Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

BACKGROUND AND AIM: Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). METHODS: This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. RESULTS: This study included 309 patients with a median age of 59 years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5 months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6 months after switching (74.8%-83.5%; P = 0.008). Adjusted eGFR significantly improved at 6 months (+5.55 ± 10.52 mL/min/1.73 m2; P < 0.001) and 12 months (+6.02 ± 10.70 mL/min/1.73 m2; P < 0.001) after switching. In the subgroup of patients with renal impairment (eGFR < 60 mL/min/1.73 m2), significant improvement in renal function was observed at 6 months (+0.6 ± 10.5 mL/min/1.73 m2; P < 0.001) and 12 months (+1.0 ± 10.7 mL/min/1.73 m2; P < 0.001) after switching to TAF. In patients with osteoporosis (n = 182), switching to TAF resulted in significant improvement in spine and hip BMD at 12 months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. CONCLUSION: In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Unilateral Biportal Endoscopy for L5-S1 Extraforaminal Stenosis (Far Out Syndrome) - Technical Note with Literature Review.

Introduction: Extraforaminal stenosis in L5-S1, or far-out syndrome (FOS), is defined as L5 nerve compression by the transverse process (TP) of the L5 and the ala of the sacrum and disc bulging with/without osteophytes and/or the thickened lumbosacral and extraforaminal ligament. This study aims to describe the unilateral biportal endoscopic decompression technique of the extraforaminal stenosis at L5-S1 or far out syndrome and evaluate its clinical results with a literature review. Case Report: A 44-year-old male presented with severe right sharp shooting pain in the buttock, thigh, leg, foot, and/or toes with numbness in the foot and toes (Visual Analog Scale [VAS] 8/10) for six months with an Oswestry disability index (ODI) score of 70%. Her pain aggravated when bending forward and performing daily routine activities. He also complained of exaggeration of pain in daily regular activities. On physical examination, power in the right lower limbs was 5/5 as per the Medical Research Council (MRC) grading, and deep tendon reflexes were normal. Pre-operative X-ray and CT scan showed no instability or calcified disc osteophyte, and magnetic resonance imaging showed extraforaminal stenosis due to disc herniation at L5-S1 in Figure 1. We performed UBE-L5-S1extraforaminal discectomy surgery to resolve his symptoms. The operative time was 68 min; blood loss was 30 mL. After surgery, the patient was followed up at one week, six weeks, three months, six months, 12 months, and two years. The pain and tingling sensation in the legs improved at the 1-week follow-up, with a VAS score of 0/10 and an ODI score of 10% at the 2-year follow-up. Patient satisfaction was surveyed using Macnab's criteria at the final follow-up visit of 2 years and was found to be excellent. Post-operative imaging showed a good extraforaminal decompression at L5-S. Conclusion: Unilateral biportal endoscopy technique has brought a paradigm shift in the treatment of spinal pathologies and has served as another treatment option for the past two decades. The UBE decompression technique for extraforaminal stenosis at L5-S1 has the advantages of minimally invasive spine surgery; it is a safe and effective treatment option for treating extraforaminal stenosis at L5-S1.

A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma.

BACKGROUND: Given its heterogeneity and diverse clinical outcomes, precise subclassification of BCLC-C hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment. METHODS: We recruited 2,626 patients with BCLC-C stage HCC from multiple centers, comprising training/test (n=1,693) and validation cohorts (n=933). The XGBoost was chosen for maximum performance among the machine learning (ML) models. Patients were categorized into low-/intermediate-/high-/very high-risk subgroups which were based on the estimated prognosis, and this subclassification was named the CLAssification via Machine learning of BCLC-C (CLAM-C). RESULTS: The areas under the receiver operating characteristic curve of the CLAM-C for predicting the 6-/12-/24-month survival of patients with BCLC-C were 0.800/0.831/0.715, respectively-significantly higher than those of the conventional models, which was consistent in the validation cohort. The four subgroups had significantly different median overall survivals, and this difference was maintained among various patient subgroups and treatment modalities. Immune-checkpoint inhibitors and transarterial therapies were associated with significantly better survival than tyrosine kinase inhibitors (TKIs) in the low- and intermediate-risk subgroups. In cases with first-line systemic therapy, the CLAM-C identified atezolizumab-bevacizumab as the best therapy particularly in the high-risk group. In cases with later-line systemic therapy, nivolumab had better survival than TKIs in the low-to-intermediate-risk subgroup, whereas TKIs had better survival in the high-to-very high-risk subgroup. CONCLUSIONS: ML modeling effectively subclassified patients with BCLC-C HCC, potentially aiding treatment allocation. Our study underscores the potential utilization of ML modeling in terms of prognostication and treatment allocation in patients with BCLC-C HCC.

