Impact of prior HBV,HAV, and HEV infection on non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV) infection and NAFLD remains unclear. We utilized the 2017–2020 National Health and Nutrition Examination Survey (NHANES) and performed multivariable logistic regression analyses to examine the association of prior HBV, HAV and HEV infection with NAFLD, as well as high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis. Our analysis included 2565 participants with available anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD (cut-off 285 dB/m) [aOR: 0.99 (95% CI, 0.77–1.29), 1.29 (95% CI, 0.95–1.75), and 0.94 (95% CI, 0.70–1.27), respectively] or high-risk NASH [aOR 0.72 (95% CI, 0.45–1.17), 0.92 (95% CI, 0.55–1.52), and 0.89 (95% CI, 0.41–1.94), respectively]. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis [aOR: 1.53 (95% CI, 1.05–2.23) and 1.69 (95% CI, 1.16–2.47), respectively]. The odds of significant fibrosis are 53%, and 69% greater for participants with prior history of HBV and HAV infection. Healthcare providers should prioritize vaccination efforts and employ a tailored approach to NAFLD in patients with prior viral hepatitis and especially HBV or HAV infection to limit disease-related outcomes.     

349例重型病毒性肝炎的临床特点及病毒标志物检测结果分析

目的了解重型病毒性肝炎住院病例的临床及病原学特点,探讨慢性肝炎重症化及其预后的关系。方法采用回顾性调查方法,对349例重型病毒性肝炎的临床特点及病毒标志物检测结果进行分析。结果349例重型病毒性肝炎患者中,发生于急性肝炎的28例,发生于慢性肝炎有明确肝病史和无明确肝病史的分别为245例和76例;引起重型肝炎的病毒中以HBV单一或重叠感染率最高,占82.2%(287/349),6例(1.72%)未能确定病原,未发现单一HAV、HDV和HGV感染者,HBV重叠HEV感染者病死率为65.2%(15/23),HEV重叠其他肝炎病毒感染者的病死率为60%(18/30),均比单一HBV或单一HEV感染者高(P<0.01和P<0.05)。结论重型肝炎仍以HBV感染为主,HBV和HEV重叠感染可以加重病情、病死率高。     

Suppression of hepatitis B virus replication mediated by hepatitis A‐induced cytokine production

Abstract: Background: Acute hepatitis A virus (HAV) infection can cause severe hepatitis especially in patients with underlying chronic liver disease. In patients with pre‐existing chronic hepatitis B (HBV) acute HAV infection can suppress HBV replication. The exact mechanism of HBV suppression during acute HAV infection is still a subject of debate. One mechanism may be the production of HAV infection‐induced cytokines leading to suppression of HBV replication and viral clearance. Aim: To evaluate cytokine production and HBV‐specific lympho‐proliferative responses (LPR) during acute HAV infection in a patient with chronic HBV infection‐clearing markers of active HBV replication. Design: Early detection of a case of acute HAV infection in an HBeAg‐positive, HBV DNA‐positive chronic HBV patient treated with lamivudine. Results: At the time of HAV infection a sharp peak in the gamma‐interferon (IFN‐γ) level occurred just before the rise in serum transaminase activity. This was subsequently followed by a decrease in HBV DNA and HBeAg below the limit of detection of the assay. However the HBV‐specific T‐cell response was not modified. After resolution of the acute HAV infection and withdrawal of antiviral therapy HBV replication relapsed. Conclusion: The sharp rise in IFN‐γ production mediated by the acute HAV infection may be pivotal in the suppression of HBV replication in chronic hepatitis B.     

Can we foresee the end of the alphabet in viral hepatitis?

