Hepatolenticular degeneration, commonly known as Wilson disease, is an autosomal recessive inherited disease of abnormal copper metabolism, characterized by the accumulation of copper in the body due ...to decreased biliary excretion of copper from hepatocytes. Wilson disease protein, ATP7B, functions in copper excretion into bile and in copper secretion to the bloodstream coupled with ceruloplasmin synthesis. Various kinds of mutations of ATP7B cause Wilson disease. Wilson disease is a rare genetic disease that can be treated pharmacologically. Recognition and prompt diagnosis are very important, because Wilson disease is fatal if left untreated. In this review, I summarize the pathogenesis and management of Wilson disease.
Blockage of hepatic autophagic degradation system occurs in obesity and is associated with the development of nonalcoholic fatty liver disease. However, the mechanism of this blockage remains ...unclear. We found a high-fat diet induced accumulation of autophagosomes in the mice livers. However, autophagy substrates such as p62 and ubiquitinated proteins also accumulated in the livers in this model. These findings indicate the possibility that a high-fat diet impairs autophagic flux in the liver. Then, to assess the autophagic flux in more detail, we performed analyses of autophagic flux in cultured hepatocytes exposed to monounsaturated fatty acids (FAs) or saturated FAs (SFAs). SFAs but not monounsaturated FAs suppressed degradation of contents in the autophagosomes. We analyzed each stage of the autophagy pathway (ie, autophagosome formation, autophagosome-lysosome fusion, lysosomal degradation) in cultured hepatocytes treated with monounsaturated FAs or SFAs and found that SFAs impaired autophagosome-lysosome fusion. This impairment occurred in an endoplasmic reticulum stress-dependent manner. Moreover, ubiquitin and p62-positive inclusions observed in high-fat diet–fed mice livers and SFA-treated cells were sequestered within autophagosomes. We also found that SFA-induced accumulation of Ser351-phosphorylated p62, which is indispensable for selective autophagy, further increased on administration of a lysosomal proteinase inhibitor. Although lipid-induced endoplasmic reticulum stress interferes with the autophagosome-lysosome fusion, selective autophagic sequestration of aggregated proteins is not inhibited.
Objective Intragastric balloon (IGB) therapy is a low-invasion treatment for obesity. Recently, a low-carbohydrate diet has shown effectiveness for encouraging weight loss, but whether or not a ...low-carbohydrate diet improves the efficacy of IGB therapy remains unclear. Therefore, we examined the effectiveness of a low-carbohydrate diet compared with a calorie-restricted diet in combination with IGB therapy. Methods A prospective study was conducted on 51 patients who had undergone IGB therapy from October 2012 to December 2017. Overall, 31 of the 51 patients were included in this study (12-month assessment after IGB placement). These 31 cases consisted of 18 IGB plus low-carbohydrate diet and 13 IGB plus calorie-restricted diet. We compared the two groups with respect to body weight loss as outcomes. Results At 12 months after IGB placement, the body weight was significantly lower than that observed at baseline in both the IGB plus low-carbohydrate diet group (baseline 101.9±25.8 kg, 12 months 88.2±21.9 kg) (p<0.0001) and the IGB plus calorie-restricted diet group (baseline 103.5±17.0 kg, 12 months 89.1±6.2 kg) (p<0.005). The percentage of excess weight loss in the IGB plus low-carbohydrate diet group was slightly higher than that in the IGB plus calorie-restricted diet group, but there was no significant difference between the 2 groups at 12 months after IGB placement (IGB plus low-carbohydrate 49.9±60.0%, IGB plus calorie-restricted diet 33.1±27.0%). Conclusion Our study demonstrated that both a low-carbohydrate diet and a calorie-restricted diet were effective interventions for weight reduction in combination with IGB therapy.
