Challenges related to clinical decision-making in hepatocellular carcinoma recurrence post-liver transplantation: Is there a hope?

Hepatocellular carcinoma(HCC)is a common liver malignancy and represents a serious cause of cancer-related mortality and morbidity.One of the favourable curative surgical therapeutic options for HCC is liver transplantation(LT)in selected patients fulfilling the known standard Milan/University of California San Francisco criteria which have shown better outcomes and longer-term survival.Despite careful adherence to the strict HCC selection criteria for LT in different transplant centres,the recurrence rate still occurs which could negatively affect HCC patients’survival.Hence HCC recurrence post-LT could predict patients’survival and prognosis,depending on the exact timing of recurrence after LT(early or late),and whether intra/extrahepatic HCC recurrence.Several factors may aid in such a complication,particularly tumour-related criteria including larger sizes,higher grades or poor tumour differentiation,microvascular invasion,and elevated serum alpha-fetoprotein.Therefore,managing such cases is challenging,different therapeutic options have been proposed,including curative surgical and ablative treatments that have shown better outcomes,compared to the palliative locoregional and systemic therapies,which may be helpful in those with unresectable tumour burden.To handle all these issues in our review.

Chronic hepatitis C virus infection and post-liver transplantation diabetes mellitus

Patients with chronic hepatitis C virus （HCV） infection have a significantly increased prevalence of type 2 diabetes mellitus compared to controls or HBV-infected patients. Moreover, the incidence rate of post-liver transplantation diabetes mellitus （PTDM） also appears to be higher among patients wibh HCM infection. PTDM is often assodated with direct viral infection, autoimmune disorders, and immunosuppressive regimen. Activation of tumor necrosis factor-α may be the link between HCV infection and diabetes. In this article, we reviewed the epidemiologic association between HCV infection and PTDM, highlighting the most recent pathophysiologic insights into the mechanisms underlying this association.

Severe and delayed immune-mediated hemolysis post-liver transplantation

To the Editor:Hemolysis,which is caused by a variety of immune and non-immune mechanisms,is a well-recognized complication of solid organ transplantation.;Hemolysis post-liver transplantation can be induced by drug,infection,autoimmune disorders,blood-group incompatible

A score model for predicting post-liver transplantation survival in HBV cirrhosis-related hepatocellular carcinoma recipients: a single center 5-year experience

BACKGROUND： The prognostic prediction of liver transplantation（LT） guides the donor organ allocation. However, there is currently no satisfactory model to predict the recipients’ outcome, especially for the patients with HBV cirrhosis-related hepatocellular carcinoma（HCC）. The present study was to develop a quantitative assessment model for predicting the post-LT survival in HBV-related HCC patients.METHODS： Two hundred and thirty-eight LT recipients at the Liver Transplant Center, First Affiliated Hospital, Zhejiang University School of Medicine between 2008 and 2013 were included in this study. Their post-LT prognosis was recorded and multiple risk factors were analyzed using univariate and multivariate analyses in Cox regression.RESULTS： The score model was as follows： 0.114×（Child-Pugh score）-0.002×（positive HBV DNA detection time）＋0.647×（number of tumor nodules）＋0.055×（max diameter of tumor nodules）＋0.231×ln AFP＋0.437×（tumor differentiation grade）.The receiver operating characteristic curve analysis showed that the area under the curve of the scoring model for predicting the post-LT survival was 0.887. The cut-off value was 1.27, which was associated with a sensitivity of 72.5% and a specificity of 90.7%, respectively.CONCLUSION： The quantitative score model for predicting post-LT survival proved to be sensitive and specific.

