Long-term Hepatitis B Surface Antigen Profile and Seroclearance after Severe Acute Flares of Chronic Hepatitis B

Hui Ka-Yin,Fung James,Cheung Ka-Shing,Mak Lung-Yi,Seto Wai-Kay,Yuen Man-Fung 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2

Background/Aims: Hepatitis B surface antigen (HBsAg) seroclearance remains uncommon in chronic hepatitis B (CHB) infection. During acute flares of CHB (AFOCHB), alanine aminotransferase elevation reflects a mounting immune response toward viral clearance. We hypothesized that severe AFOCHB is associated with a greater quantitative HBsAg (qHBsAg) decline and HBsAg seroclearance rate. Methods: A total of 75 patients with severe AFOCHB with alanine aminotransferase 10× the upper limit of normal were matched to a control group by age and sex in a 1:2 ratio. qHBsAg levels were measured at the time of flare and annually (for both cases and controls) until the last follow-up. Results: The median follow-up times for patients with severe AFOCHB and controls were 8.8 and 10.5 years, respectively. The cumulative rate of HBsAg seroclearance was higher in the severe AFOCHB group than in the control group (11.8% vs 5.0%, p=0.04) despite the former group having a trend of a higher baseline median qHBsAg (3,127 IU/mL vs 1,178 IU/mL, p=0.076). Compared with the control group, the severe AFOCHB group had a greater annual qHBsAg reduction (–242.4 IU/mL/yr vs –47.3 IU/mL/yr, p=0.002). Increasing age (p=0.049), lower baseline qHBsAg (p=0.002), and severe AFOCHB (p=0.014) were independently associated with HBsAg seroclearance. However, the cumulative rate of hepatocellular carcinoma was significantly higher in the severe AFOCHB group than in the control group (15.8% vs 1.9%, p<0.001). Conclusions: Severe AFOCHB was associated with a greater incidence of HBsAg seroclearance and qHBsAg decline. However, it was associated with a higher incidence of hepatocellular carcinoma.

Twenty-four months long-term follow-up report on the effect of poly lactic-co-glycolic acid suspension suture in Asian with mild-moderate face laxity

Lam Phoebe Kar Wai,Fung Chi Pun,Lam James Yui,Luk Wang Lung,Lee Alvin Ka Wai,Lee Cheuk Hung,Tam Paul Man Kei,Lau Edwin Kwan Chark 대한미용의학회 2022 대한미용의학회지 Vol.6 No.1

Background: There was evidence of improvement in mid-face laxity using three pairs of suspension sutures in mid-face lifting in our early and mid-term follow-up. Objective: This 24-month prospective follow-up study aimed to determine the efficacy of mid-face lifting and lower jawline contouring using poly lactic-co-glycolic acid (PLGA) sutures in Asian patients. Methods: Ten healthy volunteers received three pairs of 8-cones bidirectional cones sutures at the mid-face. One of the ten volunteers lost to follow-up, and all remaining patients followed up for 24 months. Our primary outcome measure is the change in the facial laxity rating scale (FLRS), an “improvement” defined as at least “one-grade change” in FLRS. Other assessment parameters include the severity of the nasolabial fold (NLF), assessed on the wrinkle severity rating scale (WSRS). The secondary outcome measures were the self-satisfaction rating scale (SSRS) and global aesthetic improvement scale (GAIS), rated by participants at each follow-up interval. Results: A linear improvement in the mid-face was observed almost immediately after treatment, with progressive improvement up to at least 12 months following the intervention and no deterioration by 24 months. This improvement was significant (p<0.05), and the differences between before and after treatment at each follow-up interval were large (Cohen’s d>0.8). Contour improvement for the lower face followed a similar trend, except for a delay in the observable differences at three months (Cohen’s d=0.29, 0.8 at six weeks and three months, respectively). The differences in the level of patient satisfaction were significant (p<0.05) from 6 weeks to 24 months, peaking between 12 and 18 months, based on both the GAIS and SSRS ratings. No observed complications. Conclusion: Mid-facing lifting in Asian patients with mild-to-moderate laxity is safe and effective with PLGA bidirectional cone sutures, with concurrent improvement in the lower face contour and elevated patient satisfaction over the 24-month follow-up period.

