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1.
Nihon Shokakibyo Gakkai Zasshi ; 118(11): 1063-1070, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34759103

RESUMO

An advanced small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome was resected, and we started capecitabine plus oxaliplatin (CapeOX) as adjuvant therapy. However, local recurrence was noted, and the tumor increased even after CapeOX plus bevacizumab and fluorouracil plus leucovorin plus irinotecan plus panitumumab (FOLFIRI plus panitumumab). Pembrolizumab was administered after confirming high-frequency microsatellite instability, and the tumor shrank markedly and remained shrunk for 20 months.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias Colorretais , Síndrome de Peutz-Jeghers , Adenocarcinoma Mucinoso/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Recidiva Local de Neoplasia , Síndrome de Peutz-Jeghers/tratamento farmacológico
2.
Lab Invest ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732847

RESUMO

Fibroblast growth factor (FGF) 21 is an endocrine growth factor mainly secreted by the liver in response to a ketogenic diet and alcohol consumption. FGF21 signaling requires co-receptor ß-klotho (KLB) co-acting with FGF receptors, which has pleiotropic metabolic effects, including induced hepatic fatty acid oxidation and ketogenesis, in human and animal models of obesity. We examined the hepatocyte-specific enhancer/promoter of FGF21 expression plasmids in high-fat diet-fed mice for 12 weeks. Hydrodynamic injection for FGF21 delivery every 6 weeks sustained high circulating levels of FGF21, resulting in marked reductions in body weight, epididymal fat mass, insulin resistance, and liver steatosis. FGF21-induced lipolysis in the adipose tissue enabled the liver to be flooded with fat-derived FFAs. The hepatic expression of Glut2 and Bdh1 was upregulated, whereas that of gluconeogenesis-related genes, G6p and Pepck, and lipogenesis-related genes, Srebp-1 and Srebp-2, was significantly suppressed. FGF21 induced the phosphorylation of AMPK at Thr172 and Raptor at ser792 and suppressed that of mTOR at ser2448, which downregulated mTORC1 signaling and reduced IRS-1 phosphorylation at ser1101. Finally, in the skeletal muscle, FGF21 increased Glut4 and Mct2, a membrane protein that acts as a carrier for ketone bodies. Enzymes for ketone body catabolism (Scot) and citrate cycle (Cs, Idh3a), and a marker of regenerating muscle (myogenin) were also upregulated via increased KLB expression. Thus, FGF21-induced lipolysis was continuously induced by a high-fat diet and fat-derived FFAs might cause liver damage. Hepatic fatty acid oxidation and ketone body synthesis may act as hepatic FFAs' disposal mechanisms and contribute to improved liver steatosis. Liver-derived ketone bodies might be used for energy in the skeletal muscle. The potential FGF21-related crosstalk between the liver and extraliver organs is a promising strategy to prevent and treat metabolic syndrome-related nonalcoholic steatohepatitis.

3.
J Gastroenterol ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34796398

RESUMO

BACKGROUND: Primary biliary cholangitis (PBC) is considered to be caused by the interaction between genetic background and environmental triggers. Previous case-control studies have indicated the associations of environmental factors (tobacco smoking, a history of urinary tract infection, and hair dye) use with PBC. Therefore, we conducted a multicenter case-control study to identify the environmental factors associated with the development of PBC in Japan. METHODS: From 21 participating centers in Japan, we prospectively enrolled 548 patients with PBC (male/female = 78/470, median age 66), and 548 age- and sex-matched controls. These participants completed a questionnaire comprising 121 items with respect to demographic, anthropometric, socioeconomic features, lifestyle, medical/familial history, and reproductive history in female individuals. The association was determined using conditional multivariate logistic regression analysis. RESULTS: The identified factors were vault toilet at home in childhood [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.01-2.62], unpaved roads around the house in childhood (OR, 1.43; 95% CI, 1.07-1.92), ever smoking (OR, 1.70; 95% CI, 1.28-2.25), and hair dye use (OR, 1.57; 95% CI, 1.15-2.14) in the model for lifestyle factors, and a history of any type of autoimmune disease (OR, 8.74; 95% CI, 3.99-19.13), a history of Cesarean section (OR, 0.20; 95% CI, 0.077-0.53), and presence of PBC in first-degree relatives (OR, 21.1; 95% CI, 6.52-68.0) in the model for medical and familial factors. CONCLUSIONS: These results suggest that poor environmental hygiene in childhood (vault toilets and unpaved roads) and chronic exposure to chemicals (smoking and hair dye use) are likely to be risk factors for the development of PBC in Japan.

