Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal...Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by produdng harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.展开更多
Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combinat...Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5 A inhibitors and HCV NS5 B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatmentnave patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in nullresponders and in patients with cirrhosis. Interferonfree regimens in combination with ribavirin and/or two or more DAAs could be used for treatment-nave, treatment-experienced and even for interferon-ineligible or interferon-intolerant patients. Some clinical trials have demonstrated promising results, and have shown that the efficacy and safety were not different between patients with and without cirrhosis. There are also promising regimens for genotypes other than genotype 1. Interferonis contraindicated in patients with decompensated cirrhosis, and further studies are needed to establish the optimal treatment regimen for this population. In the future, interferon-free and ribavirin-free regimens with high efficacy and improved safety are expected for HCVinfected patients with advanced liver diseases.展开更多
The ideal goal of chronic hepatitis B(CHB) treatment should be suppression of emergence of hepatocellular carcinoma through the disappearance of hepatitis B s antigen(HBs Ag) rather than the control of serum hepatitis...The ideal goal of chronic hepatitis B(CHB) treatment should be suppression of emergence of hepatocellular carcinoma through the disappearance of hepatitis B s antigen(HBs Ag) rather than the control of serum hepatitis B virus-DNA level. For this purpose, various types of combination therapies using nucleoside analogs(NAs) and interferon(IFN) have been conducted. The therapeutic effects of combination of two different kinds of agents are better than those of the monotherapy using NAs or IFN alone, probably because different pharmaceutical properties might act in a coordinated manner. Recently, combination therapies with NAs and IFN and sequential therapies with NAs administration followed by IFN therapy have been routinely employed. We previously reported that combination therapy using entecavir(ETV) and pegylated(PEG)-IFN showed antiviral effects in 71% of CHB patients; the effect of this combination was better than that using lamivudine(LAM) and PEG-IFN. This is partially explained by the better antiviral effects of ETV than those of LAM. In our analysis, the cohort of CHB consisted of the patients who showed a flare-up of hepatitis before antiviral therapy, and their baseline HBs Ag levels were relatively low. Therefore, in addition to the combination of the agents, the appropriate selection of patients is critical to achieve a good viral response.展开更多
Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs(NUCs) became established as a safe and effective treatment for hepatitis B,it was difficult to suppress the activity of the...Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs(NUCs) became established as a safe and effective treatment for hepatitis B,it was difficult to suppress the activity of the hepatitis B virus(HBV). Currently,many patients withhepatitis or cirrhosis associated with HBV are treated with NUCs for an extended period of time,and the effects,benefits,and limitations of these treatments have been apparent. This article reviews HBV-related cirrhosis,its natural course and survival,histological improvement after NUC treatments,treatment effects for decompensated cirrhosis,the incidence of hepatocellular carcinoma(HCC) after NUC treatments,and the efficacy of NUC treatments before and after the treatment of patients for HBV-related HCC. Of particular interest are the histological improvements,including regression of fibrosis,that have been achieved with NUC treatments. Liver function of patients with decompensated cirrhosis has significantly improved regardless of the type of NUC applied,and treatment with NUCs has reduced the incidence of HCC in cirrhotic patients. However,cirrhosis remains the strongest risk factor for HCC occurrence following NUC treatments,and the long-term cumulative incidence of HCC after NUC treatments remains high. When recurrence does occur,it is important to reconsider the treatment modality according to the degree of improved liver function that was achieved.展开更多
AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients w...AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients with HCC who were treated with thalido- mide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in o-fetoprotein （AFP） levels were evaluated. RESULTS： A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients （56.6%） were classified as Child-Pugh A, and 12 patients （22.6%） were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis （49.1%）, and 25 patients had extrahepatic metastasis （47.1%）. The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response （11.3%）, one achieved a complete response （1.9%） and 5 achieved a partial response （9.4%）. The disease control rate （CR ＋ PR ＋ SD） was 28.3% （95% CI： 17.8-42.4）, and the median overall survival rate was 10.5 too. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an im- proved overall survival rate of 66.8 mo. Sixteen patients （30.2%） showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better re- sponse rate （31.3%）, disease control rate （43.8%）, and overall survival time （20.7 mo）. The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION： Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor ac- tivity including response, survival, and AFP decreases of greater than 50% from baseline.展开更多
Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmenta...Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.展开更多
AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS) combined with stomach and esophageal variceal embolization(SEVE) in cirrhotic patients with a large gastrorenal vessel sh...AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS) combined with stomach and esophageal variceal embolization(SEVE) in cirrhotic patients with a large gastrorenal vessel shunt(GRVS).METHODS: Eighty-one cirrhotic patients with gastric variceal bleeding(GVB) associated with a GRVS were enrolled in the study and accepted TIPS combined with SEVE(TIPS + SEVE), by which portosystemic pressuregradient(PPG), biochemical, TIPS-related complications, shunt dysfunction, rebleeding, and death were evaluated. RESULTS: The PPGs before TIPS were greater than 12 mmH g in 81 patients. TIPS + SEVE treatment caused a significant decrease in PPG(from 37.97 ± 6.36 mmH g to 28.15 ± 6.52 mm Hg, t = 19.22, P < 0.001). The percentage of reduction in PPG was greater than 20%from baseline. There were no significant differences in albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time, or Child-Pugh score before and after operation. In all patients, rebleeding rates were 3%, 6%, 12%, 18%, and 18% at 1,3, 6, 12, and 18 mo, respectively. Five patients(6.2%)were diagnosed as having hepatic encephalopathy. The rates of shunt dysfunction were 0%, 4%, 9%, 26%,and 26%, at 1, 3, 6, 12, and 18 mo, respectively. The cumulative survival rates in 1, 3, 6, 12, and 18 mo were100%, 100%, 95%, 90%, and 90%, respectively.CONCLUSION: Our preliminary results indicated that the efficacy and safety of TIPS + SEVE were satisfactory in cirrhotic patients with GVB associated with a GRVS(GVB + GRVS).展开更多
AIM： To evaluate the predictive value of neutrophil in- filtration as a marker of Helicobacter pylori （H. pyloni） infection. METHODS： A total of 315 patients with dyspepsia symptoms who underwent upper gastrointes...AIM： To evaluate the predictive value of neutrophil in- filtration as a marker of Helicobacter pylori （H. pyloni） infection. METHODS： A total of 315 patients with dyspepsia symptoms who underwent upper gastrointestinal en- doscopy were enrolled in this study. Biopsies were evaluated using the updated Sydney system. The medication history of all patients in the preceding 4 wk was recorded. The diagnosis of H. pylori infection was based on 13C-urea breath test at least 4 wk after with- drawal of antisecretory drugs, antibiotics and related drugs. For the patients with subtotal gastrectomy, the diagnosis of H. pylori infection was based on anti-H. pylori immunoglobulin G （IgG） antibody. Serum anti-H. pylori IgG antibody was measured by enzyme-linked immunosorbent assays （Biohit, Finland）. RESULTS： The sensitivity, specificity, positive predic- tive value and negative predictive value of neutrophil infiltration in the diagnosis ofH, pylorlinfection were 92.3%, 83.5%, 77.4% and 94.7%, respectively. Neu- trophil infiltration of gastric mucosa in the histological analysis was strongly associated withH, pylorlinfection （77.4% vs 5.3% in the neutrophil infiltration negative group, P = 0.000）. Moderate neutrophil infiltration was more frequent in H. pylorl infection when compared to mild infiltration （81.8% and 75%, respectively）, but did not reach statistical significance. For those patients with negative rapid urease test, H. pylori was detected in 73.2% of patients with positive neutrophil infiltration on histology. In patients with subtotal gastrectomy, the diagnostic accuracy of neutrophil infiltration in H. pylori infection was 50%. CONCLUSION： Neutrophil infiltration is closely associ- ated withH, pylori and may be recognized as a sign of this infection.展开更多
At the time of diagnosis, 25% of patients with colorectal cancer(CRC) present with synchronous metastases, which are unresectable in the majority of patients. Whether primary tumor resection(PTR) followed by chemother...At the time of diagnosis, 25% of patients with colorectal cancer(CRC) present with synchronous metastases, which are unresectable in the majority of patients. Whether primary tumor resection(PTR) followed by chemotherapy or immediate chemotherapy without PTR is the best therapeutic option in patients with asymptomatic CRC and unresectable metastases is a major issue, although unanswered to date. The aim of this study was to review all published data on whether PTR should be performed in patients with CRC and unresectable synchronous metastases. All aspects of the management of CRC were taken into account, es-pecially prognostic factors in patients with CRC and un-resectable metastases. The impact of PTR on survival and quality of life were reviewed, in addition to the characteristics of patients that could benefit from PTR and the possible underlying mechanisms. The risks of both approaches are reported. As no randomized study has been performed to date, we finally discussed how a therapeutic strategy's trial should be designed to pro-vide answer to this issue.展开更多
