Hepatitis E virus superinfection impairs long-term outcome in hospitalized patients with hepatitis B virus-related decompensated liver cirrhosis

Introduction and objectivesHepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis.Patients and methodsA retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed.ResultsAfter a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p< 0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40–4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87–17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM.ConclusionsElder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.     

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.     

Superimposed acute hepatitis E infection in patients with chronic liver disease.

BACKGROUND: The natural history of infection with hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is not well described. Our study aims to document the presentation, course and outcome of HEV superinfection in patients with CLD. METHODS: Over an 18-month period, ten patients with CLD were diagnosed to have HEV superinfection by detection of anti-HEV IgM antibodies in a setting of acute worsening. These patients were tested for HBsAg, IgM anti-HBc, anti-hepatitis C virus antibodies and IgM anti-hepatitis A virus antibodies, and were followed-up. RESULTS: The etiology of underlying CLD in the 10 patients (9 men; mean [SD] age 42.4 [10.3] years) was alcohol in five patients, hepatitis B in two, hepatitis C in one and cryptogenic in two. Seven patients presented for the first time with recent-onset liver decompensation (median duration 27 days, range 7-45). All 10 had ascites and 7 had hepatic encephalopathy. Four patients developed renal failure during the course of illness. The median (range) bilirubin, ALT and albumin levels at presentation were 18.6 (4.9-32.6) mg/dL, 105 (28-6610) IU/L and 32 (29-41) g/L, respectively. At 8 weeks, only one patient had normalization of serum bilirubin or ALT levels. Three patients (30%) died, including two of renal failure and one of massive upper GI bleed. CONCLUSIONS: Superinfection with HEV in patients with CLD causes severe liver decompensation, which is frequently complicated with hepatic encephalopathy and renal failure. Acute hepatitis E in these patients has a protracted course with high morbidity and mortality.     

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.     

Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease

Background and Aim: Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)‐infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV‐infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Methods: Forty‐three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti‐HBc) (?); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow‐up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Results: Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (?) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (?) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8–48]vs 16 [6–36] weeks, P = 0.001). During convalescence, there was no significant difference between histological activity index score (median [range] 8 [4–11]vs 8 [4–16] weeks, P = 0.629) and fibrosis scores (median [range] 3.5 [1–4]vs 2 [1–4] weeks, P = 0.099] on liver biopsy after recovery among patients with acute exacerbation due to superinfection and spontaneous exacerbation. Conclusions: Acute exacerbations in HBeAg (+) patients are most often due to spontaneous viral activation, while in HBeAg (?) patients, superinfection with non‐B hepatitis viruses and spontaneous viral activation are equally common. HEV is an important cause of acute exacerbation in previously asymptomatic and unrecognized patients with HBV‐related CLD.     

Chronic liver disease in central Harlem: the role of alcohol and viral hepatitis

For reasons not yet determined, chronic liver disease (CLD) has been a leading cause of excess morbidity and mortality in central Harlem. We conducted a case series and case-control analysis of demographic, clinical, epidemiological, and alcohol-intake-related information from patients with CLD and age- and sex-matched hospitalized control patients. Patients' sera were tested for markers of viral hepatitis. The presumed etiology of CLD among case-patients was as follows: both alcohol abuse and hepatitis C virus (HCV) infection, 24 persons (46% of case-patients); alcohol abuse alone, 15 (29%); HCV infection alone, 6 (12%); both alcohol abuse and chronic hepatitis B virus (HBV) infection, 3 (6%); and 1 each (2%) from: 1) schistosomiasis, 2) sarcoidosis, 3) unknown causes, and 4) alcohol abuse, chronic HBV, and HCV combined. In the case-control analysis, patients who had both alcoholism and either HBV (odds ratio [OR]: 6.3; 95% CI: 0. 5-334) or HCV (OR: 2.9; 95% CI: 1.3-6.2) were at increased risk for CLD, whereas patients who had only one of these three factors were not at increased risk for CLD. Patients who tested positive for the hepatitis G virus (HGV) did not have a significantly increased risk of CLD, and neither severity of CLD nor mortality was greater among these patients. Most patients in central Harlem who had CLD had liver damage from a combination of alcohol abuse and chronic viral hepatitis. Alcohol and hepatitis viruses appear to be synergistically hepatotoxic; this synergy appears to explain both the high rate of CLD in central Harlem and the recent reductions in this rate. Persons at risk for chronic HBV and HCV infection should be counseled about their increased risk of CLD if they consume excessive alcohol. Morbidity and mortality from liver disease could be decreased further by a reduction in alcohol consumption among persons who have chronic HBV and HCV infection, avoidance of needle sharing, and hepatitis B 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.     