Simple nucleos(t)ides as HBV prophylaxis regime of post-liver transplantation:Six-year followed up

A combination of nucleos(t)ides and hepatitis B immunoglobulin (HBIg) has been found to be effective for the prevention of hepatitis B viral (HBV) reinfection after liver transplantation (LT),but its administration is costly,and not always available. We report the case of a male,33-year-old cirrhotic patient who has tested positive for serum HBsAg,and HBeAg,with 9.04 × 107 copies/mL of HBV DNA. He suffered from acute liver failure and was near death before undergoing emergency LT. No HBIg was available at the time,so only lamivudine was used. He routinely received immunosuppression medication. Serum HBV DNA and HBsAg still showed positive post-LT,and the graft re-infected. Hepatitis B flared three months later. Adefovir dipivoxil was added to the treatment,but in the 24th mo of treatment,the patient developed lamivudine resistance and a worsening of the hepatitis occurred shortly thereafter. The treatment combination was then changed to a double dosage of entecavir and the disease was gradually resolved. After 60-mo of post-LT nucleos(t)ide analogue therapy,anti-HBs seroconverted,and the antiviral was stopped. By the end of a 12-mo follow-up,the patient had achieved sustained recovery. In conclusion,the case seems to point to evidence that more potent and less resistant analogues like entecavir might fully replace HBIg as an HBV prophylaxis and treatment regimen.

Portal hypertension in polycystic liver disease patients does not affect wait-list or immediate post-liver transplantation outcomes

AIM To establish the impact of portal hypertension(PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease(PCLD) listed for liver transplantation. METHODS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLD cohort was defined by the one or more of following parameters:(1) presence of radiological or endoscopic documented varices from our own centre or the referral centre;(2) splenomegaly(> 11 cm) on radiology inabsence of splenic cysts accounting for increased imaging size;(3) thrombocytopenia(platelets < 150 × 109/L); or(4) ascites without radiological evidence of hepatic venous outflow obstruction from a single cyst. RESULTS Forty-seven PCLD patients(F: M = 42: 5) were listed for liver transplantation(LT)(single organ, n = 35; combined liver-kidney transplantation, n = 12) with 19 patients(40.4%) having PH. When comparing the PH group with non-PH group, the mean listing age(PH group, 50.6(6.4); non-PH group, 47.1(7.4) years; P = 0.101), median listing MELD(PH group, 12; non-PH group, 11; P = 0.422) median listing UKELD score(PH group, 48; non-PH group, 46; P = 0.344) and need for renal replacement therapy(P = 0.317) were similar. In the patients who underwent LT alone, there was no difference in the duration of ICU stay(PH, 3 d; non-PH, 2 d; P = 0.188), hospital stay length(PH, 9 d; non-PH, 10 d; P = 0.973), or frequency of renal replacement therapy(PH, 2/8; non-PH, 1/14; P = 0.121) in the immediate post-transplantation period. CONCLUSION Clinically apparent portal hypertension in patients with PCLD listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity.

Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus

AIM: To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV infection.METHODS: Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome.RESULTS: Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate (OR = 0.95 per mL/min per 1.73 m2, 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases.CONCLUSION: Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

Growing challenge of post-liver transplantation non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is one of the leading causes of chronic liver disease,cirrhosis,and hepatocellular carcinoma worldwide,with an estimated prevalence of 25%.Post-liver transplantation(LT)recurrent or de novo hepatic steatosis is a common complication in recipients,irrespective of transplantation indication.Risk factors for graft steatosis mainly include obesity,immunosuppression,donor steatosis,and genetic factors.Liver transplant recipients are at high risk of developing insulin resistance,new-onset diabetes,and posttransplantation metabolic syndrome that is highly associated with immunosuppressive treatment.Post-LT NAFLD is often underdiagnosed due to the poor sensitivity of most routine imaging methods.The gold standard for the diagnosis of hepatic steatosis is liver biopsy,which is,however,limited to more complex cases due to its invasive nature.There is no approved pharmacotherapy in NAFLD.Lifestyle modification remains the cornerstone in NAFLD treatment.Other treatment strategies in post-LT NAFLD include lifestyle modifications,pharmacotherapy,bariatric surgery,and tailored immunosuppression.However,these approaches originate from recommendations in the general population,as there is scarce data regarding the safety and efficacy of current management strategies for NAFLD in liver transplant patients.Future prospective studies are required to achieve tailored treatment for these patients.

