Hepatitis B

Hepatitis B causes significant morbidity and mortality worldwide. More than 400 million persons, including 1.25 million Americans, have chronic hepatitis B. In the United States, chronic hepatitis B virus infection is responsible for about 5,000 annual deaths from cirrhosis and hepatocellular carcinoma. Hepatitis B virus is found in body fluids and secretions; in developed countries, the virus is most commonly transmitted sexually or via intravenous drug use. Occupational exposure and perinatal transmission do occur but are rare in the United States. Effective vaccines for hepatitis B virus have been available since 1982; infant and childhood vaccination programs introduced in the 1990s have resulted in a marked decrease in new infections. Risk factors for progression to chronic infection include age at the time of infection and impaired immunity. From 15 to 30 percent of patients with acute hepatitis B infection progress to chronic infection. Medical therapies for chronic hepatitis B include interferon alfa-2b, lamivudine, and the nucleotide analog adefovir dipivoxil.     

Enterically transmitted hepatitis. Hepatitis A and E viruses.

Enterically-transmitted hepatitis is caused by hepatitis A virus and hepatitis E virus. The most important agent is hepatitis A virus, which is distributed worldwide and infects all age groups. Most infections in children are minimally symptomatic and immunity is long-lasting, so severe disease tends to occur in nonimmune adults. Hepatitis E virus is found in the developing world and has a greater propensity for symptomatic infection of children. Both agents are transmitted via contaminated water, often through food vehicles.     

HIV counseling, testing, and referral

Over the past decade, the annual number of new cases of human immunodeficiency virus (HIV) infection has been relatively stable but remains unacceptably high (an estimated 40,000 new cases per year). Furthermore, the demographics for HIV infection are changing. Rates of new infections are declining in newborns, older men who have sex with men, and whites. However, rates of new infections are rising in young persons, women, Hispanics, and blacks. In 2001, the Centers for Disease Control and Prevention issued revised guidelines for HIV counseling, testing, and referral. The guidelines focus on the reduction of barriers to testing, voluntary routine testing of high-risk populations and persons with risk factors, case management and partner tracing for infected persons, and universal testing of pregnant women. Effective strategies for reducing HIV infection include behavioral interventions, comprehensive school-based HIV and sex education, access to sterile drug equipment, screening of the blood supply, and postexposure prophylaxis for health care workers.     

Hepatitis B virus infection in children

For two decades, hepatitis B vaccine has been integrated into national routine childhood vaccination programs in almost all countries. The prevalence of HBsAg has decreased in children worldwide. However, there are children who miss the benefit of hepatitis B vaccine in some regions and countries. Long-term follow-up studies have revealed the clinical outcomes of chronic hepatitis B virus infection in children. A small percentage of chronically infected children develop liver cirrhosis and hepatocellular carcinoma. However, it is controversial who should be treated and when antiviral treatment should be initiated in children. Compared with adult studies, the data are insufficient to evaluate the pathogenesis of hepatitis B infection and the efficacy of antiviral treatment in childhood. New antiviral drugs have been approved for children and adults. Also, oral antiviral drugs are administered to pregnant women to reduce the hepatitis B virus mother-to-child transmission rate.     

SEN virus: epidemiology and characteristics of a transfusion-transmitted virus

SEN virus (SEN-V) is a blood-borne, single-stranded, nonenveloped DNA virus. Although its prevalence varies by geographic region, it has been detected in as many as 30 percent of postoperative transfusion recipients, compared to 3 percent of postoperative patients who did not receive transfusions. A significant association has been observed between transfusion volume and the occurrence of SEN-V infection. Transmission by transfusion also has been confirmed by the detection of greater than 99 percent homology between SEN-V in donor and recipient sera. Concurrent infections with SEN-V and hepatitis B virus, hepatitis C virus, or human immunodeficiency virus type 1 have been documented, and these observations probably reflect the blood-borne transmission of these viruses as well as SEN-V. Although SEN-V was discovered as part of a search for causes of posttransfusion hepatitis, there is no firm evidence so far that SEN-V infection either causes hepatitis or worsens the course of coexistent liver disease. Nevertheless, SEN-V appears to be transmitted by transfusion, and further studies may reveal more about its role in the future.     