4.
J Dermatol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34796992

RESUMO

Fabry disease (FD), which is a lysosomal storage disease resulting from a deficiency of α-galactosidase A, leads to the accumulation of globotriaosylceramide in various tissues and multiorgan impairment. Early diagnosis is important to improve long-term prognosis. Early clinical manifestations of FD include neuropathic pain, vascular skin lesions, and sweating abnormalities. Hypohidorosis is one of the clinical findings in the early stage of FD. However, there have been no studies on prospective screening of FD in patients with definitive diagnosis of hypohidrosis. We examined α-galactosidase A activity in white blood cells in 17 (one female and 16 male) patients with generalized hypohidorosis. Among 17 patients, one male patient (approximately 5.8%) had significantly reduced α-galactosidase A activity. He presented with a history of hypohidrosis with heat intolerance and neuropathic tingling pain in a warm environment from 6 years ago. He had a few angiokeratoma on the trunk and extremities. Ultrastructural examination of skin biopsy from the angiokeratoma revealed lamellar inclusions in endothelial cells. Kidney biopsy revealed swollen podocytes and Gb3 deposition in the glomerulus, and urinalysis revealed mulberry bodies. He was finally diagnosed with FD and started on enzyme replacement therapy with agalsidase alpha in the early stage. In addition, his family screening led to find the patients of four additional FD. Screening for FD in patients with hypohidrosis may lead to efficient early detection of FD.

5.
Free Radic Biol Med ; 177: 391-403, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34715296

RESUMO

Non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD), can progress to cirrhosis, hepatocellular carcinoma (HCC), and hepatic failure/liver transplantation. Indeed, NASH will soon be the leading cause of HCC and liver transplantation. Lifestyle intervention represents the cornerstone of NASH treatment, but it is difficult to sustain. However, no pharmacotherapies for NASH have been approved. Oxidative stress has been implicated as one of the key factors in the pathogenesis of NASH. Systematic reviews with meta-analyses have confirmed that vitamin E reduces transaminase activities and may resolve NASH histopathology without improving hepatic fibrosis. However, vitamin E is not recommended for the treatment of NASH in diabetes, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis. Nevertheless, vitamin E supplementation may improve clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis. Further studies are warranted to confirm such effects of vitamin E and that it would reduce overall mortality/morbidity without increasing the incidence of cardiovascular events. Future clinical trials of the use of vitamin E in combination with other anti-fibrotic agents may demonstrate an additive or synergistic therapeutic effect. Vitamin E is the first-line pharmacotherapy for NASH, according to the consensus of global academic societies.

