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1.
Artigo em Inglês | MEDLINE | ID: mdl-38919514

RESUMO

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

2.
Clin J Gastroenterol ; 15(6): 1101-1107, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36088514

RESUMO

A fraction of patients with hepatocellular carcinoma (HCC) shows unexpected rapid tumor growth, called hyperprogressive disease (HPD) after the initiation of atezolizumab and bevacizumab (ATZ + BEV). However, little information is available concerning salvage therapy after HPD and the possibility of resuming ATZ + BEV. A 60-year-old woman with unresectable HCCs was treated with transarterial chemoembolization (TACE) and followed by lenvatinib, which showed an unsatisfactory result. Multiple HCCs had been noted in both lobes just before ATZ + BEV treatment. After the initiation of ATZ + BEV, a tumor in the left lobe grew rapidly. The tumor growth kinetics ratio and tumor growth rate ratio of the rapidly growing lesion were 3.76 and 2.02, respectively. Thyroid dysfunction was noted after the initiation of ATZ + BEV. The neutrophil/lymphocyte ratios just before and at 3 weeks after the first ATZ + BEV treatment were 3.89 and 3.5, respectively. Drug-eluting bead (DEB)-TACE using cisplatin was performed for the rapidly growing tumor, which was effective for the targeted HCC in the left lobe as well as multiple HCCs in the right lobe. We were able to resume and continue ATZ + BEV without HPD, which was effective for HCC. We considered that DEB-TACE is an option for treating HPD.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/terapia , Cisplatino , Imunoterapia , Resultado do Tratamento
3.
World J Gastrointest Pathophysiol ; 13(3): 96-106, 2022 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-35720167

RESUMO

BACKGROUND: Vibration-controlled transient elastography (VCTE) is proposed as a second step of examination to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) after triaging by the fibrosis-4 (FIB-4) index. Recently, VCTE-based scoring systems, including FibroScan-AST (FAST), Agile 3+, and Agile 4, emerged to determine the status of NAFLD. However, the significance of these scoring systems remains unknown in narrowing the high-risk group of NAFLD patients with comorbidities, including hepatocellular carcinoma (HCC) and esophagogastric varices (EGV). AIM: To clarify the significance of VCTE-based scoring systems to narrow the high-risk group of NAFLD patients with comorbidities. METHODS: We performed a cross-sectional study to investigate the usefulness of VCTE-based scoring systems and other fibrosis markers to narrow the high-risk group of patients with NAFLD. FIB-4 index was used for the first triage. Risk groups of FAST, Agile 3+, and Agile 4 were stratified according to the published data. Among the 191 patients with NAFLD, there were 26 (14%) and 25 patients (13%) with HCC and EGV, respectively. RESULTS: When 1.3 was used as a cutoff value, the FIB-4 index narrowed the risk group to 120 patients, in which all patients with HCC and/or EGV were included. High risk group of Agile 3+ could subsequently narrow the risk group. The prevalence of HCC and EGV at this step were 33% (26/80) and 31% (25/80), respectively. In further narrowing of EGV, Agile 4 aggregated the patients with EGV into 43 patients, of whom 23 (53%) had EGV. FAST failed to narrow the risk group of patients with comorbidities. When 2.6 was used as a cutoff value of the FIB-4 index, three patients with HCC and two patients with EGV were missed at the first triage. CONCLUSION: Agile 3+ and Agile 4 are useful to narrow the NAFLD patient group, in which patients may have HCC and/or EGV.

4.
Cancers (Basel) ; 14(3)2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35159018

RESUMO

BACKGROUND: Conventional therapies, including chemoembolization and radiation therapy, have been expected to prolong the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases, which remains poor. However, little information is available on the efficacy of conventional therapies for such patients under tyrosine kinase inhibitor (TKI) treatment. METHODS: We retrospectively investigated 127 HCC patients with extrahepatic metastases, who were divided into the non-TKI (conventional therapies) and TKI groups and further subdivided into the TKI alone and TKI plus conventional therapies groups. Conventional therapies included transcatheter arterial chemoembolization, cisplatin-based chemotherapy, radiation, surgery, and UFT, an oral chemotherapeutic agent. RESULTS: The median of the overall survival (OS) of the 127 patients with extrahepatic metastases was 7.0 months. Meanwhile, the median OS of the TKI and non-TKI groups was 12.1 and 4.1 months, respectively. Imitating TKI after diagnosing metastases promoted a favorable increase in OS. Among the TKI group, the median OS in the TKI alone group was 8.9 months. TKI plus conventional therapies promoted no improvement in OS after adjusting for the patients' background data. CONCLUSION: TKI promoted a better OS in HCC patients with extrahepatic metastases compared to conventional therapies. However, TKI plus conventional therapies promoted no improvement in the prognosis of such patients.

