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Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases

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World Journal of Hepatology 2021年第12期13卷 1850-1874页

作者： man Fai Law Rita Ho Kimmy Wan Tung Law carmen ka man cheung Department of Medicine and Therapeutics Prince of Wales HospitalThe Chinese University of Hong KongHong KongChina Department of Medicine North District HospitalHong KongChina West Island School Hong KongChina

The outbreak of coronavirus disease 2019(COVID-19)is a global *** clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and *** drugs of higher interest include umifenovir,bromhexine,remdesivir,lopinavir/ritonavir,steroid,tocilizumab,interferon alpha or beta,ribavirin,fivapiravir,nitazoxanide,ivermectin,molnupiravir,hydroxychloroquine/chloroquine alone or in combination with azithromycin,and ***(GI)symptoms and liver dysfunction are frequently seen in patients with COVID-19,which can make it difficult to differentiate disease manifestations from treatment adverse *** symptoms of COVID-19 include anorexia,dyspepsia,nausea,vomiting,diarrhea and abdominal *** injury can be a result of systemic inflammation or cytokine storm,or due to the adverse drug effects in patients who have been receiving different *** monitoring of liver function should be ***-19 vaccines have been rapidly developed with different technologies including mRNA,viral vectors,inactivated viruses,recombinant DNA,protein subunits and live attenuated *** with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the *** against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.

关键词： COVID-19 treatment Gastrointestinal side effects Hepatic side effects COVID-19 vaccine Chronic liver disease Liver transplantation

Efficacy of Vaccine Protection Against COVID-19 Virus Infection in Patients with Chronic Liver Diseases

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 718-735页

作者： carmen ka man cheung Kimmy Wan Tung Law Alvin Wing Hin Law man Fai Law Rita Ho Sunny Hei Wong Department of Medicine and Therapeutics Prince of Wales HospitalHong KongChina West Island School Hong KongChina Department of Medicine North District HospitalHong KongChina Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChinaLee Kong Chian School of MedicineNanyang Technological UniversitySingapore

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vac-cine response has been observed in liver transplant recipi-ents, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data com-paring the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavi-rus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospec-tive studies are required to investigate the duration of immu-nity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.

关键词： COVID-19 SARS-CoV-2 Chronic liver disease Liver transplanta-tion Vaccine mRNA.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

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世界胃肠病学杂志:英文版 2023年第33期29卷 4942-4961页

作者： Joyce Wing Yan Mak Alvin Wing Hin Law Kimmy Wan Tung Law Rita Ho carmen ka man cheung man Fai Law Department of Medicine and Therapeutics Prince of Wales HospitalHong Kong 852China West Island School Hong Kong 852China Department of Medicine North District HospitalHong Kong 852China

Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is *** reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell *** with inactive and even resolved HBV infection still have persistence of HBV genomes in the *** expression of these silent genomes is controlled by the immune *** or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV ***,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core *** found to be positive for HBsAg should be given prophylactic antiviral *** patients with resolved HBV infection,there are two *** first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes *** second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell *** and tenofovir are the preferred antiviral *** new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV *** there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell *** studies are needed to determine the risk o

关键词： Hepatitis B Hematologic neoplasms Chimeric antigen receptor-T cell therapy Monoclonal antibodies Bruton’s tyrosine kinase inhibitors Antiviral agents

Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 257-264页

作者： Kevin Tak-Pan Ng Li Pang Jia-Qi Wang Wong Hoi She Simon Hing-Yin Tsang Chung Mau Lo Kwan man Tan To cheung Department of Surgery HKU-SZH&School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not *** study was to find out whether systemic inflammation plays an important ***:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex *** relationships of the cytokines and the postoperative outcomes were compared between LLR and ***:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative *** to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly *** POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during *** levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital ***,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver ***:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

关键词： Laparoscopic liver resection Open liver resection Hepatocellular carcinoma Postoperative cytokines Inflammatory responses

Carvedilol Versus Other Nonselective Beta Blockers for Variceal Bleeding Prophylaxis and Death: A Network Meta-analysis

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1143-1149页

作者： ka-Shing cheung Chiu-Hang Mok Lok-ka Lam Xian-Hua Mao Lung-Yi Mak Wai-kay Seto man-Fung Yuen Department of Medicine School of Clinical MedicineThe University of Hong KongQueen Mary HospitalHong KongChina Department of Medicine The University of Hong Kong-Shenzhen HospitalShenzhenGuangdongChina School of Clinical Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Background and Aims:We aimed to perform a network meta-analysis(NWM)to examine comparative effectiveness of non-selective beta blockers(NSBBs)on prophylaxis of gastroesophageal variceal bleeding(GVB)and mortality ***:MEDLINE(OVID)and EMBASE databases were searched for eligible randomized clinical trials(RCTs)from inception to July 3,*** of interest included primary/secondary prophylaxis of GVB,failure to achieve hepatic venous pressure gradient(HVPG)decremental response,liver-related and all-cause mortality.A Bayesian NWM was performed to derive relative risk(RR)with 95%credible intervals(CrIs).The ranking probability of each NSBB was assessed by surface under cumulative ranking curve(SUCRA).Results:Thirty-three RCTs including 3,188 cirrhosis patients with gastroesophageal varices were *** with placebo,nadolol ranked first for reducing variceal bleeding[RR:0.25,(95%CrI:0.11–0.51);SUCRA:0.898],followed by carvedilol[RR:0.33,(95%CrI:0.11–0.88);SUCRA:0.692]and propranolol[RR:0.52,(95%CrI:0.37–0.75);SUCRA:0.405].Carvedilol was more effective than propranolol in achieving HVPG decremental response[RR:0.43,(95%CrI:0.26–0.69)].Carvedilol ranked first for reducing all-cause mortality[RR:0.32,(95%CrI:0.17–0.57);SUCRA:0.963],followed by nadolol[RR:0.48,(95%CI:0.29–0.77);SUCRA:0.688],and propranolol[RR:0.77,(95%CI:0.58–1.02);SUCRA:0.337].Similar findings were observed for liver-related *** ranked the *** RR of adverse events was 4.38,(95%CrI:0.33–161.4);SUCRA:0.530,followed by propranolol[RR:7.54,(95%CrI:1.90–47.89);SUCRA:0.360],and nadolol[RR:18.24,(95%CrI:91.51–390.90);SUCRA:0.158].Conclusions:Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among patients with gastroesophageal varices.

