Symptomatic Acute Hepatitis Research Articles

Molecular epidemiology of hepatitis B virus genotypes circulating in acute hepatitis B patients in the Campania region.

Fifty-three HBV-DNA-positive patients with symptomatic acute hepatitis B were enrolled from 1999 to 2010 to evaluate molecular and phylogenetic changes in HBV in southern Italy. HBV polymerase region was evaluated by direct sequencing in plasma samples obtained at first observation. Different data sets were aligned and a phylogenetic tree was inferred using PhyML program. Statistical robustness was confirmed with a bootstrap analysis. A Bayesian Markov chain Monte Carlo method and a Bayesian skyline plot were used to estimate the evolution of our samples. The dN/dS rate (ω) was estimated by the maximum likelihood approach to investigate the presence of codons under positive selection. The MacClade program was used to test viral gene out/in flow only among HBV-D3 subgenotype patients with different risk factors. Of the 53 patients, 83% were born in Italy and 17% were foreigners. HBV genotype D was prevalent (64.1%), followed by genotype A (26.4%), E (3.8%), and F (5.7%). The prevalent subgenotype was D3 (70.6%). The Bayesian tree of the 24 D3 subgenotypes showed two main clades both dated 1994; 40% of viral gene flow observed was from intravenous drugs users and heterosexual patients. Phylogenetic analysis of HBV isolates showed that HBV-D3 remains the prevalent genotype, but also subgenotype A2 has become frequent in southern Italy. This may be of clinical relevance in years to come, since patients with HBV-genotype-A chronic infection less frequently than those with genotype D develop HBeAg-negative chronic hepatitis and respond more frequently to alfa-interferon treatment.

Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection

HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment. We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance. Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner. This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance.

Prevalence of hepatitis B virus seromarkers in young adults vaccinated at birth; impact on the epidemiology of hepatitis B infection in iran.

Background:The epidemiological impact and the duration of protection provided by infant hepatitis B (HB) vaccination are unknown.Objectives:This study was designed to determine the hepatitis B virus (HBV) infection seromarkers in young adults who have been vaccinated against HBV as the first group of Iranian neonates during 1993 and 1994.Patients and Methods:We recruited 510 young adults with a history of complete HB vaccination at birth. HBV seromarkers (HB surface antigen (HBs Ag), antibody against HBs Ag (Anti-HBs), and antibody against HB core antigen (Anti-HBc) were measured using ELISA method. Anti-HBs titers ≥ 10 IU/L were considered protective and titers more than 300 IU/L were indicative of a natural boosting. Positive results for Anti-HBc and HBs Ag were considered as breakthrough infection and possible vaccine failure, respectively. The history of acute symptomatic clinical hepatitis was also investigated.Results:Anti-HBs seropositivity rate was detected in 224 of 510 [95% CI: 39-47] young adults. Breakthrough infection (positive sera for Anti-HBc without chronic infection) was observed in 18 [95% CI: 2.5-3.5] subjects. There were neither HBs Ag positive results nor symptomatic hepatitis cases.Conclusions:The study results indicated that the neonatal HBV immunization induced a long-term protection against HBV and was very efficacious in reducing chronic HBV infection rate in vaccinated young adults in Iran.

Gene therapeutic approaches to inhibit hepatitis B virus replication.

Acute and chronic hepatitis B virus (HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellular carcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV.

Screening Utility, Local Perceptions, and Care-seeking for Reported Jaundeesh among Respondents Lacking Signs of Icterus in Rural Bangladesh

