Hepatitis Virus Type Research Articles

New perspectives on hepatitis E.

The infectious agent causing epidemic non-A, non-B hepatitis was identified in 1983 from a human challenge experiment. The novel hepatitis E virus (HEV) subsequently was cloned in 1990 and the genome sequenced. HEV transmission is highly endemic in Asia, the Middle East, and Africa. Fecal contamination of drinking water is the most common mode of spread. Although usually asymptomatic, HEV infection can cause fulminant hepatitis. Recent studies indicate that hepatitis E may be a zoonotic disease, with pigs and possibly rats serving as reservoirs for human infection. A recombinant HEV vaccine is currently in phase III clinical trials. The characterization of the major types of viral hepatitis during the last 20 years illustrates how modern genetic technology has revolutionized research in infectious diseases. Within less than two decades of the discovery of HEV, its epidemiology has been described, serologic tests have been developed, and a candidate vaccine has been evaluated in clinical trials.

CD34, VEGF expression and hepatitis virus type

CD34, VEGF expression and hepatitis virus type

P21 expression and hepatitis virus type

p21 expression and hepatitis virus type

Epidemiology and prophylaxis of viral hepatitis: a global perspective.

Viral hepatitis with various forms of acute and chronic liver disease as potential and ultimately fatal sequelae presents a public health problem worldwide. Recent published reports on the global epidemiology and prophylaxis of viral hepatitis were reviewed. With the advances in novel technologies, eight distinct types of hepatitis virus have been described: Hepatitis A, B, C, D, E, G, TT and SEN viruses. Hepatitis A and E viruses are transmitted by the fecal-oral route and do not induce a chronic carrier state. Due to major changes in epidemiology of hepatitis A virus their significance is more pronounced in areas of intermediate endemicity. Since the available hepatitis A vaccine is rather expensive, cost-benefit studies should be performed with emphasis on the area under consideration or specialized vulnerable groups. Parenterally transmitted hepatitis B and C viruses are major causes of chronic liver disease, including cirrhosis, hepatocellular carcinoma and end-stage liver failure. Hepatitis D virus is unable to replicate on its own, it requires an established hepatitis B virus infection to be able to replicate. Since its introduction, hepatitis B vaccine has been widely used leading to a significant decrease in HBV infection in countries with universal vaccination. Hepatitis G and TT viruses have been characterized within the latter part of the past decade but their significance as to the causation of human liver disease has yet to be elucidated. Likewise, the precise impact of the most recently described SEN virus isolated from patients with post-transfusion hepatitis awaits further studies. In the course of this review, we present the situation and focus on research activities emphasizing epidemiology and prevention of the various forms of viral hepatitis.

Histomorphological characteristics of liver tissue in patients with chronic viral hepatitis

OBJECTIVE: Chronic viral hepatitis and cirrhosis caused by hepatitis B virus (HBV), hepatitis C virus (HBC) or both constitute the majority of cases of liver diseases in China. Pathologists often need to differentiate between the morphological features of HBV and HCV. The aim of this study was to explore the differences in inflammatory activity, fibrosis and morphological characteristics in various types of chronic viral hepatitis. METHODS: Inflammatory activity and degree of fibrosis in liver biopsies taken from 224 patients with chronic hepatitis were determined according to the Diagnostic Criteria of Chronic Hepatitis, China, 1995. Each of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and the hepatitis C virus nuclear core protein (CP10) were detected on paraffin sections of the biopsies by using immunohistochemical methods. Patients were divided into HBV, HCV and HBV + HCV infection groups and the differences among these groups were assessed on the basis of histopathological characteristics including inflammatory activity, fibrosis, steatosis, intrahepatic cholestasis, Councilman bodies and ground-glass hepatocytes. RESULTS: The HCV infection group had more severe inflammatory activity, fibrosis and intrahepatic cholestasis than did the HBV infection group. The degree of inflammatory activity and fibrosis in the HBV + HCV infection group was moderate, but the degree of intrahepatic cholestasis was the most severe of the three study groups. Ground-glass hepatocytes were only noted in HBV-infected specimens. There was no difference in the occurrences of steatosis and Councilman bodies among the three study groups. CONCLUSIONS: The degree of inflammatory activity and fibrosis induced by HCV in hepatocytes is more severe than that induced by HBV. The histological changes observed in liver infected by both HBV and HCV are no more severe than those observed in liver infected with either HBV or HCV. Intrahepatic cholestasis may play an important role in aggravating damage to hepatocytes.

