A review of clinical research on using FIT screening for colorectal cancer

Colorectal cancer(CRC)has become the third most common cancer in the world and the second leading cause of death related to cancer.early screening of CRC can reduce its incidence rate and mortality.With the development of fecal immunochemical testing(FIT),FIT has been an important tool for screening CRC patients in high-risk groups worldwide.With the development of FIT,FIT has been an important tool for screening CRC patients in high-risk groups worldwide.In this paper,we describe the research progress of FIT screening for CRC.

Removal of a guide-wire sliding into abdominal cavity via transgastric natural orifice transluminal endoscopic surgery: A case report

BACKGROUND Guidewire slippage into the peritoneal cavity during clinical operations is extremely rare.Therefore,this paper aims to report a successful case of guidewire removal using transgastric natural orifice transluminal endoscopic surgery(NOTES).The goal is to enhance physicians'understanding of the management plan for this unique scenario and provide a valuable reference for clinical practice.CASE SUMMARY A 64-year-old man presented with abdominal distension and was diagnosed with cirrhosis combined with massive ascites.To proceed with treatment,the patient underwent ultrasound-guided peritoneal puncture and underwent catheterization and drainage.Unfortunately,a 0.035-inch guidewire slipped into the abdominal cavity during the procedure.Following a comprehensive evaluation and consultation by a multidisciplinary team,the guidewire was successfully removed using NOTES.CONCLUSION This case highlights the potential consideration of transgastric NOTES removal when encountering a foreign body,such as a guidewire,within the abdominal cavity.

Application of fecal immunochemical test in colorectal cancer screening:A community-based,cross-sectional study in averagerisk individuals in Hainan

BACKGROUND The incidence of colorectal cancer(CRC)in China is steadily rising,with a high proportion of advanced-stage diagnoses.This highlights the significance of early detection and prevention measures to enhance survival rates.Fecal immunochemical testing(FIT)is a globally recommended CRC screening method;however,limited research has been conducted on its application in Hainan.AIM To assess the efficacy and adherence of FIT screening among average-risk individuals in Hainan,while also examining the risk factors associated with positive FIT results.METHODS This population-based cross-sectional study implemented FIT screening for CRC in 2000 asymptomatic participants aged 40-75 years from five cities and 21 community health centers in Hainan Province.The study was conducted from August 2022 to April 2023,employing a stratified sampling method to select participants.Individuals with positive FIT results subsequently underwent colonoscopy.Positive predictive values for confirmed CRC and advanced adenoma were calculated,and the relationship between relevant variables and positive FIT results was analyzed usingχ2 tests and multivariate logistic regression.RESULTS A total of 1788 participants completed the FIT screening,with a median age of 57 years(interquartile range:40-75).Among them,503(28.1%)were males,and 1285(71.9%)were females,resulting in an 89.4%compliance rate for FIT screening.The overall positivity rate of FIT was 4.4%[79 out of 1788;95%confidence interval(CI):3%-5%].The specific positivity rates for Haikou,Sanya,Orient City,Qionghai City,and Wuzhishan City were 9.6%(45 of 468;95%CI:8%-11%),1.3%(6 of 445;95%CI:0.1%-3.1%),2.7%(8 of 293;95%CI:1.2%-4.3%),3.3%(9 of 276;95%CI:1.0%-6.3%),and 4.2%(11 of 406;95%CI:1.2%-7.3%),respectively.Significant associations were found between age,dietary habits,and positive FIT results.Out of the 79 participants with positive FIT results,55 underwent colonoscopy,demonstrating an 82.2%compliance rate.Among them,10 had a clean gastrointestinal tract,43 had polyps or adenomas,and 2 were confirmed to have CRC,yielding a positive predictive value of 3.6%(95%CI:0.9%-4.2%).Among the 43 participants with polyps or adenomas,8 were diagnosed with advanced adenomas,resulting in an advanced adenoma rate of 14.5%(95%CI:10.1%-17.7%).CONCLUSION In the Hainan region,FIT screening for CRC among asymptomatic individuals at average risk is feasible and wellreceived.