6.
J Viral Hepat ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34695288

RESUMO

Hepatocellular carcinoma (HCC) has high recurrence rates. HCC sometimes progresses from early-stage HCC (Barcelona Clinic Liver Cancer [BCLC] stage 0/A) to advanced-stage HCC after repeated recurrences and treatments. HCC progression deteriorates quality of life and prognosis. However, the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on HCC progression remains uninvestigated. We conducted a retrospective cohort study of patients with hepatitis C virus-related HCC with BCLC stage 0/A diagnosed for the first time and treated by curative resection or ablation. Using a time-varying method, we estimated the risk of tumour progression (defined as progression to BCLC stage B-D) and liver-related death and the characteristics of repeated recurrence. Overall, 165 patients were enrolled. Following curative HCC treatment, 72 patients received DAA therapy (DAA-treated group), whereas 93 did not (untreated group). Approximately 75% of the recurrences were at an early stage and expected to be disease-free by retreatment. We recorded 56 tumour progressions, of which 60.7% were observed after second recurrence. Multivariate adjusted time-varying Cox regression analysis showed that the DAA-induced SVR significantly reduced the risk of tumour progression (hazard ratio [HR] 0.28; p = .001) and liver-related death (HR 0.12; p < .001). The annual incidence of HCC treatment until tumour progression was 82.8% and 23.9% in the untreated and DAA-treated groups, respectively (HR 0.30; p < .001). DAA-induced SVR significantly reduced the risk for tumour progression and liver-related death and the frequency of HCC treatment following curative treatment for HCC at BCLC stage 0/A.

7.
J Gastroenterol ; 56(12): 1045-1061, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34718870

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver diseases worldwide, including in Japan. The Japanese Society of Gastroenterology (JSGE) and the Japanese Society of Hepatology (JSH) have established the Japanese NAFLD/NASH guidelines in 2014 and revised these guidelines in 2020. As described in these guidelines, weight reduction by diet and/or exercise therapy is important for the treatment of NAFLD patients. The I148M single nucleotide polymorphism (rs738409 C > G) of PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is widely known to be associated with the occurrence and progression of NAFLD. In the Japanese, the ratio of PNPLA3 gene polymorphisms found is approximately 20%, which is higher than that found in Westerners. In addition, the ratio of lean NAFLD patients is also higher in Japan than in Western countries. Therefore, the method for lifestyle guidance for the NAFLD patients in Japan would be different from that for the people in Western countries. The problems in the treatment of NAFLD patients include alcohol consumption and sarcopenia. Therefore, guidelines that can help clinicians treat Japanese patients with NAFLD are needed. In this expert review, we summarize evidence-based interventions for lifestyle modification (diet, exercise, alcohol, and sarcopenia) for the treatment of patients with NAFLD, especially from Japan and Asian countries.

8.
Intern Med ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34544949

RESUMO

Objective Mapping the long-term prognosis of Budd-Chiari syndrome (BCS) is difficult, as the prognosis is associated with changes in the liver function. The present study evaluated the time course changes in the liver function in a treatment group with percutaneous old balloon angioplasty (POBA) and a non-treatment group using the albumin-bilirubin score (ALBI) and Child-Pugh score during long-term follow-up. Methods In this retrospective study, 13 consecutive patients diagnosed with BCS at our hospital between 2007 and 2020 were categorized into a treatment group (n=8), which received POBA, and a non-treatment group (n=5). Differences in the liver function in the ALBI and Child-Pugh scores between the initial visit and one- and three-year follow-up were calculated and statistically evaluated. We investigated the changes in the liver function during the long-term follow-up, including events such as re-stenosis and re-treatment. Results While the Child-Pugh scores in the treatment group did not differ significantly between the initial visit and 1- or 3-year follow-up, the ALBI scores in this group improved significantly between the initial visit and the 1- or 3-year follow-up visit (p=0.0078 and 0.0156, respectively). The liver function according to the ALBI score in the treatment group showed gradual improvement from the initial value but gradual worsening in the non-treatment group. The ALBI scores also revealed that the liver function varies according to re-stenosis and re-POBA in BCS patients. Conclusion Unlike the Child-Pugh score, the ALBI score was able to capture changes in the liver function of BCS patients during the long-term course of BCS.

9.
Hepatol Commun ; 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34558835

RESUMO

Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, -0.41%, P < 0.01; BMI, -1.06 kg/m2 , P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18) of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects.

