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Hepatitis A virus (HAV) causes transient acute infection, and little is known of viral shedding via the duodenum and into the intestinal environment, including the gut microbiome, from the period of infection until after the recovery of symptoms. Therefore, in this study, we aimed to comprehensively observe the amount of virus excreted into the intestinal tract, the changes in the intestinal microbiome, and the level of inflammation during the healing process. We used blood and stool specimens from patients with human immunodeficiency virus who were infected with HAV during the HAV outbreak in Japan in 2018. Moreover, we observed changes in fecal HAV RNA and quantified the plasma cytokine level and gut microbiome by 16S rRNA analysis from clinical onset to at least 6 months after healing. HAV was detected from clinical onset up to a period of more than 150 days. Immediately after infection, many pro-inflammatory cytokines were elicited, and some cytokines showed different behaviors. The intestinal microbiome changed significantly after infection (dysbiosis), and the dysbiosis continued for a long time after healing. These observations suggest that the immunocompromised state is associated with prolonged viral shedding into the intestinal tract and delayed recovery of the intestinal environment.

Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8 + T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.

To evaluate the pathophysiology of autoimmune hepatitis (AIH) following acute hepatitis A (AHA) in immunologic aspects, we performed multi-color flow cytometry with peripheral blood mononuclear cells of a patient who underwent liver transplantation due to AIH-induced liver failure. Unlike general AHA patients, the proportion of tumor necrosis factor-α-producing Treg cells remained high for 6 months after diagnosis of AHA until she underwent a liver transplantation. The conversion of Treg cells into mediators of inflammation may have played a role in the autoimmune pathogenesis following AHA., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Introduction: Autoimmune hepatitis (AIH) is a cause of chronic liver disease. It is usually suspected based on clinical presentation and laboratory findings, but the diagnosis relies on the presence of specific autoantibodies and characteristic histology. Other unexplained findings should always prompt investigation for coexisting syndromes., Case Presentation: The patient is a 60-year-old Hispanic female with a history of mild asthma presented with exertional and pleuritic chest pain with weight loss, arthralgia, subjective fever, and night sweats for the last 3 months. Given the nonspecific nature of the presentation, further workup was pursued. Laboratory results indicated pancytopenia, elevated INR, and positive autoimmune panel including ANA, anti-chromatin, anti-histone, and rheumatoid factor as well as abnormal C3 and C4. Subsequent liver biopsy with interface hepatitis lead to a diagnosis of AIH with concurrent systemic lupus erythematosus suspected., Conclusion: The diagnostic work up for AIH is multimodal and aims to differentiate other etiologies such as congestive hepatopathy, iron overload, viral hepatitis, and other autoimmune liver diseases. In this particular case, unusual clinical and laboratory findings led to diagnosis of the overlap syndrome. Treatment for both was necessary to prevent further progression of disease.

Background: Genvoya® (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) is a recent single regimen for the treatment of Human Immunodeficiency Virus (HIV). However, because of its complexity, it is difficult to predict drug interactions, especially when associated with HMG-CoA reductase inhibitors and/or in the setting of other comorbidities. We discuss the mechanisms of these potential drug interactions as the cause of rhabdomyolysis and acute kidney injury in the context of prior and current medication therapy with possible underlying liver and kidney dysfunction., Case Presentation: We describe the case of a 54-year-old man diagnosed with HIV who developed severe rhabdomyolysis-induced anuric acute kidney injury (AKI) requiring renal replacement therapy following introduction of Genvoya® concomitantly with simvastatin, in the context of recently diagnosed hepatitis C and hepatitis A. Haemodialysis was continued over 5 weeks followed by progressive clinical and biological improvements. Five months later, a new antiretroviral regimen was started and has been well tolerated., Conclusion: Simvastatin, as well as lovastatin, because of their CYP3A4 metabolism, and to a lesser extent atorvastatin, which is only partially metabolized by CYP3A4, are the HMG-CoA reductase inhibitors with the greatest risk of drug interactions and should not be used in patients under HIV-therapy. Patients receiving HMG-CoA reductase inhibitors should be monitored regularly for the occurrence of muscular adverse effects and drug interactions should be considered with each new prescription or change in clinical status. There are many online tools that enable clinicians to rapidly check for drug interactions. We recommend the one from the University of Liverpool for patients under HIV-therapy ( https://www.hiv-druginteractions.org/checker ), while for patients under hepatitis C-therapy, we advise to consult http://www.hep-druginteractions.org/ . This case illustrates the importance of multidisciplinary collaboration in the treatment of HIV-positive patients because of their complexity, associated comorbidities and the potential of multiple drug-drug interactions potentially exacerbated by underlying liver and/or kidney dysfunction.