Role of Portosystemic Shunt and Portal Vein Stent in Managing Portal Hypertension Due to Hematological Diseases.

INTRODUCTION: Patients with hematological diseases experience complications related to portal hypertension, including life-threatening complications such as variceal bleeding. METHODS: We analyzed the prognosis of patients with hematological diseases and portal hypertension treated with transjugular intrahepatic portosystemic shunts (TIPS) or portal vein stents. We retrospectively assessed patients with hematological diseases and portal hypertension who had variceal bleeding. We evaluated the characteristics and prognosis of the enrolled patients. A total of 11 patients with hematological diseases who underwent TIPS, or portal vein stenting, were evaluated. RESULTS: The median follow-up period was 420 days. Of the 11 patients, eight showed resolution of portal hypertension and its complications following TIPS, or stent insertion. One patient experienced rebleeding due to incomplete resolution of portal hypertension, and two other patients also experienced rebleeding because they underwent TIPS closure or revision due to repetitive hepatic encephalopathy. CONCLUSION: Portosystemic shunt and stent installation are effective treatment options for portal hypertension due to hematological diseases.

Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study.

Background: Atezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial. Materials and methods: This real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177). Results: First, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments. Conclusion: Our study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies.

Philosophies and Surgical Techniques for High-Grade Spondylolisthesis Treatment with Literature Review.

Introduction: High-grade spondylolisthesis is defined as cases with more than 50% displacement and spondylolisthesis with Meyerding grade III and higher. The surgical management of high-grade spondylolisthesis is highly controversial. Many surgical methods have been reported such as posterior in situ fusion, instrumented posterior fusion with or without reduction, combined anterior and posterior procedures, spondylectomy with reduction of L4 to the sacrum (for spondyloptosis), and posterior interbody fusion with trans-sacral fixation. The literature has recently mentioned minimally invasive transforaminal lumbar interbody fusion for high-grade spondylolisthesis. This study aimed to review the recent literature that describes the surgical outcomes associated with various surgical techniques used for high-grade spondylolisthesis. Materials and Methods: Recent articles were searched on search engines such as PubMed and Google Scholar using keywords such as "high-grade spondylolisthesis," "surgical techniques," and "complications." Discussion: The surgical management of high-grade spondylolisthesis is an area of significant controversy. The literature is replete with regards to the need for reduction, decompression, levels of fusion, the nature of instrumentation, surgical approaches including open, minimally invasive, and "mini-open" procedures, and various techniques for reducing the slip and fusion strategy. The three basic options of high-grade spondylolisthesis include in-situ fusion, partial reduction and fusion, and complete reduction. Conclusion: Various techniques have been described for high-grade spondylolisthesis. Spine deformity study group classification gives guidelines about balanced and unbalanced pelvis and advises reduction and fusion in case of unbalanced pelvis for correction of biomechanical and global sagittal alignment. Each of the surgical techniques has its advantages and disadvantages. However, individual authors' experience, skill levels, and anatomic reduction with fusion techniques have yielded encouraging results.

Use of Navigable Ablation Decompression Treatment (L-DISQ) for Contained Cervical Disc Herniation - Technical Note and Literature Review.

Introduction: A new navigable percutaneous disc decompressor (L'DISQ-C, U&I Co., Uijeongbu, Korea), introduced in 2012, is designed to allow direct access to herniated disc material. The L'DISQ device can be curved by rotating a control wheel, directed into disc herniation treats, and decompresses contained herniated discs with minimal collateral thermal damage. This study reports the case of contained central disc herniation in a 34-year-old male with a 2-year follow-up successfully treated with navigable ablation decompression treatment (L-DISQ). Case Report: A 34-year-old man presented to the outpatient department with a 6-month history of neck pain and bilateral upper limb radiation. His neck pain had increased progressively. At the time of presentation, his neck pain visual analog scale score was 7/10, and his neck disability index score was 30. The magnetic resonance images showed a single fluid-containing lesion with a hyperintense zone at the C4-5 levels with central disc herniation. The patient was successfully treated with the navigable ablation decompression treatment (L-DISQ) procedure. Conclusion: The navigable ablation decompression treatment (L-DISQ) is a valuable technique in treating contained cervical disc herniation with rapid pain relief and improvements in functional outcomes without any significant injury to surrounding structures. It is safe, precise, and effective in the treatment of symptomatic cervical disc herniations. Large, randomized, and multicenter trials are needed to explore the potential of the same technique further.

