CASE REPORT HEPATITIS A Presenters Day/ Date Supervisor : Chua Wang Ching Pernanda Selpia Suaidi : Wednesday/ July

20th 2011 : dr. Supriatmo, Sp. A CHAPTER 1 INTRODUCTION 1.1. Background Hepatitis is a general term that refers to inflammation of the liver and can be caused by a variety of different viruses such as hepatitis A, B, C, D and E. This condition may result from various infectious and noninfectious etiologies. Infectious etiologies include viral, bacterial, fungal, and parasitic organisms. In the United States, viral hepatitis is most commonly caused by hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). These 3 viruses can all result in an acute disease process with symptoms of nausea, abdominal pain, fatigue, malaise, and jaundice. Since the development of jaundice is a characteristic feature of liver disease, a correct diagnosis can only be made by testing patients sera for the presence of specific anti-viral antibodies. Additionally, HBV and HCV can also lead to chronic infection. Patients who are chronically infected may go on to develop cirrhosis and hepatocellular carcinoma. Furthermore, chronic hepatitis carriers remain infectious and may transmit the disease for many years. Noninfectious hepatitis may result from medications, toxins, and autoimmune disorders. This article focuses on viral hepatitis.
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1.2.

Objective This paper is done in order to complete the task in following the doctor's

professional education program in the department of pediatrics. In addition, providing knowledge to the author and readers about Hepatitis.

CHAPTER 2 LITERATURE REVIEW : HEPATITIS A 2.1. Definition The term hepatitis describes inflammation of the liver. Hepatitis may be caused by alcohol, drugs, autoimmune diseases, metabolic diseases, and viruses. Viral infection accounts for more than 50% of the cases of acute hepatitis in the United States. The term viral hepatitis is often thought to be synonymous with diseases caused by the known hepatotropic viruses, including hepatitis viruses A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV). However, the term hepatotropic is itself a misnomer. Infections with hepatitis viruses, especially hepatitis viruses B and C, have been associated with a wide variety of extrahepatic manifestations. Infrequent causes of viral hepatitis include adenovirus, cytomegalovirus, EpsteinBarr virus, and, rarely, herpes simplex virus infection. Newly discovered pathogens (eg, virus SEN-V) may account for additional cases of non-A/non-E hepatitis. 2.2. Clinical manifestation 2.2.1. History Clinical presentation of infectious hepatitis varies from person to person as well as with the etiology of infection. Some patients may present as entirely asymptomatic or only mildly symptomatic. Others may present with rapid onset of fulminant hepatic failure. The classic presentation of infectious hepatitis involves 4 phases. Phase 1 - Viral replication o Patients are asymptomatic during this phase.

o Laboratory studies demonstrate serologic and enzyme markers of hepatitis. Phase 2 - Prodromal phase o Patients experience anorexia, nausea, vomiting, alterations in taste, arthralgias, malaise, fatigue, urticaria, and pruritus. Some develop an aversion to cigarette smoke. o 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 o Patients may note dark urine, followed by pale-colored stools. o In addition to the predominant gastrointestinal symptoms and malaise, patients become icteric and may develop right upper quadrant pain with hepatomegaly. Phase 4 - Convalescent phase o Symptoms and icterus resolve. o Liver enzymes return to normal. 2.3. Causes Infectious hepatitis, viral Five major hepatotropic viruses cause the majority of clinical cases of viral hepatitis. These are hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Other types of viral hepatitis Hepatitis G virus, characterized in 1996, is associated with acute and chronic liver disease, but studies have not clearly implicated hepatitis G virus as an etiologic agent of hepatitis. It is transmitted through blood and blood products. Other known viruses (eg, cytomegalovirus, Epstein-Barr virus, herpes simplex, varicella-zoster) may also cause inflammation of the liver, but they do not primarily target the liver.

Infectious hepatitis, nonviral Hepatic abscesses may cause infectious hepatitis. These occur more often in patients with chronic illness. The two general categories of abscess are amebic (most commonly caused by Entamoeba histolytica in developing countries) and pyogenic (tending to affect those at the extremes of age). In neonates, sepsis and catheterization of the umbilical vein may result in abscesses caused by gram-positive aerobic cocci. In adults, biliary disease can result in pyogenic abscess formation with the mortality rate of pyogenic abscesses at almost 40%. Gram-negative rods are the typical causative organisms in adults. In elderly persons, malignancy is the most common underlying disease. 2.4. Diagnosis 2.4.1. Physical Physical findings in patients with hepatitis vary with the type of hepatitis and 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 be suspicious for an abscess or tumor.

2.4.2. Laboratory Studies A simple screening test for the nonicteric patient with suspected viral hepatitis involves checking the urine for presence of bilirubin. As an alternative, a liver enzyme panel (generally a costly test) could be obtained. Serum bilirubin (total and fractionated): Total bilirubin may be elevated in infectious hepatitis. Bilirubin levels higher than 30 mg/dL indicate more severe disease. Alkaline phosphatase usually is in the reference range but may elevate to no higher than twice the normal level. If alkaline phosphatase is elevated significantly, consider abscess or biliary obstruction. Prothrombin time (PT), if prolonged, is a grave finding indicating impaired synthetic function of the liver. Draw BUN and serum creatinine to look for evidence of renal impairment. Decreased renal function suggests fulminant hepatic disease. Measure serum ammonia in patients with altered mental status or other evidence of hepatic encephalopathy. Hepatitis A antibody (immunoglobulin M [IgM] anti-HAV): Detecting the presence of IgM anti-HAV in serum is the standard for diagnosing acute infection with HAV. Hepatitis B core antibody (IgM anti-HBc): Determining the presence of IgM anti-HBc in serum is required to make the diagnosis of acute HBV infection. Hepatitis B surface antigen may be present in acute infection or in patients who are chronic carriers. Its presence in patients with symptoms of acute hepatitis strongly suggests acute HBV infection but does not rule out chronic

HBV with acute superinfection by another hepatitis virus. The presence of HBsAg in the serum for 6 months or longer is indicative of chronic infection. Hepatitis C infection can be confirmed with serologic assays to detect antibodies to HCV (anti-HCV) or by molecular tests for the presence of viral particles. The third-generation assays for anti-HCV are sensitive and specific and can detect such antibodies within 4-10 weeks of infection. Assays to detect IgM antibody to HDV do not need to be routinely performed in all patients with suspected hepatitis. 2.4.3. Imaging Studies No specific imaging studies are required to make the diagnosis of hepatitis. Obtain the appropriate diagnostic imaging studies (eg, ultrasound, computed tomography) if the differential diagnosis favors gallbladder disease, biliary obstruction, or liver abscess. 2.4.4. Other Tests Liver biopsy may be recommended for the initial assessment of disease severity in patients with chronic hepatitis B or chronic hepatitis C.