6.
Clin J Gastroenterol ; 14(4): 1227-1232, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33993428

RESUMO

Liver cirrhosis is frequently complicated by spontaneous portosystemic shunt (SPSS) due to portal hypertension. Shunt embolization is considered when symptoms related to SPSSs are refractory to endoscopic and/or medical therapies. However, little information is available on the treatment of patients with multiple and large SPSS. We report a successfully managed case in which patient with such SPSS received two embolization procedures within 6 months. A 57-year-old man with alcoholic liver cirrhosis was transferred to our hospital due to a ruptured gastric varix. CT examination showed gastrorenal and splenorenal shunts of 8 mm and 11 mm in diameter, respectively. In addition, multiple hepatocellular carcinomas (HCCs) were noted. First, balloon-occluded retrograde transvenous obliteration (BRTO) was performed for the gastrorenal shunt, resulting in the disappearance of the varix, followed by transcatheter arterial chemoembolization (TACE) for HCCs. However, the hepatic encephalopathy worsened after the BRTO and TACE, and the splenorenal shunt enlarged to 18 mm in diameter. Although the shunt was tortuous and had another drainage vein, we completed the embolization for the shunt using metallic coils without any events. The patient's hepatic encephalopathy and hepatic function were ameliorated after embolization for the splenorenal shunt, and the patient was free from hepatic encephalopathy.


Assuntos
Oclusão com Balão , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Varizes Esofágicas e Gástricas , Encefalopatia Hepática , Hipertensão Portal , Neoplasias Hepáticas , Derivação Portossistêmica Transjugular Intra-Hepática , Pré-Escolar , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/terapia , Humanos , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Masculino , Resultado do Tratamento
7.
BMC Gastroenterol ; 20(1): 427, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317473

RESUMO

BACKGROUND: Chronic liver disease (CLD) is often complicated by severe thrombocytopenia (platelet count < 50,000/µL). Platelet transfusion has been a gold standard for increasing the platelet count to prevent hemorrhagic events in such patients. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count in such patients when invasive procedures are scheduled. Former studies on lusutrombopag included patients with a platelet count of > 50,000/µL at baseline: the proportions of patients who did not require platelet transfusion were 84-96%, which might be overestimated. METHODS: The efficacy and safety of lusutrombopag were retrospectively investigated in CLD patients with platelet count of < 50,000/µL, a criterion for platelet transfusion, in real-world settings. We examined the proportion of patients who did not require platelet transfusion in 31 CLD patients, which exceeded a minimum required sample size (21 patients) calculated by 80% power at a significance level of 5%. Lusutrombopag, 3 mg once daily, was administered 8-18 days before scheduled invasive procedures. RESULTS: Among 31 patients who received lusutrombopag, 23 patients (74.2%) patients showed a platelet count of ≥ 50,000/µL (Group A) and did not require platelet transfusion. The remaining 8 patients (25.8%) did not reached platelet ≥ 50,000/µL (Group B). The means of platelet increase were 38,000/µL and 12,000/µL in groups A and B, respectively. A low platelet count at baseline was a characteristic of patients in group B. Among 13 patients who repeatedly used lusutrombopag, lusutrombopag significantly increased the platelet count as the initial treatment. When all repeated uses of lusutrombopag were counted among these 13 patients, platelet transfusion was not required in 82.1% (23/28) of treatments. Although one patient showed portal thrombosis after lusutrombopag treatment, the thrombosis was disappeared by anticoagulant treatment for 35 days. The degree of platelet increase with lusutrombopag was larger than that in their previous platelet transfusion. CONCLUSIONS: The proportion of patients who did not require platelet transfusion was 74.2%, which is smaller than that in former studies which included CLD patients with a platelet count of > 50,000/µL. However, lusutrombopag is effective and safe for CLD patients with a platelet count of < 50,000/µL.


