Comparison of acute hepatitis E infection outcome in patients with and without chronic hepatitis B infection: a 10 year retrospective study in three regional hospitals in Hong Kong.

BACKGROUND: Acute hepatitis E virus (HEV) infection has recently become the commonest cause of acute viral hepatitis in Hong Kong (HK) with majority of HEV belonging to genotype 4. Studies from China have shown that acute hepatitis E patients with underlying chronic hepatitis B virus (HBV) infection may have a worse outcome than those without. In India where genotype 1 is more prevalent, superinfection with hepatitis E on patients with chronic liver disease including chronic hepatitis B infection can cause liver decompensation. OBJECTIVES: The study aims to determine the clinical outcome of acute hepatitis E infection in patients with and without chronic hepatitis B infection in HK. STUDY DESIGN: The rates of liver failure, liver-related mortality and all-cause mortality will be compared between acute hepatitis E patients with and without chronic hepatitis B. Analysis was performed using the Statistical Package for the Social Science (SPSS version 12.0). All statistical tests were two-sided, and statistical significance was taken as p<0.05. RESULTS: Chronic HBV carriers with acute HEV infection were found to have higher liver failure rate, liver-related mortality and all-cause mortality, but the results did not reach statistical significance. Chronic HBV carriers were found to have statistically significantly lower admission ALT level, lower day 28 serum albumin level and higher day 28 serum ALT level. CONCLUSIONS: A prospective study with sufficient sample size is needed to confirm whether the clinical outcome of patients with chronic HBV infection is worse compared with patients who were not chronic HBV carriers.

Causality assessment of herb-induced liver injury using multidisciplinary approach and Roussel Uclaf Causality Assessment Method (RUCAM).

OBJECTIVE: To evaluate an algorithmic approach involving a multidisciplinary team for causality assessment of suspected herb-induced liver injury (HILI) cases and to compare the causality score using this multidisciplinary approach and Roussel Uclaf Causality Assessment Method (RUCAM). METHODS: A team consisting of hepatologist, clinical toxicologist, analytical toxicologist, and Chinese medicine (CM) pharmacist was formed to do causality assessment based on a protocol for suspected HILI cases. The likelihood of the diagnosis of individual case was first assessed systematically by a hepatologist and clinical toxicologist independently after collecting information about four aspects: (1) clinical course, (2) exclusion of alternative causes, (3) quality of the prescription and herbal product by examining the CM prescriptions and analysis of biological and herb samples, (4) scientific support on comprehensive literature review on English and Chinese medical database, and subsequently concluded in a consensus meeting held by the multidisciplinary team. The final causality score of each patient was compared with the likelihood of causality as assessed by RUCAM. RESULTS: Between 2005 and 2007, 48 consecutive patients with suspected HILI were enrolled and 21 patients were excluded due to the establishment of an alternative cause of liver impairment or the lack of any information on the herbs taken. Twenty-seven patients were recruited, among them 15 consumed Chinese herbal medicines, 10 used proprietary Chinese medicinal products, and 2 used both. The concordance between the causality assessment of the hepatologist and clinical toxicologist was moderate (weighted κ = 0.48, 95%CI 0.30-0.66). The causality assessment process concluded that the likelihood of HILI was "highly probable" in 5 cases and "probable" in 12, whereas there were 5 "highly probable" and 16 "probable" cases as assessed by RUCAM. The causality assessment by the multidisciplinary approach and RUCAM also showed moderate agreement (weighted κ= 0.51, 95%CI 0.22-0.81). CONCLUSION: A multidisciplinary approach using defined algorithms is a scientific approach in causality assessment for HILI. Further study is needed to assess its accuracy and applicability.

Reactivation of hepatitis B virus infection with persistently negative HBsAg on three HBsAg assays in a lymphoma patient undergoing chemotherapy.

In patients with occult hepatitis B virus (HBV) infection, acute exacerbation may occur when they become immunocompromised. Usually, these patients develop hepatitis B surface antigen (HBsAg) seroreversion during the flare. Here we report on a patient with occult HBV infection, who developed HBV exacerbation after chemotherapy for diffuse large B-cell lymphoma. The resurgence of HBV DNA preceded the elevation of liver enzymes for 20 weeks. Atypically, despite high viraemia, serological tests showed persistently negative HBsAg using three different sensitive HBsAg assays (i.e., Architect, Murex and AxSYM). On comparing the amino acid sequence of the index patient with the consensus sequence, five mutations were found at pre-S1, five at pre-S2 and twenty-three mutations at the S region. Six amino acid mutations were located in the 'a' determinant, including P120T, K122R, M133T, F134L, D144A and G145A. The mutants K122R, F134L and G145A in our patient have not been tested for their sensitivity to Architect and Murex assays by the previous investigators and might represent the escape mutants to these assays.

Liver injury associated with the use of Fructus Psoraleae (Bol-gol-zhee or Bu-gu-zhi) and its related proprietary medicine.