2.5. Differential diagnose

Cholangitis Cholecystitis and Biliary Colic Cholelithiasis Gastritis and Peptic Ulcer Disease Gastroenteritis Obstruction, Small Bowel Pancreatitis

Pediatrics, Gastroenteritis Pediatrics, Intussusception

2.6. Hepatitis A Hepatitis A virus HAV is a picornavirus. It consists of a 7.5-kb RNA virus with a diameter of 27 nm. The virus has 1 serotype but multiple genotypes.

Hepatitis A virus as viewed through electron microscopy. The incubation period of HAV is 15-45 days (average, 4 wk). The virus is excreted in stool during the first few weeks of infection, before the onset of symptoms. Young children who are infected with HAV usually remain asymptomatic. Acute hepatitis A is more severe and has higher mortality in adults than in children. The explanation for this is unknown.

Typical cases of acute HAV infection are marked by several weeks of malaise, anorexia, nausea, vomiting, and elevated aminotransferase levels. Jaundice develops in more severe cases. Some patients experience a cholestatic hepatitis, marked by the development of an elevated alkaline phosphatase (ALP) level, in contrast to the classic picture of elevated aminotransferase levels. Other patients may experience several relapses during the course of a year. Less than 1% of cases result in fulminant hepatic failure. HAV infection does not persist and never causes chronic hepatitis.

Epidemiology of HAV HAV is a picornavirus that is resistant to many environmental factors (eg, temperature, certain chemicals). Often, the predominant etiologic agent of viral hepatitis in the United States, HAV accounts for 25-50% of new cases per year. Based on 2006 CDC data, HAV was responsible for approximately 32% of new cases of viral hepatitis in the United States. Transmission Hepatitis A virus exists in highest concentration in the feces of infected individuals; the greatest fecal viral load tends to occur near the end of the incubation period of hepatitis A virus. Most commonly, the virus spreads from person to person via the fecaloral route. Contaminated water and food, including shellfish collected from sewage-contaminated water, have also resulted in epidemics of hepatitis A virus. The virus may also be spread through sexual (anal-oral) contact. Transmission by blood transfusion is rare.

Infection with hepatitis A virus occurs throughout the world. However, risk of infection is greatest in developing countries, areas of low socioeconomic status, and areas without sufficient sanitation. Higher infection rates also exist in settings where fecal-oral spread is likely, such as daycare centers. Other groups at high risk for hepatitis A virus infection include international travelers, users of injection and non injection drugs, and men who have sex with men. Maternal-neonatal transmission has not been established. Close contacts of infected individuals are also at risk. The secondary infection rate for hepatitis A virus in household contacts of patients with acute hepatitis A virus infection is around 20%. Thus, secondary infection plays a significant role in the maintenance of hepatitis A virus outbreaks. Clinical course Clinical symptoms then develop, often with a presentation similar to that of gastroenteritis or a viral respiratory infection. Most common signs and symptoms include fatigue, nausea, vomiting, fever, hepatomegaly, jaundice, dark urine, anorexia, and rash. Hepatitis A virus infection usually occurs as a mild self-limited disease and confers lifelong immunity to hepatitis A virus. Chronic infection with hepatitis A virus does not occur.

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Diagnosis of Hepatitis A Acute infection is documented by the presence of immunoglobulin M (IgM) anti-HAV, which disappears several months after the initial infection. The presence of immunoglobulin G (IgG) anti-HAV merely demonstrates that an individual has been infected with HAV at some point in the past, from 2 months ago to decades ago. IgG anti-HAV appears to offer patients lifelong immunity against recurrent HAV infection.

Treatment for acute of HAV infection

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Treatment for acute hepatitis caused by HAV is supportive in nature, because no antiviral therapy is available. Hospitalization is needed for patients whose nausea and vomiting places them at risk for dehydration. Patients with acute liver failure require close monitoring to ensure they do not develop fulminant hepatic failure.

Prevention of Hepatitis A Improved sanitation, strict personal hygiene, and hand washing all may help to prevent transmission of HAV. The virus is inactivated by household bleach or by heating to 85C for 1 minute. Travelers to endemic areas should not drink untreated water or ingest raw seafood or shellfish. Fruits and vegetables should not be eaten unless they are cooked or can be peeled. Certain inactivated viral vaccines have proven highly effective in preventing infection with HAV when given before exposure. These vaccines are not recommended for children younger than 2 years. In this age group, passively acquired maternal anti-HAV antibodies may decrease the immunogenicity of the vaccine. Active immunization is recommended for health care workers, daycare personnel, and travelers to endemic areas. HAV vaccine also is recommended for sewage and wastewater workers and veterinarians working with imported nonhuman primates. Passive postexposure immunization with immune globulin (dose 0.02 mL/kg) can protect persons exposed to HAV against clinical illness.
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Effectiveness is highest if given within 48 hours of exposure, but it may be helpful when given as far as 2 weeks into the incubation period. These patients also should receive active immunization with the HAV vaccine. Immune globulin also is recommended before exposure for children younger than 2 years who are at risk of exposure to HAV.

