Chun Tao Wai

The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection.

Hepatitis B virus (HBV) genotype and precore/core promoter mutations have been implicated in spontaneous and interferon alfa (IFN-α)—related hepatitis B e antigen (HBeAg) seroconversion. We performed a retrospective analysis of a previously reported randomized controlled trial to determine the effects of HBV genotype and precore/core promoter mutations on IFN-α response in patients with HBeAg-positive chronic hepatitis. Clinical data and stored sera from 109 (95%) patients in the original trial were analyzed. Seventy-three patients received IFN-α and 34 received no treatment (controls). Almost all patients had HBV genotypes B (38%) and C (60%). Antiviral response was achieved in 39% and 17% of IFN-α—treated patients ( P = 0.03) and in 10% and 8% of untreated controls ( P = 0.88) with HBV genotype B and C, respectively. Multivariate analysis identified HBV genotype B, elevated pretreatment alanine aminotransferase (ALT) levels, and low pretreatment HBV-DNA levels but not IFN-α treatment as independent factors associated with antiviral response. Among the 66 patients with elevated pretreatment ALT level, antiviral response was achieved in 57% and 21% of IFN-α—treated patients ( P = 0.019), and in 25% and 8% of untreated controls ( P = 0.45) with HBV genotype B and C, respectively. Multivariate analysis showed that genotype B and low pretreatment HBV-DNA levels were independent predictors of antiviral response. In conclusion, our data showed that HBV genotype B was associated with a higher rate of IFN-induced HBeAg clearance compared with genotype C. Stratification for HBV genotypes should be considered in future clinical trials of antiviral therapy of chronic hepatitis B. (Hepatology2002;36:1425-1430).

BACKGROUND: Colorectal Cancer (CRC) is rapidly rising in Asia, but screening uptake remains poor. Although studies have reported gender differences in screening rates, there have been few studies assessing gender specific perceptions and barriers towards CRC screening, based on behavioral frameworks. We applied the Health Belief Model to identify gender-specific predictors of CRC screening in an Asian population. METHODS: A nationwide representative household survey was conducted on 2000 subjects aged 50 years and above in Singapore from 2007 to 2008. Screening behaviour, knowledge and beliefs on CRC screening were assessed by face-to-face structured interviews. The response rate was 88.2%. RESULTS: 26.7 percent had undergone current CRC screening with no gender difference in rates. Almost all agreed that CRC would lead to suffering (89.8%), death (84.6%) and would pose significant treatment cost and expense (83.1%). The majority (88.5%) agreed that screening aids early detection and cure but only 35.4% felt susceptible to CRC. Nearly three-quarters (74.3%) of the respondents recalled reading or hearing information on CRC in the print or broadcast media. However, only 22.6% were advised by their physicians to undergo screening. Significantly more women than men had feared a positive diagnosis, held embarrassment, pain and risk concerns about colonoscopy and had friends and family members who encouraged screening. On multivariate analysis, screening uptake showed a positive association with worry about contracting CRC and a physician's recommendation and a negative association with perceived pain about colonoscopy for both genders. For women only, screening was positively associated with having attended a public talk on CRC and having a family member with CRC, and was negatively associated with Malay race and perceived danger of colonoscopy. CONCLUSIONS: CRC screening remains poor despite high levels of awareness of its benefits in this Asian population. Race, worry about contracting cancer, psychological barriers, and cues from the doctor and a public talk on CRC were associated with screening with gender specific differences. Strategies to increase CRC screening uptake should consider gender specific approaches to address psychological barriers and increase disease susceptibility through public health education and active promotion by physicians.

BACKGROUND: Chronic hepatitis B virus carriers receiving chemotherapy develop a high hepatitis B virus reactivation rate (38-53%) with a high mortality (37-60%). Few studies have characterized the efficacy of lamivudine in the treatment of chemotherapy-induced hepatitis B virus reactivation. AIM: To determine whether lamivudine prophylaxis reduces chemotherapy-induced hepatitis B virus reactivation and mortality. METHODS: The medical records of all hepatitis B surface antigen-positive patients with malignancy treated with chemotherapy since 1995 at the National University Hospital of Singapore were identified, and divided into those who received lamivudine prophylaxis before chemotherapy (P) and those who did not (NP). The parameters examined included gender, age, malignancy type, steroid usage, number of chemotherapy courses and regimens, follow-up duration and hepatitis B virus status. The outcome measures were hepatitis B virus reactivation (abrupt rise of serum alanine aminotransferase to > 200 IU/L) and reactivation death. Patients with primary hepatoma or liver metastasis were excluded. RESULTS: Thirty-five patients were identified: 16 in the P group and 19 in the NP group. The baseline characteristics of the two groups were similar. Seven of the 19 patients in the NP group and none of the 16 patients in the P group developed reactivation (36.8% vs. 0%, P=0.009). Six of the seven patients in the NP group who developed reactivation received lamivudine at that time, but five died (mortality, 71.4%), whilst no patient in the P group died from reactivation (P=0.064). CONCLUSIONS: Prophylactic lamivudine appears to prevent hepatitis B virus reactivation and its associated mortality in patients treated with chemotherapy. This should be confirmed with prospective studies.

Hepatitis B immunoglobulin with lamivudine prophylaxis (LAM/HBIG) is effective in preventing Hepatitis B (HBV) recurrence posttransplant but is expensive and inconvenient. Lamivudine-resistant HBV, which has limited the usefulness of lamivudine monoprophylaxis in transplant, can now be effectively controlled with adefovir dipivoxil. We performed a cost-effectiveness analysis on the strategies of lamivudine prophylaxis with adefovir rescue(LAM/ADV) compared to combination LAM/intravenous fixed high-dose HBIG prophylaxis(LAM/ivHBIG) or LAM/intramuscular HBIG prophylaxis(LAM/imHBIG). Markov modeling was performed with analysis from societal perspective. Probability rates were derived from systematic review of the literature and cost taken from MEDICARE database. Outcome measures were incremental cost-effectiveness ratio(ICER) and cost to prevent each HBV recurrence and death. Analysis was performed at 5 years posttransplant as well as at end of life expectancy (15 years). Combination LAM/ivHBIG cost an additional USD562,000 at 15 years, while LAM/imHBIG cost an additional USD139,000 per patient compared to LAM/ADV. Although there is an estimated increase in recurrence of 53% with LAM/ADV and 7.6% increased mortality at the end of life expectancy (15 years), the ICER of LAM/ivHBIG over LAM/ADV treatment is USD760,000 per quality-adjusted life-years and for LAM/imHBIG, USD 188,000. Cost-effectiveness is most sensitive to cost of HBIG. Lamivudine prophylaxis with adefovir dipivoxil salvage offers the more cost-effective option for HBV patients undergoing liver transplant but with higher recurrence and death rate using a model that favors LAM/HBIG. Lowering the cost of HBIG maintenance will improve cost-effectiveness of LAM/HBIG strategy. In conclusion, a tailored approach based on individual risks will optimize the cost-benefit of HBV transplant prophylaxis.