Assuntos
Hepatopatias , Trombocitopenia , Cinamatos , Humanos , Hepatopatias/complicações , Hepatopatias/terapia , Receptores de Trombopoetina , Estudos Retrospectivos , Tiazóis , Trombocitopenia/complicações , Trombocitopenia/terapia
8.
J Rural Med ; 15(4): 139-145, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33033533

RESUMO

Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in "rural" regions. Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan. Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events. Conclusion: G/P therapy is effective and safe for old-aged patients.

9.
J Med Virol ; 92(12): 3572-3583, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32609895

RESUMO

The clinical and virologic features of hepatitis E virus (HEV) infection seem to vary among regions even in developed countries. However, we have little information on the diversity of HEV infection. Here, we investigated the characteristics of 26 patients in our hospital located in Tochigi prefecture, 90 km north of Tokyo, between 2000 and 2019. The reported number of patients with acute hepatitis E is increasing in Japan because measurement of IgA-class anti-HEV antibody was commercially available from 2011. In contrast, the numbers at our hospital were 1.5/y and 1.0/y in 2000 to 2011 and 2012 to 2019, respectively. This is attributed to the fact that we have been investigating HEV as a cause of unknown hepatitis before 2011. Among isolated HEV subgenotypes, including 3a, 3b, 4b, 4c, and 4d, all three patients with subgenotype 4c infection presented acute liver failure. Four HEV strains shared more than or equal to 99% identity within the 412-nucleotide partial sequence, in which the time and place of HEV infection varied, except for one intrafamilial infection. In addition, some strains were similar to HEV strains isolated far from Tochigi prefecture. In conclusion, the number of patients with acute hepatitis E was not increasing at Jichi Medical University Hospital and some strains were found to circulate in Japan.

10.
Clin J Gastroenterol ; 13(5): 907-913, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32458219

RESUMO

Percutaneous radiofrequency ablation (RFA) is a good indication for hepatocellular carcinoma (HCC) in cases involving ≦ 3 tumors of ≦ 30 mm in size, many hepatologists are hesitant to perform the procedure for patients with hemorrhagic disorders. We herein report the successful treatment of HCC by laparoscopic RFA in a patient with hemophilia A. A 48-year-old man with moderate form of hemophilia A had a single HCC at segment 8. To perform laparoscopic RFA safely, recombinant factor VIII (rFVIII) was administered to maintain factor VIII activity (FVIII:C) > 80% on the operation day and > 40% for 6 days after the operation in accordance with the guidelines. A total of 23,000 units of rFVIII was used. Laparoscopic RFA was completed with an operation time of 105 min and < 10 mL of blood loss. As a result, blood transfusion was not required. At 2 years after the initial treatment, HCC recurred at segment 7. Under rFVIII supplementation, we performed a second laparoscopic RFA without any events. Although partial hepatectomy is the main procedure used to treat HCC in patients with hemophilia, we could reduce in total use of rFVIII, blood and operation time by laparoscopic RFA compared with those in partial hepatectomy.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Hemofilia A , Laparoscopia , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Hemofilia A/complicações , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Resultado do Tratamento
11.
Intern Med ; 58(20): 2963-2968, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31243227

RESUMO

A 65-year-old man presented with acute liver failure and grade IV coma caused by hepatitis B virus (HBV) infection in 2017. The patient died on day 12 from the disease onset. The HBV isolated from the patient was genotype/subgenotype B/B1 and had multiple genomic mutations. The patient's wife was hepatitis B surface antigen (HBsAg)-positive when she delivered her first daughter in 1979. The HBV isolates of the patient and the wife shared 100% similarity over the entire genome. Because the patient's HBsAg value had been negative one year earlier, we considered the source of HBV transmission to be his wife.


Assuntos
Hepatite B Crônica/transmissão , Falência Hepática Aguda/virologia , Cônjuges , Idoso , Evolução Fatal , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Humanos , Masculino , Mutação
12.
J Rural Med ; 14(1): 78-86, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31191770

