High-dose proton pump inhibitor treatment is associated with a higher mortality in cirrhotic patients: A multicentre study.

BACKGROUND: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. AIMS: This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. METHODS: We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high-dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low-dose PPI group) for each outcome. RESULTS: Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high-dose PPI group. High-dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38-2.11, p < 0.001). This result was reproducible after propensity score-matching (PSM) (aHR = 1.90, 95% CI = 1.49-2.44, p < 0.001). High-dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66-2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70-2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43-2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31-2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02-2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95-2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12-1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28-2.37, p < 0.001). CONCLUSIONS: The use of high-dose PPI was independently associated with increased risks of mortality and cirrhotic complications.

Comparison of Craniocaudal Spread of Lumbar Erector Spinae Plane Block With Two Volumes of Local Anesthetics.

BACKGROUND: The erector spinae plane block (ESPB) is a less invasive, safer, and technically easier procedure compared to the conventional neuraxial technique. Although the ESPB is a favored and easy technique compared to neuraxial block, there is no study with a large number of patients describing the exact spread level of injected local anesthetics. OBJECTIVES: The purpose of this study was to identify ESPB spread in the craniocaudal direction and the incidence of spread into the epidural space, psoas muscle, and intravascular system. STUDY DESIGN: Prospective design. SETTING: A tertiary university hospital, pain clinic. METHODS: Right- or left-sided ESPBs (170 at L4) with fluoroscopy subsequent to ultrasound guidance due to acute or subacute low back pain were included. In this study, 10 mL (ESPB 10 mL group, contrast medium 5 mL) or 20 mL (ESPB 20 mL group, contrast medium 7 mL) of a local anesthetic mixture was injected. After confirming a successful interfascial plane spreading under ultrasound guidance, the remaining local anesthetic was injected under fluoroscopic guidance. The spread level of ESPB in the craniocaudal direction and the occurrence of injectate into the epidural space or psoas muscle was assessed using the saved fluoroscopic images. These images were compared between the ESPB 10 mL and ESPB 20 mL groups. Also, the presence or absence of intravascular injection during ESPB was assessed and compared between the ESPB 10 mL and ESPB 20 mL groups. RESULTS: The ESPB 20 mL group had a more extensive caudal distribution of contrast medium than the ESPB 10 mL group. Also, the total number of lumbar vertebral segments was significantly higher in the ESPB 20 mL group than that of the ESPB 10 mL group (1.7 ± 0.4 vs 2.1 ± 0.4, P < 0.001). Among all injections performed in this study, epidural, psoas muscle, and intravascular injections occurred in 2.9%, 5.9%, and 12.9%, respectively. LIMITATIONS: Only the craniocaudal direction was evaluated without evaluating the spread pattern in the medial to lateral direction. CONCLUSION: The ESPB 20 mL group showed a more extensive distribution of contrast medium than that of the ESPB 10 mL group. Inadvertent injections into the epidural space, psoas muscle, and intravascular system were observed. Among them, intravascular system injections were found to be the most common (12.9%).

Transarterial chemoembolization as an alternative to radioembolization is associated with earlier tumor recurrence than in radioembolization-eligible patients.

Introduction: Although transarterial radioembolization (TARE) using yttrium-90 (90Y) is a treatment option for large hepatocellular carcinoma (HCC), a fraction of patients are ineligible for TARE due to high lung shunt fraction (LSF). Methods: We evaluated if treatment with transarterial chemoembolization (TACE), owing to TARE ineligibility was associated with early HCC progression. Consecutive patients with HCC who were initially TARE candidates were included. Patients with vascular invasion or metastasis were excluded. Primary endpoints were time-to-progression (TTP) and overall survival (OS). The secondary endpoint was objective response rate. Results: In total, 175 patients were included: 144 underwent TARE (TARE-eligible group) and 31 underwent TACE due to high LSF (TARE-ineligible group). This latter group had larger tumors (13.8 cm vs. 7.8 cm, P<0.001) and higher MoRAL scores (1,385.8 vs. 413.3, P=0.002) than the TARE-eligible group. After balancing baseline characteristics with an inverse probability of treatment weighting (IPTW), the TARE-ineligible group showed shorter TTP [adjusted hazard ratio (aHR)=2.16, 95% confidence interval (CI)=1.14-4.07, P=0.02] and OS (aHR=1.80, 95% CI=0.85-3.80, P=0.12), although the latter was not statistically significant. The TARE-ineligible group had a significantly lower objective response rate than the TARE-eligible group (9.7% vs. 56.9%, P<0.001). Conclusion: TARE-ineligible patients had larger tumors and higher MoRAL scores than TARE-eligible patients. Treatment with TACE, owing to high LSF, was associated with a shorter TTP even after balancing tumor size and MoRAL scores.

Correlation between Results of Semi-Quantitative and Quantitative Tests for Hepatitis B Virus Surface Antigen among Patients Achieving Viral Suppression with Antiviral Treatment.