Fructus Psoraleae (FP) is used by herbalists for the treatment of postmenopausal osteoporosis, vitiligo, and psoriasis. It is used alone, or in combination with other herbs, in some countries in the form of proprietary medicine. It is recognized as one of the emerging hepatotoxins and here we report three cases of acute hepatitis after exposed to FP and its related proprietary medicine. It seems possible that psoralen and its related chemicals may be responsible for the hepatotoxicity. Decoction with other herbs may result in higher concentration of toxic constituents and in more severe liver injury. In summary, FP is associated with hepatotoxicity in some individuals. Pharmacovigilance for the potential side effects of herbal products is necessary.

Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial.

BACKGROUND: Guidelines on pain management recommend that patients at risk of ulcers receive either a cyclo-oxygenase (COX 2) inhibitor or a non-steroidal anti-inflammatory drug (NSAID) with a proton-pump inhibitor (PPI). These two treatments have similar effectiveness, but they are insufficient for protection of patients at very high risk for ulcer bleeding. We aimed to test the hypothesis that in patients with previous ulcer bleeding induced by non-selective NSAIDs, combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole would be better than celecoxib alone for prevention of recurrent ulcer bleeding. METHODS: 441 consecutively presenting patients who were taking non-selective NSAIDs for arthritis were recruited to our single-centre, prospective, randomised, double-blind trial after admission to hospital with upper-gastrointestinal bleeding. Patients were enrolled after their ulcers had healed and a histological test for Helicobacter pylori was negative. All patients were given 200 mg celecoxib twice daily. 137 patients were randomly assigned to receive 20 mg esomeprazole twice daily (combined-treatment group), and 136 to receive a placebo (control group) for 12 months. The primary endpoint was recurrent ulcer bleeding during treatment or within 1 month of the end of treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00365313. FINDINGS: Combination treatment was more effective than celecoxib alone for prevention of ulcer bleeding in patients at high risk. The 13-month cumulative incidence of the primary endpoint was 0% in the combined-treatment group and 12 (8.9%) in the controls (95% CI difference, 4.1 to 13.7; p=0.0004). The median follow-up was 13 months (range 0.4-13.0). Discontinuation of treatment and the incidence of adverse events were similar in the two treatment groups. INTERPRETATION: Patients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding.

Diagnostic challenges of tuberculosis peritonitis in patients with and without end-stage renal failure.

BACKGROUND: Information about diagnostic features of tuberculosis (TB) peritonitis among patients with end-stage renal failure (ESRF), compared with those without ESRF, is limited. Here, we review our experience with TB peritonitis in patients with and without ESRF over a period of 11 years, with special reference to the clinical features of and diagnostic tools for TB peritonitis. METHODS: The records of all patients with TB peritonitis who were seen at United Christian Hospital (Hong Kong) from 1996 through 2006 were reviewed. The diagnosis of TB peritonitis was based on (1) detection of mycobacteria on smear and/or Mycobacterium tuberculosis on culture of ascitic fluid and/or peritoneal biopsy specimens and/or (2) demonstration of caseating granulomata on histological assessment of peritoneal biopsy specimens. RESULTS: During the study period, 52 patients (19 without ESRF and 33 with ESRF) had TB peritonitis. Patients with ESRF tended to have more-acute onset of symptoms and neutrophil-predominant peritoneal fluid, which mimicked bacterial peritonitis. Diagnosis was made earlier among patients without ESRF than among those with ESRF. Laparotomy or laparoscopy was the initial diagnostic tool for 12 patients (63%) without ESRF, whereas mycobacterial culture was the diagnostic method for 18 patients (55%) with ESRF. CONCLUSIONS: TB peritonitis has nonspecific and protean manifestations. It should be considered in the context of culture-negative peritonitis and in the context of culture-positive peritonitis that fails to respond to appropriate antibiotics. Laparoscopy with biopsy should be considered at an early stage when TB peritonitis is suspected.

Epidemiology and clinical features of sporadic hepatitis E as compared with hepatitis A.

OBJECTIVES: To compare the epidemiology and clinical features of two enterically transmitted hepatitis, namely hepatitis E and hepatitis A. METHODS: We analyzed clinical features and risk factors of 105 cases of hepatitis A and 24 cases of hepatitis E admitted in 2002. All patients were tested positive for IgM antibody against either hepatitis A virus (HAV) or hepatitis E virus (HEV), and all patients were tested to be negative for IgM anti-HBV or IgG anti-HCV. RESULTS: Hepatitis A patients were significantly younger (median age = 27 yr) and most had a recent history of shellfish consumption, whereas hepatitis E patients were older (median age = 53 yr) and most had a recent travel history. Whereas hepatitis A was milder and recovery was uneventful, hepatitis E was more severe, associated with significant mortality and frequently complicated by protracted coagulopathy and cholestasis. CONCLUSIONS: Hepatitis E is a more severe disease entity as compared with hepatitis A and significant proportion of them are imported cases from an endemic area.