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.

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.

Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity.

Wilson disease (WD), an autosomal recessive disorder of copper transport, is the most common inherited liver disorder in Hong Kong Chinese. This was the first local study to elucidate the molecular basis and establish an effective DNA-based diagnostic protocol. The ATP7B genes of 65 patients were amplified by polymerase chain reaction (PCR) and sequenced. Haplotype analysis was performed using D13S301, D13S314, and D13S316. The p.L770L/p.R778L status in 660 subjects was determined to estimate WD prevalence. Allele age of p.R778L was determined by the smallest homozygosity region between D13S301 and D13S270. We identified 42 different mutations with 17 being novel. p.R778L (17.3%) was the most prevalent. Exons 2, 8, 12, 13, and 16 harbored 70% mutations. Thirty-two haplotypes were associated with WD chromosomes. The estimated prevalence rate was 1 in 5,400. Three out of 660 normal subjects had p.L770L/p.R778L. In the remaining 657 individuals, neither p.L770L nor p.R778L was found. We characterized a Hong Kong Chinese-specific ATP7B mutation spectrum with great genetic diversity. Exons 2, 8, 12, 13, and 16 should be screened first. The perfect linkage disequilibrium suggested that p.R778L and its private polymorphism p.L770L originated from a single ancestor. This East-Asian-specific mutation p.R778L/p.L770L is aged at least 5,500 years.

Erratum to: Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity.

The correct name of the eighth author should be given as Sik-To Lai, not Jak-Yiu Lai.

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.

Severe acute respiratory syndrome-related diarrhea.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infectious disease and diarrhea has been reported in up to 76% of cases. The purpose of the present paper was to carry out a retrospective study of the clinical and demographic data of SARS patients with diarrhea in Princess Margaret Hospital. METHODS: From 1 to 31 March 2003, hospital records from 240 patients with confirmed SARS were studied. Patients with watery stool of >/=3 times/day for at least 3 consecutive days were defined as the diarrhea group. Clinical and demographic data were compared between the diarrhea and non-diarrhea groups. Chest X-ray (CXR) scores during the peak of diarrhea period were recorded by a respiratory physician. These CXR scores were correlated with the peak frequency of diarrhea by Spearman's correlation coefficient. RESULTS: Diarrhea occurred in 20.4% of patients after admission. Female patients were predominant with a female to male ratio of 6:1 (P < 0.001) and 69.4% of patients were living in Amoy Gardens Estate (P = 0.01). The proportions of patients requiring ventilatory care and mortality in the diarrhea group were 8.2% and 2%, respectively, which were significantly lower than those in the non-diarrhea group (27.6% and 16.2%, P < 0.005). The CXR scores during the peak of diarrhea were not correlated with the maximum frequency of diarrhea (r = -0.09, P = 0.5). CONCLUSIONS: A total of 20.4% of SARS patients had the complication of diarrhea after hospital admission. Both female sex and being a resident of Amoy Gardens Estate were associated with diarrhea. The diarrhea group had a better prognosis.

Adjustment outcomes in Chinese patients following one-month recovery from severe acute respiratory syndrome in Hong Kong.

This study aimed to examine the short-term adjustment outcomes including distress, self-esteem, and quality of life among Chinese patients after 1-month recovery from severe acute respiratory syndrome (SARS) in Hong Kong and to investigate the predictive abilities of a set of selected variables on the outcomes. At 1-month recovery, 100 SARS survivors (mean age = 37; 66 women) and 184 community subjects completed self-administered questionnaires. In the General Health Questionnaire-28, 61% of the SARS survivors were identified as distressed cases under a conservative cutoff score of 6. Compared with the community sample, SARS survivors had significantly more distress and poor quality of life. Being a healthcare worker, severity of SARS symptoms, steroid dosage, and social support accounted for a portion of variances of different measures. Early psychiatric screening and intervention may be beneficial for the adjustment of SARS survivors after short-term recovery. Future research on the long-term impact of SARS is recommended.

Value of initial chest radiographs for predicting clinical outcomes in patients with severe acute respiratory syndrome.