Abnormal liver tests in patients hospitalized with Coronavirus disease 2019: Should we worry?

While several studies from China have reported COVID‐19‐related liver injury, there are currently no data on liver dysfunction in hospitalized COVID‐19 patients in Europe. The aim of this study was to describe the prevalence and predictive value of abnormal liver function in patients hospitalized with COVID‐19. This was a retrospective cohort study of confirmed COVID‐19 patients hospitalized in two referral hospitals in France. Clinical, biological and radiological data were collected and analysed. In all, 234 patients confirmed to have COVID‐19 by RT‐PCR were included. Liver function was abnormal in 66.6% of patients on admission. In multivariate logistic regression, abnormal liver test on admission were associated with in‐hospital aggravation (OR = 4.1, 95% CI 1.5‐10.8; P = .004) and mortality (OR 3.3; 95% CI = 1.04‐10.5; P = .04). This study of liver tests in a European COVID‐19 population confirms a high prevalence of abnormal liver tests on admission that are predictive of severe disease course and higher in‐hospital mortality.     

Hepatitis E in solid organ transplant recipients: A systematic review and meta-analysis

BACKGROUNDHepatitis E virus (HEV) infection is underdiagnosed due to the use of serological assays with low sensitivity. Although most patients with HEV recover completely, HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death.AIMTo demonstrate the prevalence of HEV infection in solid organ transplant (SOT) recipients. METHODSWe searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through October 2020. The inclusion criteria consisted of adult patients with history of SOT. HEV infection is confirmed by either HEV-immunoglobulin G, HEV-immunoglobulin M, or HEV RNA assay.RESULTSOf 563 citations, a total of 22 studies (n = 4557) were included in this meta-analysis. The pooled estimated prevalence of HEV infection in SOT patients was 20.2% [95% confidence interval (CI): 14.9-26.8]. The pooled estimated prevalence of HEV infection for each organ transplant was as follows: liver (27.2%; 95%CI: 20.0-35.8), kidney (12.8%; 95%CI: 9.3-17.3), heart (12.8%; 95%CI: 9.3-17.3), and lung (5.6%; 95%CI: 1.6-17.9). Comparison across organ transplants demonstrated statistical significance (Q = 16.721, P = 0.002). The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries. The pooled estimated prevalence of de novo HEV infection was 5.1% (95%CI: 2.6-9.6) and the pooled estimated prevalence of acute HEV infection was 4.3% (95%CI: 1.9-9.4).CONCLUSIONHEV infection is common in SOT recipients, particularly in middle-income countries. The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants. More studies examining the clinical impacts of HEV infection in SOT recipients, such as graft failure, rejection, and mortality are warranted.     

Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease

BACKGROUND AND AIMS: The adverse effect of acute hepatitis A in chronic liver disease is well known. The outcome of acute hepatitis E in chronic liver disease has not been extensively studied. The present study aimed to examine the clinical profile and outcome of patients with chronic liver disease and hepatitis E virus (HEV) superinfection, and the seroprevalence of hepatitis A and E infections in patients with chronic liver disease and controls in India. METHODS: A retrospective study of patients with chronic liver disease and acute icteric hepatitis E was performed. Acute hepatitis E was diagnosed by immunoglobulin (Ig)M ELISA. Seroprevalence studies were carried out using IgG ELISA in 100 patients with chronic liver disease and 79 age- and sex-matched controls. RESULTS: From June 2001 to December 2002, nine patients with chronic liver disease were found to have superinfection with HEV. Out of these, six patients died of advanced liver failure. The etiology of liver disease was Wilson's disease in six, hepatitis B virus in one, autoimmune in one and cryptogenic in one case. The seroprevalence of hepatitis A was 99 and 100% and 56 and 21% for HEV in cases and controls, respectively. CONCLUSIONS: Acute HEV in patients with chronic liver disease has a grave prognosis. Wilson's disease was the most common cause of chronic liver disease complicated by acute HEV. Seroprevalence studies showed that 44% of patients with chronic liver disease were at risk of developing hepatitis E. Hepatitis E vaccine, when available, is indicated for use in this group.     