In rural Bangladesh, acute viral hepatitis presents a significant burden on the public-health system. As part of the formative work for a large epidemiologic study of hepatitis E in rural Bangladesh, we sought to identify local terms that could be used for population-based screening of acute viral hepatitis. Exploration of the local term jaundeesh for screening utility identified a high burden of reported jaundeesh among individuals without symptoms of icterus. Recognizing that local perceptions of illness may differ from biomedical definitions of disease, we also sought to characterize the perceived aetiology, care-seeking patterns, diagnostic symptoms, and treatments for reported jaundeesh in the absence of icteric symptoms to inform future population-based studies on reported morbidities. We conducted a cross-sectional survey among 1,441 randomly-selected subjects to identify the prevalence of reported jaundeesh and to test the validity of this local term to detect signs of icterus. To characterize the perceived aetiology and care-seeking patterns for jaundeesh among the majority of respondents, we conducted in-depth interviews with 100 respondents who self-reported jaundeesh but lacked clinical signs of icterus. To describe diagnostic symptoms and treatments, in-depth interviews were also performed with 25 kabirajs or traditional faith healers commonly visited for jaundeesh. Of the 1,441 randomly-selected participants, one-fourth (n=361) reported jaundeesh, with only a third (n=122) reporting yellow eyes or skin, representative of icterus; Jaundeesh had a positive predictive value of 34% for detection of yellow eyes or skin. Anicteric patients with reported jaundeesh perceived their illnesses to result from humoral imbalances, most commonly treated by amulets, ritual handwashing, and bathing with herbal medicines. Jaundeesh patients primarily sought folk and spiritual remedies from informal care providers, with only 19% visiting allopathic care providers. Although the local term jaundeesh appeared to have limited epidemiologic utility to screen for acute symptomatic viral hepatitis, this term described a syndrome perceived to occur frequently in this population. Future population-based studies conducting surveillance for acute hepatitis should use caution in the use and interpretation of self-reported jaundeesh. Further study of jaundeesh may provide insight into the appropriate public-health response to this syndrome.

Hepatitis E

Hepatitis E has been regarded as a disease of the developing world, where it causes large waterborne outbreaks and sporadic cases of hepatitis. Recent research has shown this received wisdom to be mistaken. Recent studies have shown that authochtonous (locally acquired) hepatitis E does occur in developed countries, is caused by hepatitis E virus (HEV) genotypes 3 and 4, and is zoonotic with pigs as the primary host. Most infections are clinically inapparent. However, acute symptomatic hepatitis E has a predilection for middle-aged and elderly men, with an excess mortality in patients with underlying chronic liver disease. Chronic infection occurs in the immunosuppressed with rapidly progressive cirrhosis if untreated, the treatment of choice being ribavirin monotherapy for 3 months. Hepatitis E has a range of extra-hepatic manifestations, including a spectrum of neurological syndromes. HEV can be transmitted by blood transfusion and has recently been found in donated blood in a number of countries. The diagnosis should be considered in any patient with a raised alanine aminotranferase, irrespective of age or travel history. The safety of blood products needs to be fully assessed, as a matter of priority, as blood donors are not currently screened for HEV.

Acute Hepatitis B in an Urban Tertiary Care Hospital in the United States

The incidence of acute hepatitis B virus (HBV) infection in the United States is declining, and precise epidemiology for newly acquired infection remains obscure. We sought to clarify the clinical presentation and management of acute symptomatic HBV infection at a hepatology referral center. We prospectively evaluated the demographic, epidemiological, clinical, and treatment data of 32 patients with acute symptomatic HBV who were referred to a single urban tertiary care hospital in the United States. Slightly more than half of the patients were male (53%) or belonged to the black race (53%) and slightly fewer than half of the patients (47%) were unemployed. The median patient age was 41.9 years, and 20 (63%) patients were unmarried. The most common HBV risk factor was a new sexual partner over the previous months (34%). Fifteen percent of the patients reported no known risk factors. Four (13%) patients were diabetic. Presenting symptoms included jaundice (75%), abdominal pain (63%), and marked fatigue (59%). The mean peak for aspartate aminotransferase/alanine aminotransferase was 1822/2109 IU/L, for total bilirubin was 12.6 mg/dL, and for International Normalized Ratio was 1.53. Eight patients (25%) were started on oral nucleot(s)ide therapy. One diabetic patient underwent liver transplantation. In a sample of patients from a US urban tertiary hepatology center, common epidemiological features of acute symptomatic hepatitis B were being middle aged and unmarried and having acquired the infection through a new sexual contact. Antiviral therapy was sometimes but not commonly started. These data reinforce the need for HBV vaccination of individuals at risk, including those not traditionally targeted.