Comparative Analysis of Atezolizumab Plus Bevacizumab and Hepatic Artery Infusion Chemotherapy in Unresectable Hepatocellular Carcinoma: A Multicenter, Propensity Score Study.

This study aimed to compare the prognosis and characteristics of patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab (AB) combination therapy and hepatic artery infusion chemotherapy (HAIC). We retrospectively assessed 193 and 114 patients treated with HAIC and AB combination therapy, respectively, between January 2018 and May 2023. The progression-free survival (PFS) of patients treated with AB combination therapy was significantly superior to that of patients treated with HAIC (p < 0.05), but there was no significant difference in overall survival (OS). After propensity score matching, our data revealed no significant differences in OS and PFS between patients who received AB combination therapy and those who received HAIC therapy (p = 0.5617 and 0.3522, respectively). In conclusion, our propensity score study reveals no significant differences in OS and PFS between patients treated with AB combination therapy and those treated with HAIC.

A Real-World Comparative Analysis of Atezolizumab Plus Bevacizumab and Transarterial Chemoembolization Plus Radiotherapy in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis.

This study aimed to compare the treatment outcomes of atezolizumab-plus-bevacizumab (Ate/Bev) therapy with those of transarterial chemoembolization plus radiotherapy (TACE + RT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and without metastasis. Between June 2016 and October 2022, we consecutively enrolled 855 HCC patients with PVTT. After excluding 758 patients, 97 patients (n = 37 in the Ate/Bev group; n = 60 in the TACE + RT group) were analyzed. The two groups showed no significant differences in baseline characteristics and had similar objective response and disease control rates. However, the Ate/Bev group showed a significantly higher one-year survival rate (p = 0.041) compared to the TACE + RT group, which was constantly displayed in patients with extensive HCC burden. Meanwhile, the clinical outcomes were comparable between the two groups in patients with unilobar intrahepatic HCC. In Cox-regression analysis, Ate/Bev treatment emerged as a significant factor for better one-year survival (p = 0.049). Finally, in propensity-score matching, the Ate/Bev group demonstrated a better one-year survival (p = 0.02) and PFS (p = 0.01) than the TACE + RT group. In conclusion, Ate/Bev treatment demonstrated superior clinical outcomes compared to TACE + RT treatment in HCC patients with PVTT. Meanwhile, in patients with unilobar intrahepatic HCC, TACE + RT could also be considered as an alternative treatment option alongside Ate/Bev therapy.

Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease.

Introduction: The continuous rise in the prevalence of nonalcoholic fatty liver disease (NAFLD) is emerging as a global health issue. Although the protective effects of N-acetylcysteine (NAC), an antioxidant, against various diseases have been reported, it is still unclear whether NAC has therapeutic potential in NAFLD. Thus, the present meta-analysis aimed to investigate the efficacy of NAC on NAFLD in preclinical studies. Methods: By searching PubMed, Web of Science, and Cochrane Library, 13 studies were included. The methodological quality was assessed based on the SYstematic Review Centre for Laboratory animal Experimentation guideline, and heterogeneity was evaluated with I 2 and p values. Publication bias was assessed by Egger's test and sensitivity analysis was performed. Results: The results showed that NAC treatment significantly improved systemic and hepatic lipid metabolism (p < 0.01), inflammation-related liver injury (p < 0.01), glucose intolerance (p < 0.05), and hepatic steatosis (p < 0.01) by restoring hepatic glutathione (GSH) (p < 0.05) and GSH reductase (p < 0.05) levels compared to controls in NAFLD-induced animals. Consistently, in bulk, single-cell, and spatial transcriptomics data, the abovementioned target pathways of NAC were strongly associated with NAFLD development in mice and patients. Conclusion: Our study suggests that NAC has therapeutic potential for NAFLD and should be considered for future clinical trials.

Association between Posttreatment Serum Platelet-to-Lymphocyte Ratio and Distant Metastases in Patients with Hepatocellular Carcinoma Receiving Curative Radiation Therapy.