Analysis of Autonomic, Respiratory and Motor Function of Infants in Pre- and Post-Liver Transplantation

Purpose: Children with liver impairment are likely to develop changes in autonomic nervous function and delay in motor development. The assessment and identification of these dysfunctions may allow an appropriate physiotherapeutic care. Method: Cross sectional study of 18 infants, 11 controls and 7 infants (post-liver transplantation) with an average age of 10 ± 4.5 months, was evaluated in pre- and post-liver transplant. All infants underwent to assessments of motor skills, body composition, chest and abdominal motion, and cardiac autonomic modulation was measured by heart rate variability. Results: Motor delay and malnutrition were found in all infants. The gravity index (PELD)—pediatric end-stage liver disease—showed a negative correlation with the Alberta Infant Motor Scale (r = 0.83, p = 0.01). In addition, reduced parasympathetic modulation was demonstrated by the rMSSD, SD1 and ApEn, pre- and post-transplant. Conclusion: Infants with liver disease, even after transplantation, have delay in motor development, as well as changes in their nutritional and autonomic dysfunction.

Endoscopic management of biliary strictures post-liver transplantation

Biliary complications play a significant role in morbidity of liver transplant recipients. Biliary strictures occur between 10%-25% of patients with a higher incidence in living donor recipients compared to deceased donors. Strictures can be classified as either anastomotic or non-anastomotic and may be related to ischemic events. Endoscopic management of biliary strictures in the posttransplant setting has become the preferred initial approach due to adequate rates of resolution of anastomotic and non-anastomotic strictures(NAS).However, several factors may increase complexity of the endoscopic approach including surgical anatomy, location, number, and severity of bile duct strictures.Many endoscopic tools are available, however, the approach to management of anastomotic and NAS has not been standardized. Multi-disciplinary techniques may be necessary to achieve optimal outcomes in select patients. We will review the risk factors associated with the development of bile duct strictures in the posttransplant setting along with the efficacy and complications of current endoscopic approaches available for the management of bile duct strictures.

Diabetes mellitus is not associated with worse short term outcome in patients older than 65 years old post-liver transplantation

BACKGROUND Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation(LT).Hence,more patients with diabetes mellitus(DM)are undergoing LT,especially,above the age of 65.AIM To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of 65.METHODS We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical record.We assessed the impact of DM on short-term outcomes,one-year,post-LT based on the following variables:Survival at one year;acute cellular rejection(ACR)rates;intensive care unit(ICU)and hospital length of stay;and readmissions.RESULTS Total of 148 patients who are 65 year or older underwent LT during the study period.The mean age is 68.5±3.3 years and 67.6%were male.The median Model for End-stage Liver Disease score at time of transplantation was 22(6-39),39%of patients had hepatocellular carcinoma and 77.7%underwent living donor LT.The one-year survival was similar between DM patients and others,91%.ACR occurred in 13.5%of patients(P=0.902).The median ICU stay is 4.5-day P=0.023.The rates of ICU and 90-d readmission were similar(P=0.821)and(P=0.194),respectively.CONCLUSION The short-term outcome of elderly diabetic patients undergoing LT is similar to others.The presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Lesson learnt from 60 years of liver transplantation:Advancements,challenges,and future directions

Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.

Fecal microbiota transplantation in allergic diseases

Microorganisms such as bacteria,fungi,viruses,parasites living in the human intestine constitute the human intestinal microbiota.Dysbiosis refers to composi-tional and quantitative changes that negatively affect healthy gut microbiota.In recent years,with the demonstration that many diseases are associated with dysbiosis,treatment strategies targeting the correction of dysbiosis in the treat-ment of these diseases have begun to be investigated.Faecal microbiota trans-plantation(FMT)is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit.FMT studies have gained popularity after probiotic,prebiotic,symbiotic studies in the treatment of dysbiosis and related diseases.FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance(T helper 1/T helper 2 cells)and thus suppression of allergic responses.In this article,the definition,application,safety and use of FMT in allergic diseases will be discussed with current data.

Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

Key challenges of post-liver transplant weight management

Liver transplantation serves as a life-saving intervention for patients with endstage liver disease,yet long-term survival remains a challenge.Post-liver transplant obesity seems to have a significant contribution to this challenge and it emerges as a significant risk factor for graft steatosis,metabolic syndrome and denovo malignancy development.This review synthesizes current literature on prevalence,risk factors and management strategies for post-liver transplant obesity,emphasizing its impact on graft and patient survival.Literature review consultation was conducted in Medline/PubMed,SciELO and EMBASE,with the combination of the following keywords:Weight management,liver transplantation,immunosuppressive therapy,lifestyle interventions,bariatric surgery.Immunosuppressive therapy has a significant influence on long-term survival of liver transplant patients,yet it seems to have lesser effect on post-transplant obesity development than previously thought.However,it significantly contributes to the development of other components of metabolic syndrome.Key predisposing factors for post-transplant obesity development encompass elevated recipient and donor body mass index,a history of alcoholic liver disease,hepatocellular carcinoma,male gender,the absence of cellular rejection and the marital status of the recipient.Tailored immunosuppressive regimens,pharmacotherapy,lifestyle interventions and bariatric surgery represent key components in mitigating post-transplant obesity and improving long-term survival and quality of life in this group of patients.Timely identification and intervention thus hold paramount importance.Further research is warranted to refine optimal management strategies and enhance outcomes in this patient population.

Prophylaxis of hepatitis B recurrence in post-liver transplantation patients with lamivudine-resistant YMDD mutant

Background The most frequently used therapy for post-transplantation recurrence of hepatitis B virus （HBV） infection is lamivudine, but this drug is associated with a high resistance rate due to YMDD mutant. In preliminary reports, adefovir dipivoxil （ADV） has been shown to have activity against lamivudine-resistant strains of HBV. However, clinical experience in treatment of HBV infection after liver transplantation （LT） is still not entirely clear. This study was aimed to evaluate the prophylactic efficacy of ADV plus hepatitis B immunoglobulin （HBIG） in patients with YMDD mutant before LT. Methods From March 2004 to March 2006, 16 patients with chronic hepatitis B had lamivudine-resistant YMDD mutants detected prior to liver transplantation and received treatment with ADV plus additional intramuscular HBIG after LT as prophylaxis against graft reinfection. Tests for liver function, serum HBsAg, anti-HBs （HBIG）, HBeAg, anti-HBc, anti-HBe, HBV-DNA, and creatinine were assessed pre- or post-liver transplantation. Results The median follow-up of these patients post-liver transplantation was 19.4 months. Fifteen patients survived and one patient died of recurrence of hepatocellular carcinoma （HCC）. There was significant difference （10.98% vs. 2.26%, P〈0.05） in YMDD mutant rate between the patients with HBV-DNA over 106 copies/ml and those with HBV-DNA less than 106 copies/mi. Fifteen patients （93.8%） had undetectable HBV-DNA at 4 weeks and 1 （6.3%） at 6 months after LT. No hepatitis B recurrence was detected by persistent testing of HBsAg, HBeAg, and HBV-DNA and no increase of serum creatinine level associated with ADV was observed in any of the patients. Conclusion ADV combined with intramuscular HBIG can effectively prevent patients with pre-transplantation YMDD mutant from HBV recurrence after LT.

Safety and efficacy of Kaffes intraductal self-expanding metal stents in the management of post-liver transplant anastomotic strictures