Transcatheter arterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, TACE can cause deterioration of liver functions. We aimed to ...identify the factors that influence deterioration of liver function after TACE. We retrospectively analyzed 262 patients who underwent TACE as initial treatment for HCC with Child-Pugh grade A. We divided them into three groups stratified by the etiology of underlying liver disease. Patients were classified into hepatitis B virus (HBV) group, hepatitis C virus (HCV) group, and non-HBV / non-HCV (NBNC) group. Liver functions at one month after TACE and time to Child-Pugh grade B or C were compared between the three groups. The HBV, HCV and NBNC groups contained 23, 123 and 116 patients, respectively. The decline in albumin level after TACE was significantly higher in NBNC group than other groups (p = 0.02). NBNC group showed a shorter time to Child-Pugh grade deterioration compared with HBV group and HCV group (p < 0.001). Multivariate Cox regression analysis showed that NBNC group was a significant factor for Child-Pugh grade deterioration (Hazard ratio 3.74, 95% confidence interval 1.89-7.40, p < 0.001). These results revealed that liver functions worsened most remarkably in NBNC group after TACE.
Lenvatinib has become a first line treatment for unresectable hepatocellular carcinoma (HCC). However, continued administration is impossible in many patients due to treatment resistance and severe ...adverse events. This study aimed to identify predicting factors to select patients likely to benefit from lenvatinib treatment.
We retrospectively analyzed 53 patients who were treated with lenvatinib for unresectable HCC. They were divided to two groups; low C-reactive protein (CRP) group with pretreatment serum CRP level < 1.0 mg/dL and high CRP group with serum CRP level ≥ 1.0 mg/dl. Overall survival (OS), total amount administered, and period of treatment were compared between the two groups.
The high CRP group showed a significantly poorer OS than the low CRP group (0.0% vs 71.5%/ 1year, p < 0.01). Multivariate analyses revealed that high CRP was a significant negative factor for OS (HR: 7.69, 95% confidence interval: 2.43-24.3, p < 0.001), and this result was independent of Child-Pugh score and existing tumor factors. Relative dose intensity at 8 weeks was lower (p = 0.01) and time to treatment failure was shorter (P < 0.001) in the high CRP group.
CRP level was associated with OS in HCC patients treated with lenvatinib. CRP could be a useful marker to identify patients most likely to benefit from lenvatinib treatment.
Liver function is a most important prognostic factor in patients with liver cirrhosis. Also, portal hypertension is a fatal complication of liver cirrhosis and variceal treatment is indispensable. ...However, changes of liver functions after endoscopic variceal treatments are unknown. The aim of this study was to evaluate prognosis and liver functions after endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL). A total of liver cirrhotic 103 patients who underwent prophylactic EIS and EVL were enrolled. Overall survival rate was higher in EIS group than EVL group (p = 0.03). Multivariate analysis showed that EIS was a negative factor for death (HR: 0.46, 95% confidence interval: 0.24-0.88, p = 0.02). Liver functions were assessed by blood test taken at before and 3 months after treatment. In EIS group, albumin and prothrombin time improved (p < 0.01), leading to improvement of Child-Pugh score, ALBI score and MELD score (p < 0.05). However, these did not improve in EVL group. EIS was a significant factor related to the elevated value of albumin after treatment in linear regression analysis (estimated regression coefficient: 0.17, 95% confidence interval: 0.05-0.29, p = 0.005). These results revealed that EIS could improve liver functions and prognosis.
Background
A 5–7 day hospital stay is usually needed after endoscopic submucosal dissection (ESD) of gastric tumor because of the possibility of delayed perforation or bleeding. The aim of this study ...was to evaluate the efficacy of combined use of a single over-the-scope clip (OTSC) and through-the-scope clips (TTSCs) to achieve complete closure of artificial gastric ulcer after ESD.
Methods
We prospectively studied 12 patients with early gastric cancer or gastric adenoma. We performed complete closure of post-ESD artificial gastric ulcer using a combination of a single OTSC and TTSCs.
Results
Mean size of post-ESD artificial ulcer was 54.6 mm. The mean operating time for the closure procedure was 15.2 min., and the success rate was 91.7 % (11/12). Patients who underwent complete closure of post-ESD artificial gastric ulcer could be discharged the day after ESD and the closing procedure.
Conclusions
Complete closure of post-ESD artificial gastric ulcer using a combination of a single OTSC and TTSCs is useful for shortening the period of hospitalization and reducing treatment cost.
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