Objectives: Since February 2017, an increase of acute hepatitis A (AHA) cases has been notified in North of France. We aimed to report clinical and virological features of 49 cases treated in three hospitals in Lille European Metropolis (LEM)., Methods: All adult patients treated for AHA in 3 LEM hospitals between 20 February and 5 July 2017 were included. Demographic characteristics, exposure risk factors to hepatitis A virus (HAV), AHA manifestations and concomitant sexually transmitted infections (STI) were retrospectively recorded., Results: Forty-nine cases of AHA were diagnosed among which 34 (69%) were hospitalised. Severe AHA occurred in 7 (14%) patients. The median age of cases was 36 years. All cases except 1 were men and 32 (65%) were identified as men having sex with men (MSM). Eleven (23%) patients were HIV-infected, 5 were under HIV pre-exposure prophylaxis (PrEP), 6 had a history of HIV postexposure prophylaxis and 19 had a history of at least one STI. Only three patients had received HAV vaccine. Proportion of patients tested for syphilis, chlamydial and gonococcal infections was 75% (18/24) in those seen by sexual health specialists and 21% (6/29) in those seen by other specialists. At least one concomitant STI was diagnosed in 13 out of 24 tested patients (54%). RT-PCR sequencing was available for 38 cases and confirmed co-circulation of 3 different strains of subgenotype IA (VRD 521 2016: n=24, RIVM-HAV16-090: n=13, V16-25801: n=1), already identified in several European countries., Conclusions: We are facing an outbreak of AHA among MSM in the North of France with a high rate of hospitalisation. Analysis of cases highlighted missed opportunities of vaccination and lack of concomitant STI screening. Awareness among healthcare providers and MSM should be increased and HAV vaccination promoted., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

To establish an animal model for the newly identified Marmota Himalayana hepatovirus, MHHAV, so as to develop a better understanding of the infection of hepatitis A viruses. Five experimental woodchucks (Marmota monax) were inoculated intravenously with the purified MHHAV from wild woodchuck feces. One animal injected with PBS was defined as a control. Feces and blood were routinely collected. After the animals were subjected to necropsy, different tissues were collected. The presence of viral RNA and negative sense viral RNA was analyzed in all the samples and histopathological and in situ hybridization analysis was performed for the tissues. MHHAV infection caused fever but no severe symptoms or death. Virus was shed in feces beginning at 2 dpi, and MHHAV RNA persisted in feces for ~2 months, with a biphasic increase, and in blood for ~30 days. Viral RNA was detected in all the tissues, with high levels in the liver and spleen. Negative-strand viral RNA was detected only in the liver. Furthermore, the animals showed histological signs of hepatitis at 45 dpi. MHHAV can infect M. monax and is associated with hepatic disease. Therefore, this animal can be used as a model of HAV pathogenesis and to evaluate antiviral and anticancer therapeutics.

Acute hepatitis due to the hepatitis A virus usually has a short, benign and self-limited course, without causing chronic hepatitis. However, some cases have an atypical presentation, such as relapsing hepatitis, prolonged or persistent cholestasis, fulminant hepatic failure, or liver failure associated with autoimmune hepatitis. The typical clinical course of acute hepatitis A virus infection is spontaneous remission in 90% of the cases, but atypical cases have a prevalence that varies from less than 1 to 20%, depending on the manifestation (overall prevalence ∼7%). There is little information on the atypical clinical courses of hepatitis A virus infection and the lack of recognizing those presentations in clinical practice often results in carrying out numerous studies and treatments that not only are unnecessary, but can also be harmful. The aim of the present article was to describe 3 clinical cases of atypical hepatitis A infection and provide a literature review of such cases., (Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

