Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.U...Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.展开更多
AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum ...AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.展开更多
AIM: To evaluate the efflicacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT).METHODS: Between August 2005 a...AIM: To evaluate the efflicacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT).METHODS: Between August 2005 and November 2008, patients with recurrent hepatitis C virus (HCV) after LT were selected for treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2 flibrosis. All patients were to receive pegylated interferon (PEG)/regimens combining ribavirin (RBV) for an additional 48 wk after HCV undetectability.RESULTS: Extended protocol treatment was initiated in thirty patients. Overall, 73% had end of treatmentresponse and 60% had SVR. Nineteen patients completed treatment per protocol, of them, sixteen (84%) had end of treatment response, and fourteen (74%) achieved SVR. Both early virological response and 24-week virological response were individually associated with SVR but this association was not signif icant on multivariate analysis. Eleven patients (37%) discontinued therapy due to adverse effects. Cytopenias were the most common and most severe adverse effect, and required frquent growth factor use, dose adjustments and treatment cessations. The risk of rejection was not increased.CONCLUSION: Recurrent HCV after LT can be safely treated with extended virological responseguided therpy using PEG/RBV, but requires close monitoring for treatment-related adverse effects, particularly cytopenias.展开更多
Hepatitis C virus(HCV)-related liver disease is the leading indication for liver transplantation(LT) worldwide. However, HCV is an independent predictor of lower survival following LT, and recurrence of HCV postLT is ...Hepatitis C virus(HCV)-related liver disease is the leading indication for liver transplantation(LT) worldwide. However, HCV is an independent predictor of lower survival following LT, and recurrence of HCV postLT is virtually universal. The historic standard of care during the interferon era of HCV therapy was expectant management-initiation of antiviral therapy in the setting of documented disease progression following LT. With the advent of new direct acting antiviral(DAA) therapies for HCV, the paradigm of expectant treatment for recurrent HCV infection post-LT is shifting. The safety, tolerability, and efficacy of DAAs, even among the sickest patients with advanced liver disease, enables treatment of HCV in the pre-transplant setting among LT waitlist registrants. Finally, emerging data are supportive of preemptive therapy with DAAs in liver transplant recipients as the preferred approach. Expectant management of HCV following LT can rarely be justified in the modern era of HCV therapy.展开更多
Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in me...Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.展开更多
BACKGROUND The coronavirus disease-2019(COVID-19)pandemic has had a profound worldwide impact.Indeed,it has led to a vast decrease in organ transplantation,including liver transplants(LT).There is little data regardin...BACKGROUND The coronavirus disease-2019(COVID-19)pandemic has had a profound worldwide impact.Indeed,it has led to a vast decrease in organ transplantation,including liver transplants(LT).There is little data regarding adjustments made by LT centers as a response to the COVID-19 pandemic.AIM To assess the experience of LT centers in the United States during the pandemic.METHODS We performed an observational survey study from May 11,2020 to June 5,2020.We sent out a 13 question survey to 15 LT centers across the southeastern United States.RESULTS Eleven LT centers responded to the survey.We found that(11/11)100%of transplant centers made adjustments because of the COVID-19 pandemic.At least 50%of transplant centers had at least one transplant recipient infected with COVID-19.To adjust,greater than 50%of centers performed fewer LT,100%of patients were tested for COVID-19,and most centers implemented a virtual platform.CONCLUSION The COVID-19 pandemic greatly affected liver transplantation in the southeastern United States.It was evident that a concerted effort was made by LT centers to protect their patients and employees from COVID-19 but also to continue the lifesaving procedure of LT in this sick patient population.Further studies are needed to assess how LT centers around the world managed the pandemic in order to learn strategies to continue life-saving procedures in this patient population.展开更多
AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched fo...AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention. Diet and exercise was more effective than exercise alone in reducing IHTG.展开更多
