Community-acquired non-A, non-B hepatitis: clinical characteristics and chronicity

The characteristics of 86 patients with acute non-A, non-B hepatitis were compared to 23 patients with acute hepatitis A and 76 with acute hepatitis B by medical record reviews of patients seen at 5 hospitals in Baltimore, Maryland, as part of case-control study of viral hepatitis. Results of serum aminotransferase levels, bilirubin, albumin, and prothrombin times alone could not distinguish the type of viral hepatitis because of extensive overlap. The alanine aminotransferase range for non-A, non-B hepatitis was 56 to 1819 IU/liters, for hepatitis A 250 to 1995 IU/liters, and for hepatitis B 203 to 2120 IU/liters. The ranges of aspartate aminotransferase and bilirubin for the types of hepatitis also overlapped. Fewer patients with non-A, non-B hepatitis or hepatitis A had a prolonged prothrombin time compared to patients with hepatitis B. Hepatic encephalopathy was seen only in two patients with hepatitis B. Forty-two percent of non-A, non-B hepatitis patients followed for 6 months or longer continued to have elevated alanine aminotransferase levels. Chronic alanine aminotransferase elevation was independent of the source of infection: transfusion, parenteral drug use, or all other sources. Prolonged follow-up is necessary to evaluate chronicity in patients with non-A, non-B hepatitis.     

Prolonged excretion of an identical cytomegalovirus strain by two siblings and the intermittent isolation of an adenovirus from the urine of one of them

Restriction endonucleases were used to show the excretion of an identical strain of cytomegalovirus (CMV) by two brothers over a 2 1/2-yr period. The same enzymes were used to show that the younger brother, case report, excreted an adenovirus over at least a 3-mo period. We are unable to determine the contribution of each virus to this child's clinical picture; however, this is the first report of a prolonged excretion of an adenovirus associated with CMV excretion in an immunocompetent host.     

Serologic markers of viral hepatitis A,B, C,and D in patients with hemophilia

Forty-one patients with hemophilia A were studied for the prevalence of serological markers for hepatitis A, hepatitis B, hepatitis C (non-A and non-B hepatitis), and delta hepatitis (hepatitis D). Ten of 41 (24.4%) patients demonstrated hepatitis A antibody and 31 of 41 (75.6%) patients had a serologic marker for previous hepatitis B infection; four of these 31 patients (13%) also demonstrated antibody to delta agent (hepatitis D). Thirty-seven of 41 (90.2%) patients demonstrated antibody for hepatitis C. Nine of 31 (29%) patients with a hepatitis B marker (no hepatitis B vaccinees) were negative for anti-HBc but positive for anti-HBs; all of these nine patients were HIV antibody positive, although they had no overt immunodeficiency. Twenty-six of 41 (63.5%) patients were HIV antibody positive. Of HIV antibody positive patients, 27%, 88%, and 100% demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C, respectively. Of HIV antibody negative patients; 20%, 53%, and 73% of the patients demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C infections, respectively. The difference between HIV antibody positive and HIV antibody negative groups was not significant for hepatitis A but was significant for hepatitis B (P < 0.001) and hepatitis C (P < .001). Of the 31 patients with a hepatitis B serologic marker, all had antibody to hepatitis C. Of 10 patients, without a hepatitis B serologic marker, only 6 (60%) had antibody to hepatitis C. Clinically, none of our patients demonstrated any evidence of liver disease; however, 10 patients reported a previous history of hepatitis. These data suggest that patients with hemophilia in the United States, particularly those with HIV antibody, have high prevalence of hepatitis B and C infections.     

