AIM To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease(NAFLD).METHODS Two individual reviewers identified relevant studie...AIM To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease(NAFLD).METHODS Two individual reviewers identified relevant studies using the Pub Med, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows:(1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and(2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. RESULTS A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference =-0.86, P = 0.08(-4.17, 2.46)]. A metaregression evaluation of serum vitamin 25(OH)D levels across the individual stages(F0-F4) of fibrosis did not show an association for the six included studies.CONCLUSION Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD.展开更多
Herbal and dietary supplements(HDS)are increasingly used worldwide for numerous,mainly unproven health benefits.The HDS industry is poorly regulated compared to prescription medicines and most products are easily obta...Herbal and dietary supplements(HDS)are increasingly used worldwide for numerous,mainly unproven health benefits.The HDS industry is poorly regulated compared to prescription medicines and most products are easily obtainable.Drug induced liver injury(DILI)is a well-recognized entity associated with prescription and over the counter medications and many reports have emerged of potential HDS-related DILI.There is considerable geographic variability in the risk and severity of DILI associated with HDS but the presentation of severe liver injury is similar with a hepatocellular pattern accompanied by jaundice.This type of injury can lead to acute liver failure and the need for liver transplantation.Patients will often fail to mention their use of HDS,considering it natural and therefore harmless.Hence physicians should understand that these products can be associated with DILI and explicitly ask about HDS use in any patient with otherwise unexplained acute liver injury.展开更多
Liver transplantation is the optimal treatment for many patients with advanced liver disease, including decompensated cirrhosis, hepatocellular carcinoma and acute liver failure. Organ shortage is the maindeterminant ...Liver transplantation is the optimal treatment for many patients with advanced liver disease, including decompensated cirrhosis, hepatocellular carcinoma and acute liver failure. Organ shortage is the maindeterminant of death on the waiting list and hence living donor liver transplantation(LDLT) assumes importance. Biliary complications are the most common post operative morbidity after LDLT and occur due to anatomical and technical reasons. They include biliary leaks, strictures and cast formation and occur in the recipient as well as the donor. The types of biliary complications after LDLT along with their etiology, presenting features, diagnosis and endoscopic and surgical management are discussed.展开更多
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 th...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. HIVinfected 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/d L, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate(OR = 0.95 per m L/min per 1.73 m^2, 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin(OR = 2.43 per mg/d L, 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.展开更多
AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus(HCV) recurrence. METHODS: From 2003, a protocolized LADR st...AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus(HCV) recurrence. METHODS: From 2003, a protocolized LADR strategy was employed to treat liver transplant(LT) recipients with recurrent HCV at our institution. Medical records of 182 adult patients with recurrent HCV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28 B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B(rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include(1) patient and graft survival;(2) effect of anti-viral therapy on liver histology(fibrosis and inflammation);(3) incidence of on-treatment development of ACR, CDR, or PCH;(4) association of recipient and donor IL28 B genotype with SVR; and(5) incidence of antiviral therapy-associated adverse events(anemia, leukopenia, thrombocytopenia, depression) and hepatic decompensation.RESULTS: The overall SVR rate was 38%(29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HCV Gt(P < 0.0001), donor age(P = 0.003), cytomegalovirus mismatch(P = 0.001), baseline serum bilirubin(P = 0.002), and baseline viral load(P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-CC/donor-non CC pairs(P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR(97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L(P = 0.01), total bilirubin ≥ 1.5 mg/d L(P = 0.001) and creatinine ≥ 2 mg/d L(P = 0.001) were independently associated with patient survival. Only 13% of patients achieving SVR died during the followup period. Treatment discontinuation and treatmentrelated mortality occurred in 35% and 2.2% of patients, respectively. EPO, G-CSF and blood transfusion were needed in 89%, 40% and 23% of patients, respectively. Overall hospitalization rate for treatment-related serious adverse events was 21%. Forty-six(25%) of the patients were deceased; among those who died, 25(54%) were due to liver-related complications, and 4 deaths(9%) occurred while receiving therapy(2 patients experienced hepatic decompensation and 2 sepsis). CONCLUSION: LADR strategy remains relevant in managing post-LT recurrent HCV where access to DAAs is limited. SVR is associated with improved survival, but fibrosis progression still occurs.展开更多
BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy optio...BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.展开更多
Hepatocytes can divide rapidly and proliferate in the absence of inflammation and fibroplasia in the damaged or partial hepatectomy(PHx)of the liver,which is essential for the recovery of related patients.Recent studi...Hepatocytes can divide rapidly and proliferate in the absence of inflammation and fibroplasia in the damaged or partial hepatectomy(PHx)of the liver,which is essential for the recovery of related patients.Recent studies have found that bile acids(BA)play an important role in the process of liver regeneration.In the early stages of PHx,bile acid overload occurs,and liver injury is aggravated by loading.Later bile acids can induce protective and proliferative responses in the liver and promote liver regeneration.In this paper,we summarize the negative effects after bile acid overload and its positive role as a signaling molecule involved in related signaling pathways on liver regeneration,including protection of the liver and promotion of liver regeneration,and its double-edswordged"in Liver regeneration.This provides a theoretical basis for subsequent in-depth study of the mechanism and benefit avoidance in clinical treatment.展开更多
BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trend...BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.展开更多
Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may a...Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may also have led to emergence of viral mutations that can escape the protection of hepatitis B surface antibody. As this phenomenon is increasingly recognized, concern for transmission to vaccinated individuals has also been raised. Herein, we describe two cases where the suspected presence of a hepatitis B surface antigen escape mutation impacted the decision to initiate early antiviral therapy, as well as provide a brief review of these mutations. Our findings described here suggest that a lower threshold for initiating therapy in these individuals should be considered in order to reduce the risk of transmission, as vaccination does not provide protection.展开更多
AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received ...AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received treatment at our institution were queried.Analysis was restricted to patients who previously failed treatment with boceprevir(BOC) or telaprevir(TVR) and started simeprevir(SMV) and sofosbuvir(SOF) ± ribavirin(RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus(HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December,31 st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics,HCV infection,and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/SOF.RESULTS: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon(PEG) and RBV who failed this triple therapy were subsequently retreated with an off-label all-oral regimen of SMV and SOF for 12 wk,with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response,but later relapsed. Eight(100%) patients were male. Mean age was 56(range,49-64). Eight(100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6(mean 3.8). Eight(100%) patients were male had liver cirrhosis as determined by Fibroscan or MRI. Seven(87.5%) patients had genotype 1a HCV. Seven(87.5%) patients had over 1 million IU/m L HCV RNA at the time of re-treatment.CONCLUSION: This study identifies factors associated with SMV/SOF treatment failure and provides evidence that twleve weeks of SMV/SOF/RBV is insufficient in cirrhotics with high-titer genotype 1a HCV.展开更多
The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk str...The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction,and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature,and discuss critical issues to successfully define,evaluate,and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab testbased fibrosis assessment methods. However,recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care,and eventually achieve "precision medicine".展开更多
Liver transplantation(LT)remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply.The advent of highly effective anti-...Liver transplantation(LT)remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply.The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C(HCV)and hepatitis B(HBV)related liver disease and yet the number of patients waiting for LT continues to increase,driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcoholrelated liver disease.In addition,human immunodeficiency virus(HIV)infection,which was previously a contra-indication for LT,is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT.The rising demand for LT is projected to increase further in the future,thus driving the need to investigate potential means of expanding the pool of potential donors.One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive,HBV-positive,and HIVpositive donors.The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV,HBV or HIV infected recipients and in some cases uninfected recipients.展开更多
AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV...AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression.RESULTS SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.展开更多