Hepatitis A virus causes acute viral hepatitis, presenting with jaundice, nausea, and vomiting. Symptoms are self-limited and treated symptomatically. Routine vaccination of infants has greatly reduced the incidence in the United States. Vaccination is recommended for all infants and adults at increased risk. Hepatitis B virus can cause acute and chronic viral hepatitis. Acute hepatitis B is usually self-limited, but can develop into a chronic infection. Patients are at highest risk for developing chronic disease if they are infected at a younger age. Routine vaccination and universal screening of pregnant women has decreased the transmission of hepatitis B virus., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aims: The clinical course of acute viral hepatitis A (AHA) is highly variable. Serum alphafetoprotein (AFP) level is often elevated in various types of acute liver injuries, indicating active liver regeneration. This study was aimed to investigate the clinical significance of serum AFP level in the aspect of the early recovery in AHA., Methodology: A total of 238 patients with AHA, confirmed by IgM anti-hepatitis A virus, were included. The patients were classified according to serum AFP level. Multivariate analysis by Cox proportional hazards model using dichotomized clinical variables was performed to identify the independent predictors for early recovery (ALT normalization within 2 weeks)., Results: The median age (range) was 30 (17-50) years and male dominant (62%, 147/238). Compared to low AFP group, high AFP group (>10 ng/mL) had significantly lower platelet counts (p <0.0001), lower albumin (p =0.003), lower AST (p <0.001), lower ALT (p = 0.001), higher total bilirubin level (p <0.0001) on univariate analysis. On Cox regression analysis, high AFP level (>10 ng/mL) was the only independent predictor for early recovery (Hazard ratio (HR); 2.392, 95% CI; 1.564-3.659, p = 0.0001)., Conclusions: High serum AFP level (>10 ng/mL) may indicate the already-started recovery through active liver regeneration or the early recovery within 2 weeks in AHA.

Introduction: Pseudothrombocytopenia (PTCP) is the phenomenon of ethylenediaminetetraacetic acid anticoagulant-activated platelet clumping, which results in artificially low platelet counts. Other investigators have reported a few cases of PTCP associated with viral infections. The objective of this study was to demonstrate the association of viral infection with PTCP., Methods: Medical records of patients with thrombocytopenia who were tested for peripheral blood smear examination between March 2009 and February 2011 were reviewed for platelet clumping and viral infection., Results: Thrombocytopenic patients with viral infection had a higher frequency of platelet clumping than those with other diseases, which was statistically significant (13.8% vs. 6.5%, respectively: P = 0.003). Among the 18 cases where PTCP or platelet clumping was related to viral infection, hepatitis A virus infection (72.2%) was most common, followed by cytomegalovirus (11.1%) and influenza A H1N1 infections (5.6%). A third (33.3%) of the patients had platelet counts <100 × 10⁹/L., Conclusion: Pseudothrombocytopenia or platelet clumping should be considered in patients with acute viral infection, particularly if the platelet count is unexpectedly low, because failure to recognize PTCP may lead to unnecessary diagnostic tests and patient mismanagement., (© 2012 Blackwell Publishing Ltd.)

Aim: In developing countries HAV infection is very common in the first years of life and it is often asymptomatic. However especially in regions of intermediate endemicity, exposure to the virus may delay and outbreaks of hepatitis A may be encountered in adults. The aim of this study is to evaluate the clinical and laboratory findings and risk factors of adults with acute viral hepatitis A., Materials and Methods: In present study we evaluated 203 patient with acute viral hepatitis A, who were admitted to four different hospitals of three cities of Turkey between January 2000-December 2011, retrospectively. The diagnosis of acute viral hepatitis A was performed by laboratory findings and clinically., Results: In a total of 203 patients, 120 (59.1%) patients were male and 83 (40.9%) were female. Mean age of cases with acute viral hepatitis A was 24.7 +11.8 years (ranged 15 to 82 years old). Acute viral hepatitis A were seen in patient who were 15-20 years and 21-30 years old, commonly. Jaundice (74%), fatigue (68%), nausea- vomiting (56%) and dark urine (48%) were the most common symptoms in cases. Prolonged cholestasis (6.8%) was the most common atypical manifestation. Prolonged jaundice was more frequent in the cases with positive HBsAg (P < 0.001)., Conclusions: Acute viral hepatitis A can cause atypical presentations such as prolonged cholestasis, acute kidney injury and fulminant hepatitis. Some precautions such as routine vaccination program, improvement of hygiene conditions and informing people about it, should be taken for reducing of acute viral hepatitis A infection incidence.