Lamivudine-resistant HBV strain rtM204V/I in acute hepatitis B

To detect HBV rtM204V/I lamivudine-resistant strains in serum of patients with acute hepatitis B and to assess their biological and clinical significance. Eighty HBV DNA-positive patients with symptomatic acute hepatitis B observed from 1999 to 2010 were enrolled. A plasma sample obtained at the first observation was tested for HBV mutants in the polymerase region by direct sequencing; the antiviral drug-resistant rtM204V/I mutations, the most frequent HBV mutants in Italy, were also sought by the more sensitive allele-specific polymerase chain reaction (PCR). No HBV mutation associated with resistance to nucleos(t)ide analogues was identified by direct sequencing, whereas allele-specific PCR identified HBV strains carrying the substitution rtM204V/I in 11 (13.7%) patients. Compared with those with the HBV wild strain, patients with rtM204V/I more frequently showed severe acute hepatitis B (36.4% vs 8.7%; p < 0.05) and lower values of serum HBV DNA (1.77 × 10(6) ± 4.76 × 10(6) vs. 1.68 × 10(8) ± 5.46 × 10(8)). In addition, a multivariate analysis identified the presence of a pre-existing HCV chronic infection as independently associated with severe acute hepatitis B (p < 0.05). HBV rtM204V/I lamivudine-resistant strains were detected in serum of 11 (13.7%) patients with acute hepatitis B by allele-specific polymerase chain reaction. The frequent association of rtM204V/I with a more severe acute hepatitis B and with a lower viral load may suggest that greater and/or more prolonged immune pressure might have induced their selection.

Window period of anti-hepatitis A virus immunoglobulin M antibodies in diagnosing acute hepatitis A

The diagnosis of acute hepatitis A virus (HAV) infection is made on the basis of the presence of anti-HAV immunoglobulin M (IgM) antibodies in patients with clinical features of acute hepatitis. Some patients show a negative serology at initial presentation, which may complicate the diagnosis of hepatitis A (HA). The aim of this study was to examine the characteristics of HA patients with an initially negative anti-HAV IgM test result. Patients with symptomatic acute hepatitis who underwent IgM anti-HAV testing at a single center were enrolled consecutively, with tests repeated in patients with negative initial serology. A total of 684 patients with acute hepatitis were tested, of whom 620 patients were initially or eventually diagnosed with HA. Anti-HAV IgM was initially negative in 67 of the 620 HA patients (10.9%), but was later confirmed by subsequent retests. These patients had on average a shorter time lapse from the onset of symptoms to the initial test, a higher rate of fever, and lower alanine aminotransferase and bilirubin levels compared with those with a positive initial serology. Cutoff index (COI) values of anti-HAV IgM were correlated positively with the duration of time from the onset of symptoms to the initial test. Fever, lower bilirubin levels, and higher COI values were predictive of seroconversion to anti-HAV positivity in patients with a negative initial serology. Taking into account the window period of HAV infection, anti-HAV IgM tests should be repeated, particularly in patients with features of the initial phase of hepatitis and a high COI value of anti-HAV IgM.

338 NK CELL SECRETED IFN-g BLOCKS HCV REPLICATION AND MAY PROMOTE SPONTANEOUS CLEARANCE OF ACUTE HEPATITIS C IN HIV(+) PATIENTS

are associated with antiviral effector T-cell dysfunction, which influences on T-cell exhaustion and persistent viral infection. These PD-1 and CTLA-4 are up-regulated in chronic viral infection such as chronic hepatitis C, chronic hepatitis B and human immunodeficiency virus infection but there is no report about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A. We investigated the expression of PD-1 and CTLA-4 during symptomatic and convalescent phases of acute hepatitis A. Methods: Seven patients with symptomatic acute hepatitis A, 5 patients with non-viral acute toxic hepatitis were enrolled for detection of PD-1 and CTLA-4 on T-cell subset of peripheral blood mononuclear cells (PBMC) isolated from these subjects during symptomatic and convalescent phases by flow cytometry. Five as healthy control were also examined for comparison with these patients. Results: Symptomatic acute hepatitis A showed significant increase of PD-1 and CTLA-4 expression compared to non-viral acute toxic hepatitis or healthy control (PD-1; 18.3±15.7% vs. 3.7±3.0% vs. 1.6±1.8%, p < 0.05, CTLA-4; 23.5±12.0% vs. 6.1±1.2% vs. 5.9±1.2%, p < 0.05) (median ± SD). In addition, highly expressed PD-1 and CTLA-4 were dramatically decreased in convalescent phase of acute hepatitis A. Conclusions: In acute hepatitis A, PD-1 and CTLA-4 are upregulated during symptomatic phase then down-regulated after recovery. This changing pattern of PD-1 and CTLA-4 expression was not seen in non-viral acute toxic hepatitis. Our findings suggest that PD-1 and CTLA-4 have protective effect as inhibitory molecules to suppress cytotoxic T-cells which induce destruction of viral infected hepatocytes.