Caring for pregnant women and newborns with hepatitis B or C

Family physicians encounter diagnostic and treatment issues when caring for pregnant women with hepatitis B or C and their newborns. When hepatitis B virus is perinatally acquired, an infant has approximately a 90 percent chance of becoming a chronic carrier and, when chronically infected, has a 15 to 25 percent risk of dying in adulthood from cirrhosis or liver cancer. However, early identification and prophylaxis is 85 to 95 percent effective in reducing the acquisition of perinatal infection. Communication among members of the health care team is important to ensure proper preventive techniques are implemented, and standing hospital orders for hepatitis B testing and prophylaxis can reduce missed opportunities for prevention. All pregnant women should be screened for hepatitis B as part of their routine prenatal evaluation; those with ongoing risk factors should be evaluated again when in labor. Infants of mothers who are positive for hepatitis B surface antigen should receive hepatitis B immune globulin and hepatitis B vaccination within 12 hours of birth, and other infants should receive hepatitis B vaccination before hospital dis- charge. There are no effective measures for preventing perinatal hepatitis C transmission, but transmission rates are less than 10 percent. Perinatally acquired hepatitis C can be diagnosed by detecting hepatitis C virus RNA on two separate occasions between two and six months of age, or by detecting hepatitis C virus antibodies after 15 months of age.     

Slowing the progression of chronic hepatitis B. Early antiviral therapy can help minimize complications

About 350 million people worldwide have chronic hepatitis B virus (HBV) infection. Up to 40% of persons infected with the virus may go on to have complications related to cirrhosis or hepatocellular carcinoma. Antiviral therapy can suppress viral replication and halt the progression of liver disease in persons with chronic infection. In this article, the authors explore the modes of HBV transmission, describe the characteristics of chronic infection, and review the drugs available to treat it.     

Management of hepatitis C: evaluating suitability for drug therapy

Chronic hepatitis C virus infection is a common and serious disease. Although an estimated 2.7 million persons in the United States have this disease, most have not yet been diagnosed. Recent advances in treatment provide successful cure in 50 to 80 percent of cases. Current drug therapy consists of a combination of pegylated interferon and ribavirin. Although all patients with chronic hepatitis C virus infection are potential candidates for treatment, pharmacologic therapy has a number of contraindications. Evaluation of suitability for treatment includes a thorough search for comorbid medical and psychiatric conditions that can be contraindications. Initial testing involves anti-hepatitis C virus antibodies, but definitive diagnosis of active disease requires detection of viral RNA. Most patients require a liver biopsy to determine the amount of hepatic fibrosis and ongoing hepatocellular inflammation. Viral genotype also should be determined: type 1 requires 12 months of treatment and does not respond as well as types 2 and 3, which require only six months of treatment. Common side effects of drug therapy include anemia, anorexia, depression, fatigue, fever, headache, myalgia, nausea, and erythema at the injection site.     

Diagnosis and treatment of Chlamydia trachomatis infection

Chlamydia trachomatis infection most commonly affects the urogenital tract. In men, the infection usually is symptomatic, with dysuria and a discharge from the penis. Untreated chlamydial infection in men can spread to the epididymis. Most women with chlamydial infection have minimal or no symptoms, but some develop pelvic inflammatory disease. Chlamydial infection in newborns can cause ophthalmia neonatorum. Chlamydial pneumonia can occur at one to three months of age, manifesting as a protracted onset of staccato cough, usually without wheezing or fever. Treatment options for uncomplicated urogenital infections include a single 1-g dose of azithromycin orally, or doxycycline at a dosage of 100 mg orally twice per day for seven days. The recommended treatment during pregnancy is erythromycin base or amoxicillin. The Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommend screening for chlamydial infection in women at increased risk of infection and in all women younger than 25 years.     