Non-alcoholic fatty liver disease(NAFLD)is closely related to insulin resistance,type 2 diabetes mellitus,and obesity.It is nowadays considered a multisystem disease with a strong association with cardiovascular disea...Non-alcoholic fatty liver disease(NAFLD)is closely related to insulin resistance,type 2 diabetes mellitus,and obesity.It is nowadays considered a multisystem disease with a strong association with cardiovascular disease and arterial hypertension,which interfere with changes in the coagulation system.Coagulation disorders are common in patients with hepatic impairment and are dependent on the degree of liver damage.Patients with NAFLD may have preserved overall hemostatic profile,but many studies suggest a trend toward a procoagulant state.Hypercoagulable state in NAFLD patients may even induce progression of hepatic injury.Endothelial dysfunction is present in the systemic and portal vein circulation in NAFLD patients,and platelets are being recognized as modulators of liver diseases through various mechanisms.Through a literature review,we discuss possible disorders in the coagulation cascade and fibrinolysis,endothelial dysfunction,and platelet abnormalities in patients with NAFLD.Considering the processes and mechanisms involved in the hemostatic abnormalities associated with NAFLD,directly related to liver disease or indirectly related through inflam-matory processes and metabolic disorders,several potential therapeutic targets have been identified and reviewed here.展开更多
Citation of this article:Attia D,Aty NA,Shawket A,Said E,Fouad Y.MAFLD Not NAFLD is Associated with Impairment of Health-related Quality of Life.J Clin Transl Hepatol 2022;10(1):4-5.doi:10.14218/JCTH.2021.00485.To the...Citation of this article:Attia D,Aty NA,Shawket A,Said E,Fouad Y.MAFLD Not NAFLD is Associated with Impairment of Health-related Quality of Life.J Clin Transl Hepatol 2022;10(1):4-5.doi:10.14218/JCTH.2021.00485.To the Editor,We read with great interest the article by Yu et al.1 who reported that the metabolic dysfunction-associated fatty liver disease(MAFLD)criteria are more practical and im-prove the identification of high-risk patients with fatty liver disease compared with the previous nonalcoholic fatty liver disease(NAFLD)criteria.展开更多
文摘Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by produdng harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.
文摘Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5 A inhibitors and HCV NS5 B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatmentnave patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in nullresponders and in patients with cirrhosis. Interferonfree regimens in combination with ribavirin and/or two or more DAAs could be used for treatment-nave, treatment-experienced and even for interferon-ineligible or interferon-intolerant patients. Some clinical trials have demonstrated promising results, and have shown that the efficacy and safety were not different between patients with and without cirrhosis. There are also promising regimens for genotypes other than genotype 1. Interferonis contraindicated in patients with decompensated cirrhosis, and further studies are needed to establish the optimal treatment regimen for this population. In the future, interferon-free and ribavirin-free regimens with high efficacy and improved safety are expected for HCVinfected patients with advanced liver diseases.
基金Supported by Grant--in--Aid for Scientific Research(in part,KAKENHI:24590997)from the Japanese Society for the Promotion of Science(to Nishida N)a grant from the Smoking Research Foundation(to Nishida N)
文摘The ideal goal of chronic hepatitis B(CHB) treatment should be suppression of emergence of hepatocellular carcinoma through the disappearance of hepatitis B s antigen(HBs Ag) rather than the control of serum hepatitis B virus-DNA level. For this purpose, various types of combination therapies using nucleoside analogs(NAs) and interferon(IFN) have been conducted. The therapeutic effects of combination of two different kinds of agents are better than those of the monotherapy using NAs or IFN alone, probably because different pharmaceutical properties might act in a coordinated manner. Recently, combination therapies with NAs and IFN and sequential therapies with NAs administration followed by IFN therapy have been routinely employed. We previously reported that combination therapy using entecavir(ETV) and pegylated(PEG)-IFN showed antiviral effects in 71% of CHB patients; the effect of this combination was better than that using lamivudine(LAM) and PEG-IFN. This is partially explained by the better antiviral effects of ETV than those of LAM. In our analysis, the cohort of CHB consisted of the patients who showed a flare-up of hepatitis before antiviral therapy, and their baseline HBs Ag levels were relatively low. Therefore, in addition to the combination of the agents, the appropriate selection of patients is critical to achieve a good viral response.
