Esophageal varices as an independent predictor of fatal outcomes after balloon-occluded retrograde transvenous obliteration in patients with hepatic encephalopathy.

BACKGROUND: To evaluate esophageal varices (EVs) as predictors of poor prognosis with low tolerability after balloon-occluded retrograde transvenous obliteration (BRTO) in patients with overt hepatic encephalopathy (HE). METHODS: This study retrospectively enrolled 107 patients who underwent BRTO for uncontrollable overt HE. The enrolled patients were divided into two groups based on the presence of EVs using propensity matching. The present study assessed the technical success rate and safety of BRTO in both the groups. Further, the event-free survival, HE-free survival, and the overall survival (OS) were compared between the two groups. Event-free survival was defined as the time period during which the patients did not developed complications related to portal hypertension, including EVs, hepatic ascites, and portal vein thrombosis. RESULTS: After propensity matching, the EV and non-EV groups had 37 and 36 patients, respectively. Only one patient experienced an unsuccessful procedure in the EV group. Procedure-related adverse events in the EV group and non-EV group occurred in 11 and 7 patients, respectively. (P=0.417) The event free survival after BRTO in the EV and non-EV group were 1,283 (95% CI: 798 - 1,767) days and 2,257 (1,722-2,792) days, respectively. Event free survival was significantly worse in the EV group than in the non-EV group (P=0.014). Furthermore, the EV group experienced worse OS than the non-EV group (P=0.001 and P<0.001, respectively). CONCLUSIONS: The presence of EVs could potentially be associated with a higher risk of adverse outcomes or mortality after BRTO treatment in individuals with HE.

[A case of advanced hepatocellular carcinoma wherein readministration was made possible due to successful transcatheter arterial embolization for intratumoral hemorrhage during Lenvatinib administration].

The subject was a man in his late 70s who was seeing a family physician for diabetes and dyslipidemia on an outpatient basis. A routine medical checkup revealed liver dysfunction, prompting an abdominal ultrasound. As a result, a large hepatic tumor was discovered, prompting a thorough examination. The patient was diagnosed with hepatocellular carcinoma and multiple liver metastases, as well as tumor shadows that could indicate pulmonary metastases, after a thorough examination at our hospital. Due to the patient not having viral hepatitis or any drinking history and had formerly been confirmed as having fatty liver, a diagnosis of cirrhosis and hepatocellular carcinoma caused by NASH (nonalcoholic steatohepatitis) was given. A Child-Pugh score of 5 (A) and modified albumin-bilirubin (mALBI) grade 2 were used to maintain liver function. As a result, a 12-mg/day Lenvatinib treatment regimen was initiated. From the 6th day of the start of oral administration, the patient developed right hypochondralgia and loss of appetite. Blood samples showed increased levels of liver enzymes and inflammatory reaction, requiring hospitalization for closer examination. Intratumoral hemorrhage from hepatocellular carcinoma was discovered by dynamic CT scans. The patient's general condition was stable, and an angiogram was performed on the 3rd day of admission. As a result, persistent extravasation was discovered, necessitating transcatheter arterial embolization (TAE) treatment of the lesion for tumor vessel embolization. Thereafter, transient deterioration of the liver function occurred but an immediate improvement was seen. The patient was discharged without a recurrence of hemorrhage. An outpatient follow-up was performed, with blood test results indicating that liver function was maintained with a Child-Pugh score of 6 (A), and a dynamic CT showing that intratumoral hemorrhage was under control, allowing for readministration. Readministration of Lenvatinib was started at 4mg/day, one level lower, because the patient's body weight had dropped below 60kg. There are few reports on Lenvatinib-induced intratumoral hemorrhage, and this is a unique case worthy of reporting, with previous literary references, in which the entire process from intratumoral hemorrhage to readministration of Lenvatinib after embolization treatment has been documented.

Clinical investigation of esophageal injury from cryoballoon ablation of persistent atrial fibrillation.