BACKGROUND: We sought to investigate whether serum immune and inflammatory parameters can help to predict distant metastasis (DM) in patients with unresectable hepatocellular carcinoma (HCC) undergoing curative radiation therapy (RT). METHODS: A total of 76 RT courses were analyzed. The following variables were included in the analysis: systemic inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), absolute lymphocyte count, lymphocyte-to-monocyte ratio, albumin, albumin-to-alkaline phosphatase ratio, RT-related parameters, and levels of total protein, hemoglobin, α-fetoprotein, and PIVKA-II. Distant control (DC) and overall survival (OS) rates were calculated and compared. RESULTS: The mean age was 61.4 years, and most patients were men (n = 62, 81.6%). The median RT fraction number and fractional doses were 12 (range, 4-30) and 5 (range, 2-12) Gy, respectively. With a median follow-up of 12 (range, 3.1-56.7) months, the 1-year DC and OS rates were 64.4% and 55.2%, respectively. The development of DM significantly deteriorated OS (p = 0.013). In the multivariate analysis, significant independent prognostic indicators for DC and OS rates were the highest posttreatment PLR (≤235.7 vs. >235.7, p = 0.006) and the lowest posttreatment PNI (≤25.4 vs. >25.4, p < 0.001), respectively. CONCLUSIONS: Posttreatment serum PLR might be helpfully used as a predictive biomarker of DM in unresectable HCC patients undergoing RT. Future research is necessary to confirm our findings.

Eukaryotic initiation factor 5A hypusine as a negative regulator of adenosine 2B receptor (A2bAR) through interaction with stem loop sequences within the A2bAR 3'-untranslated region.

PURPOSE: The aim of this study was to investigate whether eIF5A hypusine (eIF5AHyp) reduces adenosine 2b receptor (A2bAR) gene expression through interaction with highly structured stem-loop sequences within the A2bAR 3'UTR. METHODS AND RESULTS: Based on real-time PCR and western blotting, expression of A2bAR mRNA was significantly decreased upon treatment with eIF5AHyp in mouse embryonic fibroblasts of eIF5A (eIF5A-MEF) and 3T3-L1 cells. Target Scan software and RNAfold web server predicted two different structures formed by stem-loop sequences with overlapping microRNA 27 seed sequences and mutations. The EMSA results showed significantly impaired formation of the wild type (WT) biotin-labeled A2bAR probe (27 base) containing stem loop sequences-eIF5AHyp complex by mutation of stem-loop sequences or by eIF5A non-hypusine (eIF5ALys). The luciferase reporter assay showed that GC7-induced eIF5ALys accumulation increased the activity of pMIR-A2bAR WT containing the same stem-loop sequence in 3T3-L1 cells, whereas the activity with pMIR-A2bAR Mut was increased compared to WT control without dependence on GC7. Oil Red O staining showed that suppression of A2bAR expression (A2bAR siRNA and eIF5AHyp) increased the amount of lipid droplet formation and the mRNA levels of lipid droplet-related genes (C/EBP-ß, PPAR-γ, FABP4, SREBP-1, and Perilipin). In contrast, overexpression of A2bAR (A2bAR vector, eIF5ALys vector, and GC7) significantly decreased the expression of lipid droplet-associated genes and lipid droplet formation. CONCLUSIONS: eIF5AHyp acts as a negative regulator of A2bAR gene expression through stem loop sequences in A2bAR 3'UTR, allowing differentiation of adipocytes.

Unilateral Biportal Endoscopic Approach for Symptomatic Adjacent Segment Disease: Case Report and Technical Note.

Introduction: Recently, lumbar degenerative disease has been treated using unilateral biportal endoscopic (UBE) lumbar interbody fusion. However, the use of the UBE approach for symptomatic ASD following lumbar interbody fusion surgery isn't illustrated widely in the literature. This case report and technical note describe the use of the UBE approach for symptomatic ASD. Case Report: A 72-year-old female who underwent conventional fusion surgery elsewhere twelve years ago at the L5-S1 level presented with severe back pain (VAS 8/10) and radicular pain in both legs (left > right) (left VAS 7/10, right VAS 7/10) for 1 year with an ODI score of 70%. Preoperative X-ray and MRI showed dynamic instability with spondylolisthesis at L4-5. We performed an upper-level extension using UBE FES techniques to resolve ASD. The operative time was 132 minutes, blood loss was 40 ml. After surgery, the patient was followed up at 1 week, 6 weeks, 3 months, 6 months, 12 months, and 2 years. The pain and tingling sensation in the legs got better at the 1-week follow-up itself with a VAS score of 0/10 and an ODI score of 10% at the 2-year follow-up. Patient satisfaction was surveyed using Odom's criteria at each follow-up visit (at 1 week, 6 weeks,3 months, 6 months, and 2 years) and found to be excellent. Postoperative imaging showed a good reduction and canal decompression at L4-5. Conclusion: The UBE fusion extension technique for ASD is a safe, less invasive, and effective treatment option for lumbar interbody fusion extension and posterior pedicle screw revision with less morbidity and early recovery.