PURPOSE: To determine whether the initial chest radiograph is helpful in predicting the clinical outcome of patients with severe acute respiratory syndrome (SARS). METHODS: Of 343 patients who met the World Health Organization's case definition of probable SARS and who had been admitted to a regional hospital in Hong Kong, 201 patients had laboratory evidence of SARS coronavirus infection. The initial frontal chest radiographs of these 201 patients were assessed in a blinded fashion by 3 radiologists; individual findings were accepted if at least 2 of the radiologists concurred. Independent predictors of an adverse outcome, defined as the need for assisted ventilation, death, or both, were identified by multivariate analysis. RESULTS: Bilateral disease and involvement of more than two zones on the initial chest radiograph were associated with a higher risk of liver impairment and poor clinical outcome. Forty-two patients (21%) developed an adverse outcome. Multivariate analysis showed that lung involvement of more than two zones (odds ratio [OR] = 7.0; 95% confidence interval [CI]: 2.7 to 17.9), older age (OR for each decade of life = 1.5; 95% CI: 1.1 to 2.0), and shortness of breath on admission (OR = 2.8; 95% CI: 1.1 to 7.4) were independent predictors of an adverse outcome. CONCLUSION: Frontal chest radiographs on presentation may have prognostic value in patients with SARS.

SARS-associated viral hepatitis caused by a novel coronavirus: report of three cases.

Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse-transcriptase polymerase chain reaction (RT-PCR) using enhanced real-time PCR was applied to look for evidence of SARS-associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki-67. RT-PCR showed evidence of SARS-associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro- or macro-vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS-associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course.

Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong.

BACKGROUND: Severe acute respiratory syndrome (SARS) has become a global public health emergency. OBJECTIVE: To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of mortality. DESIGN: Retrospective cohort study. SETTING: Quarantine hospital for patients with SARS in Hong Kong. PATIENTS: 267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS. MEASUREMENTS: Clinical, laboratory, and radiographic measures; 3-month mortality rate. RESULTS: According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 [CI, 2.30 to 11.31]; P < 0.001) and lactate dehydrogenase level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 [CI, 1.03 to 4.71]; P = 0.04) were independent predictors of mortality. CONCLUSION: Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix.

Coronavirus-positive nasopharyngeal aspirate as predictor for severe acute respiratory syndrome mortality.

Severe acute respiratory syndrome (SARS) has caused a major epidemic worldwide. A novel coronavirus is deemed to be the causative agent. Early diagnosis can be made with reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal aspirate samples. We compared symptoms of 156 SARS-positive and 62 SARS-negative patients in Hong Kong; SARS was confirmed by RT-PCR. The RT-PCR-positive patients had significantly more shortness of breath, a lower lymphocyte count, and a lower lactate dehydrogenase level; they were also more likely to have bilateral and multifocal chest radiograph involvement, to be admitted to intensive care, to need mechanical ventilation, and to have higher mortality rates. By multivariate analysis, positive RT-PCR on nasopharyngeal aspirate samples was an independent predictor of death within 30 days.

Transjugular liver biopsy with an automated trucut-type needle: comparative study with percutaneous liver biopsy.

OBJECTIVE: Transjugular liver biopsy using the suction method usually produces small specimens with excessive fragmentation, hence the diagnosis adequacy of specimens and the clinical impact of performing the biopsy have been questioned. An alternative biopsy needle, the Quick-Core needle system, which uses an automated trucut-type mechanism, has been shown to produce non-fragmented tissue specimens. The aim of the present study was to evaluate the safety, adequacy and clinical impact of the transjugular liver biopsy by comparing it with the standard percutaneous liver biopsy. DESIGN: We recruited all patients who underwent liver biopsies by percutaneous or transjugular routes in the Department of Medicine, Princess Margaret Hospital, Hong Kong between January 1998 and December 1999. METHOD: We recorded demographics and clinical features of patients, indications and complications, and the clinical impact of the liver biopsy procedure. All liver biopsy specimens were reviewed by the histopathologist, who was blinded to the approach of taking the biopsy. All variables between patients undergoing transjugular and percutaneous liver biopsies were compared. RESULTS: During the study period, 50 percutaneous and 18 transjugular liver biopsies were performed. All transjugular liver biopsies were performed successfully with adequate tissue for diagnosis. Although specimens obtained by the transjugular technique tended to be shorter (10 mm v. 18 mm by the percutaneous approach, P < 0.001), the presence of fragmentation was similar to that in biopsies obtained by the percutaneous approach. Respectively, 100% and 98% of specimens obtained by the transjugular and percutaneous approaches were considered to be adequate for histological assessment. The clinical impact of transjugular and percutaneous liver procedures was comparable (89% v. 76%, P = 0.25). CONCLUSION: Specimens obtained by a transjugular automated trucut needle are sufficient for histological assessment, and carry clinical impact in patient management.