The mild form of hepatitis A and B with children is attended by a functional activity of pancreatic gland (tripsin), mucous coats of stomach and duodenum (gastrin) which permits to consider them as a factor of the risk of digestive organs combined pathology starting with the disease acuity. Differences in gastrin levels with children depending on hepatitis etiology were specified. Highest levels of gastrin were observed with persons suffering from hepatitis B.

Hepatitis A and hepatitis C viruses (HAV and HCV) are both positive-strand ribonucleic acid (RNA) viruses with hepatotropic lifestyles. Despite several important differences, they share many biological and molecular features and similar genome replication schemes. Despite this, HAV infections are usually effectively controlled by the host with elimination of the virus, whereas HCV most often is able to establish lifelong persistent infection. The mechanisms underlying this difference are unknown. The cellular helicases RIG-I and MDA5, and Toll-like receptor 3, are pattern recognition receptors that sense virus-derived RNAs within hepatocytes in the liver. Activation of these receptors leads to their interaction with specific adaptor proteins, mitochondrial antiviral signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β (TRIF), respectively, which engage downstream kinases to activate two crucial transcription factors, nuclear factor kappa B (NF-κB) and interferon regulatory factor 3 (IRF3). This results in the induction of interferons (IFNs) and IFN-stimulated genes that ultimately establish an antiviral state. These signaling pathways are central to host antiviral defense and thus frequent targets for viral interference. Both HAV and HCV express proteases that target signal transduction through these pathways and that block the induction of IFNs upon sensing of viral RNA by these receptors. An understanding of the differences and similarities in the early innate immune responses to these infections is likely to provide important insights into the mechanism underlying the long-term persistence of HCV., (© Thieme Medical Publishers.)

An epidemic of infectious hepatitis caused by the hepatitis A virus was detected in Pohnpei State, Federated States of Micronesia (FSM), beginning in November 2008. Epidemiologic investigation revealed that the index case occurred in late June 2008 in a traveler from nearby Chuuk State, which itself had experienced an epidemic of hepatitis A in the first half of 2008. Most cases have been confirmed by IgM serology, the rest by a clinically compatible syndrome with either jaundice or elevated liver enzymes. The most commonly affected group has been school-aged children; it is likely that the paucity of patients in the 40-50 year age group represents immunity conferred during the previous epidemic of hepatitis A in the early 1970's, as hepatitis A is not thought to be endemic in Pohnpei. As of September 17, 2009 there have been 300 reported cases with 17 hospitalizations (6%) and one death (0.3%). The epidemic peaked in April 2009, with a sharp decline in cases in June attributable with the end of the school year, as schools were found to be the major focus of infection. Efforts to control the outbreak have centered on public awareness and improved hygiene initiatives, particularly in schools. The greatest challenge to ongoing diminution of the outbreak is the recent resumption of the school year; control efforts, especially improved hygiene, will need to be sustained with renewed vigor if we are to extinguish the outbreak.

Background: Patients with chronic viral hepatitis are at a higher risk for cognitive dysfunction. Little is known about the association between hepatitis A virus (HAV) infection and cognitive function., Methods: From the National Health and Nutrition Examination Survey, 1999-2002, we selected study participants (> or =60 years, n = 1,529) without hepatitis B, C, or D virus infection; without previous hepatitis A vaccination; and without abnormal liver function. HAV-seropositive participants represented people with previous HAV infection. Psychomotor speed and executive functioning domain of cognitive function were measured by the Digit Symbol Substitution Test (DSST)., Results: HAV-seropositive participants had lower DSST scores than HAV-seronegative participants (weighted mean, 44.4 vs 53.9, p < .001). We designated HAV-seronegative participants as the reference group. Univariate analysis demonstrated that the weighted beta coefficient of DSST score was -9.55 (95% confidence interval [CI] -9.57 to -9.54, p < .001) for the HAV-seropositive participants. In a multivariable model, the weighted adjusted beta coefficient of DSST score was -2.48 (95% CI -2.49 to -2.46, p < .001) for the HAV-seropositive participants., Conclusion: HAV seropositivity is associated with slower psychomotor speed among the U.S. community-dwelling elders.