Portal ductopathy:Clinical importance and nomenclature

Non-cirrhotic portal hypertension(PHT)accounts for about 20%of all PHT cases,portal vein thrombosis(PVT) resulting in cavernous transformation being the most common cause.All known complications of PHT may be encountered in patients with chronic PVT.However,the effect of this entity on the biliary tree and pancreatic duct has not yet been fully established.Additionally,a dispute remains regarding the nomenclature of common bile duct abnormalities which occur as a result of chronic PVT.Although many clinical reports have focused on biliary abnormalities,only a few have evaluated both the biliary and pancreatic ductal systems.In this review the relevant literature evaluating the effect of PVT on both ductal systems is discussed,and findings are considered with reference to results of a prominent center in Turkey,from which the term"portal ductopathy"has been put forth to replace"portal biliopathy".

Endoscopic retrograde cholangiopancreatography-induced and non-endoscopic retrograde cholangiopancreatographyinduced acute pancreatitis:Two distinct clinical and immunological entities?

Acute pancreatitis(AP) is common gastrointestinal disease of varied aetiology. The most common cause of AP is gallstones, followed by alcohol abuse as an independent risk factor. With the increased need for invasive techniques to treat pancreatic and bile duct pathologies such as endoscopic retrograde cholangiopancreatography(ERCP), AP has emerged as the most frequent complication. While severe AP following ERCP is rare(0.5%), if it does develop it has a greater severity index compared to non-ERCP AP. Development of a mild form of AP after ERCP is not considered a clinically relevant condition. Differences in the clinical presentation and prognosis of the mild and severe forms have been found between non-ERCP AP and postendoscopic pancreatitis(PEP). It has been proposedthat AP and PEP may also have different immunological responses to the initial injury. In this review, we summarise the literature on clinical and inflammatory processes in PEP vs non-ERCP AP.

Clinical, Biological, Immunological and Therapeutic Profile of Patients Co-Infected with HIV-HBV and/or HCV in Kinshasa, in the Democratic Republic of the Congo: Multicenter Cross-Sectional Study

Background and Objective: HIV infection is often associated with HBV and HCV infection, together leading to high morbidity and mortality in developing countries. The objective of this study is to describe the clinical, biological, immunological and therapeutic profile of patients co-infected with HIV-HBV and/or HCV. Methods: A cross-sectional and descriptive study including 180 people living with HIV (PLWHIV) in the city of Kinshasa province was conducted. Socio-demographic, clinical, biological and serological characteristics were analyzed. Results: The frequency of HIV-HBV/HCV co-infection was 23.9%. The distribution of age and sex of patients did not differ significantly according to co-infection status. The notion of pedicure and manicure was significantly more observed in patients free from viral hepatitis (51.1% versus 32.6%, p = 0.034). The median duration of knowledge of the HIV status which was longer in the co-infected (4 years versus 2 years, p = 0.022). A lower median level of GPT was observed in co-infected compared to other patients (14 IU/L versus 20 IU/L, p = 0.041). Serum albumin (3.1 g/L versus 3.3 g/L, p = 0.034) and prothrombin (58.3% versus 65.6%, p = 0.045) were lower in HIV co-infected-VHB and/or VHC. The median INR was higher in co-infected than in other patients (1.6 versus 1.4;p = 0.009). Patients without therapy Antiretroviral (TARV) medication were more numerous in co-infected (20.9% versus 8.0%, p = 0.025). Conclusions: The profile of PLWHIV was dominated by the presence of pedicures and manicures with high transaminases and without anti-viral treatment.

Precision medicine in inflammatory bowel disease:Individualizing the use of biologics and small molecule therapies

The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.

Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis

BACKGROUND Primary biliary cholangitis(PBC)is a chronic progressive autoimmune cholestatic disease.The main target organ of PBC is the liver,and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis.AIM To explore the clinical characteristics of early-stage PBC,identify PBC in the early clinical stage,and promptly treat and monitor PBC.METHODS The data of 82 patients with PBC confirmed by pathology at Tianjin Second People’s Hospital from January 2013 to November 2021 were collected,and the patients were divided into stage I,stage II,stage III,and stage IV according to the pathological stage.The general data,serum biochemistry,immunoglobulins,and autoimmune antibodies of patients in each stage were retrospectively analyzed.RESULTS In early-stage(stages I+II)PBC patients,50.0%of patients had normal alanine aminotransferase(ALT)levels,and 37.5%had normal aspartate aminotransferase(AST)levels.For the remaining patients,the ALT and AST levels were mildly elevated;all of these patients had levels of<3 times the upper limit of normal values.The AST levels were significantly different among the three groups(stages I+II vs stage III vs stage IV,P<0.05).In the early stage,29.2%of patients had normal alkaline phosphatase(ALP)levels.The remaining patients had different degrees of ALP elevation;6.3%had ALP levels>5 times the upper limit of normal value.Moreover,γ-glutamyl transferase(GGT)was more robustly elevated,as 29.2%of patients had GGT levels of>10 times the upper limit of normal value.The ALP values among the three groups were significantly different(P<0.05).In early stage,the jaundice index did not increase significantly,but it gradually increased with disease progression.However,the above indicators were significantly different(P<0.05)between the early-stage group and the stage IV group.With the progression of the disease,the levels of albumin and albumin/globulin ratio tended to decrease,and the difference among the three groups was statistically significant(P<0.05).In early-stage patients,IgM and IgG levels as well as cholesterol levels were mildly elevated,but there were no significant differences among the three groups.Triglyceride levels were normal in the early-stage group,and the differences among the three groups were statistically significant(P<0.05).The early detection rates of anti-mitochondria antibody(AMA)and AMA-M2 were 66.7%and 45.8%,respectively.The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC.When AMA and AMA-M2 were negative,in the early stage,the highest autoantibody was anti-nuclear antibody(ANA)(92.3%),and in all ANA patterns,the highest was ANA centromere(38.5%).CONCLUSION In early-stage PBC patients,ALT and AST levels are normal or mildly elevated,GGT and ALP levels are not elevated in parallel,GGT levels are more robustly elevated,and ALP levels are normal in some patients.When AMA and AMA-M2 are negative,ANA especially ANA centromere positivity suggests the possibility of early PBC.Therefore,in the clinic,significantly elevated GGT levels with or without normal ALP levels and with ANA(particularly ANA centromere)positivity(when AMA and AMA-M2 are negative)may indicate the possibility of early PBC.

Construction and validation of a severity prediction model for metabolic associated fatty liver disease

Objective:To analyze the independent risk factors for the occurrence of moderate-to-severe metabolic-associated fatty liver disease(MAFLD),to construct a prediction model for moderate-to-severe MAFLD,and to verify the validity of the model.Methods:In the first part,278 medical examiners who were diagnosed with MAFLD in Medical Examination Center at the Second Affiliated Hospital of Hainan University from January to May 2022 were taken as the study subjects(training set),and they were divided into mild MAFLD group(200)and moderate-severe MAFLD group(78)based on ultrasound results.Demographic data and laboratory indexes were collected,and risk factors were screened by univariate and multifactor analysis.In the second part,a dichotomous logistic regression equation was used to construct a prediction model for moderate-to-severe MAFLD,and the model was visualized in a line graph.In the third part,the MAFLD population(200 people in the external validation set)from our physical examination center from November to December 2022 was collected as the moderate-to-severe MAFLD prediction model,and the risk factors in both groups were compared.The receiver operating characteristic(ROC)curves,calibration curves,and clinical applicability of the model were plotted to represent model discrimination for internal and external validation.Results:The risk factors of moderate-to-severe MAFLD were fasting glucose(FPG),blood uric acid(UA),triglycerides(TG),triglyceride glucose index(TyG),total cholesterol(CHOL),and high-density lipoprotein(HDL-C).UA[OR=1.021,95%CI(1.015,1.027),P<0.001]and FPG[OR=1.575,95%CI(1.158,2.143),P=0.004]were independent risk factors for people with moderate to severe MAFLD.The visualized line graph model showed that UA was the factor contributing more to the risk of moderate to severe MAFLD in this model.The ROC curves showed AUC values of 0.8701,0.8686 and 0.7991 for the training set,internal validation set and external validation set,respectively.The curves almost coincided with the reference line after calibration of the model calibration degree with P>0.05 in Hosmer-Lemeshow test.The decision curve analysis(DCA)plotted by the clinical applicability of the model was higher than the two extreme curves,predicting that patients with moderate to severe MAFLD would benefit from the prediction model.Conclusion:The prediction model constructed by combining FPG with UA has higher accuracy and better clinical applicability,and can be used for clinical diagnosis.

