Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called "diabetic hepatopathy or diabetic liver disease". NASH, a severe form ...of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.
An 82-year-old woman with autoimmune hepatitis had been treated with 5 mg prednisolone (PSL) orally to maintain normal transaminase levels. The subsequent transaminase levels were elevated and ...remained unchanged despite increasing the dose of PSL to 20 mg and introducing ursodeoxycholic acid (UDCA) at a dose of 900 mg. This combined treatment with UDCA was, however, ineffective. Treatment with Saireito at a dose of 9.0 g in conjunction with PSL was then initiated, which led to the subsequent normalization of her transaminase levels. Oral administration of PSL was discontinued eight weeks after the co-administration of Saireito. The patient had a significant response to this treatment.
Abstract
Background and study aim
Recently, a novel technique combining stent-in-stent (SIS) and side-by-side (SBS) technique (hybrid technique) has been reported. This technique may have ...application for hepatic hilar obstruction (HBO) because it reduces the number of times the stent mesh has to be passed. However, to the best our knowledge, evaluation of its use in that setting has not been reported. Recently, a new uncovered self-expandable metal stent (UCSEMS) has become available in Japan. The diameter of this stent delivery shaft is only 5.4 Fr, and the discrepancy between the guidewire and top of stent delivery system is strongly reduced. We herein report technical tips for hybrid metal stent deployment for high-grade HBO using this novel UCSEMS.
Hybrid metal stent deployment using he novel UCSEMS was attempted in seven patients. Technical success was obtained in all patients. Mean procedure time was 33.3 minutes (range, 27 to 43). Clinical success was obtained in six patients. Median stent patency was 109 days (range, 48 – 160 days).
In conclusion, the hybrid metal stent placement technique appears to be useful using the new UCSEMS because of its fine-gauge stent delivery system.
Background
Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the ...NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment.
Methods
In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed.
Results
Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naïve patients (
p
= 0.008) with HCV genotype except 3 (genotype 1 vs. 3,
p
= 2.68 × 10
–5
; genotype 2 vs. 3,
p
= 3.28 × 10
–5
) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1–3 (99.1% 1209/1220) and chronic kidney disease (CKD) stage 4–5 (98.9% 188/190) patients, or between cirrhotic (99.0% 398/402) and non-cirrhotic (99.1% 999/1008) patients. Multiple logistic regression analysis revealed that genotype 3 OR 33.404, 95% CI (7.512–148.550),
p
value (
p
= 4.06 × 10
–5
) and past experience of IFN-free DAAs OR 3.977, 95% CI (1.153–13.725),
p
value (
p
= 0.029) were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4–5 (41.6% 79/190) than CKD stage 1–3 (26.1% 319/1220) patients (
p
= 2.00 × 10
–5
). AEs were also significantly higher in cirrhotic (38.6% 155/402) than in non-cirrhotic (24.1% 243/1008) (
p
= 2.91 × 10
–18
) patients.
Conclusions
G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.
Currently, percutaneous interventions are essential for diagnosis and treatment of liver diseases. The most frequent complication of percutaneous interventions is intraperitoneal hemorrhage. ...Recently, the number of patients with liver diseases on antithrombotics has been increasing. This retrospective cohort study aimed to evaluate the risk factors for intraperitoneal hemorrhage in patients after percutaneous interventions for liver diseases. This study included 1025 patients who underwent percutaneous interventions for liver diseases from April 2015 to March 2020. All interventions were performed using an ultrasound-guided approach. The influence of antithrombotic drug administration in patients, who underwent percutaneous interventions according to the guidelines for the American Association for the Study of Liver Disease, was evaluated. Intraperitoneal hemorrhage after percutaneous interventions was detected by computed tomography. Intraperitoneal hemorrhage occurred in nine patients (0.88%); however, these adverse events were not severe. We compared clinical characteristics between the patients with and without intraperitoneal hemorrhage. Although, there was no difference based on the administration of antithrombotics (p = 0.1961), seven of nine patients who showed intraperitoneal hemorrhage received percutaneous treatments (radio frequency ablation or microwave ablation). Therefore, we divided patients who underwent treatments and liver biopsy and then investigated the influence of antithrombotics on the intraperitoneal hemorrhage. After propensity score matching in each patient group, the administration of antithrombotics was not identified as a risk factor for hemorrhage in patients who underwent interventional treatments and patients who underwent liver biopsy. When the antithrombotics were discontinued, according to the guidelines, it may not increase the risk factor for hemorrhage in patients of liver disease who underwent percutaneous interventions.
Background:
Recently, endoscopic ultrasound-guided gall bladder drainage (EUS-GBD) has been reported using a self-expandable metallic stent. To prevent stent migration and food flowing into the ...common bile duct through the cystic duct, we perform a novel EUS-guided cholecystoduodenostomy.
The aim of our study was to evaluate the safety and feasibility of EUS-guided cholecystoduodenostomy with an anti-stent migration and anti-food impaction system.
Methods:
A total of 16 consecutive patients who underwent EUS-guided cholecystoduodenostomy for acute cholecystitis were included in this study.