Clinical approach to viral hepatitis in homosexual men

The prevalence of both hepatitis A and hepatitis B is increased in homosexual men. On an annual basis, 5% to 7% of homosexual men will acquire hepatitis A. Risk factors for HAV infection include length of homosexual activity, number of sexual contacts, and oral--anal sexual contact. The HBsAg carrier rate of homosexual men is 5% to 6%, and another 50% have evidence of previous HBV infection with a positive anti-HBs. HBeAg is present in a higher precentage of HBsAg-positive homosexual men (38% to 75%) than in general population carriers (3% to 30%). The annual incidence for HBV infection in homosexual men is 16% to 28%, higher than that for hepatitis A. Transmission of HBV infection in homosexual men is facilitated by a large number of sexual partners, high HBsAg carrier rate, high infectivity of carriers (positive HBeAg), and the specific sexual practices of oral--anal and anal--genital contact with exposure to HBV on open mucosal surfaces. The prevalence of non-A, non-B and delta infection in homosexual men is probably somewhat increased, but the importance of these viruses in the development of hepatitis in this population remains uncertain. Prevention of hepatitis A and B in homosexual men will ultimately be achieved by vaccination of susceptible individuals, which currently is feasible only for hepatitis B. Appropriate use of immune globulins for postexposure prophylaxis and knowledge of specific sexual practices that transmit disease may reduce the incidence of hepatitis A and B.     

Hepatitis virus C infection in children

The prevalence of hepatitis C virus(HCV) infection has been becoming much lower in childhood. Blood transfusion was the principal transmission route of HCV in children. Since the year of 1989, screening of the blood products for HCV antibodies has markedly reduced transfusion-related HCV infection. Mother-to-infant transmission occurs in less than 10% of infants born to HCV-infected mothers. The maternal viral load is the most important factor determining the risk. The natural history and the outcome of HCV infection in childhood dependent on host and viral factors. The rate of progression to chronicity is 60% in post-transfusion infection and 80% in vertical infection. Experience of interferon therapy of chronic hepatitis C in children is limited, with about 50% having a sustained response to the therapy.     

Prevalence of hepatitis C infection in a large urban hospital-based sample of individuals with spinal cord injury

OBJECTIVE: To examine the prevalence and clinical characteristics of hepatitis C infection in individuals with chronic spinal cord injury (SCI). DESIGN: Retrospective case survey. SETTING: Outpatient clinic devoted to SCI follow-up care located in a county-government rehabilitation center. PARTICIPANTS: A total of 531 unselected individuals with chronic SCI. INTERVENTIONS: Patients underwent routine annual physical examinations at the outpatient clinic, and were tested for hepatitis C antibodies, antibodies to hepatitis core antigen, alanine aminotransferase (ALT), and bilirubin. MAIN OUTCOME MEASURES: Prevalence of hepatitis C antibodies and liver test abnormalities. RESULTS: Seventeen percent of the cohort was anti-hepatitis C virus (HCV) reactive (HCV positive). The prevalence of HCV infection in those who sustained SCI before 1990 was 21% compared with 7% (10/147) of those who were injured from 1990 onward (, P=.0002). Period of injury (Wald, P=.0042) and age (Wald, P=.048) were the only significant factors for anti-HCV reactivity. Thirty percent of the HCV-positive individuals had abnormal ALT levels compared with only 10% of the HCV-negative individuals (, P<.0001). Individuals who were HCV positive were more likely to be hepatitis B core antigen-reactive compared with those who were HCV negative (31% vs 9%;, P<.0001). CONCLUSIONS: The prevalence of HCV infection among individuals with chronic SCI is significantly higher than the general population. The majority of those with SCI and HCV infection have normal liver tests. Clinicians should maintain a high index of suspicion for HCV infection, even in the absence of elevated aminotransferase activities.     

