Hepatitis In Young Adults Research Articles

Advances in Hepatitis E Virus Biology and Pathogenesis.

Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV is a positive-sense single-stranded RNA virus. Human HEV strains mainly belong to four major genotypes in the genus Orthohepevirus A, family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. HEV infection with genotype 1 and 2 mainly presents as acute and self-limiting hepatitis in young adults. However, HEV infection of pregnant women with genotype 1 strains can be exacerbated to fulminant hepatitis, resulting in a high rate of case fatality. As pregnant women maintain the balance of maternal-fetal tolerance and effective immunity against invading pathogens, HEV infection with genotype 1 might dysregulate the balance and cause the adverse outcome. Furthermore, HEV infection with genotype 3 can be chronic in immunocompromised patients, with rapid progression, which has been a challenge since it was reported years ago. The virus has a complex interaction with the host cells in downregulating antiviral factors and recruiting elements to generate a conducive environment of replication. The virus-cell interactions at an early stage might determine the consequence of the infection. In this review, advances in HEV virology, viral life cycle, viral interference with the immune response, and the pathogenesis in pregnant women are discussed, and perspectives on these aspects are presented.

Age wise seroprevalence of hepatitis viral markers in acute infectious hepatitis patients at a tertiary care centre in India

Introduction: Age wise seroprevalence of acute viral hepatitis still remains debatable. The burden of the disease could be reduced to a considerable extent, if seroprevalence of different viruses are known for various age groups. Objectives: To determine the age wise seroprevalence of hepatitis viral markers in clinically suspected infectious hepatitis at a tertiary care hospital in urban India Methodology: This prospective study was conducted over a period of 1 year from January -December 2008. The study arm had 600 patients with clinically suspected acute infectious hepatitis while control arm had 200 age and sex matched subjects. Both groups were divided into 0-10,11-20, 21-30, 31-40 and >40 years age groups .Serum samples were tested for IgM anti HAV, IgM anti HEV, IgM anti HCV and HBsAg using commercially available enzyme linked immunosorbent assay kits. Results: Highest seropositivity of anti-HAV IgM was in 0-10 years of age for the study arm. HAV seroprevalence decreased with increasing age. Highest seropositivity of HBsAg was in 20-30 years of age group for the study group (7.6%) followed by 11-20 years (4.5%), 0-10 years (2.8%) and >40 years (2.5%). Highest seropositivity to IgM anti HCV was seen in 11-20 years(9%) in the study arm followed by 21-30 years (6.1%), 0-10 years (5.1%) and >40 years (3.7%) of age. Highest seropositivity of anti-HEV IgM was in the 21-30 years (10.7%) in the study arm followed by 31-40 years (2.9%), 11-20 years (2.7%) and 0-10 years (0.9%). Conclusion: Both HAV and HEV are significant causes of enterically transmitted acute viral hepatitis. HAV is the major cause of acute viral hepatitis in childhood. Hepatitis B virus is the major cause of acute viral hepatitis in adults. HCV is a common cause of acute hepatitis in young adults. HCV infections remain under reported while the actual disease burden is much higher. Keywords: Seroprevalence, Age wise, HBsAg, HCV, HAV, HEV

Epidemiology of Viral Hepatitis and Liver Diseases in Nepal.

Geographical and ethnic diversity in Nepal has led to interesting epidemiology of viral hepatitis and liver diseases. Before the epidemic of Biratnagar that occurred in April to June 2014, Kathmandu was the only known endemic region for hepatitis E virus infection (HEV), where at least four previous epidemics have been documented since 1973. Due to rapid urbanization with still low socioeconomic condition, other major cities are appreciated to be at increasing risk of outbreaks. Characteristics of HEV epidemics and genetic changes of HEV during last decade have been studied. While hepatitis A virus infection was only common during childhood till recent years, it is re-emerging as an important etiology of acute hepatitis in young adults. Nepal is classified as low endemic region for hepatitis B virus infection (HBV) with overall seroprevalence of 1.1%. But, some ethnic groups and geographical areas have high prevalence rates. Despite low endemicity, HBV accounts for majority of cases of hepatocellular carcinoma and liver cirrhosis in the country. Similarly, though hepatitis C virus (HCV) is present in only 0.4% of general population, high seroprevalence was found among intravenous drug abusers many of them with HIV coinfection. Apart from hepatitis viruses, alcohol use also contributes significantly to liver cirrhosis and chronic liver failure. A unique form of hepatic venous outflow obstruction called ‘hepatic vena cava syndrome’ has been identified as an important etiology of liver cirrhosis and hepatocellular carcinoma.How to cite this articleShrestha A. Epidemiology of Viral Hepatitis and Liver Diseases in Nepal. Euroasian J Hepato-Gastroenterol 2015;5(1):40-42.

Hepatitis E Virus: Current Concepts and Future Perspectives

For many years, hepatitis E was considered a disease found only in certain developing countries. In these geographical settings, hepatitis E virus (HEV) causes a self-limiting hepatitis in young adults, except in pregnant females, in whom the mortality is 25%. Our understanding of HEV has changed radically in the past decade. It is now evident that HEV is a threat to global health. This review article considers the current concepts and future perspectives of HEV and its effects on human health, with particular reference to developed countries.