RESUMO

Objective: The development of hepatocellular carcinoma (HCC) is not uncommon in patients who achieve eradication of the hepatitis C virus through direct-acting antiviral (DAA) treatment. The aim of this study was to identify the patients at high risk for novel HCC development after a sustained virologic response (SVR) by DAA treatment. Patients and Methods: A total of 518 patients with no history of HCC treatment and who achieved SVR by DAA treatment were evaluated retrospectively. The correlations between HCC development and the patients' characteristics were evaluated. For patients who underwent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) or dynamic contrast-enhanced computed tomography, the relationship between the imaging findings and subsequent HCC development was also assessed. Results: HCC developed newly in 22 patients, and the 1-year and 3-year cumulative HCC rates were 2.0% and 8.5%, respectively. In multivariate analysis, a FIB-4 index >4.0 and a post-treatment α-fetoprotein >4.0 ng/ml were significant risk factors for HCC. In 26 of 118 patients who underwent an MRI before DAA treatment, a non-hypervascular hypo-intense nodule was seen in the hepatobiliary phase, and in 6 of 182 patients who underwent a CT, a non-hypervascular hypo-enhanced nodule was seen in the delayed phase. The sensitivity and specificity of the MRI-positive findings for the subsequent development of HCC were 0.92 and 0.87, respectively, and those of the CT were 0.40 and 0.99, respectively. In multivariate analysis of patients who underwent an MRI, a non-hypervascular hypo-intense nodule was the only factor that was significantly related to HCC development (HR 32.4, p = 0.001). Conclusion: Gd-EOB-DTPA-enhanced MRI was found to be reliable for risk evaluation of subsequent HCC development in patients after SVR by DAA treatment. Patients with a non-hypervascular hypo-intense nodule need more careful observation for incident HCC.

13.
Hepatol Res ; 49(5): 521-530, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30645783

RESUMO

AIM: The major transmission mode of hepatitis A virus (HAV) in Japan is the fecal-oral route by contaminated foods. In contrast, HAV infection is well documented as a sexually transmitted disease in Europe and North America. The present study was undertaken to determine the full-genome sequence of HAV and trace the transmission route of HAV in Japanese men who have sex with men (MSM). METHODS: In 2018, we encountered three Japanese MSM with acute hepatitis A co-infected with HIV for 4-12 years. Serum samples obtained from these patients were used for HAV full-genome analyses. RESULTS: Isolated HAV strains were segregated into subgenotype IA. The three HAV strains shared 100% identity within the 481-nucleotide partial sequence. The entire nucleotide sequence showed that the three strains were 99.97% similar to each other with only two nucleotide substitutions. At the amino acid level, the three strains differed from each other by only one or two amino acids. All three strains obtained in the present study were >99.6% identical to the 66 reported strains isolated from Taiwan and European countries during 2015-2017. In addition, these 66 strains include the RIVM-HAV16-090 (EuroPride) strain, which has been involved in HAV outbreaks among MSM worldwide. CONCLUSIONS: We determined for the first time the full-genome sequence of HAV isolated from Japanese MSM with acute hepatitis A and found that the strains were identical to those from MSM worldwide. Thus, these HAV strains were imported to Japan from foreign countries through MSM.

14.
Clin J Gastroenterol ; 12(3): 223-230, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30617852

RESUMO

Congenital hepatic fibrosis (CHF), a fibropolycystic disease, is characterized by bile duct malformation, periportal fibrosis, and renal polycystic disease. Although cholangiocellular carcinoma is the primary tumor arising from fibropolycystic diseases, hepatocellular carcinoma (HCC) is extremely rare. In addition, no algorism for determining the optimum HCC treatment has yet been available in cases of fibropolycystic disease due to variations in the background liver and renal conditions. We herein report a patient with HCC arising from CHF that was successfully treated using radiofrequency ablation (RFA) under laparoscopic assistance. A 37-year-old man with CHF was admitted to our hospital for treatment of HCC in 2014. Imaging revealed HCC located in hepatic segments II and VIII with diameters of 28 and 24 mm, respectively. There had been no histories of recurrent cholangitis or renal failure after when CHF was diagnosed in 2003. In addition, esophageal varices were well controlled. We achieved sufficient ablation using a bipolar ablation system without any complications. The post-operative course was uneventful, and the patient was free from HCC for 4 years. Thus, locoregional therapy, including RFA, is acceptable for the treatment of HCC arising from CHF when the background liver and kidney are preserved.