AIM To investigate the effect of metformin on activated hepatic stellate cells(HSCs) and the possible signaling pathways involved. METHODS A fibrotic mouse model was generated by intraperitoneal injection of carbon te...AIM To investigate the effect of metformin on activated hepatic stellate cells(HSCs) and the possible signaling pathways involved. METHODS A fibrotic mouse model was generated by intraperitoneal injection of carbon tetrachloride(CCl_4) and subsequent treatment with or without metformin. The level of fibrosis was detected by hematoxylin-eosin staining, Sirius Red staining, and immunohistochemistry. The HSC cell line LX-2 was used for in vitro studies. The effect of metformin on cell proliferation(CCK8 assay),motility(scratch test and Transwell assay), contraction(collagen gel contraction assay), extracellular matrix(ECM) secretion(Western blot), and angiogenesis(ELISA and tube formation assay) was investigated. We also analyzed the possible signaling pathways involved by Western blot analysis.RESULTS Mice developed marked liver fibrosis after intraperitoneal injection with CCl_4 for 6 wk. Metformin decreased the activation of HSCs, reduced the deposition of ECM, and inhibited angiogenesis in CCl_4-treated mice. Platelet-derived growth factor(PDGF) promoted the fibrogenic response of HSCs in vitro, while metformin inhibited the activation, proliferation, migration, and contraction of HSCs, and reduced the secretion of ECM. Metformin decreased the expression of vascular endothelial growth factor(VEGF) in HSCs through inhibition of hypoxia inducible factor(HIF)-1α in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro. The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin(m TOR) and extracellular signal-regulated kinase(ERK) pathways via the activation of adenosine monophosphate-activated protein kinase(AMPK).CONCLUSION Metformin attenuates the fibrogenic response of HSCs in vivo and in vitro, and may therefore be useful for the treatment of chronic liver diseases.展开更多
AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research...AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.展开更多
The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,...The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.展开更多
AIM: To evaluate the effect of artesunate(AS) supplementation on bacterial translocation(BT) and gut microbiota in a rat model of liver cirrhosis. METHODS: Fifty-four male Sprague-Dawley rats were randomly divided int...AIM: To evaluate the effect of artesunate(AS) supplementation on bacterial translocation(BT) and gut microbiota in a rat model of liver cirrhosis. METHODS: Fifty-four male Sprague-Dawley rats were randomly divided into a normal control group(N), a liver cirrhosis group(M) and a liver cirrhosis group intervened with AS(MA). Each group was sampled at 4, 6 and 8 wk. Liver cirrhosis was induced by injection of carbon tetrachloride(CCl4), intragastric administration of 10% ethanol, and feeding a high fat diet. Rats in the MA group were intragastrically administered with AS(25 mg/kg body weight, once daily). Injuries of the liver and intestinal mucosa were assessed by hematoxylineosin or Masson's trichrome staining. Liver index was calculated as a ratio of the organ weight(g) to body weight(g). The gut microbiota was examined by automated ribosomal intergenic-spacer analysis of fecal DNA. BT was assessed by standard microbiological techniques in the blood, mesenteric lymph nodes(MLNs), liver, spleen, and kidney. RESULTS: Compared to group N, the body weight was reduced significantly in groups M and MA due to the development of liver cirrhosis over the period of 8 wk. The body weight was higher in group MA than in group M. The liver indices were significantly elevated at 4, 6 and 8 wk in groups M and MA compared to group N. AS supplementation partially decreased the liver indices in group MA. Marked histopathologic changes in the liver and small intestinal mucosa in group M were observed, which were alleviated in group MA. Levels of pro-inflammatory interleukin-6 and tumor necrosis factor-α were significantly elevated at 8 wk in ileal homogenates in group M compared to group N, which were decreased after AS supplementation in group MA. The dysbiosis of gut microbiota indicated by the mean diversity(Shannon index) and mean similarity(Sorenson index) was severe as the liver cirrhosis developed, and AS supplementation had an apparent intervention effect on the dysbiosis of gut microbiota at 4 wk. The occurrence of BT was increased in the liver of group M compared to that of group N. AS supplementation reduced BT in group MA at 8 wk. BT also occurred in the MLNs, spleen, and kidney, which was reduced by AS supplementation. BT was not detected in the blood in any group.CONCLUSION: Dysbiosis of gut microbiota, injury of intestinal mucosal barrier and BT occurred as liver cirrhosis progressed, which might enhance inflammation and aggravate liver injury. AS may have other nonantimalarial effects that modulate gut microbiota,inhibit BT and alleviate inflammation, resulting in a reduction in CCl4, alcohol and high fat-caused damages to the liver and intestine.展开更多
Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy ...Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment, but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.展开更多