Phenotypic characteristics of natural killer cells in acute hepatitis

Natural killer (NK) cells are the principal effector cell population in innate immune defense against many types of infections. These cells are enriched in the liver, where they comprise approximately 40% to 60% of the intrahepatic lymphocyte pool compared to the peripheral blood compartment. In chronic HBV and HCV infection, NK cells were reported to be partially dysfunctional due to impaired IFN-Γ secretion. Few studies have examined phenotypic features of NK cells in acute hepatitis. We identified NK (CD56+CD3-) cell populations in patients with acute hepatitis by examining the expressions of phenotypic NK cell markers (CD16, NKG2A, and NKG2D). Peripheral blood mononuclear cells were isolated from patients with acute hepatitis A (7) and patients with non-viral acute toxic hepatitis (6) during the symptomatic and convalescent phases. Expressions of NK (CD56+CD3-) cell markers, CD16, NKG2A, and NKG2D, were measured by flow cytometry. Symptomatic acute hepatitis including non-viral hepatitis and HAV infection showed significant increases of NKG2A expression compared to healthy controls. Interestingly, there was a direct correlation between the proportion of NK cell populations and liver function parameters (AST, ALT) in HAV infection. The strong correlation was also observed between the expression of NKG2A+NK cells and ALT, which suggests that most of NK cells in severe phase of disease express high level of NKG2A on their surface. In addition, decreased number of NK cells (CD56+CD3-) in symptomatic phase began to increase in the convalescent phase of acute hepatitis A. However, the expression of NKG2A tended to be reduced, which indicates that NKG2A, the inhibitory receptor on NK cells, can be a severity parameter in acute hepatitis.

Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment. In our open-label phase 3 non-inferiority trial, we enrolled adults (≥18 years) with acute hepatitis C but no HIV or hepatitis B co-infection at 72 centres in Germany. We randomly allocated patients with symptomatic acute hepatitis C (1:1) to receive immediate pegylated interferon alfa-2b treatment for 24 weeks or delayed treatment with pegylated interferon alfa-2b plus ribavirin (for 24 weeks) starting 12 weeks after randomisation if HCV RNA remained positive. We used a computer-generated randomisation sequence and block sizes of eight, stratified by bilirubin concentration. We assigned all asymptomatic patients to immediate treatment with pegylated interferon alfa-2b for 24 weeks. The primary endpoint was sustained HCV RNA negativity in all randomly allocated participants who completed screening (intention-to-treat analysis), with a non-inferiority margin of 10%. For the primary analysis, we calculated the virological response of patients in the immediate and delayed treatment groups and an absolute risk difference stratified by bilirubin status. The trial was stopped early on advice from the study advisory committee because of slow recruitment of participants. This study is registered, number ISRCTN88729946. Between April, 2004, and February, 2010, we recruited 107 symptomatic and 25 asymptomatic patients. 37 (67%) of 55 symptomatic patients randomly allocated to receive immediate treatment and 28 (54%) of 52 symptomatic patients randomly allocated to receive delayed treatment had a sustained virological response (difference 13·7%, 95% CI -4·6 to 32·0; p=0·071). 18 (72%) of 25 asymptomatic patients had a sustained virological response. 22 (42%) of 52 symptomatic patients allocated to receive delayed treatment did not complete follow-up compared with 20 (25%) of 80 symptomatic or asymptomatic patients assigned immediate treatment (p=0·037). 11 symptomatic patients (21%) assigned delayed treatment had spontaneous HCV clearance. 14 patients who received delayed pegylated interferon alfa-2b plus ribavirin treatment and completed follow-up achieved sustained virological response. Delayed treatment is effective although not of equal efficacy to immediate treatment; coupled with the rate of spontaneous clearance it can reduce unnecessary treatment in closely monitored populations. Immediate treatment seems preferable in populations where loss to follow-up is great. German Network of Competence on Viral Hepatitis (HepNet, funded by the German Federal Ministry of Education and Research, grants 01KI0102, 01KI0401, and 01KI0601), MSD, Schering-Plough.

IL-28B Genotype is not associated with early HCV-RNA negativity in patients with symptomatic acute HCV infection

Patients with acute hepatitis C are able to cure the infection spontaneously in 10–50% of cases. Factors being associated with spontaneously clearance are female sex, viral load, early HCV RNA declines kinetics and symptoms of hepatitis at presentation. The IL-28B genotype has also been associated with clearance of HCV infection but controversial data have been published in patients with symptomatic versus asymptomatic acute hepatitis C.

Immunosuppression-mediated hepatitis B reactivation diagnosed following an investigation into suspected transfusion-transmitted hepatitis B

In August 2006, the regional unit for nosocomial infection control (ARLIN) was notified of a case of symptomatic acute hepatitis B (HBV) infection in an immunosuppressed 87-year-old patient who had received a blood transfusion five months previously. Immunosuppression for the treatment of a variety of conditions is increasing. Immunosuppressed patients should be investigated for previous HBV infection and given pre-emptive therapy where indicated. We report our experience investigating a case of HBV reactivation in an immunosuppressed patient. We describe the investigation and highlight the continued need for vigilance for HBV reactivation in immunosuppressed patients who may present to a range of clinicians.