Results:
Technical and clinical success was obtained in all patients. The median procedure time was 26.9 min (range 19–42 min). Median follow-up time was 181.5 days (range 18–604 days), and in this time, recurrence of acute cholecystitis was not seen in all patients. Adverse events such as stent migration and cholangitis were not seen in any patients, although pneumoperitoneum was seen in one patient.
Conclusion:
Our technique may be favorable and effective for the prevention of adverse events on EUS-GBD.
Hepatectomy is currently recommended as the most reliable treatment for colorectal liver metastases. However, the association between the choice of treatment for recurrence and the timing of ...recurrence remains controversial.
Two-hundred ninety-five patients who underwent hepatectomy were retrospectively analyzed for the risk factors and the outcomes for early recurrence within 6 months. The remnant liver volumes (RLVs) and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after the operation.
Early recurrence developed in 88/295 patients (29.8%). Colorectal cancer lymph node metastasis, synchronous liver metastasis, and multiple liver metastases were independent risk factors for the occurrence of early recurrence (p < 0.001, 0.032, and 0.019, respectively). Patients with early recurrence had a poorer prognosis than did patients who developed later recurrence (p < 0.001). Patients who underwent surgery or other local treatment had better outcomes. The changes in RLV and laboratory data after postoperative month 2 were not significantly different between the 2 groups.
Patients with early recurrence within 6 months had a poorer prognosis than did patients who developed later recurrence. However, patients who underwent repeat hepatectomy for recurrence had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.
Aim
To investigate the possible correlation between the development of adverse events (AEs) and prognosis in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus ...bevacizumab (Atez/Bev).
Methods
A total of 286 patients with unresectable HCC treated with Atez/Bev as first‐line systematic therapy were included.
Results
Regarding treatment‐related AEs, decreased appetite of any grade, proteinuria of any grade, and fatigue of any grade were found with a frequency of ≥20%. Multivariate analysis adjusted for immune‐related liver injury, immune‐related endocrine dysfunction, proteinuria, fatigue, decreased appetite, hypertension, sex, age, Eastern Cooperative Oncology Group performance status, HCC etiology, HCC stage, Child–Pugh score, and α‐fetoprotein showed that hypertension of any grade (hazard ratio HR, 0.527; 95% confidence interval CI, 0.326–0.854; p = 0.009) and α‐fetoprotein ≥100 ng/ml (HR, 1.642; 95% CI, 1.111–2.427; p = 0.013) were independently associated with progression‐free survival. Multivariate analysis adjusted for the same AEs showed that fatigue (HR, 2.354; 95% CI, 1.299–4.510; p = 0.010) was independently associated with overall survival. Median progression‐free survival was 6.5 months (95% CI, 5.2–8.1) in patients without hypertension of any grade and 12.6 months (95% CI, 6.7–not available) in patients with hypertension of any grade (p = 0.035). The overall survival was significantly shorter in patients in whom treatment‐related fatigue of any grade was observed (p < 0.001). Regarding response rates, the disease control rate of patients who developed treatment‐related hypertension (94.2%) was significantly higher than those who did not (79.1%) (p = 0.009).
Conclusions
Treatment‐related hypertension is associated with good outcomes in patients with HCC treated with Atez/Bev.
Treatment‐related decreased appetite, proteinuria, and fatigue were found with a frequency of =20% during atezolizumab plus bevacizumab therapy for hepatocellular carcinoma. Treatment‐related hypertension was associated with good outcomes in patients treated with atezolizumab plus bevacizumab. Treatment‐related fatigue was associated with poor outcome in patients treated with atezolizumab plus bevacizumab.
Background:
Few reports have described endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) for biliary lesions. In addition, adverse events were not completely examined in previous ...reports, due to the inclusion of cases in which biliary stents had already been placed. The present study aimed to investigate the diagnostic yield and adverse events of EUS-FNA for biliary lesions as the first-line diagnostic modality for consecutive prospectively registered patients.
Methods:
Inclusion criteria were as follows: (1) patients with suspected cholangiocarcinoma (CCA) based on computed tomography or other imaging modalities; (2) patients who had not previously undergone endoscopic retrograde cholangiopancreatography or EUS-FNA; (3) absence of surgically altered anatomy, such as Roux-en-Y anastomosis or duodenal obstruction caused by tumor invasion, through which an endoscope could not pass; and (4) provision of written informed consent to all procedures associated with the study.
Results:
A total of 47 consecutive patients with suspected CCA were registered to this study. Sensitivity and accuracy were 89% and 87%, respectively. On multivariate analysis, puncture site was the only factor associated with reduced diagnostic yield (hazard ration, 6.879; 95% confidence interval, 1.172–40.374; P = 0.033). Remarkably, no adverse events such as bleeding or bile leakage were associated with EUS-FNA in any of the 47 patients.
Conclusions:
Our results suggest that EUS-FNA can be safely performed for biliary disease without biliary stenting. Furthermore, this procedure may warrant use as the first-line diagnostic method, although our results need to be validated in future prospective studies.
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