Hepatitis B virus. Update on the spectrum of clinical infections and on prophylaxis

Knowledge about hepatitis B virus (HBV) has expanded vastly over the past 20 years, elucidating not only the spectrum of clinical illnesses it causes but also its biologic characteristics. HBV is an important cause of both acute and chronic liver disease in the United States. The most serious outcome of hepatitis B infection is chronic liver disease, which can range from chronic hepatitis eventuating in cirrhosis to primary hepatocellular carcinoma. Molecular biologic studies have shown that HBV-DNA can be integrated into the genome of hepatocytes. This integration may be part of the natural history of chronic hepatitis B infection and may transform normal hepatocytes into neoplastic cells. Immunization with hepatitis B vaccine (Heptavax-B) of persons at high or intermediate risk is an essential means for preventing transmission of hepatitis B. Use of the vaccine after recent exposure to hepatitis B breaks the chain of transmission--an exciting capability. Postexposure immunization of neonates born of HBsAg-positive mothers is particularly important in preventing vertical, or perinatal, transmission of infection.     

Failure of interferon to prevent recurrent hepatitis B infection in hepatic allograft

Chronic liver disease associated with hepatitis B virus infection is both common and serious; no satisfactory treatment currently exists. Orthotopic liver transplantation is an option for patients with end-stage liver disease associated with hepatitis B virus infection despite the risk of allograft reinfection. Passive immunoprophylaxis has been attempted perioperatively to prevent graft infection but has not been beneficial. Some patients with chronic type B hepatitis have benefited clinically from antiviral therapy and, in particular, interferon, but its use has not previously been reported as an approach to prevent allograft infection. We administered recombinant leukocyte A interferon perioperatively to a patient who underwent liver transplantation for type B chronic active hepatitis and cirrhosis. Circulating hepatitis B virus DNA was found postoperatively while the patient was receiving interferon, and stainable viral antigen subsequently reappeared in the transplanted liver. Thus, the drug failed to prevent viral replication and allograft infection. Thus far, no evidence of progression of the chronic hepatitis has been noted.     

Liver disease in pregnancy

Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute hepatitis is unaffected by pregnancy, except in patients with hepatitis E and disseminated herpes simplex infections, in which maternal and fetal mortality rates are significantly increased. Chronic hepatitis B or C infections may be transmitted to neonates; however, hepatitis B virus transmission is effectively prevented with perinatal hepatitis B vaccination and prophylaxis with hepatitis B immune globulin. Cholelithiasis occurs in 6 percent of pregnancies; complications can safely be treated with surgery. Women with chronic liver disease or cirrhosis exhibit a higher risk of fetal loss during pregnancy. Preeclampsia is associated with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and hepatic infarction and rupture. These rare diseases result in increased maternal and fetal mortality. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. Therapy with penicillamine, trientine, prednisone or azathioprine can be safely continued during pregnancy.     

Viral hepatitis in India

Hepatitis in India is caused mainly by hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV). HAV infection occurs frequently in children, though in parts of India there is an evolving epidemiology. HEV is the most common cause of acute sporadic hepatitis in India and has been associated with several large-scale epidemics in the past. India belongs to the intermediate endemicity zone for HBV carriers. HBV is the major cause of chronic liver disease and liver cancer. Horizontal transmission of HBV plays an important role. Genotypes D, A, and C have been reported in India. HCV is transmitted mainly through suboptimal blood banking and injection practices in India. Genotype 3 is the most predominant, followed by genotype 1.     

Cytomegalovirus

Cytomegalovirus (CMV) is a prevalent viral pathogen. The majority of persons with acute CMV will experience an inapparent infection. Primary CMV infection will cause up to 7 percent of cases of mononucleosis syndrome and will manifest symptoms almost indistinguishable from those of Epstein-Barr virus-induced mononucleosis. CMV, or heterophil-negative mononucleosis, is best diagnosed using a positive IgM serology. Complications of acute CMV infection in immunocompetent persons are rare, except in newborns. The virus usually is spread through close personal contact; transmission risk can be reduced by following simple hygienic and handwashing techniques. Severe illness can occur after reactivation of the latent virus in immunosuppressed persons. The retina is the most common site of CMV-induced pathology in persons with human immunodeficiency virus infection. Advances in the treatment of human immunodeficiency virus infection with highly active antiretroviral therapy (HAART) have decreased the incidence of CMV retinitis but have resulted in a new set of ophthalmologic complications induced by restoration of immune competency and the pro-inflammatory response of the patient to CMV. If HAART restores the patient's CD4 cell count to above 100 to 150 per mm3 (100 to 150 x 10(6) per L), it may preclude lifelong treatment for CMV retinitis.     