Background: The emergence of imported hepatitis A virus (HAV) strains from other regions is a feature of acute hepatitis A in developed countries as well as the decrease in number of cases., Objectives: Between 1992 and 2003 we investigated the clinical and molecular characteristics of acute HAV infections experienced at a single institution located in a middle city of Japan., Study Design: A total of 172 patients were admitted to our institution between 1992 and 2003 with the diagnosis of acute hepatitis A. Clinical features of hepatitis and molecular epidemiology were analyzed., Results: The number of patients with acute hepatitis A markedly decreased during the study period. Phylogenetic analysis showed that all analyzed HAV strains belonged to HAV genotype IA. HAV strains clustered into four groups and strains of patients belonging to a cluster presented with HAV infection with an interval of more than 4 years., Conclusions: Several identical or closely related HAV strains with high homology continue to circulate in Ogaki, Japan, during a 12-year period, causing sporadic cases of acute hepatitis A infection with strains of genotype IA HAV.

This report describes a hepatitis A outbreak among Korean military personnel. Each case of hepatitis A in this outbreak was defined as a person who had symptoms compatible with acute viral hepatitis A and had positive HAV IgM between May 2 and August 14, 2007 in Inje district, Gangwon, Korea. We tested 70 cases with symptoms for HAV IgM, and 67 cases showed positive results. They included 4 sergeants, 1 officer and 62 privates. A positive result for HAV IgG among asymptomatic military personnel was seen in 11.8% of cases. This epidemic occurred after a heavy rainfall in the military compound area where drinking water was supplied by the stream water. After the outbreak, the supply of drinking water was switched to a public water system. All of 178 military personnel who had no HAV IgG were vaccinated on July 26, 2007. The outbreak was resolved after the control measures were implemented.

Viral hepatitis has long been under-diagnosed. Hepatitis A is an acute disease, while patients infected by hepatitis B and hepatitis C viruses are likely to develop chronical infections and severe complications (cancer, cirrhosis). The current treatment of hepatitis B and C consists in alpha interferon (preferably under its pegylated form), in combination with ribavirin for hepatitis C. The frequent and severe adverse effects of interferon-based therapy constitute, however, a major limiting factor (reactions at the injection site, flu-like syndrome, neurological disorders, ...). For hepatitis B, two alternatives are available so far, namely lamivudine and adefovir (used as a prodrug with highe oral bioavailability).

Background/aims: The development of acute renal failure (ARF) is a very rare complication in patients with acute hepatitis A (AHA)., Methods: We retrospectively investigated the overall incidence, risk factors, and clinical outcomes of ARF associated with AHA. Diagnosis of AHA was made according to the typical hepatitis symptoms and positivity of immunoglobulin M anti-hepatitis A virus in 208 patients with AHA., Results: ARF was noted in 12 (5.7%) patients, and dialysis was required in 8 (66%) patients. The median duration of hospitalization for patients with ARF was 18 days (range, 6-50 days). The development of ARF was observed in older patients (p = 0.004) and in patients with diabetes (p = 0.001), excessive alcohol consumption (p = 0.01), prolonged international normalized ratio (p = 0.019), and elevated aspartate aminotransferase concentration (p = 0.034). Multivariate analysis revealed that old age (odds ratio, OR, 1.2), elevated aspartate aminotransferase concentration (OR, 1.05), and diabetes (OR, 18.5) were independent risk factors for ARF (each p < 0.001). The prognosis of patients with ARF was good, and renal function recovered completely., Conclusion: ARF associated with AHA is not rare, and the possibility of AHA should be considered in patients with ARF with hepatic dysfunction., (Copyright 2008 S. Karger AG, Basel.)

Objective: The number of adult hepatitis A cases has progressively been increasing during the last several years in Korea. The aim of the present study was to describe the recent clinical features of hepatitis A and the seroprevalence of hepatitis A virus (HAV), and to discuss HAV vaccine strategy in Korea., Methods: Retrospective analysis of clinical characteristics of hepatitis A from 109 patients consecutively enrolled at a community hospital between 2003 and 2006 as well as cross-sectional study of seroprevalence of HAV from 307 patients of hospital population group during the same period were performed., Results: Most hepatitis A cases were young adults in their twenties or thirties, and the severity of the disease was related to the age of patients. The seroprevalence of HAV was 62%, which was dependent on the age of patients. HAV seroepidemiology in Korea is rapidly changing and a growing number of young adults are susceptible to HAV infection., Conclusions: The clinical features and the epidemiological shift of HAV urge Korea, as well as other countries which are experiencing similar issues, to promote childhood vaccination and consider catch-up vaccination for adolescents and young adults., (Copyright 2008 S. Karger AG, Basel.)