There is a number of viruses which may cause acute or chronic liver damage. Only some of them belong into the group of hepatotropic viruses and only the latter are the cause of acute or chronic viral hepatitis. So far we know seven hepatotropic viruses. The virus of hepatitis A (HAV), virus of hepatitis B (HBV), virus of hepatitis C (HCV), virus of hepatitis D (HDV), virus of hepatitis E (HEV), virus of hepatitis G (HGV) and Transfusion-Transmitted-Virus (TTV). For HAV and HEV orofaecal transmission is typical, the others are transmitted by the parenteral route. All cause acute hepatitis. Only HAV and HEV infections develop into the chronic stage. The decisive finding for the dynamic development of the problem of viral hepatitis was the discovery of the Australian antigen (Au antigen) by B. Blumberg in 1965. The discovery made it possible to recognize viral hepatitis B and by the application of new biotechnologies the genes of other viruses were detected. Some of them were not visualized so far. A great advance was alpha interferon and lamivudine treatment in patients with chronic hepatitis B and alpha interferon treatment along with ribavirine in chronic hepatitis C.     

Hepatitis e virus infection in fulminant hepatitis patients and an apparently healthy population in Bangladesh

This is the first study comparing hepatitis E virus (HEV) infection in Bangladesh in fulminant hepatitis (FH) patients presumed to have a viral cause and in the apparently healthy population. Sera from 22 FH patients were analyzed for antibodies to hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C and D viruses, and HEV and for hepatitis B surface antigen (HBsAg). Anti-HEV immunoglobulin M (IgM) was detected in the sera of 63.6% of patients, whereas 35.7% were positive for HBsAg. A high prevalence of HEV infection (83.3%) was noted in the HBV carriers. Serum samples from 273 apparently healthy individuals were tested for antibodies to HAV and HEV. Anti-HEV IgM was detected in 7.3% of the samples. The seroprevalence of HAV differed from that of HEV in the same population because all samples were negative for anti-HAV IgM. These data indicate that HEV infection is highly endemic in Bangladesh.     

Transfusion-transmitted virus in association with hepatitis A-E viral infections in various forms of liver diseases in India

AIM: To describe the prevalence of transfusion-transmitted virus (TTV) infection in association with hepatitis A-E viral infections in different forms of liver diseases in North India. METHODS: Sera from a total number of 137 patients, including 37 patients with acute viral hepatitis (AVH), 37 patients with chronic viral hepatitis (CVH), 31 patients with cirrhosis of liver and 32 patients with fulminant hepatic failure (FHF), were analyzed both for TTV-DNA and hepatitis A-E viral markers. Presence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis E virus (HEV) infections was detected in different proportions in different groups. Moreover, TTV-DNA was simultaneously tested in 100 healthy blood donors also. RESULTS: None of the patients had hepatitis A virus (HAV) and hepatitis D virus (HDV) infections. Overall prevalence of TTV-DNA was detected in 27.1% cases with AVH, 18.9% cases with CVH, 48.4% cases with cirrhosis and 9.4% cases with FHF. TTV-DNA simultaneously tested in 100 healthy blood donors showed 27% positivity. On establishing a relation between TTV infection with other hepatitis viral infections, TTV demonstrated co-infection with HBV, HCV and HEV in these disease groups. Correlation of TTV with ALT level in sera did not demonstrate high ALT level in TTV-infected patients, suggesting that TTV does not cause severe liver damage. CONCLUSION: TTV infection is prevalent both in patients and healthy individuals in India. However, it does not have any significant correlation with other hepatitis viral infections, nor does it produce an evidence of severe liver damage in patients with liver diseases.     