Helicobacter pylori infection and inflammatory bowel disease: Is there a link?

Helicobacter pylori(H.pylori)infection is one of the most widely spread infectious diseases in humans.It can cause chronic gastritis,peptic ulcer disease and gastric malignancies and has been associated with extra-gastric disorders.H.pylori elicit a chronic systemic inflammatory response which,under certain conditions,may trigger autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases.Although the pathogenesis of inflammatory bowel disease(IBD)is unknown,it is thought to result from complex interactions between environmental factors and microbiota in the gut of individuals who are genetically susceptible.Several bacterial and viral agents have been implicated in the aetiology of IBD.In theory,H.pylori infection could be involved in the pathogenesis of IBD by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material and autoimmunity via various immunological pathways.Similar mechanisms may also be responsible for the co-existence of IBD with other autoimmune diseases and/or extra-intestinal manifestations.However,the epidemiological data fail to support this association.Infact,various studies indicate that the prevalence of H.pylori infection is low in patients with IBD,suggesting a protective role for this infection in the development of IBD.In this report,we aim to shed light on proposed mechanisms and confounding factors underlying the potential link between H.pylori infection and IBD.

Gastroenteric tube feeding: Techniques, problems and solutions

Gastroenteric tube feeding plays a major role in the management of patients with poor voluntary intake,chronic neurological or mechanical dysphagia or gut dysfunction,and patients who are critically ill.However,despite the benefits and widespread use of enteral tube feeding,some patients experience complications.This review aims to discuss and compare current knowledge regarding the clinical application of enteral tube feeding,together with associated complications and special aspects.We conducted an extensive literature search on PubMed,Embase and Medline using index terms relating to enteral access,enteral feeding/nutrition,tube feeding,percutaneous endoscopic gastrostomy/jejunostomy,endoscopic nasoenteric tube,nasogastric tube,and refeeding syndrome.The literature showed common routes of enteral access to include nasoenteral tube,gastrostomy and jejunostomy,while complications fall into four major categories:mechanical,e.g.,tube blockage or removal;gastrointestinal,e.g.,diarrhea;infectious e.g.,aspiration pneumonia,tube site infection;and metabolic,e.g.,refeeding syndrome,hyperglycemia.Although the type and frequency of complications arising from tube feeding vary considerably according to the chosen access route,gastrointestinal complications are without doubt the most common.Complications associated with enteral tube feeding can be reduced by careful observance of guidelines,including those related to food composition,administration rate,portion size,food temperature and patient supervision.

Role of digital single-operator cholangioscopy in the diagnosis and treatment of biliary disorders