10.
Surg Today ; 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34568969

RESUMO

AIM: To investigate the relationship between the intrahepatic expression of podoplanin (PDPN) and Kupffer cells (KCs) in ischemia-reperfusion (I/R) liver damage. METHODS: C57Bl/6 mice were injected with 200 µl of clodronate liposomes (macrophage depletion; MDP group) to deplete KCs or control liposomes (control group) via the ophthalmic vein plexus 24 h prior to ischemia. Animals were subjected to 90 min of partial hepatic ischemia (70%), followed by reperfusion, and were then killed at designated time points. Serum and liver tissues were harvested for further analyses. RESULTS: Serum ALT levels, mortality rates, and the percentage of necrotic area in liver sections were significantly higher in the MDP group than in the control group. PDPN was expressed in the lymphatic epithelium, interlobular bile duct epithelium, and in some hepatocytes in each group. Its expression in hepatocytes was down-regulated in the MDP group. The accumulation of platelets in the sinusoid was reduced 6 h after I/R in the MDP group. Tissue HGF and IGF-1 levels decreased in the MDP group. CONCLUSIONS: These results suggest that KCs play a key role in the activation of platelets through direct contact with PDPN-positive hepatocytes in I/R livers.

11.
Nihon Shokakibyo Gakkai Zasshi ; 118(8): 749-756, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34373394

RESUMO

A 59-year-old man was treated for early gastric cancer with endoscopic submucosal dissection (ESD) 10 years prior to the study. Two months after the first ESD, he was diagnosed with recurrence on the ESD scar and treated via ESD again. The horizontal margin could not be evaluated because of cauterization, and the patient was carefully observed. He was admitted to our hospital complaining of low backache and diagnosed with disseminated carcinomatosis of the bone marrow associated with gastric cancer after examination. Although he started chemotherapy, he died after 6 months. In this study, we report a rare case of disseminated carcinomatosis of the bone marrow associated with gastric cancer, which developed 10 years after ESD.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Peritoneais , Neoplasias Gástricas , Medula Óssea , Ressecção Endoscópica de Mucosa/efeitos adversos , Mucosa Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
12.
JGH Open ; 5(7): 801-808, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34263075

RESUMO

Background and Aim: The Gut and Obesity in Asia Workgroup recently reported that a two-step approach using fibrosis scores followed by liver stiffness measurement (LSM) could accurately detect patients with non-alcoholic fatty liver disease (NAFLD) having advanced fibrosis in low-risk fibrosis populations. This study aimed to validate the utility of this approach using a Japanese health checkup registry. Methods: This cross-sectional study included subjects who underwent a health checkup from 2014 to 2019. Using estimated fibrosis stage measured by LSM as a standard, we calculated the percentage of misclassification from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score [FIB-4]) and LSM, alone or in combination. Results: Of 630 subjects with NAFLD, 4 (0.8%) had advanced fibrosis. In the first-step evaluation, only 21.4-38.0% of subjects needed further testing. This approach was associated with a high specificity of approximately 100% and a negative predictive value of 99.7%. The percentage of misclassification based on NFS or FIB-4 values followed by LSM in all subjects and using LSM after NFS or FIB-4 determination only in subjects with indeterminate/high NFS or FIB-4 values (two-step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively. In addition, very few false negatives occurred for both NFS and FIB-4. Conclusion: The two-step approach helps to identify the subjects with NAFLD who have advanced fibrosis during a routine health checkup and is associated with only a few false negatives.