Jaundice & War: Viral Hepatitis and Other Causes of Jaundice in Times of War

Outbreaks of illnesses with jaundice have long been recognised in armies during times of war. Warfare results inter alia in continuing gross disruption of all aspects of public and personal hygiene, facilitating the spread of gut borne infections. The treatment of wounds and shock with intravenous blood, serum or plasma exposed recipients to a number of blood-borne pathogens including certain agents of viral hepatitis. With our present knowledge of the different types of viral hepatitis and other infectious diseases and conditions that may be associated with jaundice, it is of interest to review accounts of such outbreaks, clinical features, and deductions made by contemporaries concerning aetiology, epidemiology and communicability. For many years the hypothesis of 'duodeno-biliary catarrh', propounded by Bamberger and Virchow in the mid-nineteenth century, was accepted as explaining the jaundice occurring in viral hepatitis.1 It was thought, on the basis of post-mortem appearances, that inflammatory swelling of the mucosa of the second part of the duodenum and the ampulla of Vater - i.e. the opening of the common bile duct into the duodenum - caused blockage to the draining of bile, resulting in jaundice, hence the name 'catarrhal jaundice'. Only in the 1940s was it recognised that viral infection of the liver itself, with resulting inflammation, was responsible. It should be noted that the first confirmatory laboratory test for any type of viral hepatitis became available in 1970 as a consequence of Baruch S. Blumberg's work that resulted in the detection of hepatitis B surface antigen.2 In 1974 we had the first serological test for hepatitis A and could at last reliably distinguish the two main varieties of viral hepatitis.3 It then came as a surprise to find that there were types of hepatitis that were neither A nor B, specific tests for which were developed much later.

フィブリン糊によるパルボウイルスと肝炎ウイルスの感染の可能性について

フィブリン糊によるパルボウイルスと肝炎ウイルスの感染の可能性について

Hepatitis B and hepatitis C virus infections in dermatological patients in west Sicily: a seroepidemiological study.

To evaluate the relative frequencies and molecular epidemiological features of viral hepatitis types B and C in dermatological patients in our geographical area. We determined the hepatitis B virus (HBV) and hepatitis C virus (HCV) antibodies and the hepatitis B virus surface antigen (HBsAg) in a cohort of 677 dermatological patients admitted to the Department of Dermatology of Palermo. An 8-mL blood sample was taken from all subjects. The following assays were used: HBsAg, anti-HB core (antigen) (anti-HBc), anti-HB surface (antigen) (anti-HBs), anti-HB early (antigen) (anti-Hbe) and anti-HCV antibodies using enzyme-linked immunosorbent assay. One hundred and eighty-nine (27.91%) of the 677 dermatological patients were positive for anti-HBc, anti-HBs, anti-HBe and/or anti-HCV antibodies. In particular 22% (149 patients) were anti-HBc, anti-HBs or anti-HBe positive, reflecting exposure to HBV, and six patients (0.88%) were chronic carriers of HBsAg; 2.36% of the dermatological patients (16 persons) were anti-HCV positive. Tests showed that 24 subjects (3.52%) were infected with hepatitis B or C. The peaks in the age bands were in the 55-80-year-old age groups. This study confirms a high rate of HBV and HCV exposure with chronic carriers in our dermatological patients. We assume that the high prevalence of HCV and HBV in dermatological patients is more likely to be age related than to represent a true and direct association with dermatological diseases in general. Definite conclusions will only be available after large epidemiological studies that can establish or refute an aetiological and pathogenetic role of HBV and HCV in certain skin diseases associated with liver infection.

HCV RNA-dependent RNA polymerase replicates in vitro the 3' terminal region of the minus-strand viral RNA more efficiently than the 3' terminal region of the plus RNA.