Due to the need for improvement in the diagnosis and minimally invasive therapy of the bile duct disorders new technologies for cholangioscopy have been recently developed. Per-oral cholangioscopy has become an important diagnostic and therapeutic tool leading to avoidance of aggressive and unnecessary surgery in many clinical scenarios. This paper focuses on the newly developed SpyGlass DS technology, its advantages, and the technique of single-operator cholangioscopy(SOC), biliary indications and possible adverse events. We also review the available literature; discuss the limitations and future expectations.Digital SOC(D-SOC) is a useful technique, which provides endoscopic imaging of the biliary tree, optical diagnosis, biopsy under direct vision and therapeutic interventions. The implementations are diagnostic and therapeutic. Diagnostic indications are indeterminate biliary strictures, unclear filling defects, staging of cholangiocarcinoma, staging of ampullary tumors(extension into the common bile duct), unclear bile duct dilation, exploring cystic lesions of the biliary tree,unexplained hemobilia, posttransplant biliary complications. Therapeutic indications are lithotripsy of difficult stones, retrieval of migrated stents, foreign body removal, guide wire placement, transpapillary gallbladder drainage and endoscopic tumor ablative therapy. Most studied and established indications are the diagnosis of indeterminate biliary stricture and intraductal lithotripsy of difficult stones. The adverse events are not different and more common compared to those of Endoscopic retrograde cholangiopancreatography(ERCP)alone. D-SOC is a safe and effective procedure, adjunct to the standard ERCP and the newly available digital technology overcomes many of the limitations of the previous generations of cholangioscopes.

Experience of a single center with congenital hepatic fibrosis:A review of the literature

Congenital hepatic fibrosis(CHF) is an autosomal recessive inherited malformation defined pathologically by a variable degree of periportal fibrosis and irregularly shaped proliferating bile ducts.It is one of the fibropolycystic diseases,which also include Caroli disease,autosomal dominant polycystic kidney disease,and autosomal recessive polycystic kidney disease. Clinically it is characterized by hepatic fibrosis,portal hypertension,and renal cystic disease.CHF is known to occur in association with a range of both inherited and non-inherited disorders,with multiorgan involvement,as a result of ductal plate malformation.Because of the similarities in the clinical picture,it is necessary to differentiate CHF from idiopathic portal hypertension and early liver cirrhosis,for which a liver biopsy is essential. Radiological tests are important for recognizing involvement of other organ systems.With regards to our experience at Hacettepe University,a total of 26 patients have been diagnosed and followed-up between 1974 and 2009 with a diagnosis of CHF.Presentation with Caroli syndrome was the most common diagnosis,with all such patients presenting with symptoms of recurrentcholangitis and symptoms related to portal hypertension. Although portal fibrosis is known to contribute to the ensuing portal hypertension,it is our belief that portal vein cavernous transformation also plays an important role in its pathogenesis.In all patients with CHF portal vein morphology should be evaluated by all means since portal vein involvement results in more severe and complicated portal hypertension.Other associations include the Joubert and Bardet-Biedl syndromes.

Risk of colorectal neoplasm in patients with acromegaly: A meta-analysis

AIM: To examine the risk of colorectal neoplasm in acromegalic patients by meta-analyzing all relevant controlled studies. METHODS: Extensive English language medical literature searches for human studies, up to December 2007, were performed using suitable keywords. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using either the fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test. RESULTS: For hyperplastic polyps the pooled ORs with 95% CI were 3.557 (2.587-4.891) by fixed effects model and 3.703 (2.565-5.347) by random effects model. The Z test values for overall effect were 7.81 and 6.984, respectively (P < 0.0001). For colon adenomas the pooled ORs with 95% CI were 2.486 (1.908-3.238) (fixed effects model) and 2.537 (1.914-3.364) (random effects model). The Z test values were 6.747 and 6.472, respectively (P < 0.0001). For colon cancer the pooled OR with 95% CI was identical for both fixed and random effects model (OR, 4.351; 95% CI, 1.533-12.354; Z = 2.762, P = 0.006]. There was no significant heterogeneity and no publication bias in all the above meta-analyses. CONCLUSION: Acromegaly is associated with an increased risk of colorectal neoplasm.

Familial aggregation in inflammatory bowel disease:Is it genes or environment?

Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.

Primary sclerosing cholangitis-What is the difference between east and west?

Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver disease characterized by inflammation and fibrotic obliteration of the hepatic biliary tree. It is commonly associated with inflammatory bowel disease (IBD). A number of complications can occur which require special consideration, the most important of which is the development of cholangiocellular carcinoma (CCC). Unfortunately, no medical therapy is currently available for the underlying liver disease. Liver transplantation is an effective, life-extending option for patients with advanced PSC. Geographical variations between East and West include a second peak for age with a lower association with IBD in a Japanese population and female predominance in a lone study from Turkey. The clinical and biochemical Mayo criteria may not be universally applicable, as different patients show variations regarding the initial presentation and natural course of the disease. Directing research towards explaining these geographical differences and understanding the pathogenesis of PSC is required in order to develop better therapies for this devastating disease.

Brain metastasis of hepatocellular carcinoma:A case report and review of the literature

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. It is more common in far eastern countries and relatively rare in the United States and western European countries where at autopsy it accounts for only 1-2% of malignant rumors, The disease is usually manifested in the the 6^th and 7^th decade of life. HCC is one of the highly malignant neoplasms, Extrahepatic metastases are seen in 64% of patients with HCC. The lungs, regional lymph nodes, kidney, bone marrow and adrenals are common sites of HCC metastasis^[1-3], But, metastasis to brain and skull is extremely rare. Table I shows some of the reported cases of HCC with brain metastasis. These case reports reaffirms the complex and multidisciplinary care of these patients^[4-5].

Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples for diagnosis of early colorectal cancer

AIM:To investigate the feasibility of detecting aberrantly hypermethylated Wnt-antagonist gene promoters(SFRP2 and WIF-1)in fecal DNA as non-invasive biomarkers for early colorectal cancer(CRC).METHODS:The methylation-specific polymerase chain reaction assay was performed to blindly analyze the methylation status of SFRP2 and WIF-1 gene promoters in fecal samples from 48 subjects with CRC,35 with adenomas,32 with hyperplastic polyps and 30 endoscopically normal subjects.Additionally,we comparedthe diagnostic efficiency of measuring the hypermethylated SFRP2 and WIF-1 genes in the feces to the fecal occult blood test(FOBT)for the early detection of CRC.RESULTS:Hypermethylated SFRP2 was detected in the feces of 56.3%(27/48)of CRC cases,51.4%(18/35)of adenoma cases and 12.5%(4/32)of patients with hyperplastic polyps.The hypermethylation of WIF-1was detected in 60.4%(29/48),45.7%(16/35)and18.7%(6/32)of fecal samples from CRC,adenoma and hyperplastic polyp patients,respectively.At least one hypermethylated gene was detected in 81.3%(39/48)of CRC and 65.7%(23/35)of adenoma samples.In contrast,only a hypermethylated WIF-1 gene was detected in one case of normal fecal samples.Moreover,no significant associations were observed between SFPR2 and WIF-1 hypermethylation and clinicopathological features.Additionally,81.8%of CRC cases diagnosed as Dukes A stage or advanced adenomas had at least one hypermethylated gene detected,while the detection rate with the FOBT was only 31.8%(P<0.001).CONCLUSION:Hypermethylated SFRP2 and WIF-1genes in fecal DNA are novel and promising molecular biomarkers that have great diagnostic potential for early CRC.

Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis

Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.

A new treatment strategy for acute liver failure

Acute liver failure (ALF) is a syndrome def ined by coa g ulopathy and encephalopathy and no effective treat ments have been established, except for liver transplantation. However, considering the limited supply of donors, we should endeavor to prevent the progre ssion of this syndrome in its early stage to improve the prognosis of patients with ALF. Recently, several authors have reported that over-activation of intrahepatic macrophages plays an important role in the progression of ALF and we have developed a new treatment method, transcatheter arterial steroid injection therapy (TASIT), to suppress macrophage activation. We have now used TASIT for 5 years and have found that TASIT is effective for patients with over-activation of macrophages in the liver but not for those with les ser activation of macrophages. Therefore, to identify the most appropriate patients for TASIT, we tried to categorize patients with ALF or acute liver injury according to markers for the degree of intrahepatic macrophage activation. This approach was helpful to select the appro-priate treatment including liver transplantation. We believe that it is essential to analyze disease progression in each patient before selecting the most appropriate treatment.