Clinical and virological characteristics associated with severe acute hepatitis B

To identify early predictors of a severe or fulminant course in patients with acute viral hepatitis B (AVH-B). One hundred and thirty-eight patients with symptomatic acute hepatitis B observed from 1999 to 2012 were enrolled. For each patient, the demographics, risk factors for the acquisition of hepatitis B virus (HBV) infection, clinical, biochemical and virological data (HBV DNA, HBV DNA sequences) were recorded and analysed. The HBV mutants in the polymerase region were sought in 110 (87%) patients by direct sequencing, and the rtM204V/I mutations also by an allele-specific PCR. AVH-B was severe in 13 (9.4%) of the 138 patients enrolled, fulminant in 6 (4.3%) and with a normal clinical course in 119. The 19 patients with severe or fulminant AVH-B more frequently than the 119 with a normal course stated intravenous drug use (63.2% versus 36.1%, p 0.04) and were HBV-DNA negative (31.6% versus 11.8%, p 0.03) and anti-hepatitis C virus (HCV) positive (57.9% versus 19.3%, p 0.0008); the prevalences of different HBV genotypes and of the rtM204V/I mutant were similar in these three forms of AVH-B. A multivariate logistic regression analysis identified a pre-existing HCV chronic infection as the only factor independently associated with a severe or fulminant clinical course of AVH-B (OR 4.89, 95% CI 1.5–15.94, p 0.01). A pre-existing HCV chronic infection was identified as the only factor independently associated with a severe clinical presentation of acute hepatitis B, an association most probably due to the combination of the liver lesions caused by acute hepatitis B and the pre-existing histological abnormalities related to HCV chronic infection.     

Prevalence of hepatitis C in South Africa: detection of anti-HCV in recent and stored serum

The prevalence of anti-HCV was studied in a cohort of 2,072 South Africans. The results were compared in selected recently collected sera and in stored sera. The serum ALT and anti-HBc were also studied as surrogate markers in this population. The following groups were tested: (a) 498 urban, black blood donors (b) 500 white blood donors (c) 500 Asian blood donors (d) 216 rural hospitalized patients (e) 358 rural mineworkers. Sera found positive by the original ELISA were retested, and reproducibly positive tests in rural black men (group d) were confirmed both by recombinant immunoblot assay and by a second ELISA. An anti-HCV prevalence of 1.2%, 0.8%, and 0.6% in urban blacks, Asians, and whites was found. Antibodies to hepatitis B core antigen were found in 42.9%, 3.4%, and 1.2% of black, Asian, and white donors, respectively; 76% of donors positive for anti-HCV were anti-HBc negative. In rural African men, 17% of stored serum samples and 9.2% of recently collected serum samples were positive for anti-HCV. In this cohort 3.84% were positive by all three assays. These results suggest that the prevalence of anti-HCV in low and high-risk South African urban blood donors is comparable to high and low prevalence areas in Europe, the United States, and Japan, but indicates a relatively high degree of exposure to hepatitis C in rural African men. The reactivity of stored, frozen sera in this population requires further investigation. In South African urban blood donors, surrogate marker testing will not expedite HCV screening.     

Severe exacerbation of liver disease during pregnancy in a thalassemic GBV-C/HGV–positive patient and neonatal hepatitis in offspring

The case of a young woman with GB virus C/hepatitis G virus (GBV-C/HGV) infection and with a severe exacerbation of chronic hepatitis of unknown etiology during pregnancy is described. In the offspring, severe neonatal hepatitis with subsequent mild chronic liver disease of at least 16-month duration was followed by the development of antibodies to the envelope protein (E2) of GBV-C/HGV, suggesting that the child was recovering from GBV-C/HGV infection. There was an improvement in clinical and biochemical parameters in the mother following delivery and alpha-interferon therapy was associated with a transient biochemical response. J. Med. Virol. 57:122–125, 1999. © 1999 Wiley-Liss, Inc.     

Persistent delta antigenaemia in chronic delta hepatitis and its relation with human immunodeficiency virus infection.

