Hepatitis and Cirrhosis

Published on 07/03/2015 by admin

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Chapter 48 Hepatitis and Cirrhosis

Zechariah S. Gardner, MD , Jaina Clough, MD

1 What is hepatitis?

Hepatitis is defined as inflammation of the liver. It can be divided into infectious and noninfectious causes.

2 What are liver function tests?

The term liver function tests (LFTs) commonly refers to alkaline aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, bilirubin, albumin, and protein. ALT and AST (transaminases) are enzymes found in hepatocytes whereas alkaline phosphatase is found in cells in the bile ducts. Gamma-glutamyl transpeptidase is an additional test that is used to determine whether alkaline phosphatase elevations originate from hepatobiliary sources. Prothrombin time is used to assess liver synthetic function.

3 Elevations of which LFTs are associated with hepatitis?

Hepatitis is a process of hepatocellular inflammation and damage that causes spillage of cellular elements into the blood. Hepatitis therefore results primarily in elevations in ALT and AST. Elevations can be modest in some forms of hepatitis (alcoholic) or extreme in others (acute viral hepatitis). Alkaline phosphatase levels can also be elevated in hepatitis, but elevations are generally less significant than those of the transaminases. Bilirubin can reach very high levels in hepatitis but usually lags behind the transaminases.

4 What are the types of infectious hepatitis?

Hepatitis viruses primarily infect the liver and include hepatitis A, B, C, D, and E. Other nonhepatitis viruses can cause hepatitis including cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus (HIV).

5 What is hepatitis A, how is it diagnosed, and what are the disease course and management?

Hepatitis A is a disease caused by an RNA virus that is transmitted by the fecal-oral route, is endemic in the developing world, and occurs sporadically in the United States. Most childhood infections are asymptomatic. Adults are more likely to have acute symptoms. The incubation period is 2 to 6 weeks, after which patients have fatigue, malaise, fever, and abdominal pain followed by jaundice. Transaminase levels are markedly elevated.

Diagnosis is by a positive anti–hepatitis A virus (HAV) immunoglobulin (Ig) M antibody that denotes active infection and remains elevated for 3 to 6 months. HAV anti-IgG antibody positivity occurs later, remains elevated for decades, and indicates past infection.

Treatment is supportive. Significant morbidity and mortality are uncommon, but development of fulminant hepatic failure (FHF) can occur (< 1%) and carries significant mortality (see question 20). HAV vaccine is effective and widely available. It is recommended for individuals with chronic liver disease, child-care workers, and those traveling to endemic areas.

6 What is hepatitis E?

Like HAV, hepatitis E virus (HEV) is an RNA virus that is transmitted by the fecal-oral route. It is endemic to Southeast Asia, Africa, India, and Central America. Infection in the United States is uncommon and is almost always associated with individuals who have recently traveled to endemic areas. It causes a self-limiting hepatitis similar to HAV infection but has a significantly higher tendency to progress to FHF in pregnant women. Laboratory tests for diagnosis include HEV IgG and IgM antibody testing, as well as HEV RNA polymerase chain reaction (PCR).

7 What is hepatitis B?

Hepatitis B is a disease caused by a DNA virus that is transmitted through blood and body fluids. Risk factors include intravenous (IV) and intranasal drug use, unprotected sex with multiple partners, men who have sex with men, health care workers exposed to blood, children born to infected mothers, incarceration, and spouses of infected individuals. Acute infection is most commonly asymptomatic but can cause constitutional symptoms including fatigue, malaise, nausea, vomiting, headache, arthralgias, myalgias, and low-grade fever, as well as jaundice, dark urine, clay-colored stools, and tender hepatomegaly. FHF occurs in 1% of infections. Other complications include a serum sickness–like syndrome (5%-10% of cases), glomerular nephritis with nephrotic syndrome, systemic vasculitis, and progression to chronic hepatitis B infection, which occurs in approximately 5% of cases. Some individuals go on to a carrier state in which they have persistent hepatitis B virus (HBV) in the liver without any significant inflammation. These individuals can be infectious and are termed inactive carriers.