Hepatocellular carcinoma (HCC) develops in the context of environmental risk factors like chronic viral hepatitis, diabetes and alcohol exposure, often associated to an increased risk of cirrhosis. Antiviral treatment...Hepatocellular carcinoma (HCC) develops in the context of environmental risk factors like chronic viral hepatitis, diabetes and alcohol exposure, often associated to an increased risk of cirrhosis. Antiviral treatments that are effective to counteract hepatitis B and C may also attenuate the risk of tumor development. However, since hepatitis B-related carcinogenesis is promoted independently of the onset of cirrhosis, such antiviral treatments as nucleo(t)side analogs can promote regression of cirrhosis, prevent clinical decompensation and variceal bleeding but not HCC. This means that in successfully treated patients with cirrhosis, HCC is often the consequence of their extended survival. In hepatitis C patients, a sustained virological response to interferon-based therapies can reduce the rate of HCC development, even in patients with cirrhosis who experience histological regression of their liver disease. Future therapies aimed at this endpoint in at risk populations should take into consideration pretreatment patient stratification for host, viral and environmental risk factors. In this context the recent discovery of single nucleotide polymorphisms involved in the immune system function and tumorigenesis, might permit enrollment of populations of patients enriched with HCC risk factors for targeted chemopreventive therapies. This could finally pave the way to personalized algorithms, as already seen in the diagnosis and treatment schemes for chemoprevention.展开更多
To compare the oligonucleotide chip, real-time PCR and sequencing for genotyping of hepatitis B virus in Chinese patients with chronic hepatitis B. METHODS： Mixture of samples with different genotypes and clinical se...To compare the oligonucleotide chip, real-time PCR and sequencing for genotyping of hepatitis B virus in Chinese patients with chronic hepatitis B. METHODS： Mixture of samples with different genotypes and clinical serum samples from 126 chronic hepatitis B patients was tested for hepatitis B virus genotypes by oligonucleotide chip, real-time PCR and sequencing of PCR products, respectively. Clinical performances, time required and costs of the three assays were evaluated. RESULTS： Oligonucleotide chips and real-time PCR detected 1% and 0.1% genotypes, respectively, in mixed samples. Of the 126 clinical samples from patients with chronic hepatitis B, genotype B was detected in 41 （33%）, 41 （33%） and 45 （36%） samples, and genotype C in 76 （60%）, 76 （60%） and 81 （64%） samples, by oligonucleotide chip, real-time PCR and sequencing, respectively. Oligonucleotide chip and real-time PCR detected mixed genotypes B and C in 9 samples. Real- time PCR was the rapidest and cheapest among the three assays. CONCLUSION： Oligonucleotide chip and real-time PCR are able to detect mixed genotypes, while sequencing only detects the dominant genotype in clinical samples.展开更多
The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are ...The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP) associated with Peg-IFN-α 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection. She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course, neurological findings, an electromyogram (EMG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits.展开更多
We present a case of fetal liver failure caused by the activation of larnivudine-resistant hepatitis B virus （HBV） nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of ...We present a case of fetal liver failure caused by the activation of larnivudine-resistant hepatitis B virus （HBV） nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decornpensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase （ALT） decreased transiently. However, after the start of m-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtLSOI/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtLSOI/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.展开更多
End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver...End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28 B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5 B polymerase inhibitors and NS5 A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.展开更多
AIM： To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS： We prospectively analyzed 73 patients with ...AIM： To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS： We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk alter the start of combination therapy. RESULTS： Fourteen patients （19%） developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients （64%） despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy （P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2）.CONCLUSION： Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.展开更多