Background: Hepatitis B virus (HBV) infection remains a threat to global public health. Serum hepatitis B surface antigen (HBsAg) has been used in screening for HBV infection. Quantitative HBsAg assays are useful for monitoring the natural history of HBV infection and its response to therapy. The aim of this study was to determine the relationship between quantitative (qHBsAg; IU/mL) and semi-quantitative (sqHBsAg; signal-to-cutoff ratio [S/Co]) HBsAg titers in patients with chronic hepatitis B (CHB). Methods: We retrospectively included 284 samples with HBV DNA < 20 IU/mL from patients who had simultaneous qHBsAg (using electrochemiluminescence assay) and sqHBsAg tests. Patients were grouped according to their serum HBV-envelope antigen (HBeAg) status (HBeAg-negative, n = 239 and HBeAg-positive, n = 45). The Spearman test was used to analyze the correlation between the quantitative and semi-quantitative assays. Results: There was a significant linear correlation between sqHBsAg and qHBsAg in the HBeAg-negative patients (qHBsAg [IU/mL] = 0.0094 × sqHBsAg [S/Co]1.323; adjusted R2 = 0.8445; p < 0.001). There was a substantial hook effect in the assays from the HBeAg-positive patients, so we performed a stratified analysis according to qHBsAg <1000 IU/mL or ≥1000 IU/mL and found a significant positive linear correlation between sqHBsAg S/Co and qHBsAg (qHBsAg [IU/mL] = 0.072 × sqHBsAg [S/Co]1.331; adjusted R2 = 0.7878; p < 0.001) in HBeAg-positive patients with qHBsAg titers of <1000 IU/mL and a significant negative correlation in HBeAg-positive patients with qHBsAg titers of ≥1000 IU/mL (qHBsAg [IU/mL] = 8.987 × 1014 × sqHBsAg [S/Co]−3.175; adjusted R2 = 0.6350; p < 0.001). Conclusions: There was a highly linear, positive correlation between qHBsAg and sqHBsAg in HBeAg-negative CHB patients. The hook effect led to a negative correlation in HBeAg-positive CHB patients with qHBsAg titers ≥1000 IU/mL.

Binary cutpoint and the combined effect of systolic and diastolic blood pressure on cardiovascular disease mortality: A community-based cohort study.

OBJECTIVES: This study aimed to examine the risk of cardiovascular disease (CVD) death according to blood pressure levels and systolic and/or diastolic hypertension. METHODS: From 20,636 cohort participants, 14,375 patients were enrolled after patients with prior hypertension on antihypertensive drugs were excluded. For the combination analysis, participants were divided into four groups (systolic/diastolic hypertension, systolic hypertension only, diastolic hypertension only, and non-hypertension). The risk of CV death was calculated using the hazard ratio (HR) and 95% confidence intervals (95% CI) in a Cox regression model. RESULTS: The risk of CVD death increased in systolic hypertension (HR = 1.59, 95% CI 1.26-2.00) and systolic/diastolic hypertension (HR = 1.84, 95% CI 1.51-2.25). The highest risks of hemorrhagic and ischemic stroke were observed in the diastolic hypertension (HR = 4.11, 95% CI 1.40-12.06) and systolic/diastolic hypertension groups (HR = 2.59, 95% CI 1.92-3.50), respectively. The risk of CVD death was drastically increased in those with SBP≥120 mmHg/DBP≥80 mmHg. The highest risk was observed in those with SBP of 130-131 mmHg and 134-137 mmHg. CONCLUSION: The combined analysis of systolic and/or diastolic hypertension appears to be a good predictor of CVD death. The risk of CVD death in the prehypertensive group could be carefully monitored as well as in the hypertensive group, presumably due to less attention and the lack of antihypertensive treatment.

Comparison of the outcomes between sorafenib and lenvatinib as the first-line systemic treatment for HBV-associated hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND/AIM: In a randomized controlled trial, lenvatinib was non-inferior to sorafenib in overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to compare the effects of sorafenib and lenvatinib as first-line systemic therapy against uHCC with real-world data in chronic hepatitis B patients. METHODS: This retrospective single-center study involved 132 patients with HBV-related uHCC. Propensity score matching (PSM) was used to balance the baseline characteristics, including age, sex, serum alpha-fetoprotein levels, Child-Pugh class, tumor size, and tumor stage. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), time to progression (TTP), and tumor response. RESULTS: After PSM, the final analysis included 44 patients treated with lenvatinib and 88 with sorafenib. The OS (7.0 vs 9.2 months, p = 0.070) and PFS (4.6 vs 2.4 months, p = 0.134) were comparable between the two drugs. Multivariable analysis showed that lenvatinib and sorafenib were not independent prognostic factors of OS (adjusted hazard ratio = 1.41, 95% confidence interval = 0.96-2.08, p = 0.077) after adjustment for baseline alpha-fetoprotein levels, total bilirubin levels, alanine aminotransferase level, performance status, tumor stage, and tumor size. However, the lenvatinib group had a significantly prolonged TTP (5.2 vs 2.5 months, p = 0.018) and a higher objective response rate (18.2% vs 4.5%, p = 0.020) and disease control rate (77.3% vs 47.7%, p = 0.001) than the sorafenib group. CONCLUSIONS: Our study demonstrated that lenvatinib had a comparable OS and PFS but longer TTP and better tumor response compared to sorafenib in patients with HBV-related uHCC.