Morbidity and death Although hepatitis A virus usually causes mild disease, older patients are at greater risk for severe disease. While icteric disease occurs in fewer than 10% of children younger than 6 years, it occurs in 40-50% of older children and in 70-80% of adults with hepatitis A virus. Other complications can include acute liver failure, cholestatic hepatitis, and relapsing hepatitis. The overall mortality rate for hepatitis A virus is approximately 0.01%. Children younger than 5 years and adults older than 50 years have the highest case-fatality rates.

2.7.

Hepatitis B

Hepatitis B virus HBV is a member of the Hepadnaviridae family. The complete negative strand has 4 overlapping genes. Gene S codes for HBsAg, also known as surface antigen, a viral surface polypeptide. Gene C codes for HBcAg, also known as core antigen, the nucleocapsid protein. It also codes for HBeAg, whose function is unknown. Gene P codes for a DNA polymerase

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that has reverse transcriptase activity. Gene X codes for the X protein that has transcription-regulating activity. The viral core particle consists of a nucleocapsid, HBcAg, which surrounds HBV DNA, and DNA polymerase. The nucleocapsid is coated with HBsAg. The intact HBV virion is known as the Dane particle. Dane particles and spheres and tubules containing only HBsAg are found in the blood of infected patients. In contrast, HBcAg is not detected in the circulation. It can be identified by immunohistochemical staining of infected liver tissue. Eight genotypic variants of the HBV (genotypes A-H) are described. Although preliminary studies suggest that particular HBV genotypes may predict the virus's response to therapy or may be associated with more aggressive disease, it is premature to routinely incorporate HBV genotype testing into clinical practice.

Epidemiology of Hepatitis B A major cause of infectious hepatitis worldwide, hepatitis B virus belongs to the class of hepadna viruses. Hepatitis B virus is responsible for almost half of the cases of acute viral hepatitis cases reported in the United States. In 2006, the highest rates of acute infection occurred in patients aged 25-44 years. Estimates suggest that 350 million people worldwide are hepatitis B virus carriers. The virus leads to 1 million deaths annually as a result of viral hepatitis induced liver disease. The incidence of childhood hepatitis B virus infection is not well established because more than 90% of hepatitis B virus infections in this age group are asymptomatic.

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Transmission of Hepatitis B The major reservoir of hepatitis B virus in the United States consists of the 1.25 million people with chronic hepatitis B virus infection. In this group, those with hepatitis B e antigen (HBeAg) in their serum tend to have higher viral titers and thus greater infectivity. Hepatitis B virus is transmitted both parenterally and sexually, most often by mucous membrane exposure or percutaneous exposure to infectious body fluids. Saliva, serum, and semen all have been determined to be infectious. Percutaneous exposures leading to the transmission of hepatitis B virus include transfusion of blood or blood products, injection drug use with shared needles, hemodialysis, and needlesticks (or other wounds caused by sharp implements) in health care workers. Globally and in the United States, perinatal transmission is one of the major modes of transmission. The greatest risk of perinatal transmission occurs in infants of HBeAg-positive women. By age 6 months, these children have a 70-90% risk of infection and, of those, about 90% will go on to develop chronic infection with hepatitis B virus. For infants born to HBeAg-negative women, risk of infection approximates 10-40%, with a chronic infection rate of 40-70%. Even if transmission does not occur in the perinatal period, these children still have a significant risk of developing infection during early childhood. High-risk groups for infection with hepatitis B virus include intravenous drug users, persons born in endemic areas, and men who have sex with men.

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Other groups at risk include health care workers with exposure to infected blood or bodily fluids, recipients of multiple blood transfusions, patients undergoing hemodialysis, heterosexual persons with multiple partners or a history of sexually transmitted disease, institutionalized persons including prisoners, people who are developmentally disabled, and household contacts or sexual partners of HBV carriers. Clinical course The incubation period for hepatitis B virus varies from 30-180 days, with the average approximately 75 days. Patients then enter the prodromal or preicteric phase, developing 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. Fifteen percent 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, patients may have quite a variable course. Some experience fairly rapid improvements in their symptoms, while others go on to a prolonged disease course with slow resolution. Still others may have symptoms that periodically improve, only to worsen later (relapsing hepatitis). Finally, an unfortunate subset of patients suffers rapid progression of their disease to the point of fulminant hepatic failure. This may occur over days to weeks. Diagnosis of Hepatitis B Diagnosis of acute self-limited HBV infection
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HBsAg is the first serum marker seen in persons with acute infection. It represents the presence of HBV virions (Dane particles) in the blood. HBeAg, a marker of viral replication, is also present. When viral replication slows, HBeAg disappears and anti-HBe is detected. Anti-HBe may persist for years. The first antibody to appear is anti-HBc (HBcAb). Initially, it is of the IgM class. Indeed, the presence of IgM anti-HBc is diagnostic for acute HBV infection. Weeks later, IgM anti-HBc disappears and IgG anti-HBc is detected. Anti-HBc may be present for life. The anti-HBc (total) assay detects both IgM and IgG antibodies. The presence of anti-HBc (total) demonstrates that the patient has had a history of infection with HBV at some point in the past. In patients who clear the HBV, HBsAg usually disappears 4-6 months after infection, as titers of anti-HBs (HBsAb) become detectable. Anti-HBs is believed to be a neutralizing antibody, offering immunity to subsequent exposures to HBV. Anti-HBs may persist for the life of the patient. Knowing key points helps in the interpretation of serology findings in acute HBV infection. The presence of HBsAg does not indicate whether the infection is acute or chronic. The presence of anti-HBc (IgM) is the sine qua non of acute HBV infection. The presence of anti-HBc (total) indicates that a patient has been infected with HBV at some point. The anti-HBc (total) remains positive both in patients who clear the virus and in patients with persistent infection.