New Biomarkers of Chronic Hepatitis B

Lung-Yi Mak,Wai-Kay Seto,James Fung,Man-Fung Yuen 거트앤리버 소화기연관학회협의회 2019 Gut and Liver Vol.13 No.6

Chronic hepatitis B (CHB) infection leads to clinically heterogeneous disease outcomes. Different viral markers are utilized to monitor treatment effects and predict risk of complications in patients with CHB. Hepatitis B core-related antigen (HBcrAg) is a novel serum composite viral protein whose performance has been proven to be superior to that of existing viral markers. It showed good correlation with intrahepatic covalently closed-circular DNA. Its profile differs drastically in patients in different disease phases, and the level declines with antiviral therapies. HBcrAg may be helpful for predicting hepatocellular carcinoma development and hepatitis B virus (HBV) reactivation in immunosuppressed patients. Another emerging measurable serum marker, HBV RNA, exists in the form of pregenomic RNA-containing virions. Its profile differs between patients in different disease phases in a similar manner to that of HBcrAg. HBV RNA is present in serum at lower levels than HBV DNA in treatment-naïve patients by 1–2 logs. In contrast, its level is higher than HBV DNA in patients receiving nucleos(t)ide analogues (NAs). A significant decline in serum RNA was observed in patients receiving novel antiviral therapies, including core protein allosteric modulators and RIG-1/NOD2 agonists. Both HBcrAg and HBV RNA may be helpful for predicting off-therapy sustained virological control in patients who stop long-term NA treatment.

The role of different viral biomarkers on the management of chronic hepatitis B

Lung-Yi Mak,Rex Wan-Hin Hui,James Fung,Wai Kay Seto,Man-Fung Yuen 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.2

Chronic hepatitis B infection is a major public health challenge. With the advancement in technology, various components of the viral cycle can now be measured in the blood to assess viral activity. In this review article, we summarize the relevant data of how antiviral therapies impact viral biomarkers, and discuss their potential implications. Viral nucleic acids including hepatitis B virus (HBV) double-stranded deoxy-ribonucleic acid (DNA) and to a lesser extent, pre-genomic RNA, are readily suppressed by nucleos(t)ide analogues (NUCs). The primary role of these markers include risk prediction for hepatocellular carcinoma (HCC) and risk stratification for partial cure, defined as off-therapy virological control, or functional cure, defined as hepatitis B surface antigen (HBsAg) seroclearance plus undetectable serum HBV DNA for ≥6 months. Viral translational products including hepatitis e antigen, quantitative HBsAg and hepatitis B core-related antigen can be reduced by NUCs and pegylated interferon a. They are important in defining disease phase, delineating treatment endpoints, and predicting clinical outcomes including HCC risk and partial/ functional cure. As the primary outcome of phase III trials in chronic hepatitis B is set as HBsAg seroclearance, appropriate viral biomarkers can potentially inform the efficacy of novel compounds. Early viral biomarker response can help with prioritization of subjects into clinical trials. However, standardization and validation studies would be crucial before viral biomarkers can be broadly implemented in clinical use.

Defining Optimal Surgical Treatment for Recurrent Hepatocellular Carcinoma: A Propensity Score Matched Analysis

( Ka Wing Ma ),( Kenneth Siu Ho Chok ),( Albert Chi Yan Chan ),( James Yan Yue Fung ),( Chung Mau Lo ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Salvage liver transplantation (sLT) and repeated resection (RR) are effective treatment for recurrent hepatocellular carcinoma (HCC), comparison of the oncological outcomes between these two modalities were scarce. Methods: Consecutive patients admitted for either sLT or RR for recurrent HCC were recruited. All patients in the present series received either prior hepatectomy, ablative therapy or both before RR and sLT. Paedatric patients and patients treated by non-curative approach were excluded. Patient demographic, perioperative and outcome data were analyzed. Survival analysis was performed after propensity score matching. Results: There were 277 eligible patients recruited, 67 and 210 of them underwent sLT and RR respectively. Significant difference in preoperative haemoglobin, albumin, hepatitis B carrier status, MELD score, and tumor number were found (all P<0.001) between sLT and RR group. Multivariate analysis revealed that type of treatment (P=0.002, OR=2.13 95%CI 1.2-3.2), lapse time from last curative treatment (P=0.022, OR=0.994 95%CI 0.988-0.999), alpha fetal protein (AFP) (P=0.01 OR=1.00 95%CI 1.00-1.00) and tumor number (P<0.001, OR=1.23 95%CI 1.14-1.32) were independent factors associated with overall survival. After 1:3 PS matching, there were 36 sLT and 108 RS patients for comparison. The median age, MELD, AFP, tumor size and umber of the matched population were 57, 7.5, 16U/ml, 2.5cm and 1 respectively. There was no difference in the hospital mortality and complication rate (Clavien IIIa or above) between the groups, while the blood loss (P<0.001), operation time (P<0.001) and hospital stay (P=0.002) were significantly more in the sLT group. Patients in sLT group had significantly longer disease free (140 vs 49 months, P=0.031) and overall survival (176 vs 55.3 months, P=0.026). Conclusions: Salvage LT is superior to repeated resection for treatment of recurrent HCC and is associated with more than two fold increase in long term survival.