关键词： NSBB Carvedilol Nadolol Propranolol Varices Cirrhosis CPSH

Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

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World Journal of Gastroenterology 2017年第44期23卷 7863-7874页

作者： ka-Shing cheung Wai-kay Seto James Fung Lung-Yi Mak Ching-Lung Lai man-Fung Yuen Department of Medicine The University of Hong Kong Queen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index(APRI) in predicting hepatocellular carcinoma(HCC) risk in primary biliary cholangitis(PBC).METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio(HR) of HCC with different risk factors was determined by Cox proportional hazards model. RESULTS One hundred and forty-four PBC patients were recru-ited. Patients were diagnosed at a median age of 57.8 years [interquartile range(IQR): 48.7-71.5 years), and 41(28.5%) patients had cirrhosis at baseline. The median follow-up duration was 6.9 years(range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10-and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4%(95%CI: 1.8%-14.5%) and 21.6%(6.8%-34.1%), respectively. Older age(HR = 1.07), cirrhosis(HR = 4.38) and APRI at 1 year after treatment(APRI-r1) > 0.54(HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk(log rank P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC was 0.77(95%CI: 0.64-0.88).CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

关键词： Aspartate aminotransferase Platelet ratio index Hepatocellular carcinoma Primary biliary cholangitis Ursodeoxycholic acid Cirrhosis

Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016

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World Journal of Gastroenterology 2017年第43期23卷 7716-7726页

作者： ka-Shing cheung Wai-kay Seto James Fung Lung-Yi Mak Ching-Lung Lai man-Fung Yuen Department of Medicine The University of Hong KongQueen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the epidemiology and natural history of Wilson's disease in the *** Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital Authority,which covers all the public healthcare services. We identified cases of Wilson's disease between 2000 and 2016 by the International Classification of Diseases(ICD)-9 code. We analyzed the incidence rate,prevalence and adverse outcomes of Wilson's *** We identified 211 patients(male cases 104; female cases 107; median age 27.2 years,IQR: 17.1-38.6 years; duration of follow-up 8.0 years,IQR: 5.0-14.0 years). The average annual incidence rate was 1.44 per million person-years while the prevalence was 17.93 per million. Between 2000 and 2016,there was a decrease in the annual incidence rate from 1.65 to 1.23 per million person-years(P = 0.010),whereas there was an increase in the annual prevalence from 7.80 to 25.20 per million(P < 0.001). Among the 176 cases with hepatic involvement,38(21.6%) had cirrhosis,three(1.7%) developed hepatocellular carcinoma,24(13.6%) underwent liver transplantations,and 26(14.8%) died. Seven patients had concomitant chronic viral hepatitis B or C. The 5-year and 10-years rates of overall survival were 92.6% and 89.5%,and for transplant-free survival rates 91.8% and 87.4%,respectively. Cirrhosis and possibly chronic viral hepatitis were associated with poorer overall survival. CONCLUSION There was a significant increase in the prevalence of Wilson's disease in Hong Kong. The prognosis was favorable except for those with cirrhosis or concomitant viral hepatitis.

关键词： Hepaticolenticular degeneration Cirrhosis Hepatocellular carcinoma Transplantation

Cancer stem-like cells in Epstein-Barr virus-associated nasopharyngeal carcinoma

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Chinese Journal of Cancer 2014年第11期33卷 529-538页

作者： Samantha Wei-man Lun Siu-Tim cheung Kwok-Wai Lo Department of Anatomical and Cellular Pathology State Key Laboratory in Oncology in South ChinaPrince of Wales Hospital Department of Surgery The University of Hong Kong Li ka Shing Institute of Health Science The Chinese University of Hong Kong

Although the Epstein-Barr virus(EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma(NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cells. These cancer stem-like cells(CSCs) have the ability to selfrenew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBVassociated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1(LMP1) and latent membrane protein 2A(LMP2A)], cellular microRNAs, and adenosine triphosphate(ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.

关键词：肿瘤干细胞 EB病毒鼻咽癌潜伏膜蛋白1 上皮细胞东南亚地区三磷酸腺苷 EBV

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

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World Journal of Gastroenterology 2016年第28期22卷 6484-6500页

作者： man Fai Law Rita Ho carmen KM cheung Lydia HP Tam karen Ma Kent CY So Bonaventure Ip Jacqueline So Jennifer Lai Joyce Ng Tommy HC Tam Department of Medicine and Therapeutics Prince of Wales HospitalHong Kong China Department of Medicine North District HospitalHong Kong China

Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although ther

关键词： Hepatitis B virus reactivation Hematological malignancies Rituximab Hematopoietic stem cell transplant Prophylactic antiviral therapy