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The presence of anti-HBc (total) with a negative HBsAg and a negative anti-HBs indicates 1 of 4 things. First, the test result is a false positive. Second, the patient is in a window of acute hepatitis, between the elimination of HBsAg and the appearance of anti-HBs. This scenario is not
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observed in patients with chronic HBV infection. Third, the patient has cleared the HBV virus but has lost anti-HBs over the years. Fourth, the patient is one of the uncommon individuals with active HBV replication who is negative for HBsAg. This situation is diagnosed when either a positive HBeAg or a positive HBV DNA result is found. In the author's opinion, the discovery of a lone positive anti-HBc (total) finding in the setting of negative HBsAg and negative anti-HBs findings mandates the performance of an HBV DNA assay by polymerase chain reaction (PCR). Diagnosis of chronic HBV infection HBsAg may remain detectable for life in many patients. Individuals who have positive findings for HBsAg are termed carriers of HBV. They may be inactive carriers or they may have chronic hepatitis. Anti-HBc is present in all patients with chronic HBV infections. HBeAg and HBV DNA may or may not be present. They reflect a state of active viral replication. HBV DNA levels are typically low or absent in inactive carriers. HBV DNA levels are higher in patients with chronic hepatitis B. High HBV DNA levels are associated with increased infectivity. Anti-HBs are usually absent in patients with chronic infection. If anti-HBs are present in a patient who has positive HBsAg findings, it reflects the presence of a low level of antibody that was unsuccessful at inducing viral clearance.

Treatment of hepatitis B
Treatment of acute hepatitis B As with the treatment of acute hepatitis A, no well-established antiviral therapy is available for acute HBV infection. Supportive treatment

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recommendations are the same as for acute hepatitis A. Lamivudine, adefovir dipivoxil, or other antiviral therapies appear to have a positive impact on the natural history of severe cases of acute HBV infection. A study by Schmilovitz-Weiss described a rapid clinical and biochemical response in 13 of 15 patients with severe acute hepatitis B who received lamivudine.

Treatment of chronic hepatitis B In an ideal world, the treatment of patients with chronic hepatitis B would routinely achieve the loss of HBsAg. Indeed, the loss of HBsAg is associated with a decreased incidence of HCC and a decreased incidence of liver-related death in patients with HBV-induced cirrhosis. However, loss of HBsAg is only achieved infrequently in patients with chronic hepatitis B: in 3-7% of patients undergoing treatment with pegylated interferon (PEG-IFN) and in 0-5% of patients undergoing treatment with oral nucleoside or nucleotide agents. At this time, the key goal of antiviral treatment of HBV is the inhibition of viral replication. This is marked by the loss of HBeAg (in patients with HBeAg-positive chronic hepatitis B) and by the suppression of HBV DNA levels. Secondary aims are to reduce symptoms, if any, and prevent or delay the progression of chronic hepatitis to cirrhosis or HCC. The agents currently in use for the treatment of hepatitis B include PEG-IFN-alfa 2a and the oral nucleoside or nucleotide analogues. Typically, PEG-IFN treatment is continued for 48 weeks for both HBeAg-positive and HBeAg-negative chronic hepatitis. The oral agents may be used for as little as 1-2 years. However, the majority of HBeAg-positive chronic hepatitis patients

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and almost all HBeAg-negative chronic hepatitis patients require indefinite therapy with the oral agents. Withdrawal of oral nucleoside/nucleotide analogue therapy in these individuals usually results in virologic relapse. Candidates for antiviral therapy must have evidence of active HBV infection. At present, the typical threshold for treatment is a viral load of 2 X 104 IU/mL or more for patients with HBeAg-positive chronic hepatitis, 2 X 103 IU/mL or more for patients with HBeAg-negative chronic hepatitis, and 200 IU/mL or more for patients with decompensated cirrhosis. Patients with chronic hepatitis tend to have abnormal liver chemistry findings. Treatment may be offered to patients with a normal ALT level, but it may be less efficacious. Although performing a liver biopsy is not mandatory before treatment, the author recommends it. Liver biopsy is helpful for confirming the clinical diagnosis of chronic hepatitis B and for documenting the severity of liver disease.

Complication One of the major complications of hepatitis B virus infection is the development of chronic infection. An estimated 350 million people worldwide are chronically infected with hepatitis B virus. Patients with chronic HBV infection are at risk of later developing chronic active hepatitis, cirrhosis of the liver, and eventual hepatocellular cancer. Each year, approximately 1 million deaths occur worldwide as a result of chronic hepatitis B virus infection.

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Patients infected at an early age have the greatest risk of developing chronic hepatitis B virus infection. While 90% of those infected at birth develop chronic hepatitis B virus, 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 hepatitis B virus infection have a significantly increased risk of developing hepatocellular cancer. In fact, hepatocellular cancer is the leading cause of cancer-related deaths in areas where hepatitis B virus is endemic. Globally, hepatitis B virus is responsible for 60-80% of the worlds primary liver cancers. Cancer in this setting is postulated to result from repeated bouts of chronic inflammation and cellular regeneration. Hepatocellular cancer develops an average of 25-30 years after initial infection. Another major complication of hepatitis B virus infection is development of fulminant hepatic failure. In approximately 0.5-1% of HBVinfected patients, the disease progresses to fulminant hepatic failure, with coagulopathy, encephalopathy, and cerebral edema. The case-fatality rate for these patients approaches 80%.

2.8.

Hepatitis C

Hepatitis C virus HCV is a flavivirus. It is a 9.4-kb RNA virus with a diameter of 55 nm. It has one serotype and multiple genotypes. HCVs have profound genetic variability throughout the world. At least 6 major genotypes and more than 80

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subtypes are described, with as little as 55% genetic sequence homology. The genetic variability of HCV hampers the efforts of scientists to design an effective anti-HCV vaccine. Epidemiology of Hepatitis C Hepatitis C is a single-stranded ribonucleic acid (RNA) virus that is the most frequent cause of parenteral non-A, non-B hepatitis worldwide. Estimates suggest that, worldwide, 170 million people are chronically infected with hepatitis C virus. Highest rates of disease prevalence are found in patients with hemophilia and in injection drug users. Before the newer universal plasma and donor screening measures, hepatitis C virus accounted for 90% of posttransfusion hepatitis cases. Hepatitis C virus is the most common cause of chronic viral hepatitis in the United States. About 70-90% of people infected progress to chronic hepatitis C virus infection. Transmission of Hepatitis C Hepatitis C virus can be transmitted parenterally, perinatally, and sexually. Transmission occurs by percutaneous exposure to infected blood and plasma. Hepatitis C virus is transmitted most reliably through transfusion of infected blood or blood products, transplantation of organs from infected donors, and sharing contaminated needles among intravenous drug users. Transmission by sexual activity and household contact occurs less frequently. Perinatal transmission occurs but is uncommon.

