Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease

Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption and storage.In addition,gut microbiota are a source of Toll-like receptor(TLR)ligands,and their compositional change can also increase the amount of TLR ligands delivered to the liver.TLR ligands can stimulate liver cells to produce proinflammatory cytokines.Therefore,the gut-liver axis has attracted much interest,particularly regarding the pathogenesis of NAFLD.The abundance of the major gut microbiota,including Firmicutes and Bacteroidetes,has been considered a potential underlying mechanism of obesity and NAFLD,but the role of these microbiota in NAFLD remains unknown.Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD.For instance,a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability,which allows the leakage of bacterial components.Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD.In children,the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis(NASH)compared with those in obese control.Escherichia can produce ethanol,which promotes gut permeability.Thus,normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD.In addition,TLR signaling in the liver is activated,and its downstream molecules,such as proinflammatory cytokines,are increased in NAFLD.To data,TLR2,TLR4,TLR5,and TLR9 have been shown to be associated with the pathogenesis of NAFLD.Therefore,gut microbiota and TLRs are targets for NAFLD treatment.

Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine

AIM: To evaluate the clinical outcome of enteroscopy, using the double-balloon method, focusing on the involvement of neoplasms in strictures of the small intestine.METHODS: Enteroscopy, using the double-balloon method, was performed between December 1999 and December 2002 at Jichi Medical School Hospital, Japan and strictures of the small intestine were found in 17 out of 62 patients. These 17 consecutive patients were subjected to analysis.RESULTS: The double-balloon enteroscopy contributed to the diagnosis of small intestinal neoplasms found in 3out of 17 patients by direct observation of the strictures as well as biopsy sampling. Surgical procedures were chosen for these three patients, while balloon dilation was chosen for the strictures in four patients diagnosed with inflammation without involvement of neoplasm.CONCLUSION: Double-balloon enteroscopy is a useful method for the diagnosis and treatment of strictures in the small bowel.

Skull metastasis from hepatocellular carcinoma with chronic hepatitis B

A 56-year-old male visited our hospital for evaluation of an occipital mass.Contrast computed tomography showed hypervascular enhancement with osteolytic change in the skull and a huge enhanced mass in the liver.Magnetic resonance imaging showed bone metastasis in the thoracic vertebrae.Assays for hepatitis B surface antigen and hepatitis B core antibody were positive and his liver condition was Child-Pugh grade A.Our diagnosis was hepatocellular carcinoma(HCC) with skull and vertebrae metastases on chronic hepatitis B.He was treated with radiation therapy for bone metastases and transcatheter arterial chemoembolization for HCC.But he developed acute respiratory failure because of aspiration pneumonia,congestion and oedema with haemorrhage of the lungs and died.Dissection showed HCC with multiple bone metastases.The liver tumor was categorized as well-differentiated HCC,Edmondson classification Ⅰ,trabecular type and pseudoglandular type.In the liver mild infiltration of lymphocytes was seen in Glisson's capsules which were signif icantly enlarged with well preserved limiting plates.Piecemeal necrosis was not obvious.No fibrosis was noted.An 8 cm × 7 cm × 3 cm metastatic lesion had formed in the left occipitotemporal part of the cranial bone.The lesion was osteolytic and showed invasion into the dura mater.Neither the subdural cavity nor the brain showed involvement from the metastatic tumor.However,skull metastasis from HCC is very rare and it affects the patient's prognosis and the quality of life.Therefore,it is very important to make an early diagnosis and carry out proper management of skull metastasis from HCC.

Normalization of Serum Alkaline Phosphatase in Primary Sclerosing Cholangitis Associated with Ulcerative Colitis

Primary sclerosing cholangitis (PSC) is commonly associated with ulcerative colitis (UC). PSC progresses independently of UC ultimately resulting in liver failure. There is no established medical treatment to improve the natural course of PSC. Normalization of serum alkaline phosphatase (ALP) in early stage might delay the progress of PSC. A 20-year-old female, had a sudden attack of right hypochondralgia with high fever and abnormal liver function tests without elevation of bilirubin: ALP 478 IU/L, aspartate aminotransferase 360 IU/L, alanine aminotransferase 174 IU/L. Abnormal liver function tests returned to normal after the attacks. Morphological examinations initially indicated then confirmed a diagnosis of PSC. One month after displaying PSC symptoms administration of ursodeoxycholic acid was initiated. Similar attacks of cholangitis were repeated several times over the following two years. Even in the absence of these attacks, she always suffered postprandial hypochondralgia. There was no acute cholangitis in the year prior to the last hospitalization due to abdominal pain and bloody diarrhea. Findings were consistent with UC in the form of entire colitis. Sulfasalazine, metronidazole and semi-vegetarian diet (SVD) were initiated. Metronidazole is routinely used in inflammatory bowel disease (IBD) in our practice with the expectation of elimination of any potentially pathogenic bacteria. SVD was designed for IBD hoping to increase beneficial bacteria. A remission of UC was ascertained during hospitalization. Elevated ALP, in the absence of clinical cholangitis, was decreased to normal after the therapy for UC.