Viral Hepatitis Clinical Presentation
- Author: Adrienne M Buggs, MD, FACEP, FAAEM; Chief Editor: Steven C Dronen, MD, FAAEM more...
The clinical presentation of infectious hepatitis varies with the individual, as well as with the specific causative virus. Some patients may be entirely asymptomatic or only mildly symptomatic at presentation. Others may present with rapid onset of fulminant hepatic failure (FHF). The classic presentation of infectious hepatitis involves 4 phases, as follows:
Phase 1 (viral replication phase) – Patients are asymptomatic during this phase; laboratory studies demonstrate serologic and enzyme markers of hepatitis
Phase 2 (prodromal phase) – Patients experience anorexia, nausea, vomiting, alterations in taste, arthralgias, malaise, fatigue, urticaria, and pruritus, and some develop an aversion to cigarette smoke; when seen by a health care provider during this phase, patients are often diagnosed as having gastroenteritis or a viral syndrome
Phase 3 (icteric phase) – Patients may note dark urine, followed by pale-colored stools; in addition to the predominant gastrointestinal (GI) symptoms and malaise, patients become icteric and may develop right upper quadrant pain with hepatomegaly
Phase 4 (convalescent phase) – Symptoms and icterus resolve, and liver enzymes return to normal
The incubation period of hepatitis A virus (HAV) is 2-7 weeks (average, 28 days). Clinical symptoms then develop, often with a presentation similar to that of gastroenteritis or a viral respiratory infection. The most common signs and symptoms include fatigue, nausea, vomiting, fever, hepatomegaly, jaundice, dark urine, anorexia, and rash.
HAV infection usually occurs as a mild self-limited disease and confers lifelong immunity to the virus. Chronic HAV infection does not occur.
The incubation period for hepatitis B virus (HBV) is 30-180 days (average, approximately 75 days). Patients then enter the prodromal or preicteric phase, characterized by the gradual onset of anorexia, malaise, and fatigue. During this phase, as the liver becomes inflamed, liver enzymes start to elevate, and the patient may experience right upper quadrant pain. About 15% of patients develop an illness resembling serum sickness. These patients may experience fever, arthritis, arthralgias, or an urticarial rash.
As the disease progresses to the icteric phase, the liver becomes tender, and jaundice develops. Patients may note that their urine darkens and that their stools lighten in color. Other symptoms in this stage include nausea, vomiting, and pruritus.
From this point on, the clinical course may be highly variable. Whereas some patients experience fairly rapid improvements in their symptoms, others go on to experience prolonged disease with slow resolution. Still others may have symptoms that periodically improve, only to worsen later (relapsing hepatitis). Finally, there is an unfortunate subset of patients in whom the disease rapidly progresses to FHF; this may occur over days to weeks.
The incubation period for hepatitis C virus (HCV) is 15-150 days, with symptoms developing anywhere from 5-12 weeks after exposure. During acute HCV infection, symptoms may appear similar to those of HBV infection. In up to 80% of cases, however, patients are asymptomatic and do not develop icterus.[1, 16]
The incubation period of hepatitis D virus (HDV) is approximately 35 days. Patients simultaneously infected with HBV and HDV often have an acute, self-limited infection.[19, 27] Fewer than 5% of these patients develop chronic HDV infection.
Chronic HBV carriers who become superinfected with HDV tend to have a more severe acute hepatitis; 80% of these patients go on to develop chronic HDV infection. Chronic infection with HBV and HDV may lead to fulminant acute hepatitis and severe chronic active hepatitis with progression to cirrhosis.[19, 27] Over the long term, as many as 70-80% of these patients have evidence of chronic liver disease with cirrhosis, compared with only 15-30% of patients with chronic HBV alone.
The incubation period of hepatitis E virus (HEV) is 2-9 weeks (average, 45 days). HEV usually causes an acute self-limited disease similar to HASV infection. Fulminant disease does occur in about 10% of cases. In women who are pregnant, HEV infection has a case-fatality rate of 15-20%. No reports exist of chronic infection with HEV.
Physical findings in patients with hepatitis vary with the type of hepatitis and the time of presentation.