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Clinical course of Hepatitis C Incubation period for hepatitis C virus runs 15-150 days, with symptoms developing anywhere from 5-12 weeks after exposure. During acute infection with hepatitis C virus, symptoms may appear similar to those of hepatitis B virus infection. In up to 80% of cases, however, patients are asymptomatic and do not develop icterus.

Diagnosis of Hepatitis C The most common tests used in the diagnosis of hepatitis C include liver chemistries, serologic tests, HCV RNA tests, and liver biopsies.

Treatment Acute hepatitis C is detected infrequently. When it is identified, early therapy with interferon should be considered. In one study, 44 patients with acute hepatitis C were treated with IFN-alfa-2b at 5 million U/d subcutaneously for 4 weeks and then 3 times per week for another 20 weeks. About 98% of patients developed a sustained virologic response (SVR) (ie, undetectable level of serum HCV RNA).

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Complications Acute infection with hepatitis C virus may rarely cause fulminant hepatic failure. Approximately 70-90% of patients with hepatitis C virus 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 hepatitis C virus infection is also strongly linked to the development of hepatocellular cancer, which usually develops after 30 years in patients who are chronically infected. Of patients with HCVassociated cirrhosis, 20-25% may progress to liver failure and death.

2.9.

Hepatitis D

Hepatitis D virus HDV is a single-stranded, 1.7-kb RNA virus. The viral particle is 36 nm in diameter and contains HDAg and the RNA strand. It uses HBsAg as its envelope protein. Thus, HBV coinfection is necessary for the packaging and release of HDV virions from infected hepatocytes. Epidemiology of Hepatitis D

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Hepatitis D virus is a defective, single-stranded RNA virus that requires the presence of hepatitis B virus to replicate. Hepatitis D virus infection develops only in patients who are positive for the hepatitis B surface antigen (HBsAg). Patients may acquire hepatitis D virus as a co-infection (at the same time that they contract hepatitis B virus), or the hepatitis D virus may superinfect patients who are chronic hepatitis B virus carriers. Although hepatitis D virus is not a reportable disease, the CDC estimates that it results in 7500 infections each year. Approximately 4% of cases of acute hepatitis B virus are thought to involve co-infection with hepatitis D virus. Transmission of Hepatitis D A serologic diagnosis of HDV infection is made by using IgM antiHDV and IgG anti-HDV tests. HBcAb IgM should be used to help distinguish between coinfection (HBcAb IgMpositive) and superinfection (HBcAb IgMnegative). Detecting HDV RNA in serum is also possible. Clinical Course The incubation period of hepatitis D virus is approximately 35 days. Patients co-infected (simultaneously infected) with hepatitis B virus and hepatitis D virus often have an acute, self-limited infection. Less than 5% of these patients develop chronic hepatitis D virus infection. Chronic hepatitis B virus carriers who become super-infected with hepatitis D virus tend to have a more severe acute hepatitis; 80% of these patients go on to develop chronic HDV infection. Chronic infection with hepatitis B virus and hepatitis D virus may lead to fulminant acute hepatitis and severe chronic, active hepatitis with progression to cirrhosis.

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Over the long term, as many as 70-80% of these patients have evidence of chronic liver disease with cirrhosis, compared to only 15-30% of patients with chronic hepatitis B virus alone. Diagnosis A serologic diagnosis of HDV infection is made by using IgM antiHDV and IgG anti-HDV tests. HBcAb IgM should be used to help distinguish between coinfection (HBcAb IgMpositive) and superinfection (HBcAb IgMnegative). Detecting HDV RNA in serum is also possible. Treatment The treatment of patients coinfected with HBV and HDV is not well studied. Multiple small studies have demonstrated that HBV/HDV coinfected patients are less responsive to interferon therapy than patients infected with HBV alone. Treatment with PEG-IFN-alfa-2b produced HDV RNA negativity in only 17-19% of patients. Lamivudine appears to be ineffective against HBV/HDV coinfection. 2.10. Hepatitis E Hepatitis E virus HEV is a calicivirus. It is a 7.5-kb single-stranded RNA virus and is 32-34 nm. The virus has an incubation period of 2-9 weeks. Epidemiology of Hepatitis E Hepatitis E virus is the primary cause of enterically transmitted non-A, non-B hepatitis; most outbreaks occur in developing countries. Transmission of Hepatitis E

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Hepatitis E virus is transmitted primarily by the fecal-oral route, with fecally contaminated water providing the most common means of transmission. Person-to-person transmission is rare. Maternal-neonatal transmission does occur. Zoonotic spread is possible as some nonhuman primates (cows, pigs, sheep, goats, and rodents) are susceptible to the disease. Clinical Course The incubation period of hepatitis E virus is 2-9 weeks, with an average of 45 days. Hepatitis E virus usually causes an acute self-limited disease similar to hepatitis A virus. Fulminant disease does occur in about 10% of cases. In women who are pregnant, hepatitis E virus infection has a case-fatality rate of 15-20%. No reports exist of chronic infection with hepatitis E virus. Diagnosis of hepatitis E The serologic diagnosis is made by using IgM anti-HEV and IgG antiHEV. HEV RNA can be detected in the serum and stool of infected patients. Treatment of Hepatitis E The treatment of those infected with HEV is supportive in nature.

