Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy.

AIM: A recombinant monoclonal antibody against the hepatitis B surface antigen glycan isomer (HBsAgGi) was newly developed using the O-glycosylated PreS2 peptide in M-HBsAg of hepatitis B virus (HBV) genotype C. However, the association between HBsAgGi and the development of hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy remains unknown. METHODS: A total of 112 HBV genotype C-infected patients who were treated with NA were included in this study. We assessed the association between HBV markers, including HBsAgGi and other conventional markers, and the development of HCC during NA therapy. RESULTS: Ten patients developed HCC during the follow-up period. Of the HBV markers, HBsAg (≤3.53 log IU/mL; p = 0.047), HBsAgGi/HBsAg ratio (≥1.10; p = 0.035), and HBV DNA (≤6.3 log copies/mL; p = 0.012) at baseline and HBsAg (≤3.19 log IU/mL; p = 0.033) and HBsAgGi/HBsAg ratio (≥1.09; p = 0.003) at 48 weeks after NA therapy were significantly associated with the development of HCC according to the log rank test. In contrast, no significant association was observed between HBsAgGi and the development of HCC. Multivariate analysis revealed that a platelet count at baseline ≤88 × 103/mm3 (p = 0.026; hazard ratio [HR], 10.577) and an HBsAgGi/HBsAg ratio at 48 weeks after NA therapy ≥1.09 (p = 0.040; HR, 10.099) were independently and significantly associated with the development of HCC. CONCLUSIONS: Our findings suggest that a combination of on-treatment HBsAgGi and HBsAg predicts the development of HCC during NA therapy.

Risk factors for liver-related and non-liver-related mortality following a sustained virological response after direct-acting antiviral treatment for hepatitis C virus infection in a real-world cohort.

A direct-acting antiviral (DAA)-induced sustained virological response (SVR) reduces the risk of mortality. However, the risk factors associated with liver-related and non-liver-related mortality following a SVR after DAA treatment are unclear. We assessed the incidence and risk factors of liver-related and non-liver-related mortality in 1180 patients who achieved a SVR after DAA treatment. During the follow-up period after DAA treatment (median duration, 1099 [range: 84-2345] days), 53 (4.5%) patients died: 15 due to liver-related mortality, 25 due to non-liver-related mortality and 13 due to unknown causes. The all-cause, liver-related and non-liver-related mortality rates were 14.9, 4.2 and 7.0/1000 person-years, respectively. In a multivariate analysis, the development of hepatocellular carcinoma (HCC) after DAA treatment (p = .009; hazard ratio [HR], 31.484), an estimated glomerular filtration rate (eGFR) at baseline ≤61.68 ml/min/1.73 m2 (p = .015; HR, 6.607), and an α-fetoprotein level post-treatment ≥7.6 ng/ml (p = .041; HR, 18.490) were significantly associated with liver-related mortality. Furthermore, eGFR ≤67.94 ml/min/1.73 m2 at baseline (p = .012; HR, 3.407) and albumin-bilirubin (ALBI) grade ≥ 2 at SVR (p = .024; HR, 3.449) were significantly associated with non-liver-related mortality. Early diagnosis and therapeutic interventions for HCC development after DAA treatment are important to reduce liver-related mortality. The ALBI grade, which reflects the hepatic functional reserve, is a useful predictor of non-liver-related mortality after a SVR induced by DAA treatment. Furthermore, the renal dysfunction caused by metabolic syndrome may affect prognosis even after eliminating hepatitis C virus.

Direct-acting antivirals reduce the risk of tumour progression of hepatocellular carcinoma after curative treatment.

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.

Lenvatinib-Induced Tumor-Related Hemorrhages in Patients with Large Hepatocellular Carcinomas.

INTRODUCTION: Lenvatinib has been approved as a systemic therapy for patients with unresectable hepatocellular carcinoma (HCC). We recently experienced lenvatinib-induced tumor-related hemorrhage in patients with HCC. The full details of tumor-related hemorrhage as a lenvatinib-related adverse event have not been elucidated. METHODS: This was a retrospective single-center study that enrolled consecutive patients treated with lenvatinib for unresectable HCC from April 2018 to February 2020. RESULTS: Sixty-eight consecutive patients were enrolled in this study. Among them, 5 cases developed intraperitoneal or intratumoral hemorrhages. The patients with hemorrhage had larger tumors (maximum tumor size, 97.5 ± 46.4 and 38.2 ± 28.8 mm, respectively; p = 0.009) than the patients without hemorrhage. The dosing period of lenvatinib (median, 3 and 93 days, respectively; p < 0.001) and the survival time from initial administration of lenvatinib (median, 77 and 495 days, respectively; p < 0.001) of the patients with hemorrhage were shorter than those of the patients without hemorrhage. Especially, in 4 cases with large HCCs (maximum tumor diameter was >90 mm), tumor hemorrhage with vascular lake-like phenomenon was evident, although most tumor blood flow was suppressed. DISCUSSION/CONCLUSION: It becomes clear that lenvatinib treatment brings about tumor-related hemorrhages despite rapid suppression of tumor blood flow. We speculate that lenvatinib quickly blocks the feeding circulation, resulting in tumor hemorrhage by necrosis. Clinicians should pay careful attention to the development of life-threatening hemorrhages when treating large HCCs with lenvatinib.