文摘Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs(NUCs) became established as a safe and effective treatment for hepatitis B,it was difficult to suppress the activity of the hepatitis B virus(HBV). Currently,many patients withhepatitis or cirrhosis associated with HBV are treated with NUCs for an extended period of time,and the effects,benefits,and limitations of these treatments have been apparent. This article reviews HBV-related cirrhosis,its natural course and survival,histological improvement after NUC treatments,treatment effects for decompensated cirrhosis,the incidence of hepatocellular carcinoma(HCC) after NUC treatments,and the efficacy of NUC treatments before and after the treatment of patients for HBV-related HCC. Of particular interest are the histological improvements,including regression of fibrosis,that have been achieved with NUC treatments. Liver function of patients with decompensated cirrhosis has significantly improved regardless of the type of NUC applied,and treatment with NUCs has reduced the incidence of HCC in cirrhotic patients. However,cirrhosis remains the strongest risk factor for HCC occurrence following NUC treatments,and the long-term cumulative incidence of HCC after NUC treatments remains high. When recurrence does occur,it is important to reconsider the treatment modality according to the degree of improved liver function that was achieved.
文摘AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients with HCC who were treated with thalido- mide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in o-fetoprotein （AFP） levels were evaluated. RESULTS： A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients （56.6%） were classified as Child-Pugh A, and 12 patients （22.6%） were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis （49.1%）, and 25 patients had extrahepatic metastasis （47.1%）. The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response （11.3%）, one achieved a complete response （1.9%） and 5 achieved a partial response （9.4%）. The disease control rate （CR ＋ PR ＋ SD） was 28.3% （95% CI： 17.8-42.4）, and the median overall survival rate was 10.5 too. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an im- proved overall survival rate of 66.8 mo. Sixteen patients （30.2%） showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better re- sponse rate （31.3%）, disease control rate （43.8%）, and overall survival time （20.7 mo）. The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION： Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor ac- tivity including response, survival, and AFP decreases of greater than 50% from baseline.
文摘Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.
基金Supported by National Natural Science Foundation of China,Nos.81070337 and 81271736
文摘AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS) combined with stomach and esophageal variceal embolization(SEVE) in cirrhotic patients with a large gastrorenal vessel shunt(GRVS).METHODS: Eighty-one cirrhotic patients with gastric variceal bleeding(GVB) associated with a GRVS were enrolled in the study and accepted TIPS combined with SEVE(TIPS + SEVE), by which portosystemic pressuregradient(PPG), biochemical, TIPS-related complications, shunt dysfunction, rebleeding, and death were evaluated. RESULTS: The PPGs before TIPS were greater than 12 mmH g in 81 patients. TIPS + SEVE treatment caused a significant decrease in PPG(from 37.97 ± 6.36 mmH g to 28.15 ± 6.52 mm Hg, t = 19.22, P < 0.001). The percentage of reduction in PPG was greater than 20%from baseline. There were no significant differences in albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time, or Child-Pugh score before and after operation. In all patients, rebleeding rates were 3%, 6%, 12%, 18%, and 18% at 1,3, 6, 12, and 18 mo, respectively. Five patients(6.2%)were diagnosed as having hepatic encephalopathy. The rates of shunt dysfunction were 0%, 4%, 9%, 26%,and 26%, at 1, 3, 6, 12, and 18 mo, respectively. The cumulative survival rates in 1, 3, 6, 12, and 18 mo were100%, 100%, 95%, 90%, and 90%, respectively.CONCLUSION: Our preliminary results indicated that the efficacy and safety of TIPS + SEVE were satisfactory in cirrhotic patients with GVB associated with a GRVS(GVB + GRVS).