Influence of chronic HBV infection on superimposed acute hepatitis E

AIM:To investigate the influence of chronic hepatitis B virus(HBV)infection[based on the status of hepatitis B e antigen(HBeAg),HBV DNA,and cirrhosis]on superimposed acute hepatitis E.METHODS:A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital,Sun Yat-sen University,from January 2003 to January 2012.The patients were classified into two groups:an HBV+hepatitis E virus(HEV)group(a group with chronic HBV infection that was superinfected with acute hepatitis E,n=118)and an HEV group(a group with acute hepatitis E,n=176).We retrospectively analyzed and compared the clinical features of the two groups.Statistical analyses were performed using theχ2test or Fisher’s exact test for categorical variables and the Student’s t test forcontinuous variables.A P value<0.05 was considered statistically significant.RESULTS:The peak values of prothrombin time,serum total bilirubin,and Model for End-Stage Liver Disease scores were significantly higher in the HBV+HEV group.More patients in the HBV+HEV group had complications(39.8%vs 16.5%,P=0.000)and developed liver failure(35.6%vs 8.5%,P=0.000).Additionally,the mortality of the HBV+HEV group was significantly higher(20.3%vs 7.4%,P=0.002).Further analysis of the HBV+HEV group showed that there were no significant differences in complication occurrence,liver failure incidence,or mortality between patients with different HBeAg and HBV DNA statuses.However,in patients with underlying cirrhosis,complication occurrence and liver failure incidence significantly increased.In total,12.7%of the patients in the HBV+HEV group received anti-HBV treatment,but this therapy failed to reduce mortality in patients who developed liver failure.CONCLUSION:The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E.AntiHBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.     

Hepatitis C Virus Infection among Patients with Chronic Liver Disease in an Area Hyperendemic for Hepatitis B

Tsai J-F, Jeng J-E, Chang W-Y, Lin Z-Y, Tsai J-H. Hepatitis C virus infection among patients with chronic liver disease in an area hyperendemic for hepatitis B. Scand J Gastroenterol 1994;29:550-552.

Background: The prevalence of hepatitis C virus (HCV) infection was assessed in patients with nonalcoholic chronic liver disease (CLD).

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

Results: The prevalence of anti-HCV was higher in patients (26.0%) than in controls (2.0% p = 0.0001). The patient group with anti-HCV was older (p equals; 0.0001) and had more smokers (p equals; 0.034), fewer hepatitis B surface antigen carriers (p equals; 0.0001), and more patients with active liver disease (p equals; 0.023) and a history of blood transfusion (p equals; 0.026). Multivariate analysis showed that anti-HCV (odds ratio, 8.1; 95% confidence intervals, 3.7-17.6) was strongly associated with CLD.

Conclusions: HCV infection is a risk factor of non-alcoholic CLD, and HCV causes more severe hepatocellular damage than HBV.     

慢性乙型肝炎患者重叠戊型肝炎病毒感染的临床与病理学研究

目的：观察重叠戊型肝炎病毒（HEV）感染对慢性乙型肝炎（CHB）肝脏损害及HBV复制的影响。方法：应用ELISA法对122例CHB患者血清进行了抗－HEV IgkM,IgG检测,同时应用肝穿刺活检、荧光定量PCR及免疫组化等技术对重叠与未重叠HEV感染者分别进行了ALT、总胆红素（TBil)、凝血酶原活动度（PTA）、白蛋白／球蛋白（A／G）、电泳γ球蛋白（γ－EP）水平、肝脏病理学、血清HBeAg及肝组织HBcAg阳性率、血清及肝组织中HBV DNA含量对比。具有可比性的重叠（7例）与未重叠HEV感染者（14例）1年后做第2次肝穿活检并做病理学比较;HBeAg阴性重叠HEV感染者8例做HEV感染急性期、恢复期血清HBeAg定性、HBV DNA含量对比。结果：重叠HEV感染者21例（17．2％）。重叠HEV感染者较未重叠感染者ALT、TBil增高,PTA降低（P＜0．05）,但A／G、γ－EP水平未见显著差别（P＞0．05）;血清HBeAg及肝组织HBcAg阳性率、血清及肝组织HBV DNA含量低（P＜0．05）;肝组织炎症活动度重（P＜0．05）,但纤维化程度未见明显差别（P＞0．05）。两组患者1年前肝组织炎症活动度及纤维化程度无显著差别,1年后仍无显著差别（P＞0．05）。HEV感染恢复期血清HBeAg阳性率、HBV DNA含量高于急性期（P＜0．05）。结论：重叠HEV感染可加重CHB肝组织炎症活动度;对HBV复制具有短暂抑制作用。     