13.
Sci Rep ; 11(1): 13844, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226630

RESUMO

This study aimed to prove that the FibroScan-aspartate aminotransferase (FAST) scores can be used to stratify disease severity in a Japanese cohort with fatty liver diseases [metabolic dysfunction-associated fatty liver disease (MAFLD) and nonalcoholic fatty liver disease (NAFLD)]. All the participants (n = 2254) underwent liver stiffness measurements and controlled attenuation parameter assessments. We compared the clinical characteristics of the patients with MAFLD and NAFLD using the FAST scores and explored the independent determinants of FAST scores ≥ 0.35, which indicated possible progressive disease. Overall, MAFLD was diagnosed in 789 patients (35.0%), while NAFLD was diagnosed in 618 (27.4%). The proportion of patients that had a condition that suggested progressive liver disease was higher in those with MAFLD than in those with NAFLD [68 (8.6%) vs 48 (7.7%)]. The area under the receiver-operating characteristic curve of the FAST score for diagnosing advanced fibrosis was 0.969 in MAFLD and 0.965 in NAFLD. Multivariate analyses determined that diabetes mellitus, alanine aminotransferase (ALT) levels, fatty liver index, and Fibrosis-4 index independently predict FAST scores ≥ 0.35 in patients with MAFLD. ALT levels had the strongest correlation with the FAST scores (p = 0.7817). The FAST score could stratify the disease severity in the Japanese cohort with fatty liver diseases.


Assuntos
Aspartato Aminotransferases/isolamento & purificação , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Índice de Gravidade de Doença , Adulto , Alanina Transaminase/genética , Alanina Transaminase/isolamento & purificação , Aspartato Aminotransferases/genética , Biópsia , Estudos de Coortes , Técnicas de Imagem por Elasticidade , Humanos , Japão/epidemiologia , Fígado/enzimologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia
14.
Clin Exp Nephrol ; 25(11): 1224-1230, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34128148

RESUMO

BACKGROUND: Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-galactosidase A. Males are usually severely affected, while females have a wide range of disease severity. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Previous studies examined this correlation using the classical methylation-dependent method; however, conflicting results were obtained. This study was established to ascertain the existence of skewed XCI in nine females with heterozygous pathogenic variants in the GLA gene and its relationship to the phenotypes. METHODS: We present five female patients from one family and four individual female patients with Fabry disease. In all cases, heterozygous pathogenic variants in the GLA gene were detected. The X-chromosome inactivation patterns in peripheral blood leukocytes and cells of urine sediment were determined by both classical methylation-dependent HUMARA assay and ultra-deep RNA sequencing. Fabry Stabilization Index was used to determine the clinical severity. RESULTS: Skewed XCI resulting in predominant inactivation of the normal allele was observed only in one individual case with low ⍺-galactosidase A activity. In the remaining cases, no skewing was observed, even in the case with the highest total severity score (99.2%). CONCLUSION: We conclude that skewed XCI could not explain the severity of female Fabry disease and is not the main factor in the onset of various clinical symptoms in females with Fabry disease.

15.
J Orthop ; 25: 93-97, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994705

RESUMO

Repairing released posterior soft tissues is important in preventing dislocation after total hip arthroplasty (THA) via the posterior approach. We clarify the functional and the clinical anatomy of obturator externus. We performed cadaveric studies and investigated clinically in primary THA cases. The location, trajectory, and size of the muscular tendon was recorded. The trajectory of the obturator externus ran orthogonal to the femoral axis with the hip in 90° flexion whereas that of the obturator internus muscle ran parallel. Because the trajectory of obturator externus and the obturator internus differ, their functions also differ.

17.
Intern Med ; 60(21): 3441-3445, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34024853

RESUMO

Glecaprevir/pibrentasvir (GLE/PIB) is a pan-genotype anti-hepatitis C virus (HCV) therapy with high efficacy and safety. However, evidence supporting retreatment following failure of the GLE/PIB regimen is limited. We herein report 3 non-cirrhotic cases involving two men aged 51 and 58 years old and a woman aged 68 years old infected with HCV genotype 1a, 2a, and 3b respectively who failed anti-HCV therapies including GLE/PIB therapy. With combination therapy of sofosbuvir/velpatasvir plus ribavirin (SOF/VEL+RBV) for 24 weeks, all 3 patients had achieved a sustained viral response (SVR) at 24 weeks after completing treatment. SOF/VEL+RBV therapy was effective for retreatment of HCV after failure of GLE/PIB therapy.