The prevalence of persistent hepatitis delta (HD) antigenaemia and associated factors in patients with chronic infection with the hepatitis delta virus (HDV) were investigated. Among 157 consecutive patients known to be carriers of hepatitis B surface antigen (HBsAg), 36 (23%) had one serum marker of HDV infection (anti-HD and/or HDAg). Nine of the patients with an HDV marker were HDAg positive, including three who were anti-HD negative. A follow-up over a mean period of 13 months showed that five of five patients had a persistent HD antigenaemia. This serological profile was associated with the presence of antibody to the human immunodeficiency virus (anti-HIV) (P < 0.01), serum HIV antigen (HIVAg) (P < 0.2), and the female sex (P < 0.05). Persistent HD antigenaemia could be the consequence of the suppression of T cell cytotoxic activity against hepatocytes expressing HDAg, a lower humoral response, and/or hormonal factors.     

丁型肝炎病人肝组织HDVRNA与 HBVDNA的表达及关系

目的 探讨丁型肝炎病人肝组织中ＨＤＡｇ、ＨＤＶＲＮＡ与ＨＢＶＤＮＡＧ表达及关系。方法 应用免疫组化和原位杂交技术检测了７９全丁型肝炎病人肝组织ＨＤＡｇ、ＨＤＶＲＡＮ～ＨＢＶＤＮＡ表达,以５２例型肝炎病人肝组织作对照。结果 丁型肝炎ＨＢＶＤＮＡ检出率（２７％）低于乙型肝炎（４４％）（Ｐ〈０．０５）。在坏死灶边缘肝细胞和气球样变肝细胞浆内有大量的ＨＤＶＲＮＡ蓄积或ＨＤＡｇ呈强型强表达,ＨＤＶＲＮＡ表达     

Prevalence of hepatitis B,C, and D virus markers in yemeni patients with chronic liver disease

A serological survey for hepatitis B, C, and D markers was carried out in the Yemen Republic. Serum samples from 243 pregnant females, 294 male blood donors, and 108 patients with chronic liver disease were examined. Hepatitis B surface antigen (HBsAg) was found in 18.5% healthy individuals and 24.1% patients with chronic liver disease (P = 0.03). Evidence of any marker for hepatitis B virus (HBV) infection was found in 59.8% healthy individuals and 75.9% of patients with chronic liver disease (P = 0.0016). HBeAg was detected in 32.1% of the HBsAg-positive pregnant females, indicating that vertical transmission probably plays a part in forming the pool of HBV carriers. Vaccination against HBV as part of the extended programme of immunisation (EPI) is recommended. Antibodies to hepatitis D were found in only 2 of 100 HBsAgpositive sera. Antibodies to hepatitis C (anti- HCV) were found in 2.1% healthy individuals and 21.5% patients with chronic liver disease (P = 0.0001). These results indicate that hepatitis B is hyperendemic in the Yemen Republic but that hepatitis D is very uncommon. The prevalence of anti-HCV is higher than in Europe and similar to neighbouring Arab countries. Infection with both HBV and HCV are important causes of chronic liver disease in the Yemen Republic.© 1993 Wiley-Liss, Inc.     

Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriers

Hepatitis B virus (HBV) is classified into eight genotypes (A-H), and genotype C is associated with more aggressive liver disease compared to genotype B. However, the mechanisms responsible for the clinical differences remain unclear. To test whether genotype C patients had with lower rates of spontaneous hepatitis B ge antigen (HBeAg) seroconversion than genotype B patients, stored serum samples from 146 Taiwanese adult HBeAg-positive hepatitis B carriers followed-up for a mean of 52 months (range, 12-120 months) were tested for HBV genotype by a molecular method. Genotype C patients were significantly older than genotype B patients (mean age, 37 +/- 12 vs. 29 +/- 10 years, P < 0.001). During the follow-up period, genotype C patients had a significantly lower rate of spontaneous HBeAg seroconversion than genotype B patients (27 vs. 47%, P < 0.025). Spontaneous HBeAg seroconversion occurred one decade later in genotype C patients compared with genotype B patients. Multivariate analyses identified age < or =35 years (odds ratio: 2.08; 95% confidence interval [CI], 1.07-4.0; P < 0.05), high baseline serum alanine aminotransferase level (odds ratio: 2.34; 95%CI, 1.39-4.09; P < 0.005), and HBV genotype B (odds ratio: 1.94; 95%CI, 1.03-3.63; P < 0.05) as independent factors associated with spontaneous HBeAg seroconversion. In conclusion, genotype C patients, compared to genotype B patients, have a delayed HBeAg seroconversion in the immune clearance phase of chronic HBV infection, which may contribute to a more progressive liver disease and more refractory to antiviral therapy.     