Serum Mac-2-binding protein glycosylation isomer predicts esophagogastric varices in cirrhotic patients with chronic hepatitis C virus infection treated with IFN-free direct-acting antiviral agent: M2BPGi levels predict varices in SVR patients.

INTRODUCTION AND OBJECTIVES: We examined whether Mac-2-binding protein glycosylation isomer (M2BPGi) levels could be a predictive marker for the presence of esophagogastric varices (EGV) in cirrhotic patients after hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs). PATIENTS AND METHODS: A total of 102 cirrhotic patients with HCV infection treated with DAAs were enrolled. Esophagogastroduodenoscopy was performed in 84 of the patients before treatment (Cohort A), in 66 after treatment (Cohort B), and in 48 at both time points (Cohort C). We examined factors associated with EGV before and after DAA treatment. RESULTS: In Cohort A, M2BPGi levels and liver stiffness were significantly higher in the EGV-positive group than the EGV-negative group (p=0.034, and p=0.042, respectively). The proportion of EGV-positive patients with before-treatment levels of M2BPGi ≧ 7.3 C.O.I. was significantly higher than in patients with M2BPGi levels<7.3 C.O.I. (p=0.015). In Cohort B, M2BPGi levels were significantly higher in the EGV-positive group than EGV-negative group (p=0.003). The proportion of EGV-positive patients with after-treatment levels of M2BPGi ≧ 3.4 C.O.I. was significantly higher than in patients with M2BPGi levels<3.4C.O.I. (p=0.001). In Cohort C, M2BPGi levels decreased during DAA treatment regardless of EGV development, but there was no significant difference in the reduction of M2BPGi among the EGV-improvement, EGV-invariant, and EGV-exacerbation groups (p=0.659). CONCLUSIONS: M2BPGi levels may be a novel serum marker for the presence of EGV before and after DAA treatment.

Evaluation of ablation of thyroid remnants with 1850 MBq iodine-131 in 67 patients with thyroid cancer.

BACKGROUND: Radioiodine remnant ablation (RRA) is used to destroy residual normal thyroid tissue after total thyroidectomy in differentiated thyroid carcinoma (DTC) patients. As 1850-MBq RRA is routinely performed at our facility, we evaluated the outcomes. METHODS: Sixty-seven DTC patients without macroscopic residual lesions after total thyroidectomy were evaluated. Thyroglobulin (Tg) was measured 2-3 months before RRA with thyroxin administration (pretreatment); just before ablation after a 3-week iodine intake restriction with thyroxin withdrawal (THW) (N.=16) or recombinant human thyroid-stimulating hormone (rhTSH) stimulation (N.=51); and 3 months after RRA, after a 2-week iodine intake restriction and 3-week THW (N.=57) or rhTSH stimulation (N.=10). All patients received 131I (1850 MBq) treatment followed by 131I scintigraphy about 8 days later (8.18±0.91) and 131I scintigraphy (185 MBq) after the dosage 24 hours later 3months after RRA. Initial RRA goal was defined as negatively visible uptake in 131I thyroid bed (VUT) and a Tg level of <2 ng/mL 3 months after RRA. RESULTS: Rest 60 patients whose TSH levels were below 0.5 µIU/mL of all 67 patients were evaluated. Negatively VUT on 3 months after RRA was shown in 56 out of 60 patients (93.3%). Initial RRA goal was achieved in 21 (42.0%) of 50 patients, excluding 3 patients whose Tg levels 3 months after RRA were not measured and 7 patients with anti-Tg antibodies. Pretreatment Tg levels (P=0.0003) was significant predictive factor for Initial RRA goal on multivariate logistic regression analysis. CONCLUSIONS: RRA with 1850 MBq is effective by visual diagnosis, about 40% of all intermediate or high-risk DTC patients achieved initial RRA goals by both visual and Tg levels diagnosis.

[Imaging of hyperparathyroidism-Ultrasonography and 99mTc-MIBI scintigraphy-].