Long-Term Outcomes of Transarterial Radioembolization for Large Single Hepatocellular Carcinoma: A Comparison to Resection.

The surgical treatment for large hepatocellular carcinoma (HCC) remains controversial because of a high risk of recurrence after resection. This study aimed to compare long-term outcomes of transarterial radioembolization (TARE) with resection for patients with large HCC. Methods: This retrospective cohort study included 557 patients who were initially treated with either resection (n = 500) or TARE (n = 57) for large (≥5 cm), single nodular HCC at 2 tertiary centers in Korea. Patients with major portal vein tumor thrombosis or extrahepatic metastasis were excluded. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), time to intrahepatic progression (TTIP), and safety. Results: The resection group was younger (median, 60 vs. 69 y) and had a smaller tumor size (median, 7.0 vs. 10.0 cm) (all P < 0.05). After baseline characteristics were balanced using inverse-probability-of-treatment weighting, the OS (hazard ratio [HR], 0.98; 95% CI, 0.40-2.43; P = 0.97), TTP (HR, 1.10; 95% CI, 0.55-2.20; P = 0.80), and TTIP (HR, 1.45; 95% CI, 0.72-2.93; P = 0.30) of the TARE group was comparable to the resection group. TARE was not an independent risk for OS (adjusted HR, 1.04; 95% CI, 0.42-2.59; P = 0.93), TTP (adjusted HR, 0.98; 95% CI, 0.50-1.95; P = 0.96), or TTIP (adjusted HR, 1.30; 95% CI, 0.65-2.58; P = 0.46). The TARE group had a shorter hospital stay and fewer adverse events than the resection group. Conclusion: Compared with surgical resection for large single nodular HCC, TARE showed a comparable OS, TTP, and TTIP and a better safety profile.

Comparison of Overall Survival between Surgical Resection and Radiofrequency Ablation for Hepatitis B-Related Hepatocellular Carcinoma.

It remains controversial whether surgical resection, compared to radiofrequency ablation (RFA), improves overall survival (OS) in patients with early hepatocellular carcinoma (HCC). This study aimed to compare OS after RFA with that after resection for HCC. This retrospective study included patients who underwent RFA or surgical resection as initial treatment for hepatitis B virus (HBV)-related HCC at a very early or early stage. A total of 761 patients (RFA, n = 194; resection, n = 567) from Seoul National University Hospital (Seoul, South Korea) and 1277 patients (RFA, n = 352; resection, n = 925) from the Korean Primary Liver Cancer Registry were included in the hospital and nationwide cohorts, respectively. Primary and secondary endpoints were OS and recurrence-free survival (RFS), respectively. Additional analysis was performed when the history of the antiviral treatment and the type of prescribed nucleos(t)ide analogue were confirmed. The rate of complications was compared between the two treatment groups in the hospital cohort. Baseline characteristics were balanced, using inverse probability of treatment weighting (IPTW). In the hospital cohort, the RFA group had a smaller mean tumor size (1.7 vs. 3.9 cm) but a higher proportion of cirrhotic patients than the resection group (85.6% vs. 63.1%) (both p < 0.01). During 81.0 (interquartile range, 62.3-107.1) months of follow-up, there was no difference in OS (adjusted hazard ratio (aHR) = 0.870, 95% confidence interval (CI) = 0.400-1.897, p = 0.73) and RFA was associated with shorter RFS (aHR = 1.562, 95% CI = 1.099-2.219, p = 0.01) after employing IPTW. Antiviral treatment was independently associated with longer OS (aHR = 0.444, 95% CI = 0.251-0.786, p = 0.01) as well as RFS (aHR = 0.544, 95% CI = 0.391-0.757, p < 0.01) in the hospital cohort. In the nationwide cohort, there was no difference in OS (aHR = 0.981, 95% CI = 0.661-1.456, p = 0.92) between the two treatment groups when adjusted for antiviral treatment, which was a negative independent risk factor for mortality (aHR = 0.655, 95% CI = 0.451-0.952, p = 0.03) after IPTW. Among patients treated with tenofovir (n = 96) or entecavir (n = 184) in the hospital cohort, there was no difference in either OS (aHR = 0.522, 95% CI = 0.058-4.724, p = 0.56) or RFS (aHR = 1.116, 95% CI = 0.738-1.688, p = 0.60). The overall incidence of complications was higher in the resection group (26.3%) than in the RFA group (13.9%) (p < 0.01). RFA may provide comparable OS to resection in the treatment of very early or early HCC with a lower rate of complications, although RFS is marginally shorter than in the resection group after adjusting for antiviral treatment. Regardless of the type of NA, antiviral treatment in patients with HBV-related HCC is strongly associated with both OS and RFS.