Control of HBV and HDV infection in an isolated Pacific Island: 1. Pattern of infection

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections are known to be hyperendemic in Nauru. Because of the consequences of chronic HBV infection, the Nauruan Government has commenced a program that aims to reduce and eventually eliminate hepatitis B infection by immunizing susceptible adults and children on the island and every newborn baby. At the outset of this program, a national seroepidemiological survey was undertaken. Eighty-eight percent of the population were tested, of whom 69.1% had markers of HBV infection. Evidence of superinfection with HDV was found in 22.7% of HBV carriers, with the highest prevalence in adolescents and young adults. All seronegative individuals were offered three doses of plasma derived hepatitis B vaccine. A post-vaccination survey of 64% of those vaccinated showed that 98% had developed circulating antibodies.     

Seroprevalence and risk factors for hepatitis A, B, and C among Roma and non-Roma children in a deprived area of Athens, Greece

The prevalence and risk factors of hepatitis A, B, and C (HAV, HBV, and HCV) markers were compared in non-Roma and Roma children who lived in a deprived suburb of Athens, Greece. The study included 216 children, 118 Roma and 98 non-Roma of 9 years median age (range 5-15 years). Among Roma children 98.3% had detectable antibodies to HAV, compared with 32.7% among non-Romas (P < 0.0001). Regarding HBV, 22% Roma children were identified with evidence of past infection (anti-HBc(+)), among whom five (4% of the total) were chronic carriers (HBsAg(+)), whereas no past infection was detected among the non-Romas (P < 0.0001). Markers of past HBV vaccination (anti-HBs(+), anti-HBc(-)) were detected in only 14% Roma but 96% non-Roma children (P-value < 0.0001). There was some indication for intrafamilial transmission of HAV and HBV in Roma school children. Unfavorable living conditions, frequent residency change, lack of child insurance and primary healthcare delivery were significantly associated with seroprevalence of HBV infection among Romas. No child in either group was found positive for HCV markers. These findings document high socioeconomic differentials with regards to preventable communicable diseases, such as HAV and HBV and underline the need for enhancing health policy action targeting pockets of minority childhood populations. Whereas, uptake of HBV vaccination is rather optimal in this general population, the high seroprevalence of HAV among Romas, also calls for implementing general vaccination for HAV, early in life.     

Peroxidase-anti-peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis

Liver biopsy specimens from 58 American patients with chronic type B hepatitis were investigated for the presence and distribution of the hepatitis B core (HBcAg) and surface (HBsAg) antigens by peroxidase-anti-peroxidase techniques. HBsAg was detected in 43 (77%) and HBcAg in 52 (90%) patients. HBcAg was present in 50 of 51 (98%) patients with hepatitis B e antigen (HBeAg) but in only two of seven (29%) of patients with antibody to HBeAg (anti-HBe). There was no correlation between severity of hepatitis or height of aminotransferase activities and the amount of HBsAg or HBcAg in hepatocytes but there was a positive correlation between amount of HBcAg and height of HBV-DNA and DNA polymerase activity in serum. Follow-up liver biopsies, taken 1 to 3 yr later, were available from 39 patients. HBcAg remained detectable in 25 of 26 patients with persistence of HBeAg but disappeared in 12 patients who had lost HBeAg. In nine patients, HBcAg was cytoplasmic as well as nuclear in distribution. Seven of these patients had an intense lobular hepatitis with marked elevations in aminotransferase activities. These findings indicate that the amount of HBcAg in liver correlates with the amount of serum hepatitis B virus as quantified by serum levels of DNA polymerase and HBV-DNA. The amount of nuclear HBcAg does not correlate with the severity of the liver disease, but the presence of cytoplasmic HBcAg usually reflects an active and severe ongoing hepatitis.     