Objective Genome-wide association studies(GWAS)have linked many single nucleotide polymorphisms(SNPs)to the outcomes of a variety of liver diseases.The aim of the present study was to evaluate the association of sever...Objective Genome-wide association studies(GWAS)have linked many single nucleotide polymorphisms(SNPs)to the outcomes of a variety of liver diseases.The aim of the present study was to evaluate the association of several candidate SNPs with the risk and severity of cirrhosis due to chronic hepatitis B in a Chinese population.Methods A total of 714 Chinese participants with persistent HBV infection were studied.Patients were divided into cirrhotic(n=429)and non-cirrhotic(n=285)groups based on clinical and pathological evidence.The progression rate and severity of liver cirrhosis were evaluated with an arbitrary t-score system.Genotypes of six SNPs in five candidate genes were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The genotypic distributions of the SNPs were compared between the age-matched cirrhotic and non-cirrhotic subjects.The association between the risk of SNPs and the severity and progression rate of cirrhosis was further analyzed.Results Rs2679757 polymorphism of the antizyme inhibitor 1(AZIN1)gene and Rs886277 in the transient receptor potential cation channel subfamily M,member 5 gene(TRPM5)were found to be associated with cirrhosis risk in CHB.They were also correlated with the overall severity and progression rate of cirrhosis.Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups.Conclusions AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk and the progression rate of HBV-related liver fibrosis in Chinese patients.The emerging SNPs associated with cirrhosis prognosis warrant further clinical validation in other CHB cohorts or ethnic groups,and merit mechanistic studies to reveal their roles in fibrosis progression.展开更多
AIM To evaluate new therapies for hepatitis C virus(HCV), data about real-world outcomes are needed.METHODS Outcomes of 223 patients with genotype 1 HCV who started telaprevir-or boceprevir-based triple therapy(May 20...AIM To evaluate new therapies for hepatitis C virus(HCV), data about real-world outcomes are needed.METHODS Outcomes of 223 patients with genotype 1 HCV who started telaprevir-or boceprevir-based triple therapy(May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency viruspositive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response(SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response(FVR) was defined as undetectable HCV RNA at week-4(telaprevir) or week-8(boceprevir). RESULTS The median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis(FIB-4 ≥ 3.25). Only 42%(94/223) of patients achieved SVR24 on an intention-totreat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio(OR) = 5.92, 95% confidence interval(CI): 2.34-14.96], HCV sub-genotype 1b(OR = 2.81, 95%CI: 1.45-5.44), platelet count(OR = 1.10, per x 104 cells/μL, 95%CI: 1.05-1.16), and IL28 B CC genotype(OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 103/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25%(27/104) of patients with an end-oftreatment response and was associated with non-FVR(OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a(OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25(OR = 2.77; 95%CI: 1.07-7.22). CONCLUSION The SVR rate was 42% with telaprevir-or boceprevirbased triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.展开更多
Early detection of hepatocellular carcinoma(HCC)while in its early stages is critical for reducing HCC mortality in high-risk patients.However,highly sensitive and specific surveillance biomarkers for early-stage HCC ...Early detection of hepatocellular carcinoma(HCC)while in its early stages is critical for reducing HCC mortality in high-risk patients.However,highly sensitive and specific surveillance biomarkers for early-stage HCC detection are still lacking.In recent years,great efforts have been made to research tumor-derived molecular features that are detectable in circulation,such as circulating tumor deoxyribonucleic acid and circulating tumor ribonucleic acid,in order to explore their potential as noninvasive biomarker candidates in many tumor types.In this review,we summarize current studies on these new approaches and their application in early HCC detection.展开更多
BACKGROUND Data that assess maternal and infant outcomes in hepatitis C virus(HCV)-infected mothers are limited.AIM To investigate the frequency of complications and the associated risk factors.METHODS We performed a ...BACKGROUND Data that assess maternal and infant outcomes in hepatitis C virus(HCV)-infected mothers are limited.AIM To investigate the frequency of complications and the associated risk factors.METHODS We performed a cohort study to compare pregnancy and fetal outcomes of HCVviremic mothers with those of healthy mothers.Risk factors were analyzed with logistic regression.RESULTS Among 112 consecutive HCV antibody-positive mothers screened,we enrolled 79 viremic mothers.We randomly selected 115 healthy mothers from the birth registry as the control.Compared to healthy mothers,HCV mothers had a significantly higher frequency of anemia[2.6%(3/115)vs 19.0%(15/79),P<0.001]during pregnancy,medical conditions that required caesarian section[27.8%(32/115)vs 48.1%(38/79),P=0.004],and nuchal cords[9.6%(11/115)vs 34.2%(27/79),P<0.001].In addition,the mean neonatal weight in the HCV group was significantly lower(3278.3±462.0 vs 3105.1±459.4 gms;P=0.006),and the mean head circumference was smaller(33.3±0.6 vs 33.1±0.7 cm;P=0.03).In a multivariate model,HCV-infected mothers were more likely to suffer anemia[adjusted odds ratio(OR):18.1,95%confidence interval(CI):4.3-76.6],require caesarian sections(adjusted OR:2.6,95%CI:1.4-4.9),and have nuchal cords(adjusted OR:5.6,95%CI:2.4-13.0).Their neonates were also more likely to have smaller head circumferences(adjusted OR:2.1,95%CI:1.1-4.3)and lower birth weights than the average(≤3250 gms)with an adjusted OR of 2.2(95%CI:1.2-4.0).The vertical transmission rate was 1%in HCV-infected mothers.CONCLUSION Maternal HCV infections may associate with pregnancy and obstetric complications.We demonstrated a previously unreported association between maternal HCV viremia and a smaller neonatal head circumference,suggesting fetal growth restriction.展开更多
Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Th...Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.展开更多
BACKGROUND Necrolytic acral erythema(NAE) is a rare dermatological disorder,which is associated with hepatitis C virus(HCV) infection or zinc deficiency.It is characterized by erythematous or violaceous lesions occurr...BACKGROUND Necrolytic acral erythema(NAE) is a rare dermatological disorder,which is associated with hepatitis C virus(HCV) infection or zinc deficiency.It is characterized by erythematous or violaceous lesions occurring primarily in the lower extremities.The treatment includes systemic steroids and oral zinc supplementation.We report a case of NAE in a 66-year-old human immunodeficiency virus(HIV)/HCV co-infected woman with NAE.NAE is rarely reported in co-infected patients and the exact mechanisms of pathogenesis are still unclear.CASE SUMMARY A 66-year-old HIV/HCV co-infected female patient presented with painless,nonpruritic rash of extremities for one week and underwent extensive work-up for possible rheumatologic disorders including vasculitis and cryoglobulinemia.Punch skin biopsies of right and left thigh revealed thickened parakeratotic stratum corneum most consistent with NAE.Patient was started on prednisone and zinc supplementation with resolution of the lesions and improvement of rash.CONCLUSION Clinicians should maintain high clinical suspicion for early recognition of NAE in patients with rash and HCV.展开更多
文摘AIM To investigate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and fibrosis stage in patients with non-alcoholic fatty liver disease(NAFLD).METHODS Two individual reviewers identified relevant studies using the Pub Med, EMBASE, Cochrane, and Scopus databases. Inclusion criteria were as follows:(1) Studies that evaluated adults with NAFLD and serum or plasma 25(OH)D levels; and(2) assessed fibrosis stage using liver biopsy. A rigorous analysis yielded six articles as having sufficient data to employ in evaluating the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. To meta-analyze vitamin D levels in F0-F2 vs F3-F4 fibrosis, a random-effects meta-analysis fit using restricted maximum likelihood was applied. To examine trends across each stage of fibrosis with respect to vitamin D levels, a meta-regression was performed. P < 0.05 was considered statistically significant. RESULTS A total of 937 subjects from six studies were included in the final analysis to evaluate the association of serum vitamin D levels in patients with NAFLD based on their liver fibrosis stage by histopathological analysis. The lead investigators of each of the six studies were contacted and the data were collected. First, the investigators performed a meta-analysis to compare serum vitamin D levels in patients with NAFLD with stage F0-F2 compared to F3-F4, which did not show significance [meta-estimate of the pooled mean difference =-0.86, P = 0.08(-4.17, 2.46)]. A metaregression evaluation of serum vitamin 25(OH)D levels across the individual stages(F0-F4) of fibrosis did not show an association for the six included studies.CONCLUSION Low vitamin D status is not associated with higher stages of liver fibrosis in patients with NAFLD.
文摘Herbal and dietary supplements(HDS)are increasingly used worldwide for numerous,mainly unproven health benefits.The HDS industry is poorly regulated compared to prescription medicines and most products are easily obtainable.Drug induced liver injury(DILI)is a well-recognized entity associated with prescription and over the counter medications and many reports have emerged of potential HDS-related DILI.There is considerable geographic variability in the risk and severity of DILI associated with HDS but the presentation of severe liver injury is similar with a hepatocellular pattern accompanied by jaundice.This type of injury can lead to acute liver failure and the need for liver transplantation.Patients will often fail to mention their use of HDS,considering it natural and therefore harmless.Hence physicians should understand that these products can be associated with DILI and explicitly ask about HDS use in any patient with otherwise unexplained acute liver injury.
文摘Liver transplantation is the optimal treatment for many patients with advanced liver disease, including decompensated cirrhosis, hepatocellular carcinoma and acute liver failure. Organ shortage is the maindeterminant of death on the waiting list and hence living donor liver transplantation(LDLT) assumes importance. Biliary complications are the most common post operative morbidity after LDLT and occur due to anatomical and technical reasons. They include biliary leaks, strictures and cast formation and occur in the recipient as well as the donor. The types of biliary complications after LDLT along with their etiology, presenting features, diagnosis and endoscopic and surgical management are discussed.