Assuntos
Hepatite C Crônica , Sofosbuvir , Idoso , Ácidos Aminoisobutíricos , Antivirais/uso terapêutico , Benzimidazóis , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas , Resultado do Tratamento
18.
Hepatol Commun ; 5(4): 559-572, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33860115

RESUMO

This study aimed to examine whether the diagnostic accuracy of four noninvasive tests (NITs) for detecting advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is maintained or is inferior to with or without the presence of type 2 diabetes. Overall, 874 patients with biopsy-proven NAFLD were enrolled. After propensity-score matching by age, sex, and the prevalence of dyslipidemia, 311 patients were enrolled in each group of with or without diabetes. To evaluate the effect of diabetes, we compared the diagnostic accuracy of the fibrosis-4 (FIB-4) index, the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and type IV collagen 7S (COL4-7S) in patients with NAFLD with and without diabetes. The areas under the receiver operating characteristic curve (AUROC) for identifying advanced fibrosis in patients without diabetes were 0.879 for the FIB-4 index, 0.851 for the NFS, 0.862 for the APRI, and 0.883 for COL4-7S. The AUROCs in patients with diabetes were 0.790 for the FIB-4 index, 0.784 for the NFS, 0.771 for the APRI, and 0.872 for COL4-7S. The AUROC of COL4-7S was significantly larger than that of the other NITs in patients with NAFLD with diabetes than in those without diabetes. The optimal high and low cutoff points of COL4-7S were 5.9 ng/mL and 4.8 ng/mL, respectively. At the low cutoff point, the accuracy of COL4-7S was better than that of the other NITs, especially in patients with diabetes. Conclusion: COL4-7S measurement might be the best NIT for identifying advanced fibrosis in NAFLD, especially in NAFLD with diabetes.

19.
Life (Basel) ; 11(2)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672864

RESUMO

The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of NAFLD should be updated to metabolic-dysfunction-associated fatty liver disease (MAFLD). Hepatic fibrosis is the most significant determinant of all cause- and liver -related mortality in MAFLD. The non-invasive test (NIT) is urgently required to evaluate hepatic fibrosis in MAFLD. The fibrosis-4 (FIB-4) index is the first triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness, especially for general physicians or endocrinologists, although the FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration-controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the second step after triaging by the FIB-4 index. The leading cause of mortality in MAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. MAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation. The FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocellular carcinoma, but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, the FIB-4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of the FIB-4 index in the management of MAFLD.

20.
Clin Kidney J ; 14(1): 325-331, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33564435

RESUMO

Background: Within the class of tyrosine kinase inhibitors (TKIs), which are used for the treatment of numerous advanced cancers, lenvatinib is associated with a higher prevalence of hypertension (HT) compared with other TKIs. In this study, we investigated the effect of lenvatinib on blood pressure (BP) and associated factors. Methods: This single-centre, retrospective observational study included 25 consecutive patients treated with lenvatinib for unresectable hepatocellular carcinoma from April 2018 to December 2018 at the study institution. We assessed changes in BP using ambulatory BP monitoring, urinary sodium excretion, kidney function, use of antihypertensive agents and diuretics, and fluid retention following treatment initiation with lenvatinib. Results: At 1 week after treatment initiation, the mean BP and the percentage of patients with riser pattern significantly increased compared with those at the baseline. Although there were no significant changes at 1 week, urinary sodium excretion (153.4 ± 51.7 and 112.5 ± 65.0 mEq/day at 1 and 3 weeks, respectively, P < 0.05) and estimated glomerular filtration rate significantly decreased and the number of patients with fluid retention increased at 3 weeks. Furthermore, patients with fluid retention had significantly higher BP or required more intensive BP treatment compared with those without fluid retention. Conclusions: Lenvatinib might lead to HT without fluid retention soon after the initiation of treatment, subsequently leading to a reduction in urinary sodium excretion, thereby contributing to a rise in BP by fluid retention.

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