Autochthonous hepatitis E in Southwest England: a comparison with hepatitis A.

The incidence of hepatitis A is falling. In contrast, autochthonous hepatitis E is an emerging infection in developed countries. The objective of this study was to compare both laboratory-confirmed cases of hepatitis A and autochthonous hepatitis E over a 2-year period in Cornwall and Devon and anti-hepatitis A virus (HAV) IgG and anti-hepatitis E virus (HEV) IgG seroprevalence in blood donors. The databases of microbiology laboratories in Cornwall and Devon were searched for the number of diagnostic HEV and HAV assays performed during 2005-2006 and the number of confirmed cases of acute hepatitis A and hepatitis E detected. Patients were followed up until recovery or death. Sera from 500 blood donors from the regional centre were tested for HEV and HAV IgG. In total, 28 cases of autochthonous hepatitis E were identified from 838 assays, and 20 cases of hepatitis A were identified from 4503 assays. Compared to hepatitis A cases, patients with hepatitis E were older (mean age 61 vs. 45 years, P = 0.003), less likely to present in winter (P = 0.028) and had more complications (five vs. one). The IgG seroprevalence rates in blood donors were 45% for HAV and 16% for HEV. There was no relationship between HAV and HEV IgG seropositivity. Autochthonous hepatitis E may be more common than hepatitis A, affects older patients, is less likely to occur in winter and may be associated with more complications. Patients with acute hepatitis, whatever their age or travel history, should be tested for HEV.

The role of hepatitis E virus testing in drug-induced liver injury.

BACKGROUND: Locally acquired hepatitis E is an emerging infection in developed countries and can be misdiagnosed as drug-induced liver injury. AIM: To study the role of hepatitis E virus (HEV) testing in drug-induced liver injury. METHODS: Retrospective review of a cohort of patients with suspected drug-induced liver injury (n = 69) and hepatitis E (n = 45). The standard criteria for drug-induced liver injury were applied. Patients with suspected drug-induced liver injury who met these criteria were retrospectively tested for HEV on stored sera taken at the time of presentation. The two cohorts were compared to determine variables that predicted either of the diagnoses. RESULTS: Forty-seven out of 69 patients had criterion-referenced drug-induced liver injury. 22/47 were HEV negative and thus had confirmed drug-induced liver injury. 19/47 were not tested for HEV, as there was no sera available from the time of presentation. 6/47 were HEV positive and thus did not have drug-induced liver injury, but had hepatitis E infection. Compared to patients with confirmed drug-induced liver injury, patients with hepatitis E were significantly more likely to be male (OR 3.09, CI 1.05-9.08); less likely to present in November and December (0.03, CI 0.01-0.52); have lower serum bilirubin (P = 0.015); and higher serum alanine aminotransferase (P < 0.001) and alanine aminotransferase/alkaline phosphatase ratio (P < 0.001). CONCLUSION: The diagnosis of drug-induced liver injury is not secure without testing for HEV.

Design, synthesis, and biological evaluation of analogues of the antitumor agent, 2-(4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469).

2-(4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469) is among the most highly and broadly active antitumor agents to have been evaluated in our laboratories and is currently scheduled to enter clinical trials in 2001. The mechanism or mechanisms of action of XK469 remain to be elaborated. Accordingly, an effort was initiated to establish a pharmacophore hypothesis to delineate the requirements of the active site, via a comprehensive program of synthesis of analogues of XK469 and evaluation of the effects of structural modification(s) on solid tumor activity. The strategy formulated chose to dissect the two-dimensional parent structure into three regions-I, ring A of quinoxaline; II, the hydroquinone connector linkage; and III, the lactic acid moiety-to determine the resultant in vitro and in vivo effects of chemical alterations in each region. Neither the A-ring unsubstituted nor the B-ring 3-chloro-regioisomer of XK469 showed antitumor activity. The modulating antitumor effect(s) of substituents of differing electronegativities, located at the several sites comprising the A-ring of region I, were next ascertained. Thus, a halogen substituent, located at the 7-position of a 2-(4-[(2-quinoxalinyl)oxy]phenoxy)propionic acid, generated the most highly and broadly active antitumor agents. A methyl, methoxy, or an azido substituent at this site generated a much less active structure, whereas 5-, 6-, 8-chloro-, 6-, 7-nitro, and 7-amino derivatives all proved to be essentially inactive. When the connector linkage (region II) of 1 was changed from that of a hydroquinone to either a resorcinol or a catechol derivative, all antitumor activity was lost. Of the carboxylic acid derivatives of XK469 (region III), i.e., CONH2, CONHCH3, CON(CH3)2, CONHOH, CONHNH2, CN, or CN4H (tetrazole), only the monomethyl- and N,N-dimethylamides proved to be active.