Assuntos
Carcinoma Hepatocelular/cirurgia , Doenças Genéticas Inatas/complicações , Cirrose Hepática/complicações , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência , Adulto , Carcinoma Hepatocelular/etiologia , Humanos , Laparoscopia , Neoplasias Hepáticas/etiologia , Masculino
15.
Intern Med ; 58(4): 477-485, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30333396

RESUMO

Objective Regional disparities were observed in the outcomes of interferon (IFN)-based therapy for chronic hepatitis C virus (HCV) infection in a Japanese nationwide study. However, whether or not these regional disparities are observed in the outcomes of direct-acting antiviral drugs, including sofosbuvir (SOF) plus ribavirin (RBV) therapy, remains unclear. Methods We conducted a multicenter study to assess the efficacy of SOF plus RBV therapy for HCV genotype 2 infection in Tochigi Prefecture and its vicinity, in which IFN-based therapy yielded a low sustained virologic response (SVR) rate. In addition, we divided Tochigi Prefecture into six regions to examine regional disparities in the SVR. Patients We enrolled patients with chronic HCV genotype 2 infection. Results Of the 583 patients enrolled, 569 (97.6%) completed the treatment, and 566 (97.1%) also complied with post-treatment follow-up for 12 weeks. The overall SVR12 rate was 96.1% by per protocol and 93.7% by intention-to-treat analyses. No marked differences were observed in the SVR12 between subjects ≥65 and <65 years of age. Although large gaps were observed in the characteristics of patients and accessibility to medical resources, there was no significant difference in the SVR12 rate among the six regions in Tochigi Prefecture. Conclusion SOF plus RBV therapy was effective for HCV genotype 2 infection in an area where IFN-based therapy had previously shown unsatisfactory results. In addition, no regional disparities in the SVR12 were observed in Tochigi Prefecture.


Assuntos
Antivirais/uso terapêutico , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Idoso , Feminino , Genótipo , Geografia , Hepatite C Crônica/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Resposta Viral Sustentada
16.
Cancer Sci ; 110(2): 771-783, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30520543

RESUMO

Nonalcoholic steatohepatitis (NASH) is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC). However, effective therapeutic strategies for preventing and treating NASH-mediated liver cirrhosis and HCC are lacking. Cholesterol is closely associated with vascular endothelial growth factor (VEGF), a key factor that promotes HCC. Recent reports have demonstrated that statins could prevent HCC development. In contrast, we have little information on ezetimibe, an inhibitor of cholesterol absorption, in regards to the prevention of NASH-related liver cirrhosis and HCC. In the present study, a steatohepatitis-related HCC model, hepatocyte-specific phosphatase and tensin homolog (Pten)-deficient (PtenΔhep ) mice were fed a high-fat (HF) diet with/without ezetimibe. In the standard-diet group, ezetimibe did not reduce the development of liver tumors in PtenΔhep mice, in which the increase of serum cholesterol levels was mild. Feeding of a HF diet increased serum cholesterol levels markedly and subsequently increased serum levels of VEGF, a crucial component of angiogenesis. The HF diet increased the number of VEGF-positive cells and vascular endothelial cells in the tumors of PtenΔhep mice. Kupffer cells, macrophages in the liver, increased VEGF expression in response to fat overload. Ezetimibe treatment lowered cholesterol levels and these angiogenetic processes. As a result, ezetimibe also suppressed inflammation, liver fibrosis and tumor growth in PtenΔhep mice on the HF diet. Tumor cells were highly proliferative with HF-diet feeding, which was inhibited by ezetimibe. In conclusion, ezetimibe suppressed development of liver tumors by inhibiting angiogenesis in PtenΔhep mice with hypercholesterolemia.


Assuntos
Inibidores da Angiogênese/farmacologia , Dieta Hiperlipídica/efeitos adversos , Ezetimiba/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Animais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/sangue , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/sangue , Neovascularização Patológica/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue
17.
Clin J Gastroenterol ; 11(6): 501-506, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29909559

RESUMO

Hepatocellular carcinoma (HCC) can be difficult to diagnose and treat in patients with Osler-Rendu-Weber disease due to vascular malformation and regenerative nodular hyperplasia. In addition, percutaneous liver puncture should be avoided for the diagnosis and treatment as the procedure carries a high risk of bleeding. We herein report the successful treatment of HCC in a patient with Osler-Rendu-Weber disease using radiofrequency ablation (RFA) under laparoscopy. A 71-year-old man with Osler-Rendu-Weber disease was admitted to our hospital for the treatment of HCC. He also had chronic hepatitis C virus infection. The arterioportal shunts in the liver were detected by computed tomography (CT) and angiography. A tumor 20 mm in size was detected as a defected-lesion in the hepatic segment IV during the portal phase by CT. RFA under laparoscopy was performed for the curative treatment for HCC, with sufficient ablation obtained. Although the blood gushed out from the needle tract at the end of the procedure, complete hemostasis was achieved promptly using coagulation forceps. The post-operative course was favorable. Thus, laparoscopic RFA is a useful treatment modality for HCC in patients with Osler-Rendu-Weber disease, as a hemostasis device can be used with direct visualization.