The NS5B protein, or RNA-dependent RNA polymerase of the hepatitis virus type C, catalyzes the replication of the viral genomic RNA. Little is known about the recognition domains of the viral genome by the NS5B. To better understand the initiation of RNA synthesis on HCV genomic RNA, we used in vitro transcribed RNAs as templates for in vitro RNA synthesis catalyzed by the HCV NS5B. These RNA templates contained different regions of the 3' end of either the plus or the minus RNA strands. Large differences were obtained depending on the template. A few products shorter than the template were synthesized by using the 3' UTR of the (+) strand RNA. In contrast the 341 nucleotides at the 3' end of the HCV minus-strand RNA were efficiently copied by the purified HCV NS5B in vitro. At least three elements were found to be involved in the high efficiency of the RNA synthesis directed by the HCV NS5B with templates derived from the 3' end of the minus-strand RNA: (a) the presence of a C residue as the 3' terminal nucleotide; (b) one or two G residues at positions +2 and +3; (c) other sequences and/or structures inside the following 42-nucleotide stretch. These results indicate that the 3' end of the minus-strand RNA of HCV possesses some sequences and structure elements well recognized by the purified NS5B.

Risk of parenterally transmitted hepatitis following exposure to surgery or other invasive procedures: results from the hepatitis surveillance system in Italy

Background/Aims : To evaluate the strength of association between parenterally transmitted viral hepatitis and specific types of invasive procedures. Methods : Data from the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1994–1999 were used. The association of acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the potential risk factors (odds ratios (OR)) was estimated comparing 3120 hepatitis B and 1023 hepatitis C cases with 7158 hepatitis A cases, used as controls, by multiple logistic regression analysis. Results : Most procedures resulted in being associated with the risk of acquiring acute HBV or HCV. The strongest associations were: for HBV infection, abdominal surgery (adjusted OR=3.9; 95% confidence intervals (CI)=2.0–7.5), oral surgery (OR=2.7; 95% CI=1.6–4.5) and gynaecological surgery (OR=2.6; 95% CI=1.2–5.5); for HCV infection, obstetric/gynaecological interventions (OR=12.1; 95% CI=5.6–26.3), abdominal surgery (OR=7.0; 95% CI=3.2–14.9) and ophthalmological surgery (OR=5.2; 95% CI=1.1–23.2). Biopsy and/or endoscopy were associated with HCV, but not with HBV infection. Conclusions : Invasive procedures represent an important mode of HBV and HCV transmission. Since a large proportion of the adult general population is exposed to these procedures and an effective HCV vaccine is not yet available, non-immunological means of controlling iatrogenic modes of transmission are extremely important.

P21WAF1/CTP1 expression and hepatitis virus type.

Since p21WAF1/CIP1 (p21) is a universal inhibitor of cyclin-dependent kinases and is regulated transcriptionally by p53, which is activated by DNA stress, its expression reflects DNA stress in chronic hepatitis. Recently an association with both hepatitis B and C virus and the expression of p53 or p21 was reported. We analyzed p21 expression in 18 cases of HBV-associated chronic liver diseases and 32 cases of HCV-associated chronic liver diseases by immunohistochemical analysis, and investigated the possible association between hepatocyte p21 expression and hepatic inflammation, fibrosis, and especially hepatitis virus type. The p21-positive hepatocytes were more numerous in areas of intense inflammation and spotty necrosis and areas close to fibrosis, and they increased according to the degrees of grading and staging. The p21 labeling index (LI) in patients with liver cirrhosis was significantly higher than that in patients with chronic hepatitis of both hepatitis viral types (5.84 +/- 0.61 vs 12.0 +/- 0.83, P < 0.0001 in hepatitis B, 10.28 +/- 0.80 vs 15.6 +/- 1.09, P = 0.0004 in hepatitis C), Furthermore, the p21 LI was significantly higher in HCV-associated liver disease than in HBV-associated liver disease in every group (4.02 +/- 0.48 vs 7.74 +/- 0.96, P = 0.021 in low grade group, 7.35 +/- 0.46 vs 12.8 +/- 0.57, P < 0.0001 in high grade, 12.0 +/- 0.83 vs 15.6 +/- 1.09, P = 0.034 in liver cirrhosis). In, conclusion, p21 expression was up-regulated by the stress of inflammation and fibrosis and might be influenced by viral proteins in human chronic liver disease.