Predictors of peri-opertative morbidity and liver dysfunction after hepatic resection in patients with chronic liver disease

BackgroundHepatic resection in patients with chronic liver disease (CLD) is associated with a risk of post-operative liver failure and higher morbidity than patients without liver disease. There is no universal risk stratification scheme for CLD patients undergoing resection.ObjectivesThe aim of the present study was to evaluate the association between routine pre-operative laboratory investigations, model for end-stage liver disease (MELD), indocyanine green retention at 15 min (ICG15) and post-operative outcomes in CLD patients undergoing liver resection.MethodsA retrospective review of patients undergoing resection for hepatocellular carcinoma (HCC) at the University Health Network was preformed. ICG15 results, pre- and post-operative laboratory results were obtained from clinical records. Adjusted odds ratios (AOR) were calculated for associations between pre-operative factors and post-operative outcomes using multivariate logistic regression adjusting for patient age and number of segments resected.ResultsBetween 2001 and 2005, 129 CLD patients underwent surgical resection for HCC. Procedures included 51 (40%) resections of ≤2 segments, 52 (40%) hemihepatectomies and 25 (19%) extended hepatic resections. Thirty- and 90-day post-operative mortality was 1.6% and 4.1%, respectively. Prolonged (>10 days) hospital length of stay (LOS) was independently associated with an ICG15 >15% {AOR [95% confidence interval (CI)]= 8.5 (1.4–51)} and an international normalized ratio (INR) > 1.2 [AOR (95% CI) = 5.0 (1.4–18.6)]. An ICG15 > 15% and MELD score were independent predictors of prolonged LOS. An ICG15 > 15% was also independently associated with MELD > 20 on post-operative day 3 [AOR (95% CI) = 24.3 (1.8–319)].ConclusionsElevated ICG retention was independently associated with post-operative liver dysfunction and morbidity. The utility of ICG in combination with other biochemical measures to predict outcomes after hepatic resection in CLD patients requires further prospective study.A possible role for ICG clearance in predicting outcome following hepatic resection for hepatocellular carcinoma     

Severe hepatitis E infection during pregnancy

In areas with endemic hepatitis E virus (HEV), acute liver failure secondary to hepatitis E infection is common in pregnancy and associated with a mortality rate of up to 20%. However, there is little information on the clinical course of severe hepatitis E infection during pregnancy in non-endemic areas such as the UK. Here we describe two cases of severe hepatitis E in pregnancy in patients returning from the Indian subcontinent. These cases were diagnosed by the detection of IgM anti-HEV antibody using an enzyme immunoassay with recombinant hepatitis E viral antigens. The first case describes acute hepatic failure, with coagulopathy and encephalopathy, warranting intensive therapy and elective ventilation. In the other case, the patient had severe hepatitis with coagulopathy. Both cases spontaneously resolved with no foetal loss. These cases highlight the need for suspicion of HEV infection in patients returning from endemic areas and presenting with acute non-A non-B hepatitis, especially when pregnant. Furthermore, the intensive treatment of acute liver failure caused by HEV may reduce the high mortality reported in Asia.     

Relationship between polymorphisms near the IL28B gene and spontaneous HBsAg seroclearance: a systematic review and meta‐analysis

Polymorphisms near the interleukin (IL) 28B gene have been proposed to be associated with spontaneous clearance of the hepatitis C virus. The purpose of this study was to assess the relationship between IL28B polymorphisms and the rate of spontaneous hepatitis B surface antigen (HBsAg) seroclearance by means of meta‐analysis. MEDLINE/PubMed and EMBASE were utilized to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together to assess the strength of the association. Subgroup analyses were mainly performed according to ethnicity. A total of 4028 cases with persistent chronic hepatitis B and 2327 spontaneously recovered controls were included from 11 studies. The single nucleotide polymorphism (SNP), rs12979860, had no significant association with HBsAg seroclearance (OR = 0.98, 95% CI: 0.84–1.14 in the dominant model; OR = 1.00, 95% CI: 0.68–1.46 in the recessive model; and OR = 0.95, 95% CI: 0.82–1.09 in the allelic model). The SNP, rs12980275, had no significant association either (OR = 1.03, 95% CI: 0.84–1.26 in the dominant model; OR = 1.17, 95% CI: 0.46–2.96 in the recessive model; and OR = 1.04, 95% CI: 0.86–1.26 in the allelic model), nor did the SNP, rs8099917 (OR = 0.94, 95% CI: 0.77–1.15 in the dominant model; OR = 0.74, 95% CI: 0.34–1.62 in the recessive model; and OR = 0.93, 95% CI: 0.77–1.13 in the allelic model). Similarly, the results of subgroup analyses by ethnicity also showed no association in either the Asian group or non‐Asian group. We concluded that there was no significant association between common IL28B polymorphisms and the rate of spontaneous HBsAg seroclearance.     

