PIVKA­II is associated with liver function, bone metabolism, and muscle function in patients with liver disease.

Protein induced by vitamin K (VK) absence-II (PIVKA-II) is a sensitive marker for diagnosing hepatoma but is occasionally detected in patients without hepatoma Here, the clinical significance of serum PIVKA-II levels in patients who were not administered warfarin and did not have hepatoma or liver disease were evaluated. As VK is related to muscle and bone metabolism, PIVKA-II and clinical factors related to bone and muscle were compared. A total of 441 patients with various liver diseases were evaluated. Of these, 236 patients were female. Clinical factors and anthropometric measurements were obtained for each participant during outpatient visits. Among the clinical factors, type I procollagen N-propeptide (P1NP), a low titer of undercarboxylated osteocalcin (ucOC), and 25(OH) vitamin D (VD) were used as bone metabolic markers, and SARC-F and grip strength were used as muscle-related markers. Serum PIVKA-II levels above the upper limit were associated with Child B/C (Child-Pugh score), high titers of total P1NP, and low titers of ucOC in females, and alcohol-related liver disease and low VD in males. The titer of PIVKA-II were associated with immunoglobulin (Ig) A and prothrombin time (PT)-international normalized ratio (INR) in females, and fibrosis-4-4, IgG, total bilirubin, PT-INR, and SARC-F in males. Elevated PIVKA-II levels were associated with abnormal bone physiology in females, weak muscles in males, and severe liver disease in both sexes. Assessing PIVKA-II may assist in evaluating the clinical and bone-muscle metabolic stages in liver disease. Nutrition and supplementation with fat-soluble vitamins, including VK and VD may thus serve as a potential method to alleviate or prevent bone-muscle pathophysiology in patients with liver disease.

Respiratory support with nasal high flow without supplemental oxygen in patients undergoing endoscopic retrograde cholangiopancreatography under moderate sedation: a prospective, randomized, single-center clinical trial.

BACKGROUND: Nasal high flow (NHF) may reduce hypoxia and hypercapnia during an endoscopic retrograde cholangiopancreatography (ERCP) procedure under sedation. The authors tested a hypothesis that NHF with room air during ERCP may prevent intraoperative hypercapnia and hypoxemia. METHODS: In the prospective, open-label, single-center, clinical trial, 75 patients undergoing ERCP performed with moderate sedation were randomized to receive NHF with room air (40 to 60 L/min, n = 37) or low-flow O2 via a nasal cannula (1 to 2 L/min, n = 38) during the procedure. Transcutaneous CO2, peripheral arterial O2 saturation, a dose of administered sedative and analgesics were measured. RESULTS: The primary outcome was the incidence of marked hypercapnia during an ERCP procedure under sedation observed in 1 patient (2.7%) in the NHF group and in 7 patients (18.4%) in the LFO group; statistical significance was found in the risk difference (-15.7%, 95% CI -29.1 - -2.4, p = 0.021) but not in the risk ratio (0.15, 95% CI 0.02 - 1.13, p = 0.066). In secondary outcome analysis, the mean time-weighted total PtcCO2 was 47.2 mmHg in the NHF group and 48.2 mmHg in the LFO group, with no significant difference (-0.97, 95% CI -3.35 - 1.41, p = 0.421). The duration of hypercapnia did not differ markedly between the two groups either [median (range) in the NHF group: 7 (0 - 99); median (range) in the LFO group: 14.5 (0 - 206); p = 0.313] and the occurrence of hypoxemia during an ERCP procedure under sedation was observed in 3 patients (8.1%) in the NHF group and 2 patients (5.3%) in the LFO group, with no significant difference (p = 0.674). CONCLUSIONS: Respiratory support by NHF with room air did not reduce marked hypercapnia during ERCP under sedation relative to LFO. There was no significant difference in the occurrence of hypoxemia between the groups that may indicate an improvement of gas exchanges by NHF. TRIAL REGISTRATION: jRCTs072190021 . The full date of first registration on jRCT: August 26, 2019.

Fully covered metallic stents for anastomotic biliary strictures after living donor liver transplantation.