血液透析与病毒性肝炎的关系

目的：探讨血液透析与病毒性肝炎的关系。方法：采用酶联免疫法检测每例患者的ＨＡＶ，ＨＣＶ，ＨＤＶ，ＨＥＶ及ＨＢｓＡｇ并对血透各组和非透析组进行对比分析，结果：ＨＡＶ，ＨＤＶ，ＨＥＶ和ＨＢｓＡｇ的阳性率在各组单元差异；ＨＣＶ的阳性率在血透组和非血透组之间差异非常显著，且随着血透时间延长而增加，５年以上组达１００％，ＨＣＶ阳性率与是否输过血无关，结论：血透并不导致增加甲，乙，丁，戊型肝炎的感染，但明显增     

广州市自然人群病毒性肝炎血清流行病学研究

目的了解广州市自然人群病毒性肝炎的血清流行病学特征。方法采取分层多级整群系统随机抽样方法抽取研究对象,对其作流行病学个案调查,并应用酶联免疫吸附试验（ELISA法）检测病毒性肝炎各感染标志物。结果广州市自然人群HAV、HBV、HCV、HDV、HEV、HGV感染率分别为74．47％、64．10％、0．65％、0．13％、1．69％和0．65％;HAV、HBV和HEV的感染率在老城区、新城区和郊市区中的差异有高度显著性意义（P〈0．01）,而HCV、HDV和HGV的差异无显著性意义（P〉0．05）;HBV感染率在男女之间差异有高度显著性意义（P〈0．01）,HCV感染率在男女之间差异有显著性意义（P〈0．05）,而HAV、HDV、HEV和HGV的感染率则无性别差异（P〉0．05）;HAV、HBV、HCV、HDV、HEV、HGV最低感染年龄分别为2岁、2岁、20岁、31岁、5岁和13岁,最高感染年龄分别为90岁、86岁、46岁、67岁、74岁和71岁;HAV、HBV和HEV感染率均与年龄呈正相关（P〈0,01、P〈0,01和P〈0．05）。结论广州市自然人群各型病毒性肝炎感染具有不同的流行病学特征,其中HAV和HBV的感染率较高,HCV、HDV、HEV和HGV的感染水平则较低。     

妊娠期病毒性肝炎对围产儿的影响

目的 探讨妊娠期病毒性肝炎对围产儿的影响。方法 测定４７名正常孕妇和４９５例病毒性肝炎孕妇所生新生儿Ａｐｇａｒ评分和出生时体重,并检测新生儿血清肝炎病毒标志。结果 肝炎孕妇所生新生儿Ａｐｇａｒ评分和出生时体重均显著低于对照组（均Ｐ〈０．０１）,急性肝炎孕妇所生新生儿１ｍｉｎ Ａｐｇａｒ评分和出生时体重均显著低于乙型肝炎病毒（ＨＢＶ）携带和慢性肝炎组（均Ｐ〈０．０１）,甲型肝炎未见宫内感染。ＨＢＶ,     

Incidence of HAV and HBV infections and vaccination rates in patients with autoimmune liver diseases

OBJECTIVES: Hepatitis A virus (HAV) or hepatitis B virus (HBV) superinfection is associated with an increased mortality in patients with chronic liver diseases (CLD). Despite official recommendations, it was reported that the vaccination rate against HAV is low in patients with chronic hepatitis C infection. To evaluate the situation in patients with autoimmune liver diseases, we conducted a retrospective cohort study. METHODS: Susceptibility to HAV and HBV infections, course of HAV and HBV infections, vaccination rates against HAV and HBV, and efficacy of hepatitis A/B vaccines were evaluated by antibody testing in 225 patients with autoimmune liver diseases during 1,677 person-years. RESULTS: Susceptibility to HAV/HBV infection was 51/86%. Incidence of HAV/HBV infection was 1.3/1.4 per 1,000 person-years. One HAV infection occurred, but the patient recovered spontaneously. Two patients were HBV-infected after receiving an anti-HBc-positive (antibody to hepatitis B core antigen) donor graft during orthotopic liver transplantation, and one of them developed chronic HBV infection. Vaccination rates were 11% (HBV) and 13% (HAV), respectively. Seventy-six percent of the vaccinated patients (HBV vaccine) developed anti-HBs (antibody to hepatitis surface antigen) >or=10 UI/L. Ten out of 13 vaccinated patients, showing a low or nonresponse to hepatitis B vaccine, had concomitant immunosuppressive therapy. Anti-HAV was detectable in all patients after administration of HAV vaccine. CONCLUSIONS: Patients with autoimmune liver diseases have a high susceptibility to HAV and HBV infections. Vaccination rates are low in this patient cohort and efficacy of hepatitis B vaccine is reduced due to immunosuppressive therapy. Improving adherence to vaccine recommendations is essential to prevent HAV and HBV infections in patients with autoimmune liver diseases.     