BACKGROUND: The cryoballoon (CB) can be utilized for extra pulmonary vein (PV) ablation such as for a left atrial (LA) posterior wall (LAPW) isolation. However, scrutiny of the esophageal injuries during the LAPW isolation has never been performed. We sought to thoroughly investigate the esophageal lesions (ELs) and gastric hypomotility (GH) caused by an LAPW isolation using a CB. METHODS: A total of 101 persistent atrial fibrillation patients who underwent an LAPW isolation using a CB were enrolled. The CB was applied on the roof and bottom area of the LAPW after a PV isolation. The luminal esophageal temperature (LET) was monitored by a thermistor probe during the CB applications. When the LET reached 15°C, the freezing application was prematurely interrupted. Esophagogastroscopy was performed on the next day following the ablation. RESULTS: All PVs were successfully isolated in all patients. A successful LAPW isolation solely with CB ablation was performed in 72 (71.3%) patients. Cryofreezing applications were prematurely interrupted due to low LETs in 49 (48.5%) patients predominantly during the LA bottom line ablation. ELs and GH were observed in 11 (10.9%) and 16 patients (15.8%), respectively. The nadir LET tended to be lower in patients with ELs and GH than in those without (ELs: 14.8 ± 4.5°C vs 17.4 ± 6.0°C, P = 0.17; GH: 15.5 ± 4.5°C vs 17.5 ± 6.1°C, P = 0.23, respectively). CONCLUSIONS: Esophageal complications such as ELs and GH occur during the LAPW isolation with a CB. There was no reliable predictor of those adverse events.

Efficacy of daclatasvir plus asunaprevir in patients with hepatitis C virus infection undergoing and not undergoing hemodialysis.

AIM: To evaluate the virologic responses and clinical course of daclatasvir plus asunaprevir treatment in non-hemodialysis (non-HD) and hemodialysis (HD) patients infected with genotype 1 hepatitis C virus (HCV). METHODS: A total of 1113 non-HD patients and 67 HD patients were assessed. To evaluate pretreatment factors contributing to sustained virological response at 12 weeks (SVR12), univariate and multivariate analyses were carried out. To adjust for differences in patient background, propensity score matching was undertaken. RESULTS: The overall SVR12 rates were 91.6% in non-HD patients and 95.5% in HD patients. Compared with non-HD patients, HD patients were younger, were more likely to be male, were less likely to have received interferon-based pretreatment, had a lower viral load, and had lower levels of alanine transaminase, hemoglobin, and α-fetoprotein. Multivariate analysis revealed that viral load, α-fetoprotein, L31 substitution negative, and Y93 substitution negative were independent predictive factors for SVR12 in non-HD patients. The proportion of patients with undetectable HCV-RNA during the initial 4 weeks was significantly higher in HD patients than in non-HD patients. The SVR12 rate was clearly higher in HD patients than in non-HD patients, although the difference was not statistically significant. After propensity score matching to adjust for viral load, α-fetoprotein, L31 substitution, and Y93 substitution, these trends disappeared. CONCLUSIONS: For treatment of HCV genotype 1 infection, daclatasvir plus asunaprevir is useful not only in non-HD patients but also in HD patients. Viral load, α-fetoprotein levels, L31 substitution, and Y93 substitution influence treatment course and outcome.

COVID-19 severity is associated with the risk of gastrointestinal bleeding.