AIM:To translate into Serbian and to investigate the validity of the cross-culturally adapted the chronic liver disease questionnaire(CLDQ).METHODS:The questionnaire was validated in 103 consecutive CLD patients treat...AIM:To translate into Serbian and to investigate the validity of the cross-culturally adapted the chronic liver disease questionnaire(CLDQ).METHODS:The questionnaire was validated in 103 consecutive CLD patients treated between October 2009 and October 2010 at the Clinic for Gastroenterology,Clinical Centre of Serbia,Belgrade(Serbia).Exclusion criteria were:age < 18 years,psychiatric disorders,acute complications of CLD(acute liver failure,variceal bleeding,and spontaneous bacterial peritonitis),hepatic encephalopathy(grade > 2)and liver transplantation.Evaluation of the CLDQ was done based on the following parameters:(1)acceptance is shown by the proportion of missing items;(2)internal reliabilities were assessed for multiple item scales by using Cronbach alpha coefficient;and(3)in order to assess whether the allocation of items in the domain corresponds to their distribution in the original questionnaire(construction validity),an exploratory factor analysis was conducted.Discriminatory validity was determined by comparing the corresponding CLDQ score/sub-score in patients with different severity of the diseases.RESULTS:The Serbian version of CLDQ questionnaire completed 98% patients.Proportion of missing items was 0.06%.The total time needed to fill the questionnaire was ranged from 8 to 15 min.Assistance in completing the questionnaire required 4.8% patients,while 2.9% needed help in reading,and 1.9% involved writing assistance.The mean age of the selected patients was 53.8 ± 12.9 years and 54.4% were men.Average CLDQ score was 4.62 ± 1.11.Cronbach's alpha for the whole scale was 0.93.Reliability for all domains was above 0.70,except for the domain "Activity"(0.49).The exploratory factor analysis model revealed 6 factors with eigenvalue of greater than 1,explaining 69.7% of cumulative variance.The majority of the items(66%)in the Serbian version of the CLDQ presented the highest loading weight in the domain assigned by the CLDQ developers:"Fatigue"(5/5),"Emotional function"(6/8),"Worry"(5/5),"Abdominal symptoms"(0/3),"Activity"(0/3),"Systemic symptoms"(3/5).The scales "Fatigue" and "Worry" fully corresponded to the original.The factor analysis also revealed that the factors "Activity" and "Abdominal symptoms" could not be replicated,and two new domains "Sleep" and "Nutrition" were established.Analysis of the CLDQ score/sub-score distribution according to disease severity demonstrated that patients without cirrhosis had lower total CLDQ score(4.86 ± 1.05)than those with cirrhosis Child's C(4.31 ± 0.97).Statistically significant difference was detected for the domains "Abdominal symptoms" [F(3)= 5.818,P = 0.001] and "Fatigue" [F(3)= 3.39,P = 0.021].Post hoc analysis revealed that patients with liver cirrhosis Child's C had significantly lower sub-score "Abdominal symptoms" than patients without cirrhosis or liver cirrhosis Child's A or B.For domain "Fatigue",patients with cirrhosis Child's C had significantly lower score,than non-cirrhotic patients.CONCLUSION:The Serbian version of CLDQ is well accepted and represents a valid and reliable instrument in Serbian sample of CLD patients.展开更多
文摘Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.
文摘AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.
文摘AIM: To evaluate the efflicacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT).METHODS: Between August 2005 and November 2008, patients with recurrent hepatitis C virus (HCV) after LT were selected for treatment if liver biopsy showed at least grade 2 inflammation and/or stage 2 flibrosis. All patients were to receive pegylated interferon (PEG)/regimens combining ribavirin (RBV) for an additional 48 wk after HCV undetectability.RESULTS: Extended protocol treatment was initiated in thirty patients. Overall, 73% had end of treatmentresponse and 60% had SVR. Nineteen patients completed treatment per protocol, of them, sixteen (84%) had end of treatment response, and fourteen (74%) achieved SVR. Both early virological response and 24-week virological response were individually associated with SVR but this association was not signif icant on multivariate analysis. Eleven patients (37%) discontinued therapy due to adverse effects. Cytopenias were the most common and most severe adverse effect, and required frquent growth factor use, dose adjustments and treatment cessations. The risk of rejection was not increased.CONCLUSION: Recurrent HCV after LT can be safely treated with extended virological responseguided therpy using PEG/RBV, but requires close monitoring for treatment-related adverse effects, particularly cytopenias.
文摘Hepatitis C virus(HCV)-related liver disease is the leading indication for liver transplantation(LT) worldwide. However, HCV is an independent predictor of lower survival following LT, and recurrence of HCV postLT is virtually universal. The historic standard of care during the interferon era of HCV therapy was expectant management-initiation of antiviral therapy in the setting of documented disease progression following LT. With the advent of new direct acting antiviral(DAA) therapies for HCV, the paradigm of expectant treatment for recurrent HCV infection post-LT is shifting. The safety, tolerability, and efficacy of DAAs, even among the sickest patients with advanced liver disease, enables treatment of HCV in the pre-transplant setting among LT waitlist registrants. Finally, emerging data are supportive of preemptive therapy with DAAs in liver transplant recipients as the preferred approach. Expectant management of HCV following LT can rarely be justified in the modern era of HCV therapy.
基金This study was supported by a grant from Sanofi(China)Investment Co.,Ltd.
文摘Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.