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CHAPTER 3 MEDICAL RECORD HEPATITIS 3.1. Objective The aim of doing this paper is to report a case of hepatitis non-B, non-C of a 11-year-old girl that was admitted at Pediatrics Department of Haji Adam Malik General Hospital. 3.2. Case DF, a 11-years-old girl with body weight 33 kg and body length 143 cm, was admitted to the Pediatrics Department of Haji Adam Malik General Hospital on June 22nd 2011 with upper right abdominal pain as the main complaint. She has been suffering abdominal pain for almost 3 months and getting severe since six days ago before she was admitted to the hospital. The abdominal pain was intense during deep inhalation. Yellowish discoloration of the skin was found in this patient since six days ago. The yellowish discoloration was at first found on the whites of the eyes, then progressively to the face and at last to the trunk. History of jaundice has been recognized past one year. This patient is complaint about high degree of fever since six days ago. The fever was relieved by antipyretic medication. Seizures and shivers were not found. History of vomiting was found in this patient. Vomiting occurred since three days ago before she was admitted to the hospital. The frequency of vomiting was 3

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times a day and the volume of the vomit was about 2 tea spoons full. The vomit contained food and drink which had been consumed before. She has been suffering anorexia and malaise since 7 days ago with the weight lost about 2 kg in 3 months time according to the patients mother said. Urination was abnormal with the color of concentrated tea since five days ago. Defecation was normal (yellow in color). This patient was hospitalized at Kabupaten Aceh Tamiang Hospital before referred to Pediatrics Department of Haji Adam Malik General Hospital. According to her family, she suffered the same symptoms one year ago which preceding by her own younger sister with the same disease, Hepatitis A. However, her younger sister never relapse anymore. History of immunization during her childhood was not clear. History of previous illness History of previous medication : Hepatitis A : IVFD D5% Nacl 0.45%, Cefotaxime inj., curcuma, urdafalk Physical Examination Presence Status : sensorium: compos mentis, temperature: 38.2C anemic (-), dyspnea (-), cyanotic (-), edema (-) icteric (+) Body weight (BW) : 33 kg, body length (BL) : 143 cm BW/BL : 91% (normoweight) Localized Status Head Eyes Ear/Mouth/Nose Neck : : :light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-), sclera icteric (+/+) : within normal limit : lymph node enlargement (-)

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Thorax

: symmetrical fusiform , retraction (-) HR: 112 x/i, regular, murmur (-), icteric (+) RR : 32 x/i, regular, ronchi (-)

Abdomen

: soepel, peristaltic (+) normal - liver was palpate 4cm under costal margin, edge of liver is sharp and the surface is smooth and tender, pain during palpation (+) - spleen: not palpable

Genitalia Extremities

: female, within normal limit : Pulse 112 x/i regular, pressure/volume : adequate Blood pressure 120/ 90 mmHg

Laboratory Results (June 22th 2011) : Test Complete blood count Hb RBC WBC Ht PLT Na/K/Cl KGD adrandom SGOT/SGPT Ureum/Creatine Results 11,20g% 5,09 x 106/mm3 25,28 x 103/mm3 34,2 193 x 103/mm3 120/3.8/88 mEq/L 161,70 mg/dl 48/98 U/L 16,2/0,4 mg/dL Normal Value 12,0-14,4 4,75-4,85 4,5-11,0 36-42 150-450 135-155/3.6-5.5/96-106 <200 <32/<31 <50/0,53-0,79

URINALISIS Complete Urine : - Colour - Glucose - Bilirubin - Keton

Negative Positive Negative

Negative Negative

31

- Berat Jenis - pH - Protein - Urobilinogen - Nitrit - Darah Sedimen Urine : - Eritrosit - Leukosit - Epitel - Casts - Kristal

1,005 7,0 Negative Positive Negative Negative 02 01 34 Negative Oksalat +

1,005 -1,030 5-8 Negative Negative Negative <3 <6

Results of urine dipstick : protein (-); BIL (+++); pH (5); BJ (1,010); LEU(-); BLO (-); KET (-); URO(+); NIT (-); GLU (-) Differential Diagnose : - Hepatitis - Cholescystitis - Cholelithiasis Working Diagnose Treatment : - Hepatitis ???? : - IVFD D5% NaCL 0.45% 20 gtt/i macro - Liver Diet 1750 kcal with 65 gram protein - Ceftriaxone injection 4gr/8hr/IV in 50cc NaCL 0,9% within 20 minutes. - Ibuprofen 3x 300g (if necessary) - Multivitamin syr 2 x CI - Urdafalk 3 x 1 tab. Further Investigation plans: - Hepatitis marker screening for Hep.A and Hep.B and Hep. C - USG abdomen - feces routine check

32

- Consul to gastrohepatology department. Follow Up on June 23rd 2011 S : Upper right abdominal pain (-) O: Sens : compos mentis, temperature : 37C BW: 33 kg, BL: 143 cm BW/BL : 91% (normoweight) Head Eyes Ear/Mouth/Nose Neck Thorax : :face icteric(+), light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-), sclera icteric (+/+) : within normal limit : lymph node enlargement (-) : symmetrical fusiform , retraction (-) HR: 98 x/i, regular, murmur (-), icteric (+) RR : 28 x/i, regular, ronchi (-) Abdomen : soepel, peristaltic (+) normal - liver was palpate 4cm under costal margin, edge of liver is sharp and the surface is smooth and tenderness(+) - spleen: not palpable Genitalia Extremities Dipstick Urine pukul 18.00 :
-

: female, within normal limit : Pulse 98 x/i regular, pressure/volume : adequate Blood pressure 100/ 70 mmHg Leukosit : (-) Nit (-) Urobilinogen (+) Protein (-) Ph (6) Blood (-) SG (1,005) Keton (-) Bil (+3) Glukosa (-)

Dipstick Urine pukul 00.00 : Leukosit : (-) Nit (-) Urobilinogen (+) Protein (-) Ph (6,5) Blood (-) SG (1,010) Keton (-) Bil (+2) Glukosa (-) Dipstick Urine pukul 06.00 :
33

Leukosit : (-) Nit (-) Urobilinogen (+) Protein (-) Ph (6) Blood (-) SG (1,010) Keton (-) Bil (+3) Glukosa (-)

A : - Hepatitis - Cholecystitis - Cholelithiasis P : - IVFD D5% NaCL 0.45% 20 gtt/i macro - Diet of Liver Plan 1750 kcal with 65 gram protein - Ceftriaxone injection 4gr/8hr/IV in 50cc NaCL 0,9% within 20 minutes. - Ibuprofen 3x 300g (if necessary) - Multivitamin syr 2 x CI - Urdafalk 3 x 1 tab.