HIV Screening in the Health Care Setting: Status, Barriers, and Potential Solutions

Thirty years into the human immunodeficiency virus (HIV) epidemic in the United States, an estimated 50,000 persons become infected each year: highest rates are in black and Hispanic populations and in men who have sex with men. Testing for HIV has become more widespread over time, with the highest rates of HIV testing in populations most affected by HIV. However, approximately 55% of adults in the United States have never received an HIV test. Because of the individual and community benefits of treatment for HIV, in 2006 the Centers for Disease Control and Prevention recommended routine screening for HIV infection in clinical settings. The adoption of this recommendation has been gradual owing to a variety of issues: lack of awareness and misconceptions related to HIV screening by physicians and patients, barriers at the facility and legislative levels, costs associated with testing, and conflicting recommendations concerning the value of routine screening. Reducing or eliminating these barriers is needed to increase the implementation of routine screening in clinical settings so that more people with unrecognized infection can be identified, linked to care, and provided treatment to improve their health and prevent new cases of HIV infection in the United States.     

Heterosexually acquired human immunodeficiency virus infection and the United States blood supply: considerations for screening of potential blood donors. HIV Blood Donor Study Group

The impact of heterosexual transmission of the human immunodeficiency virus (HIV) on the United States blood supply was assessed, and deferral criteria that may exclude potential donors who are at high risk for heterosexually acquired HIV infection were evaluated. Interviews were conducted with 508 HIV-seropositive blood donors from May 1, 1988, to August 31, 1989 (Phase 1), and with 472 donors from January 1, 1990, to May 31, 1991 (Phase 2), at 20 blood centers. From Phase 1 to Phase 2, the overall HIV prevalence decreased from 0.021 to 0.018 percent (p < 0.001). HIV risk factors among HIV-1-seropositive donors were similar during both study phases. Eleven percent of the men and 56 percent of the women reported as their only risk that they had a heterosexual partner who was at increased risk for HIV or was known to have HIV. These percentages were similar during both study periods. During Phase 2, 13 percent of the men and 17 percent of the women with heterosexual transmission risk had a positive serologic test for syphilis, hepatitis B core antibody, or hepatitis C antibody. Among HIV- 1-seropositive donors reporting heterosexual risk, the median numbers of previous-year and lifetime sex partners for men were 2 and 30, respectively; for women, those numbers were 1 and 7, respectively. Thirty-one percent of the men and 6 percent of the women reporting heterosexual transmission risk also reported having had syphilis or gonorrhea within 3 years of donation. It is concluded that the impact of heterosexual transmission of HIV infection on transfusion safety is not worsening at this time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human T-lymphotropic virus type II in Panamanian Guaymi Indians

BACKGROUND: Currently, human T-lymphotropic virus type II (HTLV-II) is the most prevalent human retrovirus, detected in persons presenting to donate blood in the United States. Only scant information is available with which to counsel HTLV-II-seropositive deferred donors or other persons about the ways in which they may spread HTLV-II to others. STUDY DESIGN AND METHODS: To increase understanding of the modes of transmission of HTLV-II, a seroepidemiologic study was conducted among Panamanian Guaymi Indians, a recently identified focus of endemic HTLV- II infection. Subjects were tested for serologic evidence of infection by HTLV-II, HTLV type I, hepatitis B virus, and nine other infectious agents by enzyme immunoassays and specific confirmatory tests. RESULTS: Nine (8.3%) of 109 persons tested HTLV-II-seropositive. HTLV-II seropositivity was more likely in persons with serologic evidence of prior hepatitis B virus infection. Sexual contact with HTLV-II- seropositive partners, but neither parenteral exposure nor breast- feeding, was identified as a risk factor for HTLV-II. CONCLUSION: In Guaymi Indians, HTLV-II appears to be spread primarily through sexual transmission.