Hepatocellular carcinoma （HCC） is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the d...Hepatocellular carcinoma （HCC） is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus （HBV） vacdnation programs, better food hygiene, increased global hepatitis C virus {HCV） prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV- related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways： chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein （AFP） are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients＇ survival and match best treatment option.展开更多
Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver b...Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/ inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE),as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural histor...Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection.High-risk infected individuals can now be identified by the usage of risk predictive scores.Vaccination plays a central role in the prevention of HBV-related HCC.Treatment of chronic HBV infection,especially by nucleoside analogue therapy,could also reduce the risk of HBV-related HCC.Concerning HCV infection,besides the advocation of universal precautions to reduce the rate of infection,pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response.Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV-and HCV-related HCC.The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.展开更多
In the past few decades,chronic hepatitis B(CHB)has evolved from a disease that was untreatable and progressive,to one that can be easily controlled with antiviral therapy.However,patients with severe liver disease st...In the past few decades,chronic hepatitis B(CHB)has evolved from a disease that was untreatable and progressive,to one that can be easily controlled with antiviral therapy.However,patients with severe liver disease still remain difficult to treat despite the availability of highly potent nucleos(t)ide analogs.These include those with underlying cirrhosis,severe flares of CHB,hepatocellular carcinoma(HCC),and for those undergoing liver transplantation.For those with established cirrhosis,antiviral therapy should be considered for all,as unpredictable flares can still occur,which can be fatal for those with advanced chronic liver disease.However,even with effective viral suppression,the development of HCC can still occur.For patients with severe flares of CHB,although the use of antiviral can improve long term outcomes,a significant proportion may still die without liver transplantation.The short term prognosis of these patients is dependent on both the severity of flare and underlying pre-existing liver disease.In patients with decompensated cirrhosis,liver failure secondary to severe flares,or those with HCC,liver transplantation may be curative.After liver transplantation,long term antiviral therapy is required to prevent graft loss from recurrent hepatitis B infection.The use of hepatitis B immune globulin(HBIG)in combination with an oral antiviral agent has been the mainstay of post-transplant antiviral regimen for over adecade.With newer and more potent antiviral agents such as tenofovir and entecavir,use of these agents along with HBIG have demonstrated to be effective in preventing significant recurrence in the long term.展开更多
AIM To investigate the epidemiology and natural history of Wilson's disease in the Chinese.METHODS Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital Authority,which c...AIM To investigate the epidemiology and natural history of Wilson's disease in the Chinese.METHODS 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 disease.RESULTS 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.展开更多
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 bet...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.展开更多
BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for f...BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for fibrosis. The role of M2 BPGi in prediction of HCC is unknown.AIM To examine the role of serum M2 BPGi in predicting HCC development in hepatitis B e antigen(HBeAg)-negative patients.METHODS Treatment-naive CHB patients with documented spontaneous HBeAg seroconversion were recruited. Serum M2 BPGi was measured at baseline(within3 years from HBeAg seroconversion), at 5 years and 10 years after HBeAg seroconversion and expressed as cut-off index(COI). Multivariate cox regression was performed to identify predictors for HCC development. ROC analysis was used to determine the cut-off value of M2 BPGi.RESULTS Among 207 patients(57% male, median age at HBeAg seroconversion 40 years old) with median follow-up of 13.1(11.8-15.5) years, the cumulative incidence of HCC at 15 years was 7%. Median M2 BPGi levels were significantly higher in patients with HCC compared to those without HCC(baseline: 1.39 COI vs 0.38 COI, P < 0.001; 5-year: 1.45 COI vs 0.47 COI, P < 0.001; 10-year: 1.20 COI vs 0.55 COI, P = 0.001). Multivariate analysis revealed age at HBeAg seroconversion[odds ratio(OR) = 1.196, 95% confidence interval(CI): 1.034-1.382, P = 0.016] and baseline M2 BPGi(OR = 4.666, 95%CI: 1.296-16.802, P = 0.018) were significant factors predictive of HCC. Using a cut-off value of 0.68 COI, baseline M2 BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% specificity.CONCLUSION High serum M2 BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients.展开更多
BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infe...BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.展开更多
Chronic hepatitis B(CHB)infection is characterized by ongoing viral replication in infected hepatocytes,leading to persistent production of viral nucleic acids and expression of viral antigens.Hepatitis B surface anti...Chronic hepatitis B(CHB)infection is characterized by ongoing viral replication in infected hepatocytes,leading to persistent production of viral nucleic acids and expression of viral antigens.Hepatitis B surface antigen(HBsAg)is one of the most important viral antigens,secreted at levels at least 1,000-fold higher than infectious virions in the bloodstream.1 HBsAg consists of three isoforms:large(LHBs),middle(MHBs),and small(SHBs)surface proteins,transcribed and translated from the open reading frame S of the HBV genome.展开更多