Objectives: Anastomotic biliary strictures (ABSs) are common complications following living donor liver transplantation (LDLT). We evaluated the feasibility of a novel removable, intraductal, fully covered, self-expandable metallic stent (FCSEMS) for the treatment of ABSs following LDLT. Methods: Nine patients with duct-to-duct ABSs that developed following LDLT were prospectively enrolled in this study. We placed a short FCSEMS with a long lasso and middle waist formation in each patient's ABS above the papilla and removed it 16 weeks later. Results: The FCSEMS placements were successful in all nine cases. Four patients experienced mild cholangitis, which was resolved with conservative treatment. Additionally, there was one case of distal migration. The FCSEMSs were successfully removed from all the patients, and the clinical success rate was 100%. Stricture recurrence occurred in one (11.1%) patient during the follow-up period. Limitations: The small number and lack of comparison with other types of FCSEMSs and plastic stents. Conclusions: Intraductal placement of FCSEMSs is useful for treating refractory ABSs after LDLT, although further studies are required with larger sample sizes.

Long-term Outcomes and Prognostic Factors of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma.

BACKGROUND/AIM: This study was conducted to determine the prognosis and risk factors for survival in patients treated with stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This retrospective study analyzed 73 patients who underwent SBRT for HCC at Nagasaki University Hospital from December 2012 to July 2019 and examined the relationship between baseline information and prognosis. The Kaplan-Meier analysis and log-rank test were used to estimate the survival rate. Cox regression analysis was performed to determine the factors associated with overall survival (OS) after SBRT. RESULTS: The 1- and 2-year local control rates were 98.6% and 89.9%, respectively. Survival rates at 1, 3, and 5 years were 94.5%, 63.9%, and 45.5%, respectively. In the univariate analysis, baseline modified albumin-bilirubin grade (mALBI grade) [2b/3, hazard ratio (HR)=2.762, p=0.001], tumor size (≥2 cm, HR=2.479, p=0.003), and Barcelona Clinic Liver Cancer stage (BCLC) (B/C, HR=3.284, p<0.001) were significantly associated with poor prognosis. In multivariate analysis, baseline mALBI grade (2b/3, HR=2.283, p=0.009) and BCLC stage (B/C, HR=2.330, p=0.013) were significantly associated with poor prognosis. Only three patients (4.1%) developed grade 3 adverse events related to SBRT. CONCLUSION: SBRT is effective and safe in patients with HCC. The baseline mALBI grade is useful for predicting patient prognosis after SBRT. Patients with an mALBI grade of 1/2a are expected to have a better prognosis than patients with an mALBI grade of 2b/3.

Evaluating the Role of Hepatobiliary Phase of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Predicting Treatment Impact of Lenvatinib and Atezolizumab plus Bevacizumab on Unresectable Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab therapy has high response rates in patients with unresectable hepatocellular carcinoma (HCC). The hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) has been reported to be useful as an imaging biomarker for detecting ß-catenin mutations. We evaluated whether the pretreatment of the hepatobiliary phase of EOB-MRI could predict the therapeutic effect of lenvatinib and atezolizumab plus bevacizumab. METHODS: This study included 68 patients (lenvatinib group (n = 33) and atezolizumab plus bevacizumab group (n = 35)). The visual assessment and relative enhancement ratio (RER) of the largest HCC lesions were evaluated using the hepatobiliary phase of EOB-MRI. RESULTS: The hyperintensity type (RER ≥ 0.9) was 18.2% in the lenvatinib group and 20.0% in the atezolizumab plus bevacizumab group. In the lenvatinib group, progression-free survival (PFS) was not different between the heterogeneous and homogenous types (p = 0.688) or between the hyperintensity and hypointensity types (p = 0.757). In the atezolizumab plus bevacizumab group, the heterogeneous type had significantly shorter PFS than the homogenous type (p = 0.007), and the hyperintensity type had significantly shorter PFS than the hypointensity type (p = 0.012). CONCLUSIONS: The hepatobiliary phase of EOB-MRI was useful for predicting the therapeutic effect of atezolizumab plus bevacizumab therapy on unresectable HCC.

Study on prevention of hypercapnia by nasal high flow in patients undergoing endoscopic retrograde cholangiopancreatography during intravenous anesthesia.