OBJECTIVE: The association between the severity of COVID-19 and gastrointestinal (GI) bleeding is unknown. This study aimed to determine whether the severity of COVID-19 is a risk factor for GI bleeding. DESIGN: A multicentre, retrospective cohort study was conducted on hospitalised patients with COVID-19 between January 2020 and December 2021. The severity of COVID-19 was classified according to the National Institute of Health severity classification. The primary outcome was the occurrence of GI bleeding during hospitalisation. The main analysis compared the relationship between the severity of COVID-19 and the occurrence of GI bleeding. Multivariable logistic regression analysis was performed to evaluate the association between the severity of COVID-19 and the occurrence of GI bleeding. RESULTS: 12 044 patients were included. 4165 (34.6%) and 1257 (10.4%) patients had severe and critical COVID-19, respectively, and 55 (0.5%) experienced GI bleeding. Multivariable analysis showed that patients with severe COVID-19 had a significantly higher risk of GI bleeding than patients with non-severe COVID-19 (OR: 3.013, 95% CI: 1.222 to 7.427). Patients with critical COVID-19 also had a significantly higher risk of GI bleeding (OR: 15.632, 95% CI: 6.581 to 37.130). Patients with severe COVID-19 had a significantly increased risk of lower GI bleeding (OR: 10.349, 95% CI: 1.253 to 85.463), but the risk of upper GI bleeding was unchanged (OR: 1.875, 95% CI: 0.658 to 5.342). CONCLUSION: The severity of COVID-19 is associated with GI bleeding, and especially lower GI bleeding was associated with the severity of COVID-19. Patients with severe or critical COVID-19 should be treated with caution as they are at higher risk for GI bleeding.

Complex Pattern of Resistance-Associated Substitutions of Hepatitis C Virus after Daclatasvir/Asunaprevir Treatment Failure.

BACKGROUNDS & AIMS: We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection. METHODS: This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment. RASs in NS5A and NS3 were determined by population sequencing. RESULTS: The frequency of signature RASs at position D168 of NS3 was 68%, and at positions L31 and Y93 of NS5A was 79 and 76%, respectively. The frequency of dual signature RASs in NS5A (L31-RAS and Y93-RAS) was 63%. RASs at L28, R30, P32, Q54, P58, and A92 in addition to dual signature RAS were detected in 5, 5, 1, 22, 2, and 0 patients, respectively. In total, triple, quadruple, and quintuple RASs in combination with dual signature RAS were detected in 35, 10, and 1.5% patients, respectively. These RASs were detected in patients without baseline RASs or who prematurely discontinued therapy. Co-existence of D168 RAS in NS3 and L31 and/or Y93 RAS in NS5A was observed in 62% of patients. CONCLUSION: Treatment-emergent RASs after failure with DCV/ASV combination therapy are highly complex in more than 50% of the patients. The identification of complex RAS patterns, which may indicate high levels of resistance to NS5A inhibitors, highlights the need for RAS sequencing when considering re-treatment with regimens including NS5A inhibitors.

Acute vigorous exercise primes enhanced NO release in human platelets.

Activation of platelets by acute vigorous exercise has been demonstrated by various parameters, including an increase in agonist-induced platelet [Ca2+]i levels. However, direct evidence is lacking regarding how acute exercise affects platelet-derived NO. Twenty-three healthy male non-smokers (21-59 years) underwent a symptom-limited treadmill exercise test. Washed platelets were prepared from blood samples obtained before and immediately after exercise. All subjects completed at least Bruce stage 2 and were each negative for ischemia. With a low dose (2 microg/ml) of collagen, NO release from washed platelets, detected by the NO-selective microelectrode, was significantly increased after exercise (pmols/10(8) platelets, before: 0.64+/-0.11, after: 1.03+/-0.18; P<0.005) without changes in aggregation ability. This enhanced NO release was accompanied by increased platelet [Ca2+]i levels (before: 232+/-25, after: 296+/-37; P<0.01). With a high dose (5 or 10 microg/ml) of collagen, NO release and aggregation were both modestly, but significantly, enhanced after exercise. The exercise-induced enhancement of platelet NO release in response to collagen was also suggested by increase in platelet cyclic guanosine monophosphate accumulation and augmenting effect of N(G)-monomethyl-L-arginine on platelet aggregation. In summary, acute strenuous exercise primes enhanced NO release and may play a protective role against exercise-induced activation of platelets in normal subjects.