection may have more severe acute disease and greater risk of developing fulminant (sudden/severe) hepatitis.

RNA virus, transmitted through fecal-oral route (contaminated food or drinking water). Incubation 15-64 days (avg. 26-42). Primarily occurs in developing countries. Currently, no serologic tests to diagnose are commercially available in USA.

RNA virus, poorly characterized percutaneous (blood; needles, IV drug use) and sexually transmitted virus. Coexists with other viral infections including HBV, HCV, and HIV. Does not appear to cause liver damage by itself.

• A is like E: RNA virus, incubation period 15 to 50-64 days, fecal-oral route.
• D requires B: D, a defective RNA virus, requires B, a DNA virus, to replicate; transmission is same (percutaneous/IV needles, sexual activity, perinatal).
• G is harmless form of C: Same transmission (percutaneous/IV needles, sexual activity, perinatal), opposite effects; C results in chronic hepatitis whereas G by itself is benign.

During acute infection, cytotoxic cytokines and natural killer cells cause lysis of infected hepatocytes. Liver damage results in hepatic cell necrosis. There is proliferation and enlargement of Kupffer cells. Inflammation in periportal areas may interrupt bile flow (cholestasis). With time, liver cells can regenerate and, if no complications occur, resume normal appearance and function.

The antigen-antibody complexes between virus and corresponding antibody form circulating immune complex in early phase of hepatitis. Clinical manifestations are rash, angioedema, arthritis, fever, and malaise. Cryoglobulinemia (abnormal proteins in blood), glomerulonephritis, and vasculitis may be found secondary to immune complex activation.

Specialized phagocytes found on luminal surface of hepatic sinusoids; they filter bacteria and small foreign proteins and dispose of old worn-out RBCs. Excess activation of Kupffer cells may result in liver damage.

• Usually lasts 1-4 months
• During incubation period, symptoms may include malaise, anorexia, fatigue, nausea, vomiting, and RUQ abdominal discomfort
• Weight loss
• Distaste for previously enjoyed items including food and cigarettes
• Decreased sense of smell
• Other symptoms may include headache, low-grade fever, arthralgias, and skin rashes
• Physical exam - hepatomegaly, lymphadenopathy, and sometimes splenomegaly
• Jaundice stage - bilirubin excess may result in darkened urine (excess bilirubin in urine), light or clay-colored stool, and pruritis (bile salt accumulation beneath skin); fever usually subsides when jaundice occurs
• Convalescent phase begins as jaundice disappears (lasting weeks to months)

Hepatitis without symptoms including lack of jaundice. A high percentage of persons with HAV are anicteric (without symptoms).

• Male gender
• Heavy alcohol consumption
• Excess iron deposition in liver (hemosiderin deposits)
• Elevated cholesterol or triglycerides, obesity, and diabetes mellitus (HCV to cirrhosis)

• No specific therapy or treatment, most patients managed at home
• Emphasis on rest and assisting the liver to regenerate
• Adequate nutrition and rest are most beneficial for healing and liver regeneration
• Avoid alcohol consumption and other hepatotoxic substances
• Drugs include antiemetics (dimenhydrinate/Dramamine or trimethobenzamide/Tigan) and sedatives (diphenhydramine/Benadryl or chloral hydrate)

• Blocks viral entry into cells
• IM or SQ injection 1-3x weekly
• For chronic HBV and HCV
• Side effects (dose related, decrease with continued treatment) - flu-like symptoms, arthralgia, myalgia, fatigue, headache, fever, nausea, anorexia, depression or irritability, alopecia, insomnia, dry/itchy skin, diarrhea, weight loss, injection site reaction

• Nucleoside analog, suppresses HBV replication by inhibiting Viral DNA synthesis
• Take orally for one year
• Seroconversion (loss of HBeAg) occurs in less than 17-27% of patients; when medication DC'd, non-seroconverted patients return to pretreatment liver inflammatory levels
• Drug resistance may occur after one year, so limited to pregnant and immunosuppressed patients
• Caution with patients with renal impairment
• Monitor BUN and creatinine
• May combine with alpha interferon (Intron A) to treat HBV

• Nucleoside analog, suppresses HCV by inhibiting RNA synthesis
• Synergistic effect when combined with alpha interferon
• Pegylated alpha interferon injections 1x weekly with ribavirin PO 2x weekly
• Side effects - hemolytic anemia
• Pregnancy category X - during treatment, pregnancy must be avoided (both female & male reproduction)

• Hep A vaccine - preexposure prophylasis; Havrix, Vaqta, and Avaxim; Twinrix (HAV & HBV) vaccine on 0, 1, and 6 month schedule
• Hep A immune globulin - use either before or after exposure, provides temporary (1-2 months) passive immunity, prevents hep A if given within 2 weeks of exposure; recommended for persons who lack anti-HAV antibodies and are known to have been been exposed

• Hep B vaccine - most effective method of preventing HBV infection; Recombivax hB, Engerix-B contain HBsAg, promotes synthesis of antibodies for HBV, three IM deltoid injections on 0, 1, and 6 month schedule; successful result shows anti-HBs titer of 10 mlU/ml
• Postexposure prophylaxis - Hep B vaccine + Hep B immune globulin (HBIG); HBIG contains antibodies to HBV, confers temporary passive immunity

• No HCV vaccine
• CDC does not recommend IG or antiviral agents (e.g., alpha interferon) for postexposure prophylaxis
• Following exposure, person should have baseline anti-HCV and ALT levels measured with follow-up tests q.4-6 months for anti-HCV and ALT activity
• While there is no definitive recommendation, improvements have been seen in reported trials using interferon monotherapy

• High calorie diet; no special diet, but patient at risk for weight loss
• If fat content poorly tolerated (decreased bile production), reduce dietary fats
• Vitamin supplements may include B complex and vitamin K
• If anorexia, nausea, and vomiting are severe, IV glucose or supplemental tube feedings may be indicated
• Maintain fluid and electrolyte balance

• The patient will have relief of discomfort
• The patient will be able to resume normal activities
• The patient will return to normal liver function without complications

• Toxic substances - carbon tetrachloride, gold compounds, acetaminophen; liver necrosis generally occurs within 2-3 days of acute exposure
• Drug substances - idiosyncratic drug reactions due to patient susceptibility (metabolic reactivity) to agents or immunologically mediated hypersensitivity response; halothane (Fluothane), isoniazid (INH), chlorothiazide (Diuril), methotrexate, and methyldopa (Aldomet); some responses occur 2-5 weeks after exposure
• Symptoms - anorexia, nausea, vomiting, hepatomegaly, splenomegaly, and abnormal LFT
• Treatment - supportive, identify/remove hepatoxocin, rest/nutrition; transplant if severe damage