基金Supported by National Institutes of Health,No.DA031095 and No.DK090317
文摘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. HIVinfected 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/d L, 95%CI: 0.40-0.88, P < 0.01), estimated glomerular filtration rate(OR = 0.95 per m L/min per 1.73 m^2, 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin(OR = 2.43 per mg/d L, 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.
基金Supported by JTD(an employee of Mount Sinai Medical Center)in part was provided by Genentech Pharmaceuticals
文摘AIM: To describe our experience using a low-acceleratingdose regimen(LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus(HCV) recurrence. METHODS: From 2003, a protocolized LADR strategy was employed to treat liver transplant(LT) recipients with recurrent HCV at our institution. Medical records of 182 adult patients with recurrent HCV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28 B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B(rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include(1) patient and graft survival;(2) effect of anti-viral therapy on liver histology(fibrosis and inflammation);(3) incidence of on-treatment development of ACR, CDR, or PCH;(4) association of recipient and donor IL28 B genotype with SVR; and(5) incidence of antiviral therapy-associated adverse events(anemia, leukopenia, thrombocytopenia, depression) and hepatic decompensation.RESULTS: The overall SVR rate was 38%(29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HCV Gt(P < 0.0001), donor age(P = 0.003), cytomegalovirus mismatch(P = 0.001), baseline serum bilirubin(P = 0.002), and baseline viral load(P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-CC/donor-non CC pairs(P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR(97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L(P = 0.01), total bilirubin ≥ 1.5 mg/d L(P = 0.001) and creatinine ≥ 2 mg/d L(P = 0.001) were independently associated with patient survival. Only 13% of patients achieving SVR died during the followup period. Treatment discontinuation and treatmentrelated mortality occurred in 35% and 2.2% of patients, respectively. EPO, G-CSF and blood transfusion were needed in 89%, 40% and 23% of patients, respectively. Overall hospitalization rate for treatment-related serious adverse events was 21%. Forty-six(25%) of the patients were deceased; among those who died, 25(54%) were due to liver-related complications, and 4 deaths(9%) occurred while receiving therapy(2 patients experienced hepatic decompensation and 2 sepsis). CONCLUSION: LADR strategy remains relevant in managing post-LT recurrent HCV where access to DAAs is limited. SVR is associated with improved survival, but fibrosis progression still occurs.
基金the National Key Research and Development Program of China,No.2017YFC0908104National Science and Technology Projects,No.2017ZX10203201,No.2017ZX10201201,and No.2017ZX10202202.
文摘BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.
基金General Program of National Natural Science Foundation of China(No.81774236,81960841)。
文摘Hepatocytes can divide rapidly and proliferate in the absence of inflammation and fibroplasia in the damaged or partial hepatectomy(PHx)of the liver,which is essential for the recovery of related patients.Recent studies have found that bile acids(BA)play an important role in the process of liver regeneration.In the early stages of PHx,bile acid overload occurs,and liver injury is aggravated by loading.Later bile acids can induce protective and proliferative responses in the liver and promote liver regeneration.In this paper,we summarize the negative effects after bile acid overload and its positive role as a signaling molecule involved in related signaling pathways on liver regeneration,including protection of the liver and promotion of liver regeneration,and its double-edswordged"in Liver regeneration.This provides a theoretical basis for subsequent in-depth study of the mechanism and benefit avoidance in clinical treatment.
文摘BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.
文摘Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may also have led to emergence of viral mutations that can escape the protection of hepatitis B surface antibody. As this phenomenon is increasingly recognized, concern for transmission to vaccinated individuals has also been raised. Herein, we describe two cases where the suspected presence of a hepatitis B surface antigen escape mutation impacted the decision to initiate early antiviral therapy, as well as provide a brief review of these mutations. Our findings described here suggest that a lower threshold for initiating therapy in these individuals should be considered in order to reduce the risk of transmission, as vaccination does not provide protection.