Follow Up on June 24rd 2011 S : Upper right abdominal pain (-) O: Sens : compos mentis, temperature : 37,2C BW: 33 kg, BL: 143 cm BW/BL : 91% (normoweight) Head Eyes Ear/Mouth/Nose Neck Thorax : : icteric face(+), light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-), sclera icteric (+/+) : within normal limit : lymph node enlargement (-) : symmetrical fusiform , retraction (-) HR: 80 x/i, regular, murmur (-), icteric (+)j RR : 24 x/i, regular, ronchi (-) Abdomen : soepel, peristaltic (+) normal - liver was palpate 4cm under costal margin, edge of liver is sharp and the surface is smooth and tenderness(+) - spleen: not palpable

34

Genitalia Extremities

: female, within normal limit : Pulse 80 x/i regular, pressure/volume : adequate Blood pressure 100/ 70 mmHg

A : - Hepatitis - Cholecystitis - Cholelithiasis P : - IVFD D5% NaCL 0.45% 20 gtt/i macro - Diet of Liver Plan 1750 kcal with 65 gram protein - Ceftriaxone injection 4gr/8hr/IV in 50cc NaCL 0,9% within 20 minutes. - Ibuprofen 3x 300g (if necessary) - Multivitamin syr 2 x CI - Urdafalk 3 x 1 tab.

Follow Up on June 25th 2011 S : Upper right abdominal pain (-) O: Sens : compos mentis, temperature : 36,9C BW: 33 kg, BL: 143 cm BW/BL : 91% (normoweight) Head Eyes Ear/Mouth/Nose Neck Thorax : : icteric face(+), light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-), sclera icteric (+/+) : within normal limit : lymph node enlargement (-) : symmetrical fusiform , retraction (-) HR: 100 x/i, regular, murmur (-), icteric (+) RR : 24 x/i, regular, ronchi (-) Abdomen : soepel, peristaltic (+) normal - liver was palpate 4cm under costal margin, edge of liver is

35

sharp and the surface is smooth and tenderness(+) - spleen: not palpable Genitalia Extremities A : - Hepatitis non-B non-C P : - IVFD D5% NaCL 0.45% 20 gtt/i macro - Diet of Liver Plan 1750 kcal with 65 gram protein - Ceftriaxone injection 4gr/8hr/IV in 50cc NaCL 0,9% within 20 minutes. - Ibuprofen 3x 300g (if necessary) - Multivitamin syr 2 x CI - Urdafalk 3 x 1 tab. : female, within normal limit : Pulse 100 x/i regular, pressure/volume : adequate Blood pressure 110/ 70 mmHg

Lab result on screening marker : Hepatitis A: anti HAV ??? Hepatitis B: HbsAg negative Hepatitis C: Anti HCV negative Answers from consultant Gastroenterohepatology : diagnose : Hepatitis non-B non-C Therapy : Urdafalk 3x 120mg Suggestion: USG abdomen

Follow Up on June 26th 2011 S : Upper right abdominal pain (-), fever (-)

36

O: Sens

: compos mentis, temperature : 37,1C BW: 33 kg, BL: 143 cm BW/BL : 91% (normoweight)

Head Eyes Ear/Mouth/Nose Neck Thorax

: : icteric face(-), light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-), sclera icteric (-/-) : within normal limit : lymph node enlargement (-) : symmetrical fusiform , retraction (-) HR: 90 x/i, regular, murmur (-), icteric (-) RR : 24 x/i, regular, ronchi (-)

Abdomen

: soepel, peristaltic (+) normal - liver was palpate 4cm under costal margin, edge of liver is sharp and the surface is smooth and tenderness(+) - spleen: not palpable

Genitalia Extremities

: female, within normal limit : Pulse 84 x/i regular, pressure/volume : adequate Blood pressure 90/ 50 mmHg

A : - Hepatitis non B non C P : - IVFD D5% NaCL 0.45% 20 gtt/i macro - Diet of Liver Plan 1750 kcal with 65 gram protein - Ceftriaxone injection 4gr/8hr/IV in 50cc NaCL 0,9% within 20 minutes. - Ibuprofen 3x 300g (if necessary) - Multivitamin syr 2 x CI - Urdafalk 3 x 1 tab.

Follow Up on June 27th 2011 S : Upper right abdominal pain (-), fever (-) O: Sens : compos mentis, temperature : 37C
37

BW: 33 kg, BL: 143 cm BW/BL : 91% (normoweight) Head Eyes Ear/Mouth/Nose Neck Thorax : : icteric face(-), light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-), sclera icteric (-/-) : within normal limit : lymph node enlargement (-) : symmetrical fusiform , retraction (-) HR: 96 x/i, regular, murmur (-), icteric (-) RR : 20 x/i, regular, ronchi (-) Abdomen : soepel, peristaltic (+) normal - liver was palpate 4cm under costal margin, edge of liver is sharp and the surface is smooth and tenderness(+) - spleen: not palpable Genitalia Extremities : female, within normal limit : Pulse 96 x/i regular, pressure/volume : adequate Blood pressure 100/ 60 mmHg A : - Hepatitis non-B non-C + Trichuriasis P : - IVFD D5% NaCL 0.45% 20 gtt/i macro - Diet of Liver Plan 1750 kcal with 65 gram protein - Ceftriaxone injection 4gr/8hr/IV in 50cc NaCL 0,9% within 20 minutes. - Ibuprofen 3x 300g (if necessary) - Multivitamin syr 2 x CI - Urdafalk 3 x 1 tab. - Albendazole 1 x 400mg Results of feces routine check: Macroscopic: Color Consistency Blood Mucous-like Yellow watery negative negative
38