Case-control study of hepatitis B and hepatitis C in older adults: Do healthcare exposures contribute to burden of new infections?

Reports of hepatitis B virus (HBV) and hepatitis C virus (HCV) transmission associated with unsafe medical practices have been increasing in the United States. However, the contribution of healthcare exposures to the burden of new infections is poorly understood outside of recognized outbreaks. We conducted a case-control study at three health departments that perform enhanced viral hepatitis surveillance in New York and Oregon. Reported cases of symptomatic acute hepatitis B and hepatitis C occurring in persons≥55 years of age from 2006 to 2008 were enrolled. Controls were identified using telephone directories and matched to individual cases by age group (55-59, 60-69, and ≥70 years) and residential postal code. Data collection covered exposures within 6 months before symptom onset (cases) or date of interview (controls). Forty-eight (37 hepatitis B and 11 hepatitis C) case and 159 control patients were enrolled. Case patients were more likely than controls to report one or more behavioral risk exposures, including sexual or household contact with an HBV or HCV patient, >1 sex partner, illicit drug use, or incarceration (21% of cases versus 4% of controls exposed; matched odds ratio [mOR]=7.1; 95% confidence interval [CI]: 2.1, 24.1). Case patients were more likely than controls to report hemodialysis (8% of cases; mOR=13.0; 95% CI: 1.5, 115), injections in a healthcare setting (58%; mOR=2.7; 95% CI: 1.3, 5.3), and surgery (33%; mOR=2.3; 95% CI: 1.1, 4.7). In a multivariate model, behavioral risks (adjusted OR [aOR]=5.4; 95% CI: 1.5, 19.0; 17% attributable risk), injections (aOR=2.7; 95% CI: 1.3, 5.8; 37% attributable risk), and hemodialysis (aOR=11.5; 95% CI: 1.2, 107; 8% attributable risk) were associated with case status. Healthcare exposures may represent an important source of new HBV and HCV infections among older adults.

Risk factors for and incidence of acute hepatitis C after the achievement of blood supply safety in Italy: Results from the national surveillance system

Surveillance systems for acute hepatitis C allow monitoring of disease incidence trends and transmission patterns. This study aimed to describe the epidemiological profile of reported cases of symptomatic acute hepatitis C in Italy after the achievement of blood supply safety. The incidence of symptomatic acute hepatitis C since 1991 was estimated. Risk factors for acute hepatitis C were analyzed for the period 2003-2010 through a case-control study within a population-based surveillance for acute viral hepatitis. From 1991 to 2010, the incidence decreased from 2 to 0.2 per 100,000, with a more evident decrease among persons aged 15-24 years. During 2003-2010, 1,053 cases were reported. Intravenous drug use (adjusted odds ratio [(adj) OR], 30.5; 95% confidence interval [CI], 18.9-49.1), cohabitation or sexual partnership with an hepatitis C virus (HCV) carrier ((adj) OR, 11.2; 95% CI, 6.6-19.2), nosocomial exposure ((adj) OR, 6.6; 95% CI, 4.6-9.4); unsafe sexual practices ((adj) OR, 3.1; 95% CI, 1.9-5.2), and cosmetic treatments with percutaneous exposure ((adj) OR, 1.7; 95% CI, 1.2-2.4) were independently associated with acute hepatitis C. Population attributable risk estimates indicated nosocomial exposure (39.6%) and intravenous drug use (30.5%) as responsible for most cases. In conclusion, the incidence of symptomatic acute hepatitis C is declining in Italy. Currently, the most important risk factors are: having an HCV-positive household or sexual partner, unsafe sexual practices, cosmetic percutaneous treatments, intravenous drug use, and nosocomial exposure; the latter two factors are responsible for most cases. Effective prevention programs for intravenous drug users and strict adherence to universal precautions in healthcare settings are needed.

Acute Hepatitis C in an HIV-Infected patient: A Case Report and Review of Literature

With the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)-infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease.