L’hépatite virale E : une maladie émergente

The hepatitis E virus is endemic in countries with poor sanitation, where it has many similarities with the hepatitis A virus. It causes a strictly human, feco-oral transmitted, acute, self-limited hepatitis in young adults. The outcome is excellent, except in pregnant women and cirrhotic patients, who experience a high mortality rate. The first cases described in industrialized countries were travellers coming from endemic areas. However, there is now growing evidence that locally-acquired hepatitis E is common in these areas, where it is an emergent disease, despite it is still misdiagnosed. In industrialized countries, hepatitis E spreads sporadically and has a predilection for elderly men with comorbidity, particularly chronic liver diseases. The mortality seems to be higher in this population. In these areas, hepatitis E is due to the genotype 3 virus that is thought to be zoonotically transmitted by pigs and wild boar. Hepatitis E may evolve towards a chronic infection in immunocompromised subjects, particularly in solid organ-transplanted patients. In case of chronic infection, it may cause liver fibrosis and cirrhosis. The diagnosis of hepatitis E is based on serological tests (IgM and IgG) and detection of the viral genome by reverse transcription polymerase chain reaction (RT-PCR) on blood and stools. Acute hepatitis E does not require any treatment but in chronically infected patients, a sustained viral response and finally a definitive viral clearance has been observed after a three-month course of low-dose ribavirin (600 to 800mg/day). Two vaccines underwent successful human trials but are not yet commercially available.

Gene Expression Profiles of T Cells from Hepatitis E Virus Infected Patients in Acute and Resolving Phase

Approximately 50% of acute viral hepatitis in young adults and in pregnant women is due to hepatitis E virus (HEV) infection in developing countries. T cell-mediated immune injury probably plays a key role in the pathogenesis of acute hepatitis illness. However, there is a paucity of data on the global gene expression programs activated on T cells, which are subsequently responsible for T cell recruitment to the liver and triggering of immune injury. We performed a flow cytometric analysis of T cells in individuals with acute hepatitis E (AVH-E; n=10), resolving phase of HEV (n=9), and ten healthy controls (HC). Further transcriptional profiling analysis was performed using Affymetrix GeneChip DNA microarrays to identify the genes that were differentially expressed in AVH-E and HC. Patients with AVH-E showed higher frequencies of CD8+ (27 ± 4%; P=0.02) and activated CD38+ CD69+ T cells (25% ± 3%; P=0.04) than in resolving phase patients (20 ± 2% and 9.1 ± 4%, respectively), who in turn exhibited higher CCR9 expression than cells from patients in active phase. The naïve T cell population (CD3+ CD45RA+) was decreased upon HEV infection (29 ± 4% in AVH-E vs. 53.1 ± 3.2% in HC; P=0.05); however, the CD11a high subpopulation within CD4+ CD45RA+ cells was increased in both AVH-E (6.1%) and resolving phase (7.7%) patients. Gene ontology analysis suggested that during AVH-E infection, there is in CD4+ T cells an activation of genes involved in pro-inflammatory responses. Additional RT-PCR analysis confirmed that in cells from AVH-E patients, there is an increased expression of CCR5, CCR9, CXCR3, CXCR4, STAT1, IRF-9, IFN-α, and TNF-α, together with a down-regulation of IL-2, SOCS3, and IL-10, with respect to cells from resolving phase patients. Our findings suggest the involvement of a circulating CD45RA+ CD11a high population with CCR5 expression in the pathogenesis processes of AVH-E. The obtained results help to understand the underlying inflammatory process occurring in HEV infection, which can lead to either resolution or immunopathology.

Hepatitis E: state of the art

Hepatitis E (HEV) has traditionally been thought to be a disease of developing countries. In this setting, HEV causes hepatitis in young adults. It is generally a self-limiting illness, with a good prognosis, except in pregnant women and patients with pre-existing chronic liver disease, in whom the mortality is 20% and 70% respectively. Traditionally HEV was considered rare in developed countries, and confined to travellers returning from endemic areas. However, recent data has shown that locally acquired HEV infection is common in developed countries. Acute HEV infection in this setting is caused by HEV genotype 3 and appears to have a predilection for middle aged/elderly males. It has a significant morbidity (15%) and carries an adverse prognosis in chronic liver disease. HEV infection is commonly misdiagnosed as drug-induced liver injury. The source and route of infection are currently uncertain, but evidence suggests that HEV genotype 3 is a porcine zoonosis, which can be transmitted via the human food chain. Until very recently chronic HEV infection was thought not to occur. However studies from Europe have shown that HEV genotype 3 can cause chronic infection with rapidly progressive cirrhosis in patients with immunocompromise. This includes patients taking immunosuppressive therapy following solid organ transplantation and patients with HIV-1 infection (NEJM 2009; 361(10): 1025-7). HEV IgG seroprevalence in developed countries is variable, with rates of 16% reported from the UK and SW France. These data indicate that HEV infection is either commonly subclinical, or commonly overlooked as a diagnostic possibility. However, the burden of HEV disease in both the developing and developed world is currently uncertain. The worldwide burden of chronic HEV infection may prove to be more considerable than previously thought likely, as countries where HEV is endemic also have a high seroprevalence of HIV.