戊型肝炎病毒与甲乙丙型肝炎病毒重叠感染的研究

本文对419例病毒性肝炎患者进行抗-HEV-IgM/IgG及其它病毒标志物检测。结果:HEV感染者112例(26.2％);其中单纯HEV感染者30例,两种以上肝炎病毒重叠感染占73.2％;43.75％为HBV和HEV重叠感染,HAV和HEV合并感染占急性肝炎的40.58％。在重型肝炎中HEV感染率占57.89％,均为HBV和HEV重叠感染,病死率达72.73％。16.67％的单纯HEV感染者为慢性肝炎和肝硬变。结果表明,本地区戊型肝炎以散发为主,重叠感染多见。HBV与HEV重叠感染和HAV与HEV重叠感染是较常见的感染模式。在HBV感染的基础上重叠HEV感染是肝炎重症化的重要原因。HEV感染有导致慢性化的可能性。     

Virushepatitis A und E

Infections with hepatitis A (HAV) and E viruses (HEV) represent important differential diagnoses of acute viral hepatitis. Both viruses are primarily transmitted via the fecal-oral route. A vaccine is so far only approved for HAV infections in Germany. The nationwide incidence in 2011 was 1 (HAV) and 0.3 (HEV) cases of the disease per 100,000 inhabitants although in recent years there has been a substantial increase in HEV infections. Both infections present clinically as acute and self-limiting hepatitis. Fulminant courses are rare and HAV infections are mostly associated with advanced age or preexisting liver disease and HEV infections are additionally associated with the second or third trimester of pregnancy. In immunosuppressed patients an HEV infection can become chronic while no chronic cases have been described for HAV infections. The diagnosis is based on the detection of HAV and HEV-specific antibodies as well as detection of HEV RNA. A specific therapy for acute HAV and HEV infections does not exist but a supportive therapy is normally sufficient. Fulminant and chronic HEV infections can be treated with ribavirin. In extremely rare cases a fulminant course can lead to liver failure and in this case liver transplantation represents the only therapy option.     

中国北方地区321例乙型肝炎病毒相关肝细胞癌患者的流行病学和临床特征分析

背景:我国是肝细胞癌(HCC)高发区,其中大部分HCC与乙型肝炎病毒(HBV)感染相关,有必要对其自然史和临床进程作大样本调查研究。目的:了解中国北方地区HBV相关HCC患者的流行病学和临床特征。方法:对中国北方地区321例HBV相关HCC患者作流行病学问卷调查,行肝功能、甲胎蛋白(AFP)、HBV血清标志物和HBV DNA水平检测,并进行统计分析。结果:321例HBV相关HCC患者中,仅7.2%接受过抗病毒治疗;46.4%和25.5%分别有肝硬化和肝癌家族史;38.3%有饮酒史。21.0%的患者乙型肝炎e抗原(HBeAg)阳性,62.3%乙型肝炎e抗体(HBeAb)阳性,HBeAg阳性者合并肝硬化的比例和HBV DNA水平较高。84.5%的患者HBV DNA阳性,但其中仅42.6%HBV DNA≥5.0log10,HBV DNA高水平者合并肝硬化的比例显著高于HBV DNA低水平者。无症状HBV感染、慢性乙型肝炎、代偿性和失代偿性肝硬化患者分别占4.1%、24.1%、39.0%和32.9%。71.0%的患者AFP升高,但其中仅33.8?P≥400ng/ml。结论:本组HBV相关HCC患者中,HBeAg阳性和高HBV DNA水平者不多,但病情常较重。肝硬化是HCC的重要危险因素,饮酒和肝癌家族史对HCC的发生有一定影响。血清AFP筛查有助于HCC的诊断。     