p62 Sequestosome 1/Light Chain 3b Complex Confers Cytoprotection on Lung Epithelial Cells after Hyperoxia

Liang, Xiaoliang,Wei, Shu-Quan,Lee, Seon-Jin,Fung, James K.,Zhang, Meng,Tanaka, Akihiko,Choi, Augustine M. K.,Jin, Yang American Thoracic Society 2013 American journal of respiratory cell and molecular Vol.48 No.4

Living Donor Liver Transplant Confers Better Survival for Elderly Recipients

( Chu Kevin Ka-wan ),( Chok Kenneth Siu-ho ),( Fung James Yan-yue ),( Chan Albert Chi-yan ),( Lo Chung Mau ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Increasing elderly patients are undergoing liver transplant as well as the relative percentage of elderly population. However, the perceived poor outcomes in the elderly prohibits the acceptance of living donor liver transplant in many centres. We reviewed current status of liver transplant in our centre and analyzed factors predicting survival outcome in elderly liver transplant recipients. Methods: Consecutive liver transplants for elderlies who reached age 65 performed between 2001 and 2016 were reviewed. The overall survival were compared between the deceased donor liver transplant (DDLT) and the living donor liver transplant (LDLT) groups. Results: DDLT and LDLT groups consisted of 24 and 17 recipients respectively. The overall 1-year and 3-year survival rates for the elderlies (n=41) were 87%, 78% respectively. LDLT recipients had better survival compared with DDLT, 94% vs 83% for 1-year and 94% vs 67% for 3-year, p=0.036. Univariate analysis was performed and identified predictive factors including pre-operative ICU stay (relative risk 3.74, 95% confidence interval 1.06-13.14, p=0.039), pre-operative hepatorenal syndrome (relative risk 6.01, 95% confidence interval 1.67-21.68, p=0.006) and mode of graft donation - LDLT (relative risk 0.09, 95% confidence interval 0.01-0.86, p=0.036). Long cold ischaemic time also had a negative correlation with survival (relative risk 4.30, 95% confidence interval 0.81-22.90, p=0.087). In multi multivariate analysis, LDLT (hazard ratio 0.11, 95% confidence interval 0.01-0.94, p=0.043) and pre-operative ICU stay (hazard ratio 5.60, 95% confidence interval 1.30-24.03, p=0.021) were independent predictive factors for survival. Conclusions: Good survival outcomes was achieved in selected elderly liver transplant recipients. Elderly recipients with living donors had better survival outcomes in contrast to those with deceased donors and LDLT was an independent protective factor for long term survival. Pre-operative ICU status was also an independent predictive of poorer long term survival.

Entecavir Reduced Serum Hepatitis B Core-Related Antigen in Chronic Hepatitis B Patients with Hepatocellular Carcinoma

Lung-Yi Mak,Kwan-Lung Ko,Wai-Pan To,Danny Ka-Ho Wong,Wai-Kay Seto,James Fung,Man-Fung Yuen 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.5

Serum hepatitis B core-related antigen (HBcrAg) was shown to predict the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients undergoing treatment. We investigated the longitudinal profile of HBcrAg in entecavir (ETV)-treated CHB patients with subsequent HCC development. We identified HCC cases diagnosed at ≥1 year after ETV initiation. CHB patients without HCC (matched for age, sex, cirrhosis status, baseline hepatitis B virus [HBV] DNA level, and ETV treatment duration) were identified as controls at an HCC:non-HCC ratio of 1:2. Serum samples were retrieved at baseline (ETV initiation) and at 3 and 5 years of ETV therapy for HBcrAg measurement (log IU/mL). In total, 180 patients (60 HCC patients matched with 120 CHB patients without HCC; median age, 56.5 years; 80.6% male; baseline HBV DNA, 5.9 log IU/mL; median follow-up, 6.8 years) were recruited. The median time from ETV initiation to HCC development was 3.2 years. HBcrAg levels were higher in HCC cases than in controls at all three time points: 5.69 log IU/ mL versus 5.02 log IU/mL (p=0.025), 4.23 log IU/mL versus 3.36 log IU/mL (p=0.007), and 3.86 log IU/mL versus 3.36 log IU/mL (p=0.009), respectively. ETV led to similar rates of decline in HBcrAg from baseline to 3 years in both groups (0.34 log IU/mL/year vs 0.39 log IU/mL/year, p=0.774), although the decline from 3 to 5 years was slower in the non- HCC group (0.05 log IU/mL/year) than in the HCC group (0.09 log IU/mL/year, p=0.055). ETV time-dependently reduced HBcrAg in HCC and non-HCC patients. HBcrAg interpretation should consider the antiviral treatment duration.