基金Supported by The grant for Key Laboratory of Gastroenterology and Hepatology,Ministry of Health,Renji Hospital,Shanghai Jiao Tong University School of MedicineNational Natural Science Foundation of China,No.81170355
文摘AIM： To evaluate the predictive value of neutrophil in- filtration as a marker of Helicobacter pylori （H. pyloni） infection. METHODS： A total of 315 patients with dyspepsia symptoms who underwent upper gastrointestinal en- doscopy were enrolled in this study. Biopsies were evaluated using the updated Sydney system. The medication history of all patients in the preceding 4 wk was recorded. The diagnosis of H. pylori infection was based on 13C-urea breath test at least 4 wk after with- drawal of antisecretory drugs, antibiotics and related drugs. For the patients with subtotal gastrectomy, the diagnosis of H. pylori infection was based on anti-H. pylori immunoglobulin G （IgG） antibody. Serum anti-H. pylori IgG antibody was measured by enzyme-linked immunosorbent assays （Biohit, Finland）. RESULTS： The sensitivity, specificity, positive predic- tive value and negative predictive value of neutrophil infiltration in the diagnosis ofH, pylorlinfection were 92.3%, 83.5%, 77.4% and 94.7%, respectively. Neu- trophil infiltration of gastric mucosa in the histological analysis was strongly associated withH, pylorlinfection （77.4% vs 5.3% in the neutrophil infiltration negative group, P = 0.000）. Moderate neutrophil infiltration was more frequent in H. pylorl infection when compared to mild infiltration （81.8% and 75%, respectively）, but did not reach statistical significance. For those patients with negative rapid urease test, H. pylori was detected in 73.2% of patients with positive neutrophil infiltration on histology. In patients with subtotal gastrectomy, the diagnostic accuracy of neutrophil infiltration in H. pylori infection was 50%. CONCLUSION： Neutrophil infiltration is closely associ- ated withH, pylori and may be recognized as a sign of this infection.
文摘At the time of diagnosis, 25% of patients with colorectal cancer(CRC) present with synchronous metastases, which are unresectable in the majority of patients. Whether primary tumor resection(PTR) followed by chemotherapy or immediate chemotherapy without PTR is the best therapeutic option in patients with asymptomatic CRC and unresectable metastases is a major issue, although unanswered to date. The aim of this study was to review all published data on whether PTR should be performed in patients with CRC and unresectable synchronous metastases. All aspects of the management of CRC were taken into account, es-pecially prognostic factors in patients with CRC and un-resectable metastases. The impact of PTR on survival and quality of life were reviewed, in addition to the characteristics of patients that could benefit from PTR and the possible underlying mechanisms. The risks of both approaches are reported. As no randomized study has been performed to date, we finally discussed how a therapeutic strategy's trial should be designed to pro-vide answer to this issue.
文摘Non-alcoholic fatty liver disease(NAFLD)is closely related to insulin resistance,type 2 diabetes mellitus,and obesity.It is nowadays considered a multisystem disease with a strong association with cardiovascular disease and arterial hypertension,which interfere with changes in the coagulation system.Coagulation disorders are common in patients with hepatic impairment and are dependent on the degree of liver damage.Patients with NAFLD may have preserved overall hemostatic profile,but many studies suggest a trend toward a procoagulant state.Hypercoagulable state in NAFLD patients may even induce progression of hepatic injury.Endothelial dysfunction is present in the systemic and portal vein circulation in NAFLD patients,and platelets are being recognized as modulators of liver diseases through various mechanisms.Through a literature review,we discuss possible disorders in the coagulation cascade and fibrinolysis,endothelial dysfunction,and platelet abnormalities in patients with NAFLD.Considering the processes and mechanisms involved in the hemostatic abnormalities associated with NAFLD,directly related to liver disease or indirectly related through inflam-matory processes and metabolic disorders,several potential therapeutic targets have been identified and reviewed here.
文摘Citation of this article:Attia D,Aty NA,Shawket A,Said E,Fouad Y.MAFLD Not NAFLD is Associated with Impairment of Health-related Quality of Life.J Clin Transl Hepatol 2022;10(1):4-5.doi:10.14218/JCTH.2021.00485.To the Editor,We read with great interest the article by Yu et al.1 who reported that the metabolic dysfunction-associated fatty liver disease(MAFLD)criteria are more practical and im-prove the identification of high-risk patients with fatty liver disease compared with the previous nonalcoholic fatty liver disease(NAFLD)criteria.