8 How is hepatitis B diagnosed?

Serologic testing for hepatitis B is complicated by the fact that there are multiple blood tests routinely used to assess infection.

image Hepatitis B surface antigen (HBsAg) is the lipid and protein layer that forms the outer shell of HBV. It is not infectious and is produced in excess during viral replication. It is the first viral antigen to become positive in the serum with acute infection, and its presence indicates active infection. It may be negative early in the acute infection, and it is also the first serum marker to be cleared by the host immune system, becoming undetectable 6 to 12 weeks after infection.

image Hepatitis B surface antibody (HBsAb) is the antibody to HBsAg. It develops to detectible levels 6 to 8 weeks after infection and remains detectible for life. Positive HBsAb indicates past or resolving infection. Hepatitis B vaccine uses the surface particle, and vaccinated individuals will also be HBsAb positive.

image Hepatitis B core antibody (HBcAb) is an antibody to a core viral protein. HBcAb can be measured as IgG or IgM and can also be reported as total, which includes both. IgM makes up the immune system’s early response and is later replaced by IgG. Positive HBcAb IgM indicates early or chronic infection. Positive HBcAb IgG indicates past or chronic infection.

image Hepatitis B early antigen (HBeAg) is a protein produced during viral replication, and detectible levels of this antigen indicate high levels of viral replication, increased infectivity, and higher risk of progression to fibrosis. It is positive during both acute infection and active viral phases of chronic infection.

image HBV DNA can also be measured and is one of the diagnostic criteria for chronic HBV infection.

9 What is hepatitis C?

Hepatitis C is caused by a blood-borne RNA virus. It is transmitted primarily through contact with blood products from infected individuals. Risk factors include current or past IV drug use, health care workers exposed to blood, or transfusion of infected blood products (rare since routine screening was introduced in 1992). Sexual transmission can occur but is uncommon with hepatitis C virus (HCV). Most acute infections are asymptomatic, but 20% to 30% of infected individuals will have a self-limiting illness similar to other acute viral hepatitis infections. A majority (70%-85%) of those infected with HCV will go on to have chronic infection. It is currently estimated that more than 3 million individuals have chronic HCV in the United States, where it is the leading indication for liver transplantation.

10 How is HCV infection diagnosed?

Screening for infection is by serum testing for anti-HCV antibody. Antibody positivity occurs at 4 to 10 weeks and remains positive for life regardless of whether chronic infection develops. All positive antibody tests should be followed up with an HCV RNA PCR to determine whether active infection exists. Of those infected, 15% to 25% will spontaneously clear the virus and are not at risk for complications of chronic infection. If virus is detected viral genotyping should be done.

11 What are HCV genotypes, and how do they affect management?

At least six genotypes and more than 50 subtypes of HCV have been identified. Genotype 1 is the most common genotype, accounting for 60% to 80% of all hepatitis C. Genotype 1 is more difficult to eradicate with treatment than other common genotypes. Treatment for chronic hepatitis C infection is with pegylated interferon-α and ribavirin. Treatment length is dependent on genotype and viral response. Genotype 1 traditionally requires a longer treatment course (48 weeks) and has lower response rates (50%). Recent data have shown that the addition of telaprevir or boceprevir to interferon and ribavirin for treatment of genotype 1 hepatitis C infection significantly improves achievement of sustained viral response to levels similar to those of other common hepatitis C genotypes. The Food and Drug Administration approved their use for treatment of genotype 1 hepatitis C infection in early 2011.

12 What other extrahepatic conditions can be caused by hepatitis C infection?

Some individuals with chronic hepatitis C infection can have other medical conditions that are thought to be due to the body’s immune response to the HCV infection. These conditions are uncommon but are noted to occur at increased frequency in those infected with hepatitis C. They include diabetes mellitus, glomerulonephritis, mixed cryoglobulinemia, porphyria cutanea tarda, and non-Hodgkin lymphoma.

13 What is hepatitis D?

Hepatitis D virus (HDV) or hepatitis delta virus is a small RNA viral particle that can cause infection only in the presence of hepatitis B virus. It is blood borne, and IV drug use is the most common route of infection. Infection can occur either as coinfection when both HBV and HDV viruses are acquired together or as superinfection when HDV infection occurs in a patient with chronic hepatitis B infection. Concomitant infection with hepatitis B and D results in a higher likelihood of development of FHF, more rapid progression to cirrhosis, and higher rates of hepatocellular carcinoma.

14 What viral serologies should be tested in a patient with acute hepatitis?

All patients with acute hepatitis should undergo testing for anti-HAV IgM, anti-HCV antibody, HBsAg, and HBcAb.

15 Who should be screened for HCV infection?

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