BACKGROUND: For relatively invasive upper gastrointestinal endoscopy procedures, such as an endoscopic retrograde cholangiopancreatography (ERCP), and also lower gastrointestinal endoscopy procedures, intravenous anesthesia is routinely used to reduce patient anxiety. However, with the use of intravenous anesthesia, even at mild to moderate depth of anesthesia, there is always a risk of upper airway obstruction due to a relaxation of the upper airway muscles.With the advent of nasal high flow (NHF) devices that allow humidified high flow air through the nasal cavity, can be used as a respiratory management method in the context of anesthesia. AIRVO is commonly used for patients with obstructive sleep apnea and other respiratory disorders. This device uses a mild positive pressure load (several cmH2O) that improves carbon dioxide (CO2) washout and reduces rebreathing to improve respiratory function and therefore is widely used to prevent hypoxemia and hypercapnia.This study aims to maintain upper airway patency by applying NHF with air (AIRVO) as a respiratory management method during intravenous anesthesia for patients undergoing an ERCP. In addition, this study investigates whether the use of an NHF device in this context can prevent intraoperative hypercapnia and hypoxemia. METHODS/DESIGN: This study design employed 2 groups of subjects. Both received intravenous anesthesia while undergoing an ERCP, and 1 group also used a concurrent nasal cannula NHF device. Here we examine if the use of an NHF device during intravenous anesthesia can prevent hypoxemia and hypercapnia, which could translate to improved anesthesia management.Efficacy endpoints were assessed using a transcutaneous CO2 monitor (TCM). This device measured the changes in CO2 concentration during treatment. Transcutaneous CO2 (PtcCO2) concentrations of 60 mm Hg or more (PaCO2 > 55 mm Hg) were considered marked hypercapnia. PtcCO2 concentrations of 50 to 60 mm Hg or more (equivalent to PaCO2 > 45 mm Hg) were considered moderate hypercapnia.Furthermore, the incidence of hypoxemia with a transcutaneous oxygen saturation value of 90% or less, and whether the use of NHF was effective in preventing this adverse clinical event were evaluated. DISCUSSION: The purpose of this study was to obtain evidence for the utility of NHF as a potential therapeutic device for patients undergoing an ERCP under sedation, assessed by determining if the incidence rates of hypercapnia and hypoxemia decreased in the NHF device group, compared to the control group that did not use this device. TRIAL REGISTRATION: The study was registered in the jRCTs 072190021.URL https://jrct.niph.go.jp/en-latest-detail/jRCTs072190021.

Rapid Increase in Serum Low-Density Lipoprotein Cholesterol Concentration during Hepatitis C Interferon-Free Treatment.

BACKGROUND & AIM: We performed lipid analyses at the early period of therapy in patients with chronic hepatitis C who underwent interferon (IFN)-free direct-acting antiviral (DAA) treatment, and we attempted to identify the factors that contributed to a rapid increase in the patients' serum low-density lipoprotein cholesterol (LDL-C) concentration. METHODS: We retrospectively analyzed the cases of 100 consecutive patients with HCV infection treated at the National Hospital Organization Nagasaki Medical Center: 24 patients underwent daclatasvir (DCV) and asunaprevir (ASV) combination therapy (DCV/ASV) for 24 weeks, and the other 76 patients underwent ledipasvir and sofosbuvir combination therapy (LDV/SOF) for 12 weeks. ΔLDL-C was defined as the changed in LDL-C level at 28 days from the start of therapy. To determine whether ΔLDL-C was associated with several kinds of factors including viral kinetics, we performed a stepwise multiple linear regression analysis. RESULTS: The LDL-C levels in patients treated with LDV/SOF were markedly and significantly elevated (87.45 to 122.5 mg/dl; p<10-10) compared to those in the DCV/ASV-treated patients (80.15 to 87.8 mg/dl; p = 0.0056). The median levels of ΔLDL-C in the LDV/SOF and DCV/ASV groups were 33.2 and 13.1, respectively. LDV/SOF combination therapy as an IFN-free regimen (p<0.001) and ΔHCV core antigen (0-1 day drop) (p<0.044) were identified as independent factors that were closely related to the ΔLDL-C. CONCLUSIONS: A rapid increase in the serum LDL-C concentration during the IFN-free treatment of hepatitis C was associated with the type of HCV therapy and a decline of HCV core protein.