Colorectal cancer(CRC)is the third most common cancer and the second leading cause of cancer deaths worldwide[1].A considerable proportion of CRC is attributed to metabolic risk factors including type 2 diabetes(T2D),...Colorectal cancer(CRC)is the third most common cancer and the second leading cause of cancer deaths worldwide[1].A considerable proportion of CRC is attributed to metabolic risk factors including type 2 diabetes(T2D),with the relative risk reported to be 1.4[2].It is therefore imperative to develop effective preventive strategies to reduce CRC incidence in individuals with T2D.Among individuals with T2D,growing evidence supports the role of diabetes medications for CRC prevention.The current guidelines of the American Gastroenterological Association have recommended metformin as a potential chemopreventive medication against colonic neoplasia in patients with T2D[3].However,the use of metformin may be limited by various side effects including gastrointestinal disturbances,and is contraindicated in moderate-to-severe renal impairment.Furthermore,a clinical trial found diabetic patients on metformin,as compared to rosiglitazone and glyburide,had similar CRC risk[4].展开更多
Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HC...Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).展开更多
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 bene...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 benefit.Methods:MEDLINE(OVID)and EMBASE databases were searched for eligible randomized clinical trials(RCTs)from inception to July 3,2021.Outcomes 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 included.Compared 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 mortality.Carvedilol ranked the safest.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.展开更多
Aim:Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for chronic hepatitis B (CHB) can be associated with reappearance of hepatitis B surface antigen (HBsAg). The current study determined ...Aim:Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for chronic hepatitis B (CHB) can be associated with reappearance of hepatitis B surface antigen (HBsAg). The current study determined the significance of HBsAg qualitatively and quantitatively using a highly sensitive assay in recurrent HCC after transplantation. Methods:Consecutive patients with HBV-related HCC with LT were included. Oral nucleos(t)ide analogues without hepatitis B immune globulin were used as hepatitis B virus (HBV) prophylaxis. Quantitative HBsAg levels were performed at time of transplant, at 1 month, 3 and 6 months post transplant using a highly sensitive (hs)-HBsAg assay. Results:One hundred and fourteen patients were included, with a median follow-up of 80 months, with 24 cases of HCC recurrence, and a cumulative rate of 20.7% at 5 years. There was significant correlation between time of tumor recurrence and time of HBsAg reappearance (r = 0.551,P = 0.027). Early HCC recurrence was associated with higher median level of hs-HBsAg at the time of transplant (72.85vs. 69.70 IU/mL,P = 0.018). Using a hs-HBsAg cut-off level of 0.0005 IU/mL, patients with levels above this threshold at 3 and 6 months were associated with higher rate of early HCC recurrence (28.6%vs. 3.0% and 26.9%vs. 2.9% respectively, bothP =0.0006). There was no significant difference in HCC recurrence between positive and negative HBsAg using the conventional qualitative HBsAg assay. Conclusion:Serum hs-HBsAg levels of≥ 0.0005 IU/mL at 3 to 6 months after LT is associated with higher rates of early HCC recurrence, and may be useful as an early tumor marker.展开更多
文摘Hepatocellular carcinoma （HCC） is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus （HBV） vacdnation programs, better food hygiene, increased global hepatitis C virus {HCV） prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV- related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways： chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein （AFP） are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients＇ survival and match best treatment option.
基金Supported by Liver Cirrhosis Clinical Research Center, in part by a grant from the Korea Health care technology R and D project, Ministry of Health and Welfare, Republic of Korea, NoA102065the Yonsei Liver Blood Bank, in part by a grantfrom sanofi-aventis Korea
文摘Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/ inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE),as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.
文摘Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection.High-risk infected individuals can now be identified by the usage of risk predictive scores.Vaccination plays a central role in the prevention of HBV-related HCC.Treatment of chronic HBV infection,especially by nucleoside analogue therapy,could also reduce the risk of HBV-related HCC.Concerning HCV infection,besides the advocation of universal precautions to reduce the rate of infection,pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response.Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV-and HCV-related HCC.The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.
文摘In the past few decades,chronic hepatitis B(CHB)has evolved from a disease that was untreatable and progressive,to one that can be easily controlled with antiviral therapy.However,patients with severe liver disease still remain difficult to treat despite the availability of highly potent nucleos(t)ide analogs.These include those with underlying cirrhosis,severe flares of CHB,hepatocellular carcinoma(HCC),and for those undergoing liver transplantation.For those with established cirrhosis,antiviral therapy should be considered for all,as unpredictable flares can still occur,which can be fatal for those with advanced chronic liver disease.However,even with effective viral suppression,the development of HCC can still occur.For patients with severe flares of CHB,although the use of antiviral can improve long term outcomes,a significant proportion may still die without liver transplantation.The short term prognosis of these patients is dependent on both the severity of flare and underlying pre-existing liver disease.In patients with decompensated cirrhosis,liver failure secondary to severe flares,or those with HCC,liver transplantation may be curative.After liver transplantation,long term antiviral therapy is required to prevent graft loss from recurrent hepatitis B infection.The use of hepatitis B immune globulin(HBIG)in combination with an oral antiviral agent has been the mainstay of post-transplant antiviral regimen for over adecade.With newer and more potent antiviral agents such as tenofovir and entecavir,use of these agents along with HBIG have demonstrated to be effective in preventing significant recurrence in the long term.