Epidemiological and virological characteristics of symptomatic acute hepatitis E in Greater Cairo, Egypt

The aim of the study was to describe the characteristics of acute hepatitis E in Greater Cairo. Patients with acute hepatitis E were identified through a surveillance of acute hepatitis using the following definition: recent (<3 weeks) onset of fever or jaundice, alanine aminotransferase at least three times the upper limit of normal (uln), negative markers for other causes of viral hepatitis and detectable hepatitis E virus (HEV) RNA. Comparison of the liver tests between acute hepatitis E and hepatitis A virus (HAV), case–control analysis (four sex-matched and age-matched (±1 year) HAV controls per case) to explore risk factors and phylogenetic analyses were performed. Of the 17 acute HEV patients identified between 2002 and 2007, 14 were male. Median age was 16 years (interquartile range 13-22). Compared with HAV (n = 68 sex-matched and ±1 year age-matched), HEV patients had higher bilirubin (mean (SD) 10.9 (5.7) uln versus 7.5 (4.4) uln, p 0.05) and aspartate aminotransferase levels (38.6 (27.1) uln versus 18.3 (18.1) uln, p 0.02). Co-infection (hepatitis C virus RNA or hepatitis B surface (HBs) -antigen positive/IgM anti-hepatitis B core (HBc) anitgen negative) was diagnosed in four patients. In univariate matched analysis (17 cases, 68 matched controls), HEV cases were more likely to live in a rural area than HAV controls (matched OR 7.9; 95% CI 2.0-30.4). Of the 16 isolates confirmed as genotype 1, 15 belonged to the same cluster with 94-98.5% identity in the open-reading frame 2 region. Our findings documented the sporadic nature of HEV in Greater Cairo, characterized a large number of Egyptian HEV genotype 1 strains and identified living in a rural area as a potential risk factor for infection.

Evaluation of anti-HBV drug resistant mutations among patients with acute symptomatic hepatitis B in the United States

Reported HBV drug resistance mutations among previously untreated patients with chronic hepatitis B are variable. Whether resistant HBV strains are transmitted in the acute setting is uncertain. We sought to document the presence of antiviral resistance (AVR) mutations in patients with acute HBV (AHB) infection. AHB infection was defined by HBsAg/IgM anti-HBc positivity, ALT>10X ULN and compatible clinical history. The TRUGENE HBV kit was used to perform genotyping and direct sequencing of the viral polymerase. INNO-LiPA HBV DRv2 and DRv3 were used to detect AVR mutations. Clonal sequencing was conducted on selected specimens. Twenty-three patients were evaluated (mean age, 43 years; 54% male; 39% African American, 39% Caucasian, 13% Hispanic and 4% Asian). The mean peak ALT was 1554.2IU/L and mean peak total serum bilirubin was 12 mg/dl. The HBV DNA median viral load (N = 15) was 5.14 log(10)IU/ml. Nineteen patients were genotype A, and 1 each were genotype C, D, E and G. HBV drug resistance mutations were not detected by direct sequencing or INNO-LiPA. Clonal sequencing was conducted on 192 clones isolated from three patients and showed rtA181T, rtM250V and rtS202G mutations at an overall frequency of 1.54%, 1.39%, and 1.67% respectively. We detected adefovir/lamivudine and entecavir relevant mutations in a minor population (<2%) of viral clones by clonal sequencing only. The clinical significance of these mutations is uncertain and may represent small populations of quasi-species vs. transmission of drug resistant strains.

Protective role of humoral immune responses during an outbreak of hepatitis E in Egypt

Although the seroprevalence of hepatitis E virus (HEV) is approximately 80% in adult Egyptians living in rural areas, symptomatic HEV-caused acute viral hepatitis (AVH) is sporadic and relatively uncommon. To investigate the dichotomy between HEV infection and clinical AVH, HEV-specific immune responses in patients with symptomatic and asymptomatic HEV infection during a waterborne outbreak in Egypt were examined. Of 235 acute hepatitis patients in Assiut hospitals screened for HEV infection, 42 (17.9%) were acute hepatitis patients confirmed as HEV-caused AVH; 37 (88%) of the 42 patients were residents of rural areas, and 14 (33%) were from one village (Kom El-Mansoura). Another 200 contacts of AVH cases in this village were screened for HEV and 14 (7.0%), all of whom were family members of AVH cases, were asymptomatic HEV IgM-positive. HEV infections in this village peaked during the summer. Asymptomatic HEV seroconverters had significantly higher levels of epitope-specific neutralising (p=0.006) and high avidity (p=0.04) anti-HEV antibodies than the corresponding AVH cases. In conclusion, naturally acquired humoral immune responses appear to protect HEV-exposed subjects from AVH during an HEV outbreak in Egypt.