Microscopic Egg of worm Amoeba Erythrocyte Leucocyte

Trichuris Trichiura Negative 0-1 0-1

Follow Up on June 28th 2011 S : Upper right abdominal pain (-), fever (-) O: Sens : compos mentis, temperature : 37,1C BW: 33 kg, BL: 143 cm BW/BL : 91% (normoweight) Head Eyes Ear/Mouth/Nose Neck Thorax : : light reflex (+/+), isochoric pupil, pale inferior conjunctiva palpebra (-/-), sclera icteric (-/-) : within normal limit : lymph node enlargement (-) : symmetrical fusiform , retraction (-) HR: 96 x/i, regular, murmur (-), icteric (-) RR : 24 x/i, regular, ronchi (-) Abdomen : soepel, peristaltic (+) normal - liver was palpate 4cm under costal margin, edge of liver is sharp and the surface is smooth and tenderness(+) - spleen: not palpable Genitalia Extremities : female, within normal limit : Pulse 96 x/i regular, pressure/volume : adequate Blood pressure 100/ 70 mmHg A : - Hepatitis non-B non-C + Trichuriasis

39

P : - IVFD D5% NaCL 0.45% 20 gtt/i macro - Diet of Liver Plan 1750 kcal with 65 gram protein - Ceftriaxone injection 4gr/8hr/IV in 50cc NaCL 0,9% within 20 minutes. - Ibuprofen 3x 300g (if necessary) - Multivitamin syr 2 x CI - Urdafalk 3 x 1 tab. - Albendazole 1 x 400mg Patient was allowed to go back but was treated as a outpatient in Haji Adam Malik General Hospital. 3.3. Discussion DF, a 11-years-old girl with body weight 33 kg and body height 143 cm, was admitted to the Pediatrics Department of Haji Adam Malik General Hospital on June 22nd 2011, diagnosed with Hepatitis non-B non-C. This diagnosis was made based on the patients complains such as upper abdominal pain, yellowish discoloration of skin, subfebrile fever, vomiting, anorexia, and dark color of urine while clinical findings that we can found in the patient are icteric sclera, jaundice and hepatomegaly. According to laboratory results, we found that the SGOT/SGPT level were increased as much as 3 times than normal which indicate an inflammation process going on in the liver. Besides that, from the urine analysis, bilirubin was positive. In contrast, bilirubin should not be found in urine. However, the serology tests performed on this patient are limited considering the fact that we could only perform tests for anti HCV and HbsAg only. The result we got from the screening are both negative. Although this helped us to rule out the diagnosis of Hepatitis B and Hepatitis C but we could only make our diagnosis as Hepatitis non-B non-C. Furthermore, USG scanning on the abdomen was performed to exclude the differential diagnosis we had made. The results of USG scanning showed there is no dilatation of the cystic duct.(cholecystitis).

40

The treatment conducted to this patient had already been in line. Analysis of serum electrolyte was conducted. This patient sodium level is below the normal level (120mEq). After that, the patients natrium level was corrected with Nacl 3% (580 mEq) within 6 hours. The formula is : (135 120) x 0,6 x 0,3 = 297 Meq, [ 297/513 = 580 Meq]. This is followed by maintenance fluid IVFD D5% NaCl 0,45%. Prophylaxis for infection was given to this patient, applying the use of Ceftriaxon 1 gr/8 jam/IV in 50 cc NaCl 0,9%. Ceftriaxon is a broad spectrum antibiotic and is given for around 5 days. Abendazole 400mg daily is also given to the patient after results from stool examination showed there is infection with trichuriasis. Liver plan diet is given to the patient with total calories of 1750 Kkal based on holiday segar and protein is based on 2 gr/KgBW/day. The patient is only given Multivitamin due to the fact that hepatitis infection is a self limited disease where bed rest and supportive therapy is sufficient.

3.4.

Summary It has been reported a case of a 11-year-old girl with Hepatitis non-B, non-C.

The diagnosis was established based on history taking, clinical manifestations, and laboratory findings. Treatment for this patient was only symptomatic. This patient was discharged from the hospital after the clinical condition was improved. REFERENCES
1. World Health Organization. Hepatitis: Hepatitis A. www.who.int/emc 2010. 2. Adrienne M Buggs, MD., 2010. Viral Hepatitis. Emedicine. Available from:

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http://emedicine.medscape.com/article/775507-overview http://emedicine.medscape.com/article/775507-clinical http://emedicine.medscape.com/article/775507-differential http://emedicine.medscape.com/article/775507-workup http://emedicine.medscape.com/article/775507-treatment http://emedicine.medscape.com/article/775507-medication http://emedicine.medscape.com/article/775507-followup [ accessed on June 29th 2011].
3. Donough J ODonovan, MD. Hepatitis viruses and the newborn: Clinical

manifestations and treatment. www.uptodate.com. [ accessed on January 7th 2008].

4. Halstead, Scott B. Infectious Diseases: Hepatitis. In: Behrman, Richard E.,

Kliegman, Robert M., Jenson, Hal B. (eds). Nelson Textbook of Pediatrics 18th ed. USA: Saunders. 2007;1412-1414.
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6. Richard K Gilroy, MBBS., 2011. Hepatitis A. Emedicine. Available from:

http://emedicine.medscape.com/article/177484-overview http://emedicine.medscape.com/article/177484-clinical http://emedicine.medscape.com/article/177484-differential http://emedicine.medscape.com/article/177484-workup http://emedicine.medscape.com/article/177484-treatment [ accessed on June 29th 2011].

7. Hasan, Rusepno dkk. Buku Kuliah Ilmu Kesehatan Anak . Hepatitis. Bagian

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