Spectrum of acute viral hepatitis in Southern India

Background: The incidence of hepatitis-A among adults in India is on the decline as majority develops protective immunity to it by late adolescence. Most of these studies are from northern India. Clinical spectrum of sporadic acute viral hepatitis from southern India has not been well documented. Methods: A prospective hospital based study was conducted in a large military hospital in southern India. 224 consecutive patients with acute viral hepatitis were studied for their presentation, etiology and clinical features. Result: Hepatitis-E was detected in 102 (45.4%), hepatitis A in 74 (33%) and hepatitis B in 28 (12.5%) patients. Acute hepatitis C was detected in two patients. 15 patients had a mixed infection. Hepatitis A constituted 41.2% and 31.3% of all cases in the age groups 11–20 and 21–30 years respectively. Cholestasis was present in 68 (30.4%) patients with hepatitis E accounting for most (61.8%) cases. There were four (1.8%) cases of acute liver failure. Two cases were due to hepatitis E and one case each was due to hepatitis A and hepatitis B. A relapsing course was seen in four cases due to hepatitis-A. Conclusion: Hepatitis A remains a significant cause of sporadic acute viral hepatitis in young adults in southern India.

Hepatitis E autochthonous infection in chronic liver disease

Hepatitis E virus is endemic in many parts of the developing world and causes a self-limiting hepatitis in young adults, except in pregnant women and patients with chronic liver disease, where the mortality is high. Locally acquired hepatitis E is increasingly recognized in the developed world. It is caused by hepatitis E virus genotype 3, affects the middle-aged and the elderly, and may be a zoonotic infection from pigs. We present a case of locally acquired hepatitis E infection in a patient with previously undiagnosed cirrhosis, which resulted in subacute liver failure and death. We describe our attempt to trace this infection to a free-range pig farm adjacent to the patient's place of employment. Hepatitis E infection should be considered in the differential diagnosis in patients with decompensated chronic liver disease whatever their age or travel history. When found, the prognosis may be poor.

Perspectives of Vaccination against Hepatitis E

Hepatitis E, an important cause of morbidity and mortality in humans, accounts for more than 50% of acute viral hepatitis in young adults in developing countries with a 20–30% mortality rate among infected pregnant women primarily those in their third trimester. The development of inactivated or live attenuated virus vaccine has been hampered because this virus does not replicate efficiently in cell culture. A vaccine has been developed by an alternative approach through recombinant technology. Preliminary results of the first administration in man conducted in the US at Walter Reed Army Institute of Research indicate the vaccine to be safe and immunogenic and have led to the decision to further evaluate the vaccine in an endemic setting.

Hepatitis E virus seroprevalence in acute viral hepatitis in a developed country confirmed by a supplemental assay.

Hepatitis E virus (HEV) infection is prevalent among cases of acute viral hepatitis in young adults in developing countries. HEV infection is not restricted to endemic areas, but would appear to be worldwide in distribution. In order to document the incidence of HEV infection in acute hepatitis cases in a developed country, IgG and IgM anti-HEV antibodies and HEV RNA were tested in 101 Caucasian patients with acute viral hepatitis; 92 of these cases had markers of acute viral hepatitis other than HEV. Forty-seven (46.5%) cases had IgG anti-HEV; IgM anti-HEV and HEV viremia were not detected. As the incidence of anti-HEV was higher than would be expected, the possibility of the occurrence of false positive results was subsequently investigated. Supplemental antibody testing, using a broadly reactive epitope region, reduced the frequency of anti-HEV to 17%. Therefore, supplemental antibody testing confirms the hepatitis E virus seroprevalence in a developed country. Since IgM anti-HEV and HEV viremia were not detected, persons with IgG anti-HEV may be "subclinical HEV cases," or have long-lived antibodies in their circulation.

Australia antigen and hepatitis in Accra, Ghana.

Viral hepatitis in young adults in Accra, Ghana, is associated with Australia antigen (H.A.A.). Sera from 85 patients in hospital with viral hepatitis were available for determinations of H.A.A. Of the 16 patients whose serum was obtained within the first week of symptoms, 15 were positive. The only factor related to finding H.A.A. was the time between onset of symptoms and the collection of the serum sample. Persistence of H.A.A. was associated with persistence of jaundice in men but not in women. Previous epidemiological studies in Accra found no evidence for parenteral transmission of viral hepatitis and showed a shanty-town predilection pointing to faecal-oral transmission. It thus seems that H.A.A.-associated hepatitis is transmitted in West Africa either faecal-orally or by shanty-town associated arthropods. The finding that H.A.A. hepatitis is the usual hepatitis in young adults in Accra is in accord with the high prevalence of H.A.A. elsewhere in the general population in Africa and may be related to the high rate of cirrhosis and hepatoma in Africa.