Treatments for primary hyperparathyroidism due to adenoma, hyperplasia and carcinoma and secondary hyperparathyroidism are mainly surgical resections of them. Accurate imaging diagnoses of the existences and the regions are very important for reductions of invasiveness. We describe ultrasonography and (99m)Tc-MIBI scintigraphy of hyperparathyroidism. We explain an advantage, a disadvantage and diagnosability of these modalities. We mention utilities of SPECT/CT, too. We show echogram and (99m)Tc-MIBI scintigraphy images about 3 cases of hyperparathyroidism.

Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension.

The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor-ß, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism.

Role of per-rectal portal scintigraphy in long-term follow-up of congenital portosystemic shunt.

BACKGROUND: Congenital portosystemic shunt (CPSS) has the potential to cause hepatic encephalopathy and thus needs long-term follow-up, but an effective follow-up method has not yet been established. We aimed to evaluate the importance of per-rectal portal scintigraphy (PRPS) for long-term follow-up of CPSS. METHODS: We retrospectively examined shunt severity time course in patients (median: 9.6 y, range: 5.2-16.6 y) with intrahepatic (n = 3) or extrahepatic (n = 3) CPSS by using blood tests, ultrasonography or computed tomography, and PRPS. Per-rectal portal shunt index (cutoff: 10%) was calculated by PRPS. RESULTS: PRPS demonstrated that the initial shunt index was reduced in all intrahepatic cases (from 39.7 ± 9.8% (mean ± SD) to 14.6 ± 4.7%) and all extrahepatic cases (from 46.2 ± 10.9 to 27.5 ± 12.6%) during the follow-up period. However, ultrasonography and computed tomography disclosed different shunt diameter time courses between intrahepatic and extrahepatic CPSSs. Initial shunt diameter (5.8 ± 3.5 mm) reduced to 2.0 ± 0.3 mm in intrahepatic cases, but the initial diameter (6.3 ± 0.7 mm) increased to 10.6 ± 1.0 mm in extrahepatic cases. All patients had elevated serum total bile acid or ammonia levels at initial screening, but these blood parameters were insufficient to assess shunt severity because the values fluctuate. CONCLUSION: PRPS can track changes in the shunt severity of CPSS and is more reliable than ultrasonography and computed tomography in patients with extrahepatic CPSS.

Positioning of 18F-fluorodeoxyglucose-positron emission tomography imaging in the management algorithm of hepatocellular carcinoma.

BACKGROUND AND AIM: (18) F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) may detect primary lesions (PLs) and extrahepatic metastases (EHMs) only in advanced hepatocellular carcinoma (HCC) patients. We investigated the requirement of PET and the optimal timing of PET scanning for accurate staging and treatment planning. METHODS: We conducted a retrospective investigation of 64 HCC patients who underwent PET (median age, 74 years; male/female, 41/23; etiology, 46 hepatitis C virus/4 hepatitis B virus/4 alcoholic/10 others). To determine the best timing for PET examinations, we analyzed PET result-based recommended treatment changes and characteristics of patients with FDG-avid PLs or EHMs. RESULTS: FDG-avid PLs were detected by PET in 22 patients (34%): 18 with hypervascular PL, 11 with serum α-fetoprotein levels ≥ 200 ng/mL, and 11 beyond Milan criteria. EHMs were detected in 21 patients (33%: lymph nodes, 8; lung, 5; abdominal wall, 4; bone, 3; other organs, 4 [including overlapping]). Recommended treatments changed for 16 patients (25%) because of Barcelona Clinic Liver Cancer stage increases based on PET scanning. In multivariate analyses, serum α-fetoprotein levels ≥ 200 ng/mL and beyond Milan criteria were independent factors for FDG-avid PLs and a maximum standardized uptake value (SUVmax) of PLs of ≥ 4.0 was an independent factor for FDG-avid EHMs (P = 0.002, 0.008, and 0.045, respectively). CONCLUSIONS: PET allows detection of HCC spread in patients with elevated serum α-fetoprotein levels or those beyond Milan criteria and detects EHMs in patients with PLs with high SUVmax values. Optimally timed PET scans can complement conventional imaging for accurate staging and treatment strategy determination.

Diagnostic ability of (99m)Tc-HSA-DTPA scintigraphy in combination with SPECT/CT for gastrointestinal bleeding.