Background: In our recent study of the full-length hepatitis A virus (HAV) genome from some patients with fulminant hepatitis and acute hepatitis, possible associations were suggested between the severity of hepatitis A and the amino acid substitutions in the nonstructural protein 2B. We therefore analyzed HAV 2B from many patients with various clinical disease severities., Methods: Serum samples from 30 Japanese patients with sporadic hepatitis A from five widely separated regions of Japan, comprising nine patients with fulminant hepatitis (FH), six with severe acute hepatitis (AHs), and 15 with acute hepatitis (AH), were examined for HAV RNA. The entire sequences of HAV 2B were analyzed., Results: Compared with the sequence of the wild-type HAV strain GBM, nucleotide sequences of 2B had homology of 94.5 +/- 1.0% in FH, 95.2 +/- 1.2% in AHs, and 95.1 +/- 1.8% in AH. Deduced amino acid sequences had homology of 97.5 +/- 2.1% in FH, 97.9 +/- 2.4% in AHs, and 98.5 +/- 1.3% in AH. Differences were not statistically significant among the three groups. The average number of amino acid mutations between amino acids 100 and 200 was 5.0 +/- 5.2 per case in FH, 4.0 +/- 6.0 in AHs, and 1.9 +/- 2.9 in AH. The differences between FH and AH, AHs and AH, and between severe cases (FH and AHs) and nonsevere cases (AH) were not statistically significant (P = 0.13, P = 0.45, and P = 0.10, respectively)., Conclusions: There were no obvious differences in the sequences among FH, AHs, and AH throughout the 2B region, but there seemed to be more mutations in the strains obtained from FH and AHs patients than in those obtained from AH patients in the central part of HAV 2B.

Objective: Serum hyaluronan (HA) is ubiquitously distributed in connective tissues. Circulating HA is degraded by hepatic sinusoidal endothelial cell. The aim of the present study was to evaluate serum HA levels and to determine their importance in dengue fever (DF)/dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) patients., Methods: Serum HA levels were measured by an ELISA-based method in 16 patients with DF, 14 patients with DHF and 10 patients with DSS. The HA levels were compared with those in 48 acute hepatitis A patients; 8 healthy blood donors serve as controls., Results: In acute phase, mean serum HA levels significantly increased in patients with DSS (7316.3+/-10,359.0 ng/ml) in comparison to patients with hepatitis A (93.8+/-50.4 ng/ml; P<0.0001), and healthy controls (48.3+/-16.3 ng/ml; P<0.0001). Serum levels of HA in patients with DSS rapidly decreased during the convalescent phase, but were still significantly higher than those in healthy controls (915.2+/-1294.8, and 48.3+/-16.3 ng/ml; P<0.0005)., Conclusions: The increased HA in dengue patients could be attributed to sinusoidal endothelial damage rendering the endothelium incapable of HA clearance. The elevation of HA production may involve the pathogenesis of dengue infection. Further studies are needed to determine whether the increase in the HA production or decrease in its clearance is responsible for the elevated serum HA.

Objectives: In acute viral hepatitis A (AVH-A), involvement of the liver is through cytotoxic cells and cytokine levels are increased Immune response of the host determines the severity of the disease. Leptin stimulates cytokines, therefore, the authors hypothesized that the relationship between leptin and cellular immunity might cause different clinical presentations of the disease., Methods: Twenty-eight children with AVH-A and 10 healthy children formed the basis of the study. Serum leptin, C-reactive protein (CRP) and alpha-1-antitrypsin (A1AT) levels were determined, Results: There was significant positive correlation between body mass index (BMI) and leptin levels both in patients and controls (p = 0.003 and p = 0.001 respectively). No significant difference in serum leptin, CRP or A1AT levels between patients and controls was detected (p > 0.05). Presence of icterus or fulminant hepatic failure (FHF) did not affect serum leptin level (p > 0.05). Mean A1AT level was significantly higher in children with FHF (p < 0.05). On the 30th day of admission, mean BMI, weight and leptin levels increased (p < 0.01, p < 0.01 and p < 0.05 respectively) and mean A1AT level decreased (p < 0.01)., Conclusion: Leptin levels are not altered in children with AVH-A. In the convalescence period, leptin increased parallel to BMI. It is suggested that expected increment in leptin due to inflammation might be balanced with the decrease due to loss of appetite during acute illness or it might be entirely due to loss of production.