Hepatitis E virus superinfection in patients with chronic liver disease

Infection with hepatitis A virus (HAV) can cause severe illness in adult patients with chronic liver disease (CLD) caused by hepatitis C. In endemic areas such as South Asia, however, most adult patients already have been exposed to HAV but could still be susceptible to hepatitis E virus (HEV) infection. We document that HEV superinfection in 4 of our CLD patients caused severe liver decompensation. We then determined the seroprevalence of HAV and HEV in 233 patients with stable CLD, with the goal of defining the need for protection against these viruses in these patients. Overall, 41 (17.5%) of 233 CLD patients were HEV antibody immunoglobulin G (IgG)-positive, and 228 of 233 (97.8%) were HAV IgG-positive. As controls, we tested 90 age- and sex-matched healthy volunteer blood donors for HAV and HEV antibodies IgG. There was no difference in the percentage of CLD patients and blood donors positive for HEV antibody IgG (17.7% vs. 17.5%) or for HAV IgG (97.8% vs. 94%). No differences were observed in the severity of liver disease between previously HEV-exposed and -nonexposed patients. In conclusion, superinfection with HEV in patients with underlying CLD can cause severe hepatic decompensation leading to increased morbidity and mortality. The large majority of adult CLD patients in endemic countries are vulnerable to infection with HEV, but are protected against hepatitis A, and are ideal candidates for an HEV vaccine.     

庚型肝炎临床和病理特征

目的探讨庚型肝炎（ＨＧ）临床和病理特征。方法采用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）检测血清ＨＧＶＲＮＡ；用庚型肝炎病毒（ＨＧＶ）ＮＳ５区抗原制备单克隆抗体（ＭｃＡｂ），对２２例临床和／或病理确诊的急、慢性庚型肝炎进行肝脏免疫组化。结果ＨＧＶ感染的血清学模式以重叠ＨＢＶ，ＨＣＶ，ＨＡＶ或ＨＥＶ二重感染为主，占６３．６％（１４／２２），单独ＨＧＶ感染者占３６．４％（８／２２）；ＨＧＶ在肝脏内分布呈散在胞浆型。结论ＨＧＶ单独感染者临床多呈隐匿性发病，症状轻，慢性化程度高     

What did we learn from the Shanghai hepatitis A epidemic?

A major outbreak of hepatitis A (HAV), associated with consumption of raw clams, occurred in Shanghai, China in 1988. Over 300 000 cases were reported, of which 47 (0.015%) were fatal. An elevated mortality rate was observed in hepatitis B surface antigen (HBsAg)-positive patients (0.05%). The majority of these patients were also hepatitis B e antigen (HBeAg)-positive, indicating active liver disease and high viral replication rates. The increased mortality in hepatitis B virus (HBV)/HAV coinfected individuals is hypothesized to be the result of T-cell-mediated destruction of HBV-infected hepatocytes, enhanced by acute HAV infection. Following recovery from HAV there is an increase in HBV expression and activated cytotoxic cells and subsequent cytolysis. Patients with chronic HBV infection are clearly at considerable risk of severe disease and increased mortality in the event of HAV infection. The period of greatest risk is during the immunoeliminative phase of HBV infection, which generally occurs in early adulthood. With the prevalence of HBV approaching 10% in this group, there is a clear opportunity for benefit from vaccination.     