PURPOSE: Gastrointestinal (GI) bleeding scintigraphy in combination with single-photon emission computed tomography/computed tomography (SPECT/CT) remains to be studied in detail. This study aimed to examine the diagnostic ability of this tool. METHODS: GI bleeding scintigraphy using (99m)Tc-human serum albumin-diethylenetriaminepentaacetic acid was performed for 38 patients with suspected GI bleeding. Twenty-four patients were diagnosed using planar images alone (planar group) and 14 patients were diagnosed using planar images and additional SPECT/CT images (planar + SPECT/CT group). The diagnostic ability of each method was analyzed. RESULTS: GI bleeding was observed in 20 of the 38 patients. For the existence of GI bleeding, planar images alone showed a sensitivity of 70%, specificity of 93%, positive predictive value (PPV) of 88%, negative predictive value (NPV) of 81%, and an overall accuracy of 83%, whereas planar images + SPECT/CT showed a sensitivity of 100%, specificity of 75%, PPV of 91%, NPV of 100%, and an overall accuracy of 93%. The source of bleeding was accurately diagnosed in 50% in the planar group and 78% in the planar + SPECT/CT group. In the planar + SPECT/CT group, 44% of the evaluable patients showed correct localization of the source of GI bleeding by additional SPECT/CT images, although planar images only showed incorrect localization. CONCLUSION: GI bleeding scintigraphy in combination with SPECT/CT is a noninvasive and useful tool for the examination of GI bleeding.

Recent Advances in the Pathogenesis and Clinical Evaluation of Portal Hypertension in Chronic Liver Disease.

In chronic liver disease, hepatic stellate cell activation and degeneration of liver sinusoidal endothelial cells lead to structural changes, which are secondary to fibrosis and the presence of regenerative nodules in the sinusoids, and to functional changes, which are related to vasoconstriction. The combination of such changes increases intrahepatic vascular resistance and causes portal hypertension. The subsequent increase in splanchnic and systemic hyperdynamic circulation further increases the portal blood flow, thereby exacerbating portal hypertension. In clinical practice, the hepatic venous pressure gradient is the gold-standard measure of portal hypertension; a value of ≥10 mm Hg is defined as clinically significant portal hypertension, which is severe and is associated with the risk of liver-related events. Hepatic venous pressure gradient measurement is somewhat invasive, so evidence on the utility of risk stratification by elastography and serum biomarkers is needed. The various stages of cirrhosis are associated with different outcomes. In viral hepatitis-related cirrhosis, viral suppression or elimination by nucleos(t)ide analog or direct-acting antivirals results in recompensation of liver function and portal pressure. However, careful follow-up should be continued, because some cases have residual clinically significant portal hypertension even after achieving sustained virologic response. In this study, we reviewed the current and future prospects for portal hypertension.

A case of hepatocellular carcinoma with "pseudoprogression" followed by complete response to atezolizumab plus bevacizumab.

Atezolizumab plus bevacizumab (Atezo + Bev) is the first immunotherapy for hepatocellular carcinoma (HCC), and in the current guidelines, it is positioned as the first-line chemotherapy for unresectable cases. Herein, we report a case of HCC with pseudoprogression followed by a complete response to Atezo + Bev. A 56 year-old man was diagnosed with intermediate-stage HCC, as defined by the Barcelona Clinic Liver Cancer system stage B. Computed tomography (CT) revealed multiple lesions in the liver without any extrahepatic lesions. First, he was treated with transcatheter arterial chemoembolization (TACE); however, multiple residual lesions were observed on CT scan 2 months after TACE. Therefore, treatment with Atezo + Bev was initiated 4 months after TACE. After the third administration of Atezo + Bev, a CT scan showed progressive disease in intrahepatic lesions, along with increased serum levels of tumor markers. Although TACE was planned again, Atezo + Bev was continued while the patient was waiting for hospitalization. After the fifth administration of Atezo + Bev, serum levels of tumor markers decreased to the normal range. Magnetic resonance imaging showed prominently reduced tumor size. Therefore, Atezo + Bev was continued, and after the eighth administration, the CT scan showed the disappearance of all the liver lesions, indicating a complete response. In immunotherapy, the therapeutic response can sometimes be obtained in an atypical pattern due to either an increase in tumor burden or the appearance of new lesions, called "pseudoprogression," which is rare in HCC.

Severity of Liver Fibrosis Is Associated with the Japanese Diet Pattern and Skeletal Muscle Mass in Patients with Nonalcoholic Fatty Liver Disease.