文摘BACKGROUND The coronavirus disease-2019(COVID-19)pandemic has had a profound worldwide impact.Indeed,it has led to a vast decrease in organ transplantation,including liver transplants(LT).There is little data regarding adjustments made by LT centers as a response to the COVID-19 pandemic.AIM To assess the experience of LT centers in the United States during the pandemic.METHODS We performed an observational survey study from May 11,2020 to June 5,2020.We sent out a 13 question survey to 15 LT centers across the southeastern United States.RESULTS Eleven LT centers responded to the survey.We found that(11/11)100%of transplant centers made adjustments because of the COVID-19 pandemic.At least 50%of transplant centers had at least one transplant recipient infected with COVID-19.To adjust,greater than 50%of centers performed fewer LT,100%of patients were tested for COVID-19,and most centers implemented a virtual platform.CONCLUSION The COVID-19 pandemic greatly affected liver transplantation in the southeastern United States.It was evident that a concerted effort was made by LT centers to protect their patients and employees from COVID-19 but also to continue the lifesaving procedure of LT in this sick patient population.Further studies are needed to assess how LT centers around the world managed the pandemic in order to learn strategies to continue life-saving procedures in this patient population.
文摘AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention. Diet and exercise was more effective than exercise alone in reducing IHTG.
基金Supported by The National Key Basic Research Project,No.2012CB517501Chinese Foundation for Hepatitis Prevention and Control–"WANG Bao-En"Liver Fibrosis Research Fund,No.XJS20120501+1 种基金Shanghai Science and Technology Committee,No.09140903500 and No.10411956300the 100-Talents Program of the Shanghai Municipal Health Bureau,No.XBR2011007
文摘AIM: To evaluate the performance of a novel non-invasive controlled attenuation parameter (CAP) to assess liver steatosis.
基金Supported by National Natural Science Foundation of China,No.81370590
文摘AIM To investigate the effect of metformin on activated hepatic stellate cells(HSCs) and the possible signaling pathways involved. METHODS A fibrotic mouse model was generated by intraperitoneal injection of carbon tetrachloride(CCl_4) and subsequent treatment with or without metformin. The level of fibrosis was detected by hematoxylin-eosin staining, Sirius Red staining, and immunohistochemistry. The HSC cell line LX-2 was used for in vitro studies. The effect of metformin on cell proliferation(CCK8 assay),motility(scratch test and Transwell assay), contraction(collagen gel contraction assay), extracellular matrix(ECM) secretion(Western blot), and angiogenesis(ELISA and tube formation assay) was investigated. We also analyzed the possible signaling pathways involved by Western blot analysis.RESULTS Mice developed marked liver fibrosis after intraperitoneal injection with CCl_4 for 6 wk. Metformin decreased the activation of HSCs, reduced the deposition of ECM, and inhibited angiogenesis in CCl_4-treated mice. Platelet-derived growth factor(PDGF) promoted the fibrogenic response of HSCs in vitro, while metformin inhibited the activation, proliferation, migration, and contraction of HSCs, and reduced the secretion of ECM. Metformin decreased the expression of vascular endothelial growth factor(VEGF) in HSCs through inhibition of hypoxia inducible factor(HIF)-1α in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro. The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin(m TOR) and extracellular signal-regulated kinase(ERK) pathways via the activation of adenosine monophosphate-activated protein kinase(AMPK).CONCLUSION Metformin attenuates the fibrogenic response of HSCs in vivo and in vitro, and may therefore be useful for the treatment of chronic liver diseases.
文摘AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.
基金Supported by the National Key Research and Development Program,No.2017YFC0908903National Natural Science Foundation of China,No.81873565 and No.81900507Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.17CSK04.
文摘The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.