Antibodies to Hepatitis E and A Viruses among Patients with Non-Alcoholic Chronic Liver Disease in Taiwan

Tsai J-F, Jeng J-E, Chang W-Y, Lin Z-Y, Tsai J-H. Antibodies to hepatitis E and A viruses among patients with non-alcoholic chronic liver disease in Taiwan. Scand J Gastroenterol 1994;29:651-654

Background: The prevalence of hepatitis E virus (HEV) and hepatitis A virus (HAV) infection in patients with non-alcoholic chronic liver disease (CLD) was assessed.

Methods: Antibody levels to HEV (anti-HEV) and HAV (anti-HAV) were evaluated in 100 pairs of CLD patients and healthy controls.

Results: The prevalence of anti-HEV was higher in patients (10.0%) than in controls (0%; p = 0.0001). There was no difference in anti-HAV positivity between patients (95%) and controls (93%). The patient group with anti-HEV was older (p equals; 0.024) and had more smokers (p equals; 0.03), having a higher prevalence of antibodies to hepatitis C virus (p equals; 0.02). Patients with anti-HAV were older than patients without (p equals; 0.0001). The prevalence of anti-HAV in patients more than 30 years old was higher than younger patients (95.1% versus 73.6%, p equals; 0.011). Conclusion: HEV may superinfect on chronic liver disease in an area hyperendemic for hepatitis A and B.     

Double infections with hepatitis A and B viruses

Ten (2.8%) asymptomatic carriers of HBsAg and four (1.1%) patients with acute hepatitis B virus (HBV) infection were detected among 356 adults with acute viral hepatitis A (HAV) consecutively admitted to the Athens Hospital for Infectious Diseases from May 1981 to March 1984. These patients did not differ in clinical, epidemiologic (except in age), biochemical or serologic characteristics from patients acutely infected with HAV alone. Transient suppression of the HBV replication and disappearance of the HBV DNA accompanied by seroconversion from HBeAg positive to anti-HBe positive were detected in one and two carriers respectively. The titer of non-class-specific anti-HBc was low (less than or equal to 10(-2)) in all cases. These data suggest that superinfection of HBsAg carriers with HAV does not cause more severe disease or influence adversely the course of chronic hepatitis B disease. However, accurate diagnosis of double infections is necessary for prognosis of the liver disease and appropriate management of the patient's environment. This is quite important in areas with a high prevalence of HBV infections, like Greece, where double infections are relatively common.     

Seroprevalence of anti-HAV among patients with chronic viral liver disease

AIM:To investigate the current seroprevalence of hepatitis A virus(HAV) antibodies in patients with chronic viral liver disease in Korea.We also tried to identify the factors affecting the prevalence of HAV antibodies. METHODS:We performed an analysis of the clinical records of 986 patients(mean age:49±9 years,714 males/272 females) with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009.RESULTS:The overall prevale...     

Spectrum of viral hepatitis in thalassemic children receiving multiple blood transfusions.

AIM: To investigate the prevalence of infection with hepatitis viruses in children with thalassemia receiving multiple blood transfusions. METHODS: Sera from 50 children with thalassemia aged 5-15 years (30 boys), who had each received over 80 units of blood, were evaluated for the presence of markers for hepatitis A virus (HAV; IgG and IgM anti-HAV), hepatitis B virus (HBV; HBsAg, and IgG and IgM anti-HBc), hepatitis C virus (HCV; IgG and IgM anti-HCV, and HCV RNA) and hepatitis E virus (HEV; IgG and IgM anti-HEV). IgM anti-hepatitis D virus (HDV) was looked for only in HBsAg or IgM anti-HBc positive sera. RESULTS: No child had evidence of recent HAV or HDV infection. IgG anti-HAV was positive in 12 children. One patient had acute HBV infection. Nine patients were HBsAg-positive. HCV infection was present in 15 cases; six of them were HCV RNA positive, and three had superinfection with hepatitis B. Recent HEV infection was present in 5 cases. CONCLUSION: Thalassemic patients receiving multiple blood transfusions often acquire hepatitis B (20%) and C (30%) infections. Recent hepatitis E infection was documented in 10% in this one-point study.