文摘AIM To investigate the epidemiology and natural history of Wilson's disease in the Chinese.METHODS 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 disease.RESULTS 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.
文摘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.
文摘BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for fibrosis. The role of M2 BPGi in prediction of HCC is unknown.AIM To examine the role of serum M2 BPGi in predicting HCC development in hepatitis B e antigen(HBeAg)-negative patients.METHODS Treatment-naive CHB patients with documented spontaneous HBeAg seroconversion were recruited. Serum M2 BPGi was measured at baseline(within3 years from HBeAg seroconversion), at 5 years and 10 years after HBeAg seroconversion and expressed as cut-off index(COI). Multivariate cox regression was performed to identify predictors for HCC development. ROC analysis was used to determine the cut-off value of M2 BPGi.RESULTS Among 207 patients(57% male, median age at HBeAg seroconversion 40 years old) with median follow-up of 13.1(11.8-15.5) years, the cumulative incidence of HCC at 15 years was 7%. Median M2 BPGi levels were significantly higher in patients with HCC compared to those without HCC(baseline: 1.39 COI vs 0.38 COI, P < 0.001; 5-year: 1.45 COI vs 0.47 COI, P < 0.001; 10-year: 1.20 COI vs 0.55 COI, P = 0.001). Multivariate analysis revealed age at HBeAg seroconversion[odds ratio(OR) = 1.196, 95% confidence interval(CI): 1.034-1.382, P = 0.016] and baseline M2 BPGi(OR = 4.666, 95%CI: 1.296-16.802, P = 0.018) were significant factors predictive of HCC. Using a cut-off value of 0.68 COI, baseline M2 BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% specificity.CONCLUSION High serum M2 BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients.
基金Supported by Collaborative Research Fund Scheme,University Grants Committee,No.C7154-20GFData Discovery for Health(D24H)Innovation and Technology Commission,AIR@InnoHK.
文摘BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.
文摘Chronic hepatitis B(CHB)infection is characterized by ongoing viral replication in infected hepatocytes,leading to persistent production of viral nucleic acids and expression of viral antigens.Hepatitis B surface antigen(HBsAg)is one of the most important viral antigens,secreted at levels at least 1,000-fold higher than infectious virions in the bloodstream.1 HBsAg consists of three isoforms:large(LHBs),middle(MHBs),and small(SHBs)surface proteins,transcribed and translated from the open reading frame S of the HBV genome.
文摘Colorectal cancer(CRC)is the third most common cancer and the second leading cause of cancer deaths worldwide[1].A considerable proportion of CRC is attributed to metabolic risk factors including type 2 diabetes(T2D),with the relative risk reported to be 1.4[2].It is therefore imperative to develop effective preventive strategies to reduce CRC incidence in individuals with T2D.Among individuals with T2D,growing evidence supports the role of diabetes medications for CRC prevention.The current guidelines of the American Gastroenterological Association have recommended metformin as a potential chemopreventive medication against colonic neoplasia in patients with T2D[3].However,the use of metformin may be limited by various side effects including gastrointestinal disturbances,and is contraindicated in moderate-to-severe renal impairment.Furthermore,a clinical trial found diabetic patients on metformin,as compared to rosiglitazone and glyburide,had similar CRC risk[4].
基金partially supported by an investigator-initiated research grant(IN-US-334-4309)from Gilead Sciences to Stanford University.
文摘Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).
文摘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 benefit.Methods:MEDLINE(OVID)and EMBASE databases were searched for eligible randomized clinical trials(RCTs)from inception to July 3,2021.Outcomes 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 included.Compared 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 mortality.Carvedilol ranked the safest.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.
文摘Aim:Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for chronic hepatitis B (CHB) can be associated with reappearance of hepatitis B surface antigen (HBsAg). The current study determined the significance of HBsAg qualitatively and quantitatively using a highly sensitive assay in recurrent HCC after transplantation. Methods:Consecutive patients with HBV-related HCC with LT were included. Oral nucleos(t)ide analogues without hepatitis B immune globulin were used as hepatitis B virus (HBV) prophylaxis. Quantitative HBsAg levels were performed at time of transplant, at 1 month, 3 and 6 months post transplant using a highly sensitive (hs)-HBsAg assay. Results:One hundred and fourteen patients were included, with a median follow-up of 80 months, with 24 cases of HCC recurrence, and a cumulative rate of 20.7% at 5 years. There was significant correlation between time of tumor recurrence and time of HBsAg reappearance (r = 0.551,P = 0.027). Early HCC recurrence was associated with higher median level of hs-HBsAg at the time of transplant (72.85vs. 69.70 IU/mL,P = 0.018). Using a hs-HBsAg cut-off level of 0.0005 IU/mL, patients with levels above this threshold at 3 and 6 months were associated with higher rate of early HCC recurrence (28.6%vs. 3.0% and 26.9%vs. 2.9% respectively, bothP =0.0006). There was no significant difference in HCC recurrence between positive and negative HBsAg using the conventional qualitative HBsAg assay. Conclusion:Serum hs-HBsAg levels of≥ 0.0005 IU/mL at 3 to 6 months after LT is associated with higher rates of early HCC recurrence, and may be useful as an early tumor marker.