Severe hepatitis E infection during pregnancy

In areas with endemic hepatitis E virus (HEV), acute liver failure secondary to hepatitis E infection is common in pregnancy and associated with a mortality rate of up to 20%. However, there is little information on the clinical course of severe hepatitis E infection during pregnancy in non-endemic areas such as the UK. Here we describe two cases of severe hepatitis E in pregnancy in patients returning from the Indian subcontinent. These cases were diagnosed by the detection of IgM anti-HEV antibody using an enzyme immunoassay with recombinant hepatitis E viral antigens. The first case describes acute hepatic failure, with coagulopathy and encephalopathy, warranting intensive therapy and elective ventilation. In the other case, the patient had severe hepatitis with coagulopathy. Both cases spontaneously resolved with no foetal loss. These cases highlight the need for suspicion of HEV infection in patients returning from endemic areas and presenting with acute non-A non-B hepatitis, especially when pregnant. Furthermore, the intensive treatment of acute liver failure caused by HEV may reduce the high mortality reported in Asia.     

Hepatitis E virus antibody prevalence among persons who work with swine.

Prevalence of antibody and risk factors to hepatitis E virus (HEV) infection were determined in a cross-sectional study of 2 group-matched populations: swine farmers (n=264) and persons without occupational exposure to swine (n=255) in Moldova, a country without reported cases of hepatitis E. The prevalence of HEV infection was higher among swine farmers than among the comparison group (51.1% vs. 24.7%; prevalence ratio, 2.07; 95% confidence interval [CI], 1.62-2.64). In multivariate analysis, HEV infection was associated with an occupational history of cleaning barns or assisting sows at birth (odds ratio [OR], 2.46; 95% CI, 1.52-4.01), years of occupational exposure (OR, 1.04 per year; 95% CI, 1.01-1.07), and a history of drinking raw milk (OR, 1.61; 95% CI, 1.08-2.40). HEV infection was not associated with civilian travel abroad or having piped water in the household. The increased prevalence of HEV infection among persons with occupational exposure to swine suggests animal-to-human transmission of this infection.     

Novel predictors and adverse long-term outcomes of No-reflow phenomenon in patients with acute ST elevation myocardial infarction undergoing primary percutaneous coronary intervention

ObjectivesThe no-reflow phenomenon occurs in 25% of patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), and may be associated with adverse outcomes. The aim of our study was to detect novel predictors of no-reflow phenomenon and the resulting adverse long term outcomes.MethodsWe enrolled 400 STEMI patients undergoing primary PCI; 228 patients had TIMI flow 3 after PCI (57%) and the remaining 172 patients had TIMI flow <3 (43%). Fibrinogen to albumin ratio (FAR), high sensitive C-reactive protein to albumin ratio (CAR), and atherogenic index of plasma (AIP) were calculated. Long term mortality and morbidity during 6 months follow up were recorded. These data were compared among both groups.ResultsIn multivariate regression analysis, old age (OR = 1.115, 95% CI: 1.032–1.205, P = 0.006), higher troponin level >5.6 ng/mL (OR = 1.040, 95% CI: 1.001–1.080, P = 0.04), diabetes mellitus (OR = 4.401, 95% CI: 1.081–17.923, P = 0.04) and heavy thrombus burden (OR = 16.915, 95% CI: 5.055–56.602, P < 0.001) could be considered as predictors for the development of no-reflow. Interestingly, CAR >0.21, FAR >11.56, and AIP >0.52 could be considered as novel powerful independent predictors (OR = 3.357, 95% CI: 2.288–4.927, P < 0.001, OR = 4.187, 95% CI: 2.761–6.349, P < 0.001, OR = 16.794, 95% CI: 1.018–277.01, P = 0.04, respectively). Higher long term mortality (P < 0.001) and heart failure (P < 0.001) was also strongly related to incidence of no-reflow.ConclusionNo-reflow could be attributed to novel predictors as CAR, FAR, and AIP. This phenomenon was associated with long term adverse events as higher mortality and pump failure.