Prevalence of hepatitis virus infections in Kosovar refugees

Objectives: To assess the prevalence of viral hepatitis infections in a sample of Kosovar refugees having arrived in southern Italy as a result of the 1999 war in the Balkans. Methods: The 526 subjects who enrolled on voluntary basis from all age groups were tested for the prevalence of serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV, HDV, HEW Results: Among the 526 refugees, the prevalence of total anti-HAV antibodies was 81%. A relevant finding was the presence of total anti-HAV antibodies in 61% of the children up to 10 years of age. The prevalence of anti-HEV antibodies was 2.5% among the subjects. Fifteen subjects (2.9%) were positive for hepatitis B surface antigen (HBsAg), whereas 17.5% tested positive for anti-hepatitis B core antigen (anti-HBc). In children up to 10 years of age, the prevalence of HBsAg and anti-HBc was found to be 0.4% and 6%, respectively. In subjects aged 11 to 20 years, 4.2% tested positive for HBsAg and 20.2% for anti-HBc. In the age group 21 to 30 years, 7.1% of the subjects were found to be HBsAg carriers, whereas 25.9% were found to be positive for anti-HBc. Among the refugees over 30 years of age, the prevalence of HBsAg was 4.2%, whereas anti-HBc was 43.7%. None of the refugees tested positive for anti-HDV. The prevalence of anti-HCV antibodies was 0.7%. Conclusions: The results of this seroepidemiologic study indicate a high circulation of HAV in the Kosovar population, whereas the prevalence of HEV antibodies was low and comparable to that of other European countries. The HBV infection seems to be at an intermediate level of endemicity and an immunization policy against HBV infection, through vaccination of all newborns and children before adolescence, may be advisable. Results of this study indicate that the level of endemicity of HCV infection in the Kosovar population is low.

Acute Viral Hepatitis.

The mainstay of treatment for acute viral hepatitis is supportive care, as most cases are self-limited. General measures in all types of acute viral hepatitis include bedrest if the patient is very symptomatic, a high-calorie diet, avoidance of hepatotoxic medications, and abstinence from alcohol with the anticipation that most patients will recover uneventfully. In severe cases, hospitalization may be necessary for intravenous rehydration if the patient is unable to maintain adequate oral intake due to nausea and vomiting or if there is any alteration of mental status to suggest evolving fulminant hepatic failure. Acute hepatitis A is a self-limited disease, but can be fulminant. Lamivudine at a dosage of 100 mg/d orally may be beneficial in acute hepatitis B. Interferon-alpha therapy in acute hepatitis C may decrease the risk of developing chronic hepatitis C. Fulminant liver failure due to acute viral hepatitis is uncommon, but orthotopic liver transplantation occasionally may be life saving.

Hepatocellular carcinoma associated with chronic hepatitis B and C: pathogenesis, treatment and prevention

Primary liver cancer, of which hepatocellular carcinoma (HCC) is the dominant histological subtype, is the third most common cancer in males and the sixth most common cancer in females world-wide. The differing geographical prevalence of HCC in high and low incidence areas of the world reflects the varying prevalence of HBV and HCV infection. Chronic infection with the hepatitis virus (types B and C) is an important cause of HCC accounting for approximately 77% of cases. HCC is difficult to treat and has a poor prognosis with most tumours diagnosed at an advanced stage. The pathogenesis of both HBV- and HCV-related HCC is poorly understood, restricting the identification of targets for treatment. Primary or secondary prevention of HBV through vaccination should dramatically reduce the number of cases of HBV-associated liver disease and HCC. Unfortunately no vaccine exists for the prevention of HCV. Treatment of individuals already chronically infected with hepatitis B or C is important from the perspective of public health to limit spread, and to the individual to prevent progression to cirrhosis or carcinogenesis. However, because of the high cost of the currently available agents, the restrictive eligibility criteria usually used for their use and the extensive adverse effects associated with them, this will remain a challenge to the medical and allied professions. © 2000 Lippincott Williams & Wilkins

Liver-specific alpha 2 interferon gene expression results in protection from induced hepatitis.