It is not fully clear as to which dietary patterns are associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in Asia. We conducted a cross-sectional study of 136 consecutively recruited patients with NAFLD (49% female, median age 60 years). Severity of liver fibrosis was assessed using the Agile 3+ score, a recently proposed system based on vibration-controlled transient elastography. Dietary status was assessed using the 12-component modified Japanese diet pattern index (mJDI12). Skeletal muscle mass was assessed by bioelectrical impedance. Factors associated with intermediate-high-risk Agile 3+ scores and skeletal muscle mass (75th percentile or higher) were analyzed by multivariable logistic regression. After adjustment for confounders, such as age and sex, the mJDI12 (OR: 0.77; 95% CI: 0.61, 0.99) and skeletal muscle mass (75th percentile or higher) (OR: 0.23; 95% CI: 0.07, 0.77) were significantly associated with intermediate-high-risk Agile 3+ scores. Soybeans and soybean foods were significantly associated with skeletal muscle mass (75th percentile or higher) (OR: 1.02; 95% CI: 1.00, 1.04). In conclusion, the Japanese diet pattern was associated with the severity of liver fibrosis in Japanese patients with NAFLD. Skeletal muscle mass was also associated with the severity of liver fibrosis, and intake of soybeans and soybean foods.

Short-term hepatocyte function and portal hypertension outcomes of sofosbuvir/velpatasvir for decompensated hepatitis C-related cirrhosis.

BACKGROUND: It is unclear whether hepatocyte function and/or portal hypertension improves if a sustained virologic response (SVR) is achieved with direct-acting antivirals in patients with decompensated hepatitis C-related cirrhosis. METHODS: We examined the safety and efficacy of a 12-week course of sofosbuvir/velpatasvir (SOF/VEL) in 20 patients with decompensated hepatitis C-related cirrhosis. We also investigated changes in the hepatocyte receptor index (LHL15) and blood clearance index (HH15) by Tc-99 m-galactosyl human serum albumin scintigraphy, liver stiffness measurement (LSM) by transient elastography, and hepatic venous pressure gradient (HVPG) in patients who achieved an SVR at 24 weeks after treatment (SVR24). RESULTS: One patient discontinued treatment because of rectal variceal hemorrhage, and 19 patients completed treatment. SVR24 was achieved in 17 patients (89%). Median LHL15 increased from 0.72 pre-treatment to 0.82 after SVR24 (p = 0.012), and median HH15 decreased from 0.82 pre-treatment to 0.76 after SVR24 (p = 0.010). The percentage of patients with LSM ≥ 20 kPa was 90% before treatment and remained at 90% after SVR24. However, the percentage with severe portal hypertension (defined as HVPG ≥ 12 mmHg) decreased from 92% pre-treatment to 58% after SVR24 (p = 0.046). Patients with a decreased HVPG from pre-treatment to after SVR24 had a smaller pre-treatment spleen volume than those with an increased HVPG (median, 252 vs. 537 mL, p = 0.028). CONCLUSION: Achieving SVR24 with SOF/VEL treatment in patients with decompensated hepatitis C-related cirrhosis can be expected to improve hepatocyte function and portal hypertension on short-term follow-up.

Effect of mosapride citrate on gastric emptying in interferon-induced gastroparesis.

BACKGROUND AND OBJECTIVES: Gastroparesis, a gastrointestinal autonomic neuropathy, is a common adverse reaction in chronic hepatitis C (CHC) patients receiving interferon therapy. Current therapeutic options are limited. We evaluated the efficacy of mosapride for IFN-induced gastroparesis. METHODS: Twenty-four consecutive CHC patients were randomly assigned to either the control group, which received pegylated interferon α-2b at 1.5 µg/kg/week and ribavirin at 600-1,000 mg/day, depending on body weight (PegIFN/RBV), or the mosapride group, which received PegIFN/RBV plus mosapride at 15 mg/person/day. The solid-phase gastric emptying half-times (T1/2) of the total, proximal, and distal stomach (scintigraphy) and digestive symptoms (questionnaire) were measured within one week before and four weeks after initiation of the assigned therapy. The test meal comprised a 200-g pancake containing Tc-99m diethylenetriamine pentaacetic acid. RESULTS: In the control group, after PegIFN/RBV initiation, a significant increase was observed in the total T1/2 (before: 84.0 ± 22.1 min versus after: 100.8 ± 28.9 min, P = 0.03), the distal T1/2 (before: 95.3 ± 32.2 min versus after: 115.3 ± 41.4 min, P = 0.03), and digestive symptom score (before: 3.2 ± 1.4 versus after: 8.1 ± 4.8, P = 0.02); proximal T1/2 change was not significant. In the mosapride group, no significant delays were observed in the total, proximal, and distal T1/2 values; the change in symptom scores was not significant. CONCLUSIONS: Mosapride improved total and distal gastric motility in IFN-induced gastroparesis, and consequently relieved symptoms.

Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment.

Soluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. Pre-treatment sPD-1 is a novel predictive biomarker for HCC development during NA treatment.