基金Supported by the National Natural Science Foundation of ChinaNo.81070339+13 种基金the International Science and Technology Cooperation Project of ShanxiNo.2010081068the Key Laboratory Foundation of Cellular Physiology Department of Shanxi Medical School and Provincial Ministry of EducationNo.2010-09the Fund for Returned Students of ShanxiNo.211-091the Fund for Returned Medical Doctors of Changzhi Medical CollegeNo.2010-01Science and Technology Innovation Team Project of Changzhi Medical CollegeNo.CX201409College Student Innovation and Entrepreneurship Training Project of Shanxi ProvinceNo.2014308the US NIH(to Cheng Ji)No.R21AA023952 and No.P30DK48522-21
文摘AIM: To evaluate the effect of artesunate(AS) supplementation on bacterial translocation(BT) and gut microbiota in a rat model of liver cirrhosis. METHODS: Fifty-four male Sprague-Dawley rats were randomly divided into a normal control group(N), a liver cirrhosis group(M) and a liver cirrhosis group intervened with AS(MA). Each group was sampled at 4, 6 and 8 wk. Liver cirrhosis was induced by injection of carbon tetrachloride(CCl4), intragastric administration of 10% ethanol, and feeding a high fat diet. Rats in the MA group were intragastrically administered with AS(25 mg/kg body weight, once daily). Injuries of the liver and intestinal mucosa were assessed by hematoxylineosin or Masson's trichrome staining. Liver index was calculated as a ratio of the organ weight(g) to body weight(g). The gut microbiota was examined by automated ribosomal intergenic-spacer analysis of fecal DNA. BT was assessed by standard microbiological techniques in the blood, mesenteric lymph nodes(MLNs), liver, spleen, and kidney. RESULTS: Compared to group N, the body weight was reduced significantly in groups M and MA due to the development of liver cirrhosis over the period of 8 wk. The body weight was higher in group MA than in group M. The liver indices were significantly elevated at 4, 6 and 8 wk in groups M and MA compared to group N. AS supplementation partially decreased the liver indices in group MA. Marked histopathologic changes in the liver and small intestinal mucosa in group M were observed, which were alleviated in group MA. Levels of pro-inflammatory interleukin-6 and tumor necrosis factor-α were significantly elevated at 8 wk in ileal homogenates in group M compared to group N, which were decreased after AS supplementation in group MA. The dysbiosis of gut microbiota indicated by the mean diversity(Shannon index) and mean similarity(Sorenson index) was severe as the liver cirrhosis developed, and AS supplementation had an apparent intervention effect on the dysbiosis of gut microbiota at 4 wk. The occurrence of BT was increased in the liver of group M compared to that of group N. AS supplementation reduced BT in group MA at 8 wk. BT also occurred in the MLNs, spleen, and kidney, which was reduced by AS supplementation. BT was not detected in the blood in any group.CONCLUSION: Dysbiosis of gut microbiota, injury of intestinal mucosal barrier and BT occurred as liver cirrhosis progressed, which might enhance inflammation and aggravate liver injury. AS may have other nonantimalarial effects that modulate gut microbiota,inhibit BT and alleviate inflammation, resulting in a reduction in CCl4, alcohol and high fat-caused damages to the liver and intestine.
文摘Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment, but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.
文摘Hepatocellular carcinoma (HCC) develops in the context of environmental risk factors like chronic viral hepatitis, diabetes and alcohol exposure, often associated to an increased risk of cirrhosis. Antiviral treatments that are effective to counteract hepatitis B and C may also attenuate the risk of tumor development. However, since hepatitis B-related carcinogenesis is promoted independently of the onset of cirrhosis, such antiviral treatments as nucleo(t)side analogs can promote regression of cirrhosis, prevent clinical decompensation and variceal bleeding but not HCC. This means that in successfully treated patients with cirrhosis, HCC is often the consequence of their extended survival. In hepatitis C patients, a sustained virological response to interferon-based therapies can reduce the rate of HCC development, even in patients with cirrhosis who experience histological regression of their liver disease. Future therapies aimed at this endpoint in at risk populations should take into consideration pretreatment patient stratification for host, viral and environmental risk factors. In this context the recent discovery of single nucleotide polymorphisms involved in the immune system function and tumorigenesis, might permit enrollment of populations of patients enriched with HCC risk factors for targeted chemopreventive therapies. This could finally pave the way to personalized algorithms, as already seen in the diagnosis and treatment schemes for chemoprevention.
文摘To compare the oligonucleotide chip, real-time PCR and sequencing for genotyping of hepatitis B virus in Chinese patients with chronic hepatitis B. METHODS： Mixture of samples with different genotypes and clinical serum samples from 126 chronic hepatitis B patients was tested for hepatitis B virus genotypes by oligonucleotide chip, real-time PCR and sequencing of PCR products, respectively. Clinical performances, time required and costs of the three assays were evaluated. RESULTS： Oligonucleotide chips and real-time PCR detected 1% and 0.1% genotypes, respectively, in mixed samples. Of the 126 clinical samples from patients with chronic hepatitis B, genotype B was detected in 41 （33%）, 41 （33%） and 45 （36%） samples, and genotype C in 76 （60%）, 76 （60%） and 81 （64%） samples, by oligonucleotide chip, real-time PCR and sequencing, respectively. Oligonucleotide chip and real-time PCR detected mixed genotypes B and C in 9 samples. Real- time PCR was the rapidest and cheapest among the three assays. CONCLUSION： Oligonucleotide chip and real-time PCR are able to detect mixed genotypes, while sequencing only detects the dominant genotype in clinical samples.