The current therapy for hepatitis B and C is based on systemic administration of recombinant human alpha interferon (r-hIFN-alpha). However, systemic delivery of r-hIFN-alpha is associated with severe side effects, but more importantly, it is effective in only a small percentage of patients. In an effort to maximize IFN-alpha antiviral efficacy, we have explored the therapeutic potential of murine IFN-alpha2 (mIFNalpha2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-alpha2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-alpha2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-alpha2. Challenge of injected mice with mouse hepatitis virus type 3 showed that HD-IFN provides high liver protection. Moreover, liver protection was also observed in acute nonviral liver inflammation hepatitis induced by concanavalin A at 1 month postinfection. These results hold promise for the development of a gene therapy treatment for chronic viral hepatitis based on liver-restricted expression of IFN-alpha2.

Hepatitis C, E, F, G, and Non-A-G

Inflammation of the liver is known as hepatitis. Six or seven viruses, hepatitis viruses A through G, are responsible for most cases of viral hepatitis. In this second of a series of three articles, current knowledge regarding hepatitis C, E, F, G, and non-A-G is reviewed. Up to 80% of patients infected with hepatitis C progress to chronic liver disease. Hepatitis E is an enteric hepatitis that is endemic in Asia. Hepatitis F may be a mutant hepatitis C. Hepatitis G is a posttransfusion hepatitis. Non-A-G hepatitis consists of all of the hepatitis viruses awaiting identification. Up-to-date information regarding each of these types of hepatitis viruses is presented herein, because every phase of patient care improves when health care professionals are knowledgeable regarding the illnesses of their clients.

Risk factors for HTLV-I and II in individuals attending a clinic for sexually transmitted diseases.

To date, few studies have provided information on risk factors for human t-lymphotropic viruses (HTLV) types I and II in European countries. In particular, few data are available from published studies conducted in STD centers. To identify risk factors for HTLV-I and HTLV-II infection and to better distinguish the epidemiologic patterns of the two viruses in Italy. A cross-sectional study of individuals at high risk of sexually or parenterally transmitted infections attending a large STD center in an urban setting was conducted. Serologic tests for HTLV-I and II, HIV, hepatitis virus type B (HBV), hepatitis virus type C (HCV), and syphilis were performed. Information regarding at-risk behavior was collected using a specific questionnaire. From January 1994 to June 1996, 1,457 individuals were recruited; of them, 1,016 (69.7%) were males, 1,051 (72.4%) Italians, and 288 (19.8%) non-Europeans. One thousand seventy-five (74.8%) participants were noninjecting-drug-using heterosexuals, 285 (19.6%) were men who have sex with men, and 97 (6.6%) were injecting drug users (IDU). The mean age of the study participants was 33.6 (+/-10.5) years. Nine (0.6%) individuals were positive for HTLV-I antibodies and 9 (0.6%) for HTLV-II antibodies. The prevalence of HTLV-I among IDUs, men who have sex with men, and noninjecting-drug-using heterosexuals, was 2.1% (2/97), 1.4% (4/ 285), and 0.3% (3/1085), respectively. HTLV-II prevalence was 8.2% (8/97) among IDUs and 0.09% (1/1075) among noninjecting-drug-using heterosexuals. Among the nine HTLV-II-positive individuals, eight were Italian IDUs and one was a noninjecting-drug-using heterosexual man from India. None of the 285 men who have sex with men had HTLV-II antibodies. HTLV-infected individuals tended to be older than those who were uninfected. HTLV-I-infected individuals were more likely to be non-European and to have antibodies against Treponema pallidum. Injecting drug use tended to be independently associated with HTLV-II infection. The data suggest a role of sexual behavior in the spread of HTLV-I, which is more likely to be detected in individuals coming from endemic areas. Injecting drug use remains the most important risk factor for HTLV-II infection in Italy.