Assuntos
Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Laparoscopia/métodos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência/métodos , Telangiectasia Hemorrágica Hereditária/complicações , Idoso , Humanos , Laparoscopia/efeitos adversos , Masculino , Complicações Pós-Operatórias , Ablação por Radiofrequência/efeitos adversos
18.
Intern Med ; 57(21): 3099-3104, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29877273

RESUMO

A 79-year-old Japanese woman was diagnosed with acute hepatitis B based on laboratory tests showing positivity for IgM-class antibody against hepatitis B virus (HBV) core and hepatitis B surface antigen (HBsAg) as well as elevated transaminases. A phylogenetic analysis revealed that the HBV strain obtained from the patient belonged to genotype D/subgenotype D1, similar to strains circulating in foreign countries but different from those in Japan. The clinical course was favorable. HBsAg became negative within 10 weeks after the onset. To our knowledge, this is the first report of acute hepatitis B caused by subgenotype D1 HBV in Japan.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B/virologia , Idoso , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/análise , Humanos , Japão
19.
Kaohsiung J Med Sci ; 32(5): 255-60, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27316584

RESUMO

Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium-competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid-suppressing drug [lansoprazole 30 mg (LAC), rabeprazole 10 mg (RAC), esomeprazole 20 mg (EAC), or vonoprazan 20 mg (VAC)] twice daily for 1 week. Eradication was successful in 73% (419/573) of patients using intention-to-treat (ITT) analysis and 76% (419/549) of patients in per-protocol (PP) analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p < 0.01) and PP analysis (VAC 85%, LAC 69% and RAC 70%, p < 0.01), and had a similarly high eradication rate to the EAC group (83% in ITT and 87% in PP). Although the eradication rate in the VAC and EAC groups was not significantly higher than in the LAC and RAC groups in patients with mild gastric atrophy with both ITT and PP analyses, it was significantly higher in patients with severe gastric atrophy (p < 0.01). The VAC group had a significantly higher H. pylori eradication rate than the LAC and RAC groups, and a > 80% eradication rate regardless of the degree of atrophy.


Assuntos
Erradicação de Doenças , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/fisiologia , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Atrofia , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/farmacologia , Pirróis/farmacologia , Estômago/efeitos dos fármacos , Estômago/patologia , Sulfonamidas/farmacologia , Resultado do Tratamento
20.
Clin J Gastroenterol ; 7(6): 476-80, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25491905

RESUMO

Pulmonary complications of ulcerative colitis (UC) are relatively rare. Generally, pulmonary lesions with cavity formation are difficult to distinguish from infections or Wegener's granulomatosis lesions. A 15-year-old female with no remarkable past medical history had multiple pulmonary nodules on chest X-ray. Since empirical treatment with wide-spectrum antibiotics did not improve her symptoms, she was transferred for further evaluation. Chest radiography and computed tomography (CT) scan showed multiple bilateral pulmonary nodules with cavity formation, 8-65 mm in diameter, located mainly in the right lung. She was diagnosed with UC based on sigmoidoscopy. She was treated with mesalazine and granulocyte-monocyte apheresis (GMA). Steroids were not administered, because an infectious disease could not be excluded. Seven days after starting GMA, her symptoms and laboratory findings improved, and she was discharged. After the completion of 10 courses of GMA, chest radiography and CT scan showed marked diminution of the pulmonary lesions. UC-associated pulmonary lesions can be treated without steroid administration, and we suggest that this strategy is an option for a patient with UC-associated pulmonary lesions that cannot be differentiated from an infection.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/complicações , Leucaférese , Mesalamina/uso terapêutico , Nódulos Pulmonares Múltiplos/terapia , Diagnóstico Diferencial , Feminino , Granulócitos , Humanos , Monócitos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Radiografia
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