Association of Genetic Polymorphisms With Hepatitis C Virus-related Liver Cirrhosis in Japan.

BACKGROUND/AIM: Hepatitis C virus (HCV) infection is an important health problem in the direct-acting antivirals-era. HCV causes life-threatening diseases, such as cirrhosis and hepatocellular carcinoma. Our aim was to examine whether certain single-nucleotide polymorphisms (SNPs) are associated with the prevalence of HCV infections progressing to cirrhosis in the Japanese population by a genome-wide association study-based approach. MATERIALS AND METHODS: We used DNA extracted from blood specimens of Japanese subjects with the establishment of the BioBank Japan project. RESULTS: We observed statistically significant differences in the frequency of 4 SNPs (rs1989972, rs2293766, rs1877033 and rs4805439) between anti-HCV-positive cirrhotic patients and controls. CONCLUSION: Four SNPs are associated with susceptibility to cirrhosis among HCV-infected Japanese subjects, while further studies with cohorts other than those sourced from BioBank Japan, must be conducted.

Portal-systemic Encephalopathy due to Complicated Spleno-renal Shunt Successfully Treated with Balloon-occluded Retrograde Transvenous Obliteration Using a Double Coaxial Balloon Catheter System and Shape-memory Coils.

A 70-year-old woman with hepatitis C cirrhosis underwent balloon-occluded retrograde transvenous obliteration for hepatic encephalopathy due to spleno-renal shunt. Because the shunt was thick, long, and winding, we used a coaxial and double interruption system, which enables the effective occlusion of the drainage route, and shape-memory coils, which are more physically stable than conventional metallic coils because they form three-dimensional loops. The patient was successfully treated with the combined usage of these devices, resulting in a normal serum ammonia level. Thereafter, the patient was treated with direct-acting antivirals, and a sustained virological response was achieved.

Cyclic ADP-ribose as an endogenous inhibitor of the mTOR pathway downstream of dopamine receptors in the mouse striatum.

The role of cyclic ADP-ribose (cADPR) as a second messenger and modulator of the mTOR pathway downstream of dopamine (DA) receptors and/or CD38 was re-examined in the mouse. ADP-ribosyl activity was low in the membranes of neonates, but DA stimulated it via both D1- and D2-like receptors. ADP-ribosyl cyclase activity increased significantly during development in association with increased expression of CD38. The cADPR binding proteins, FKBP12 and FKBP12.6, were expressed in the adult mouse striatum. The ratio of phosphorylated to non-phosphorylated S6 kinase (S6K) in whole mouse striatum homogenates decreased after incubation of adult mouse striatum with extracellular cADPR for 5 min. This effect of cADPR was much weaker in MPTP-treated Parkinson's disease model mice. The inhibitory effects of cADPR and rapamycin were identical. These data suggest that cADPR is an endogenous inhibitor of the mTOR signaling pathway downstream of DA receptors in the mouse striatum and that cADPR plays a certain role in the brain in psychiatric and neurodegenerative diseases.

Hypersplenism Treated by Partial Splenic Embolization Using Guglielmi Detachable Coils.

A 52-year-old man underwent partial splenic embolization (PSE) for hypersplenism. The intrasplenic artery targeted for the embolization was large, and the distance between its trifurcated branches was short; therefore, Guglielmi detachable coils (GDC) 360° Complex Shape were used, as well as conventional metal coils, to prevent coil migration. GDC are equipped with a shape-memory function and are more physically stable than conventional metallic coils because they form three-dimensional loops. In this case, an ideal extent of the splenic infarction was successfully achieved using a small number of coils. This is the first report of the use of GDC in PSE for hypersplenism.

Utility of Partial Splenic Embolization for Hypersplenism using Guglielmi Detachable Coils.

BACKGROUND/AIMS: We examined the utility of partial splenic embolization (PSE) using a Guglielmi Detachable Coil (GDC) comparing its safety and therapeutic efficacy with those of conventional metallic coils (IDC). METHODOLOGY: The GDC group comprised 8 patients who were subjected to embolization using a GDC in combination with an IDC, and the IDC group comprised 13 patients. Treatment factors were evaluated by the total number of coils used. We assessed the mean C-reactive protein (CRP) and the increased rate of platelet counts, 2 weeks after treatment. RESULTS: The rate of increase in platelet counts at 2 weeks after PSE was 2.47 in the GDC group and 3.18 in the IDC group (p = 0.076). The mean CRP levels were 3.0 in the GDC group and 5.9 in the IDC group (p = 0.14). The mean number of coils were 5.3 in the GDC group and 15.3 in the IDC group and this difference was statistically significant (p = 0.0008). CONCLUSION: A GDC is excellent in terms of stability and allows the operator to conduct embolization of hypersplenism in an accurate and reliable manner. In summary, use of a GDC for hypersplenism reduced the total number of coils required for successful treatment.

Usefulness of balloon-occluded retrograde transvenous obliteration for gastric varices concurrent with hepatocellular carcinoma.

BACKGROUND/AIMS: We performed balloon-occluded retrograde transvenous obliteration (B-RTO) before hepatocellular carcinoma (HCC) therapy in cases with HCC and gastric varices (GV) containing porto-systemic shunts. We conducted retrospective analyses on effects of B-RTO on hepatic functional reserve and HCC, as well as associated complications, and verified HCC treatment timing. METHODOLOGY: B-RTO was performed before HCC therapy after confirming disappearance or shrinkage of gastro-renal shunt with 3-dimensional computed tomography (3D-CT). Hepatic resection (HR) was performed in 7 of 12 cases, and transcatheter chemo-embolization (TACE) was used in 5 cases. RESULTS: B-RTO significantly improved GV (P=0.002). Improvement in grade/form was observed by endoscopy after 84.1 days, and that in gastro-renal shunt was observed by 3D-CT after 13.9 days. HCC size (P=0.862) and stage didn't change after B-RTO. Two cases showed improved Child-Pugh classification, and no deterioration in hepatic functional reserve was observed. B-RTO was performed 37.9 days before HCC therapy in surgical cases, and 45 days in TACE cases. CONCLUSION: Performing B-RTO before HCC therapy did not exacerbate HCC and allowed its safe performance. Evaluation with 3D-CT after B-RTO to determine HCC therapy timing was possible after 2 weeks. However, care is needed as esophageal varices worsened in some cases.