基金Supported by The Grants No.R01 DK090317 and No.R01 DA031095(in part)
文摘AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received treatment at our institution were queried.Analysis was restricted to patients who previously failed treatment with boceprevir(BOC) or telaprevir(TVR) and started simeprevir(SMV) and sofosbuvir(SOF) ± ribavirin(RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus(HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December,31 st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics,HCV infection,and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/SOF.RESULTS: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon(PEG) and RBV who failed this triple therapy were subsequently retreated with an off-label all-oral regimen of SMV and SOF for 12 wk,with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response,but later relapsed. Eight(100%) patients were male. Mean age was 56(range,49-64). Eight(100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6(mean 3.8). Eight(100%) patients were male had liver cirrhosis as determined by Fibroscan or MRI. Seven(87.5%) patients had genotype 1a HCV. Seven(87.5%) patients had over 1 million IU/m L HCV RNA at the time of re-treatment.CONCLUSION: This study identifies factors associated with SMV/SOF treatment failure and provides evidence that twleve weeks of SMV/SOF/RBV is insufficient in cirrhotics with high-titer genotype 1a HCV.
基金Supported by FLAGS FoundationNuovo-Soldati Cancer Research Foundation+1 种基金advanced training grant from Geneva University Hospital to NG,NIH/NIDDK R01 DK099558the Irma T Hirschl Trust to YH
文摘The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction,and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature,and discuss critical issues to successfully define,evaluate,and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab testbased fibrosis assessment methods. However,recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care,and eventually achieve "precision medicine".
文摘Liver transplantation(LT)remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply.The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C(HCV)and hepatitis B(HBV)related liver disease and yet the number of patients waiting for LT continues to increase,driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcoholrelated liver disease.In addition,human immunodeficiency virus(HIV)infection,which was previously a contra-indication for LT,is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT.The rising demand for LT is projected to increase further in the future,thus driving the need to investigate potential means of expanding the pool of potential donors.One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive,HBV-positive,and HIVpositive donors.The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV,HBV or HIV infected recipients and in some cases uninfected recipients.
基金Supported by Janssen Scientific Affairs and National Institutes of Health,Nos.DA031095 and DK090317
文摘AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression.RESULTS SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.
基金supported by Shanghai Pujiang Talent Program 2009 (09PJ1402600) to Jin-sheng GuoWang Bao-En Liver Fibrosis Research Foundation (20090001) to Ji-yao Wang
文摘Objective Genome-wide association studies(GWAS)have linked many single nucleotide polymorphisms(SNPs)to the outcomes of a variety of liver diseases.The aim of the present study was to evaluate the association of several candidate SNPs with the risk and severity of cirrhosis due to chronic hepatitis B in a Chinese population.Methods A total of 714 Chinese participants with persistent HBV infection were studied.Patients were divided into cirrhotic(n=429)and non-cirrhotic(n=285)groups based on clinical and pathological evidence.The progression rate and severity of liver cirrhosis were evaluated with an arbitrary t-score system.Genotypes of six SNPs in five candidate genes were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The genotypic distributions of the SNPs were compared between the age-matched cirrhotic and non-cirrhotic subjects.The association between the risk of SNPs and the severity and progression rate of cirrhosis was further analyzed.Results Rs2679757 polymorphism of the antizyme inhibitor 1(AZIN1)gene and Rs886277 in the transient receptor potential cation channel subfamily M,member 5 gene(TRPM5)were found to be associated with cirrhosis risk in CHB.They were also correlated with the overall severity and progression rate of cirrhosis.Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups.Conclusions AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk and the progression rate of HBV-related liver fibrosis in Chinese patients.The emerging SNPs associated with cirrhosis prognosis warrant further clinical validation in other CHB cohorts or ethnic groups,and merit mechanistic studies to reveal their roles in fibrosis progression.
基金Supported by Janssen Scientific Affairs,LLC(partially)to Andrea D Branch to conduct the studyNational Institute of Health(NIH),Nos.DK090317 and DA031095(partially)to Andrea D Branch to conduct the study
文摘AIM To evaluate new therapies for hepatitis C virus(HCV), data about real-world outcomes are needed.METHODS Outcomes of 223 patients with genotype 1 HCV who started telaprevir-or boceprevir-based triple therapy(May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency viruspositive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response(SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response(FVR) was defined as undetectable HCV RNA at week-4(telaprevir) or week-8(boceprevir). RESULTS The median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis(FIB-4 ≥ 3.25). Only 42%(94/223) of patients achieved SVR24 on an intention-totreat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio(OR) = 5.92, 95% confidence interval(CI): 2.34-14.96], HCV sub-genotype 1b(OR = 2.81, 95%CI: 1.45-5.44), platelet count(OR = 1.10, per x 104 cells/μL, 95%CI: 1.05-1.16), and IL28 B CC genotype(OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 103/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25%(27/104) of patients with an end-oftreatment response and was associated with non-FVR(OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a(OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25(OR = 2.77; 95%CI: 1.07-7.22). CONCLUSION The SVR rate was 42% with telaprevir-or boceprevirbased triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.