Aim: To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4(+)/ CD8(+) lymphocyte populations that control cell-mediated immunity., Methods: Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV) RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped., Results: Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis (s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one patient with fulminant disease (encephalopathy Grade IV) dying on the 4th d. The ALT level was significantly higher both in AHA (1070.9 +/- 894.3; P = 0.0014) and s-AH (1713.9 +/- 886.3; P = 0.001) compared to normal controls (23.6 +/- 7.2). The prothrombin time in s-AH patients (21.0 +/- 2.0; P = 0.02) was significantly higher than in AHA (14.3 +/- 1.1; P = 0.44). The CD4(+)/CD8(+) ratio in AHA patients (1.17 +/- 0.11; P = 0.22) and s-AH (0.83 +/- 0.12; P = 0.0002) were lower than seen in normal healthy controls (1.52). Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15th or 30th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and ALT values collected during the entire course of the self-limited infection were directly correlated but this was not the case for s-AH patients., Conclusion: Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.

Background: Foodborne or orofecal transmitted infections can have influence on health by direct consequences of the infection and indirectly by modulating the immune system., Objectives: To investigate the prevalence and risk factors for T. gondii, H. pylori and HAV infection in the Icelandic population and their influence on atopy, allergy related lung symptoms and lung function., Material and Methods: Blood samples were collected in 1999-2001 from 505 subjects in age group 28-52, randomly selected from the Icelandic population. The presence of T. gondii, H. pylori and HAV IgG antibodies was determined by an ELISA method. Allergy related lung symptoms were assessed with questionnaire and IgE sensitization and lung function measured. X(2) test was used to test for trend but unadjusted logistic regression for comparison of IgG prevalence. Multiple logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for different infections factors., Results: The prevalence of antibodies was 9.8%, for T. gondii, 36.3% for H. pylori and 4.9% for HAV. Attending day care before the age of 3 years was a risk factor for having T. gondii antibodies. The prevalence of H. pylori increased with age and smoking. The infections were not associated with the prevalence of asthma or atopy. Having IgG antibodies against T. gondii was, however, associated with an increased risk of having FEV/FVC ratio below 70%., Conclusion: T. gondii, H. pylori and H AV infection does not influence the prevalence of atopy or asthma. The data indicated that infection with T. gondii might be associated with a diminished lung function.

The article contains present-day data on type A viral hepatitis, whose incidence in Russia has increased significantly in the recent years. The authors consider the pathogenesis of type A hepatitis, taking into account the peculiarities of immune response to the virus. Clinical manifestations of various variants, including anicteric one and combinations of type A hepatitis with hepatites of other etiologies, are described. The authors stress the diagnostical significance of anti-HAV IgM detection, the aspects of differential diagnosis, treatment, as well as specific and non-specific prophylaxis of type A viral hepatitis.

Current serologic tests provide the foundation for diagnosis of hepatitis A and hepatitis A virus (HAV) infection. Recent advances in methods to identify and characterize nucleic acid markers of viral infections have provided the foundation for the field of molecular epidemiology and increased our knowledge of the molecular biology and epidemiology of HAV. Although HAV is primarily shed in feces, there is a strong viremic phase during infection which has allowed easy access to virus isolates and the use of molecular markers to determine their genetic relatedness. Molecular epidemiologic studies have provided new information on the types and extent of HAV infection and transmission in the United States. In addition, these new diagnostic methods have provided tools for the rapid detection of food-borne HAV transmission and identification of the potential source of the food contamination.

Reversible encephalopathy has been described in association with typhoid fever as well as nontyphoidal salmonella infections. A diagnostic dilemma as to the cause of encephalopathy may arise when there is coexistent acute viral hepatitis and suspicion of fulminant liver failure. The authors report a patient who presented with acute icteric hepatitis A infection and a concomitant febrile illness due to Salmonella paratyphi associated with progressive encephalopathy and coma. The young man developed high-grade fever and coma. Concomitant infection with S. paratyphi was diagnosed and the patient's encephalopathy resolved rapidly with antibiotic therapy. This is the first report of a putative association of S. paratyphi infection and reversible encephalopathy. Salmonella and hepatitis A virus infection are both transmitted via the fecal-oral route, and awareness of this association is important in the management of such patients.