The role of TT virus infection in acute viral hepatitis.

Recently, transfusion-transmitted virus (TTV) was discovered to be a potential causative agent for non-A-E hepatitis. Little is known about the relation between TTV and the clinical courses of various types of acute viral hepatitis. One hundred twenty-five patients with acute viral hepatitis who were admitted to the Chiba University Hospital between 1984 and 1998 and 100 persons with normal liver function tests were tested for the presence of TTV in their sera. Serum samples were tested for TTV DNA and genotype by polymerase chain reaction (PCR). TTV DNA was detected in 15 of 35 patients (43%) with non-A-E hepatitis, 14 of 33 patients (42%) with hepatitis C, 8 of 28 patients (29%) with hepatitis A, 7 of 29 patients (24%) with hepatitis B, and 37 of 100 subjects with normal liver function tests (37%). The detection rate did not differ statistically between non-A-E hepatitis and hepatitis A, B, C, or controls. The distribution of TTV genotypes was similar in non-A-E, A, B, C types, and controls. The clinical characteristics of the acute illnesses were similar for patients with or without TTV in hepatitis non-A-E, A, B, or C. Although TTV was detected frequently in non-A-E acute hepatitis, no etiologic role for TTV could be established.

HEPATITIS VIRUSES A, B, C, D, E AND G: IMPLICATIONS FOR DENTAL PERSONNEL

This article provides dental personnel with a brief overview of the different types of viral hepatitis, including their epidemiology, clinical features, prevention and treatment. It also explores the ramifications of these diseases for the practice of dentistry. DESCRIPTION OF THE CONDITION: Viral hepatitis is an inflammation of the liver caused by one of at least six distinct viruses. The hepatitis A and E viruses, or HAV and HEV, are enterically transmitted viruses that produce acute disease only. The hepatitis B, C and D viruses, or HBV, HCV and HDV, are most efficiently transmitted by infected blood, but also can be transmitted by exposure to other infectious bodily fluids. These three viruses can cause acute or chronic hepatitis. People with chronic viral hepatitis can develop chronic liver disease, cirrhosis and hepatocellular carcinoma. The hepatitis G virus was recently identified, and its ability to cause clinically significant acute or chronic hepatitis is unknown. Dental health care workers, or DHCWs, should be concerned primarily with HBV, HCV and HDV, as occupational exposure to these pathogens places them at risk of developing acute or chronic infections. Vaccines and immune globulins are available and effective in protecting against infections with HAV, HBV and HDV, but not HCV. DHCWs should become knowledgeable about viral hepatitis. They should be vaccinated against hepatitis B. Adherence to infection control measures will help prevent occupational transmission of all bloodborne pathogens, including hepatitis viruses.

Prevalence and disease association of TT virus infection in Japanese patients with viral hepatitis

Prevalence and disease association of the TT virus (TTV) were studied in Japanese patients with various types of viral hepatitis. A total of 317 patients with viral hepatitis were analyzed, and the results were compared to those of 100 apparently healthy controls. TTV DNA in serum was measured by semi-nested polymerase chain reaction. Prevalence of TTV DNA was significantly higher in patients with hepatitis A (36%, 5/14), hepatitis B (35%, 35/101), hepatitis C (61%, 90/148), and non-A-E hepatitis (41%, 22/54) than in healthy controls (12%, 12/100), respectively. In each type of hepatitis, the prevalence did not differ between acute and chronic liver diseases, and did not increase with the complication of hepatocellular carcinoma. The clinical backgrounds did not differ between TTV DNA positive and negative patients, in patients with acute hepatitis or in those with chronic liver diseases. Similarly, no liver function test showed a significantly higher level of in TTV DNA positive patients than in negative ones. In conclusion, TTV infection was highly prevalent in patients with viral hepatitis, especially in those with hepatitis C. TTV was suggested to have a weak pathogenicity (or no pathogenicity), at least when co-infecting with an established hepatitis virus.