文摘The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP) associated with Peg-IFN-α 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection. She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course, neurological findings, an electromyogram (EMG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits.
文摘We present a case of fetal liver failure caused by the activation of larnivudine-resistant hepatitis B virus （HBV） nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decornpensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase （ALT） decreased transiently. However, after the start of m-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtLSOI/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtLSOI/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.
文摘End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28 B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5 B polymerase inhibitors and NS5 A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.
文摘AIM： To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS： We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk alter the start of combination therapy. RESULTS： Fourteen patients （19%） developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients （64%） despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy （P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2）.CONCLUSION： Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.
基金Supported by Grant from the Ministry of Education and Science of the Republic of Serbia,No. 175087 to Pekmezovic TD,Kisic Tepavcevic DB and Trajkovic GZ
文摘AIM:To translate into Serbian and to investigate the validity of the cross-culturally adapted the chronic liver disease questionnaire(CLDQ).METHODS:The questionnaire was validated in 103 consecutive CLD patients treated between October 2009 and October 2010 at the Clinic for Gastroenterology,Clinical Centre of Serbia,Belgrade(Serbia).Exclusion criteria were:age < 18 years,psychiatric disorders,acute complications of CLD(acute liver failure,variceal bleeding,and spontaneous bacterial peritonitis),hepatic encephalopathy(grade > 2)and liver transplantation.Evaluation of the CLDQ was done based on the following parameters:(1)acceptance is shown by the proportion of missing items;(2)internal reliabilities were assessed for multiple item scales by using Cronbach alpha coefficient;and(3)in order to assess whether the allocation of items in the domain corresponds to their distribution in the original questionnaire(construction validity),an exploratory factor analysis was conducted.Discriminatory validity was determined by comparing the corresponding CLDQ score/sub-score in patients with different severity of the diseases.RESULTS:The Serbian version of CLDQ questionnaire completed 98% patients.Proportion of missing items was 0.06%.The total time needed to fill the questionnaire was ranged from 8 to 15 min.Assistance in completing the questionnaire required 4.8% patients,while 2.9% needed help in reading,and 1.9% involved writing assistance.The mean age of the selected patients was 53.8 ± 12.9 years and 54.4% were men.Average CLDQ score was 4.62 ± 1.11.Cronbach's alpha for the whole scale was 0.93.Reliability for all domains was above 0.70,except for the domain "Activity"(0.49).The exploratory factor analysis model revealed 6 factors with eigenvalue of greater than 1,explaining 69.7% of cumulative variance.The majority of the items(66%)in the Serbian version of the CLDQ presented the highest loading weight in the domain assigned by the CLDQ developers:"Fatigue"(5/5),"Emotional function"(6/8),"Worry"(5/5),"Abdominal symptoms"(0/3),"Activity"(0/3),"Systemic symptoms"(3/5).The scales "Fatigue" and "Worry" fully corresponded to the original.The factor analysis also revealed that the factors "Activity" and "Abdominal symptoms" could not be replicated,and two new domains "Sleep" and "Nutrition" were established.Analysis of the CLDQ score/sub-score distribution according to disease severity demonstrated that patients without cirrhosis had lower total CLDQ score(4.86 ± 1.05)than those with cirrhosis Child's C(4.31 ± 0.97).Statistically significant difference was detected for the domains "Abdominal symptoms" [F(3)= 5.818,P = 0.001] and "Fatigue" [F(3)= 3.39,P = 0.021].Post hoc analysis revealed that patients with liver cirrhosis Child's C had significantly lower sub-score "Abdominal symptoms" than patients without cirrhosis or liver cirrhosis Child's A or B.For domain "Fatigue",patients with cirrhosis Child's C had significantly lower score,than non-cirrhotic patients.CONCLUSION:The Serbian version of CLDQ is well accepted and represents a valid and reliable instrument in Serbian sample of CLD patients.