The hepatitis A virus (HAV) is the most common etiological cause of acute hepatitis infections in humans in industrialized countries. Investigations into the viral load during HAV viremia, however, are rare. Therefore, correlation studies between viral load, biochemical, and specific serological markers have been undertaken. The group of sera comprised a series of multiple consecutive blood samples drawn from 11 patients at different times after onset of the disease. During the period up to 70 days after the onset of icterus, the individual range was at 1 x 10(3) to 3 x 10(4) HAV genome equivalents/ml. From day 75 until 120 after onset of the disease, the levels traced were at 10(3). In one case, it was possible to trace 1.25 x 10(4) genome equivalents/ml up to 180 days after onset of icterus and in two cases even up to 408 and 490 days viral load levels of 5 x 10(3) and 4 x 10(4) were detected, respectively. The same sera were used to measure IgM class antibodies to hepatitis A virus and the total anti-HAV. The results demonstrate that a direct correlation to peak levels of viral load exists with peak serum transaminase levels, but neither with peak anti-HAV IgM levels nor with total anti-HAV. Decreasing amounts of anti-HAV IgM tend to occur with decreasing amounts of HAV genome equivalents; and, vice versa, increasing amounts of total anti-HAV are accompanied by decreasing amounts of HAV genome equivalents. The longest duration of viremia was found in patients infected with HAV genotype IA., (Copyright 2004 Wiley-Liss, Inc.)

The correlation between the length of viremia as detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and the clinical course of hepatitis A virus (HAV) infection was studied. Sixty-six consecutive patients with acute hepatitis A who were admitted to hospital in two infectious disease units in southern Italy were enrolled: 57 had a self-limited course of the disease (typical course), 4 a prolonged course, and 5 relapsing hepatitis. Plasma HAV RNA was sought by RT-PCR, using primers made at 5'-NTR of HAV, designed to amplify a 273-bp fragment and detected by 2% agarose gel and by hybridization with a specific biotinylated probe. In four patients with prolonged acute hepatitis A, the plasma HAV RNA, which was positive on the day of admission to hospital, was found to be negative from day 62, 46, 84, and 105, respectively, after the onset of the symptoms. In patients with relapsing hepatitis, HAV viremia paralleled the clinical and biochemical course of disease. In all patients with a typical self-limiting course, clearance of plasma HAV RNA was observed within 20 days of the onset of symptoms. In most patients, plasma HAV viremia became undetectable before the normalization of serum aminotransferases, underlining the importance of the immune reaction in the pathogenesis of acute hepatitis A. The data also suggest that the detection of plasma HAV RNA after 20 days of illness may predict a prolonged course of the disease, but relapsing hepatitis remains unpredictable on the basis of plasma HAV determination., (Copyright 2003 Wiley-Liss, Inc.)

Background: Hepatitis A virus (HAV) infection is a major public health problem worldwide. The infection does not induce any visible cytopathic effects or interfere with macromolecular synthesis in host cells. However, the hepatitis B and C viruses have recently been reported to activate intracellular signals. To clarify the effects of HAV infection on intracellular signalling, we examined the influence of 9 FLAG-tagged HAV proteins (VP2, VP3, VP1-2A, 2B, 2C, 3A, 3BC, 3C and 3D) on signal transduction pathways., Methods: Viral protein expression vectors were co-transfected into HeLa cells with reporter plasmids controlled by a synthetic promoter containing direct repeats of the cyclic AMP response element (CRE), serum response factor (SRF), activator protein 1 (AP-1), nuclear factor kappaB (NF-kappaB) or serum response element (SRE). Cells were harvested 42 h after transfection and luciferase assays were performed. Viral protein activation twice that of the control was defined as significant., Results: VP3 induced an SRE-associated signal 2.2 +/- 0.3 times higher than that of control. VP3 did not activate CRE-, SRF-, AP-1- or NF-kappaB- associated signalling. The other HAV proteins tested also failed to induce these pathways., Conclusions: HAV interacts with the host signalling mechanism, and HAV VP3, different from HBX and hepatitis C core protein, may activate only SRE-associated intracellular signalling, a pathway associated with cell proliferation and differentiation.