Change of hepatitis B virus genotypes in acute and chronic infections in Japan

During 35 years from 1971 to 2005, 153 patients with acute and 4,277 with chronic HBV infection visited the Toranomon Hospital in Tokyo, Japan. They were grouped into seven 5-year periods, and HBV genotypes/subgenotypes were determined. Patients with acute HBV infection were younger (P = 0.046), predominantly male (P = 0.004), possessed higher alanine aminotransferase levels (P < 0.001), positive more frequently for HBeAg (P < 0.001), and had lower HBV DNA loads (P = 0.014) than those with chronic infection. Sexual transmission was more frequent in patients with acute than chronic HBV infection (67% vs. 3%, P < 0.001). The number of patients with acute infection increased throughout 1971-2005. Patients with chronic infection increased since 1971, peaked in 1986-1990 and then decreased. The number of patients increased since 1990-2000 again, however, reflecting recent boost of acute HBV infection. The distribution of HBV genotypes was considerably different between patients with acute and chronic infections (A, B, and C: 28.6%, 10.3%, and 59.5% vs. 3.0%, 12.3%, and 84.5%, respectively, P < 0.001). Since 1991, genotype A foreign to Japan started to increase sharply in patients with acute infection, and gradually in those with chronic infection. There was a trend for the foreign subgenotype B2/Ba to increase recently (P < 0.05). Despite immunoprophylaxis of high-risk babies born to carrier mothers with hepatitis B e antigen, implemented nationally since 1986, acute and chronic infections with HBV have been increasing in Japan. Based on genotypes/subgenotypes changing with time, the resurgence of hepatitis B could be attributed to infections, with foreign HBV genotypes/subgenotypes, spreading swiftly by sexual contact.     

Hepatitis B and C virus-related carcinogenesis

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most important causes of hepatocellular carcinoma (HCC), accounting for the majority of the cases worldwide. The geographical distribution of HCC therefore coincides with the distribution of HBV and HCV infections in those areas. Similar to nonviral liver diseases, HBV and HCV infection can cause chronic injury to the liver, with subsequent progression to severe fibrosis and cirrhosis. The presence of cirrhosis is a major risk factor for the development of HCC. However, HCC can occur in the absence of cirrhosis, suggesting that both HBV and HCV may be directly involved in hepatocarcinogenesis. Several HBV factors have been implicated in hepatocarcinogenesis, including the HBx gene, the pre-S2/S gene and the HBV spliced protein. Furthermore, HBV can be integrated into the host genome, leading to changes in genomic function or chromosomal instability. By contrast to HBV, HCV cannot integrate into the host genome. Various HCV proteins, including the core, envelope and nonstructural proteins, have been shown to have oncogenic properties. For HBV infection, antiviral therapy and vaccination have been shown to decrease the risk of HCC. Antiviral therapy for HCV can also reduce the risk of HCC.     

Comparison of safety and immunogenicity of adw and ayw hepatitis b vaccines

The safety and immunogenicity of adw and ayw hepatitis B vaccines were compared in a double-blind randomized trial in Greek Air Force recruits. One hundred and ten out of 240 eligible nonimmune recruits were randomly selected and allocated to thc two vaccine treatment groups. Two 20-m?g doses 1 month apart and a third 20-m?g booster dose, at 6 months, were given intramuscularly. Severe local or general side effects were not observed. The frequency of mild side effects (local discomfort or pain, fever less than 37.5°C, and malaise) was slightly higher with the adw than with the ayw vaccine. Antibodies developed earlier and in higher titers in adw vaccinees. However, after the booster dose all ayw and all but one adw vaccinees developed anti-HBs in almost similar titers. It is concluded that both vaccines are equally safe and immunogenic after administration of two doses at a 1-month interval followed by a booster dose at 6 months.