BACKGROUND Endoscopic management is the first-line therapy for post-liver-transplant anas-tomotic strictures.Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months,data on safety and duration for metal stents in this setting is scarce.Due to limited access to endoscopic retrograde cholan-giopancreatography(ERCP)during the coronavirus disease 2019 pandemic in our centre,there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy.This was mainly due to the theoretical benefit of Kaffes stents allowing for longer indwelling periods compared to the traditional plastic stents.METHODS Adult liver transplant recipients aged 18 years and above who underwent ERCP were retrospectively identified during a 10-year period through a database query.Unplanned admissions post-Kaffes stent insertion were identified manually through electronic and scanned medical records.The main outcome was the incidence of complications when stents were left indwelling for 3 months vs 6 months.Stent efficacy was calculated via rates of stricture recurrence between patients that had stenting courses for≤120 d or>120 d.RESULTS During the study period,a total of 66 ERCPs with Kaffes insertion were performed in 54 patients throughout their stenting course.In 33 ERCPs,the stent was removed or exchanged on a 3-month interval.No pancreatitis,perfor-ations or deaths occurred.Minor post-ERCP complications were similar between the 3-month(abdominal pain and intraductal migration)and 6-month(abdominal pain,septic shower and embedded stent)groups-6.1%vs 9.1%respectively,P=0.40.All strictures resolved at the end of the stenting course,but the stenting course was variable from 3 to 22 months.The recurrence rate for stenting courses lasting for up to 120 d was 71.4%and 21.4%for stenting courses of 121 d or over(P=0.03).There were 28 patients that were treated with a single ERCP with Kaffes,21 with removal after 120 d and 7 within 120 d.There was a significant improvement in stricture recurrence when the Kaffes was removed after 120 d when a single ERCP was used for the entire stenting course(71.0%vs 10.0%,P=0.01).CONCLUSION Utilising a single Kaffes intraductal fully-covered metal stent for at least 4 months is safe and efficacious for the management of post-transplant anastomotic strictures.

Management of Hepatitis C Post-liver Transplantation: a Comprehensive Review

Infection with hepatitis C virus (HCV) is a common cause of chronic liver disease,and HCV-related cirrhosis and hepatocellular carcinoma are the leading causes for liver transplantation in the Western world.Recurrent infection of the transplanted liver allograft is universal in patients with detectable HCV viremia at the time of transplant and can cause a spectrum of disease,ranging from asymptomatic chronic infection to an aggressive fibrosing cholestatic hepatitis.Recurrent HCV is more aggressive in the post-transplant population and is a leading cause of allograft loss,morbidity,and mortality.Historically,treatment of recurrent HCV has been limited by low rates of treatment success and high side effect profiles.Over the past few years,promising new therapies have emerged for the treatment of HCV that have high rates of sustained virological response without the need for interferon based regimens.In addition to being highly effective,these treatments have higher rates of adherence and a lower side effect profile.The purpose of this review is to summarize current therapies in recurrent HCV infection,to review the recent advances in therapy,and to highlight areas of ongoing research.

Meta-analysis of the immunogenicity of standard and booster SARS-CoV-2 vaccination in patients with chronic liver disease and post-liver transplantation

Aims:Patients with liver disease may exhibit higher infection rates and mortality rates from coronavirus disease 2019(COVID-19)than healthy individuals,and vaccination against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an effective prevention strategy.This metaanalysis aimed to assess the effectiveness and safety of SARS-CoV-2 vaccines in patients with chronic liver disease(CLD)and post-liver transplantation(LT).Methods:The PubMed,Embase,and Cochrane databases were searched.A random-effects model meta-analysis was used to determine the seropositivity rates of SARS-CoV-2 antibodies,odds ratio(OR)compared with healthy controls(HC),risk ratio(RR)between the booster and standard vaccination regimen,and the rate of adverse reactions(ADR).Results:In the standard vaccination regimen analysis,17 controlled articles were included for effectiveness analysis,and six articles for ADR analysis.The pooled seropositivity rates of SARS-CoV-2 antibodies in patients with CLD and post-LT were 93.3%(95%confidence interval[CI]:89.0%-97.6%)and 69.1%(95%CI:63.0%-75.3%),respectively.Both rates were lower than those in HC(p<0.001).The differences remained significant after sorting by detection interval,vaccine type,antibody type,or CLD type.LT recipients showed much lower seropositivity rates of antibodies than patients with CLD(69.1%vs.93.3%)or HC(OR:0.055).The pooled total ADR rate of patients was 24.0%(95%CI:16.2%-31.8%).In the booster vaccination regimen analysis,11 prospective studies were enrolled,and the seropositivity rates of antibodies after the booster dose were increased by 27%compared with those of the standard vaccination regimen(RR:1.27,95%CI:1.15-1.41,p<0.001).Conclusion:Patients with CLD and post-LT can gain protection against COVID-19 from standard vaccines,demonstrating a potentially weaker immunogenic response than HC.Booster vaccines can compensate for this deficiency.Therefore,patients with CLD and post-LT should be prioritized for receiving the COVID-19 booster vaccine.