Patients often present with low-grade fever. Patients experiencing significant vomiting and anorexia may show signs of dehydration, such as tachycardia, dry mucous membranes, loss of skin turgor, and delayed capillary refill.
Patients in the icteric phase may have icterus of the sclerae or mucous membranes or discoloration of the tympanic membranes. The skin may be jaundiced and may reveal macular, papular, or urticarial rashes.
In viral hepatitis, the liver may be tender and diffusely enlarged with a firm, sharp, smooth edge. If the patient has a nodular liver or a mass is palpated, clinicians should suspect an abscess or tumor.
In general, complications of viral hepatitis may include the following:
Acute or subacute hepatic necrosis
Chronic active hepatitis
Hepatocellular carcinoma (HCC) in patients with HBV or HCV infection
One of the major complications of hepatitis B is the development of chronic infection. An estimated 350 million people worldwide are chronically infected with HBV. In the United States, 1.25 million people are estimated to have chronic HBV infection. Patients with such infection are at risk for the subsequent development of chronic active hepatitis, cirrhosis of the liver, and eventual HCC. Each year, approximately 1 million deaths occur worldwide as a result of chronic HBV infection.
Patients infected at an early age are at greatest risk for chronic HBV infection: Whereas 90% of those infected at birth develop chronic HBV infection, only 5-10% of older children or adults go on to develop chronic infection. The risk of chronic infection is also higher in patients who are immunocompromised.
Patients with chronic HBV infection are at significantly higher risk for HCC. In fact, HCC is the leading cause of cancer-related deaths in areas where HBV is endemic. Globally, HBV is responsible for 60-80% of the world’s primary liver cancers. Cancer in this setting is postulated to result from repeated bouts of chronic inflammation and cellular regeneration. HCC develops an average of 25-30 years after initial infection.
Another major complication of HBV infection is development of FHF. In approximately 0.5-1% of HBV-infected patients, the disease progresses to FHF, with coagulopathy, encephalopathy, and cerebral edema. The case-fatality rate for these patients approaches 80%.
Acute infection with HCV may rarely cause FHF. Approximately 70-90% of patients with hepatitis C become chronically infected. More than 60% of patients will have ongoing chronic liver disease with laboratory evidence of fluctuating or persistently elevated liver enzymes. Of those with chronic infection, 5-20% may go on to develop cirrhosis. The progression from initial infection to the development of cirrhosis may take more than 20 years.
Cirrhosis related to chronic HCV infection is also strongly linked to the development of HCC, which usually develops after 30 years in patients who are chronically infected. Of patients with HCV-associated cirrhosis, 20-25% may progress to liver failure and death. In the United States, cirrhosis associated with chronic hepatitis C is a leading indication for liver transplant.
Patients with chronic hepatitis C are also at risk for extrahepatic complications. In essential mixed cryoglobulinemia, HCV may form immune complexes with anti-HCV immunoglobulin G (IgG) and with rheumatoid factor (RF). The deposition of immune complexes may cause small-vessel damage. Complications of cryoglobulinemia include rash, vasculitis, and glomerulonephritis.
Other extrahepatic complications of HCV infection include focal lymphocytic sialadenitis, autoimmune thyroiditis, porphyria cutanea tarda, lichen planus, and Mooren corneal ulcer. Some cases of non-Hodgkin lymphoma can be attributed to HCV infection.
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|Test||CHB HBeAg Positive||CHB HBeAg Negative||Inactive Carrier|
|HBV DNA||>2 × 104 IU/mL*
|>2 × 103 IU/mL
|< 2 × 103 IU/mL
(< 104 copies/mL)
|ALT = alanine aminotransferase; anti-HBc = antibody to hepatitis B core antigen; anti-HBe = antibody to HBeAg; anti-HBs = antibody to HBsAg; CHB = chronic hepatitis B; HBV = hepatitis B virus; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; IgM = immunoglobulin M.
*Increasingly, experts in the field use IU/mL rather than copies/mL.
|Grade||Portal Inflammation||Interface Hepatitis||Lobular Necrosis|
|1 - Minimal||Mild||Scant||None|
|2 - Mild||Mild||Mild||Scant|
|3 - Moderate||Moderate||Moderate||Spotty|
|4 - Severe||Marked||Marked||Confluent|