文摘Early detection of hepatocellular carcinoma(HCC)while in its early stages is critical for reducing HCC mortality in high-risk patients.However,highly sensitive and specific surveillance biomarkers for early-stage HCC detection are still lacking.In recent years,great efforts have been made to research tumor-derived molecular features that are detectable in circulation,such as circulating tumor deoxyribonucleic acid and circulating tumor ribonucleic acid,in order to explore their potential as noninvasive biomarker candidates in many tumor types.In this review,we summarize current studies on these new approaches and their application in early HCC detection.
基金Supported by The Ministry of Science and Technology of China for the National Five-Year Key Projects in Infectious Diseases,No. 2015ZX10004801
文摘BACKGROUND Data that assess maternal and infant outcomes in hepatitis C virus(HCV)-infected mothers are limited.AIM To investigate the frequency of complications and the associated risk factors.METHODS We performed a cohort study to compare pregnancy and fetal outcomes of HCVviremic mothers with those of healthy mothers.Risk factors were analyzed with logistic regression.RESULTS Among 112 consecutive HCV antibody-positive mothers screened,we enrolled 79 viremic mothers.We randomly selected 115 healthy mothers from the birth registry as the control.Compared to healthy mothers,HCV mothers had a significantly higher frequency of anemia[2.6%(3/115)vs 19.0%(15/79),P<0.001]during pregnancy,medical conditions that required caesarian section[27.8%(32/115)vs 48.1%(38/79),P=0.004],and nuchal cords[9.6%(11/115)vs 34.2%(27/79),P<0.001].In addition,the mean neonatal weight in the HCV group was significantly lower(3278.3±462.0 vs 3105.1±459.4 gms;P=0.006),and the mean head circumference was smaller(33.3±0.6 vs 33.1±0.7 cm;P=0.03).In a multivariate model,HCV-infected mothers were more likely to suffer anemia[adjusted odds ratio(OR):18.1,95%confidence interval(CI):4.3-76.6],require caesarian sections(adjusted OR:2.6,95%CI:1.4-4.9),and have nuchal cords(adjusted OR:5.6,95%CI:2.4-13.0).Their neonates were also more likely to have smaller head circumferences(adjusted OR:2.1,95%CI:1.1-4.3)and lower birth weights than the average(≤3250 gms)with an adjusted OR of 2.2(95%CI:1.2-4.0).The vertical transmission rate was 1%in HCV-infected mothers.CONCLUSION Maternal HCV infections may associate with pregnancy and obstetric complications.We demonstrated a previously unreported association between maternal HCV viremia and a smaller neonatal head circumference,suggesting fetal growth restriction.
基金This work was supported by the Beijing Natural Science Foundation(M23008)the National Key Research and Development Program of China(2018YFE0207300)+2 种基金Beijing Municipal Science&Technology Commission(Z211100002521021)the National High Level Hospital Clinical Research Funding(2022-PUMCH-B-124)Key Research and Development Plan of Hebei Province,Special Health Innovation Project(22377744D).
文摘Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.
文摘BACKGROUND Necrolytic acral erythema(NAE) is a rare dermatological disorder,which is associated with hepatitis C virus(HCV) infection or zinc deficiency.It is characterized by erythematous or violaceous lesions occurring primarily in the lower extremities.The treatment includes systemic steroids and oral zinc supplementation.We report a case of NAE in a 66-year-old human immunodeficiency virus(HIV)/HCV co-infected woman with NAE.NAE is rarely reported in co-infected patients and the exact mechanisms of pathogenesis are still unclear.CASE SUMMARY A 66-year-old HIV/HCV co-infected female patient presented with painless,nonpruritic rash of extremities for one week and underwent extensive work-up for possible rheumatologic disorders including vasculitis and cryoglobulinemia.Punch skin biopsies of right and left thigh revealed thickened parakeratotic stratum corneum most consistent with NAE.Patient was started on prednisone and zinc supplementation with resolution of the lesions and improvement of rash.CONCLUSION Clinicians should maintain high clinical suspicion for early recognition of NAE in patients with rash and HCV.