The Past, Present, and Future of Unilateral Biportal Endoscopy with a Technical Note on Novel Endoscopic Visualization Pedicle Screw Insertion Technique and UBE-transforaminal Lumbar Interbody Fusion Technique with Literature Review.

Introduction: Over the past two decades, unilateral biportal endoscopy (UBE) has brought a new paradigm shift in the surgical treatment of spinal disorders with its innovative technique. This study aims to review the development of the UBE technique with a technical note on the novel endoscopic visualization pedicle screw (EVPS) insertion technique and UBE-transforaminal lumbar interbody fusion technique (UBE-TLIF). Case Report: A 66-year-old female presented with severe back pain (Visual Analog Scale [VAS] 8/10) and radicular pain in both legs (left > right) (left VAS 7/10 and right VAS 7/10) for one year with an Oswestry disability index (ODI) score of 70%. Her pain aggravated when bending forward and performing daily routine activities. She also complained of severe intermittent neurological claudication at a distance of <50 m. On physical examination, power in the lower limbs was 5/5 as per the Medical Research Council grading, and deep tendon reflexes were normal. She had a known case of diabetes mellitus and hypertension and was on treatment with oral medications. Pre-operative X-ray and magnetic resonance imaging showed dynamic instability with spondylolisthesis at L4-5. We performed UBE-TLIF with the EVPS insertion technique to resolve her symptoms. The operative time was 122 min; blood loss was 40 mL. After surgery, the patient was followed up at one week, six weeks, three months, six months, 12 months, and two years. The pain and tingling sensation in the legs improved at the 1-week follow-up, with a VAS score of 0/10 and an ODI score of 10% at the 2-year follow-up. Patient satisfaction was surveyed using Macnab's criteria at the final follow-up visit of 2 years and was found to be excellent. Post-operative imaging showed a good reduction and canal decompression at L4-5. Conclusion: The novel EVPS insertion technique and UBE-TLIF have the advantages of minimally invasive spine surgery; they are a safe and effective treatment option for treating lumbar spine pathologies.

Safety and effectiveness of direct-acting antivirals in patients with chronic hepatitis C and chronic kidney disease.

BACKGROUND/AIMS: To evaluate the effectiveness and safety of direct acting antivirals (DAAs) available in chronic kidney disease (CKD) patients with hepatitis C virus (HCV) infection in Korea. METHODS: In a retrospective, multicenter cohort study, 362 patients were enrolled from 2015 to 2019. The effectiveness and safety of DAAs including glecaprevir/pibrentasvir, sofosubvir/ribavirin, ledipasvir/sofosbuvir, and daclatasvir/asunaprevir were analyzed for patients according to CKD stage. We evaluated sustained virologic response at week 12 after treatment (SVR12) as primary endpoint. The effectiveness and safety were also evaluated according to CKD stage. RESULTS: Among 362 patients, 307 patients completed DAAs treatment and follow-up period after end of treatment. The subjects comprised 87 patients (62 with CKD stage 3 and 25 with CKD stage (4-5), of whom 22 were undergoing hemodialysis). HCV patients with CKD stage 1 and 2 (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2) showed SVR12 of 97.2% and 95.4% respectively. SVR12 of CKD stage 3 and 4-5 (eGFR < 60 mL/min/1.73 m2) patients was 91.9% and 91.6% respectively. Patients undergoing hemodialysis achieved SVR12 (90.9%). Treatment failure of DAAs in stage 1, 2, 3, and 4-5 was 2.8%, 2.7%, 1.6%, and 4%. DAAs showed good safety profile and did not affect deterioration of renal function. CONCLUSION: DAAs shows comparable SVR12 and safety in CKD patients (stage 3, 4, and 5) with HCV compared with patients with stage 1 and 2. The effectiveness and safety of DAAs may be related to the treatment duration. Therefore, it is important to select adequate regimens of DAAs and to increase treatment adherence.

Real-life experience of ledipasvir and sofosbuvir for HCV infected Korean patients: a multicenter cohort study.

BACKGROUND/AIMS: To evaluate the efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) therapy in hepatitis C virus (HCV)-infected Korean patients in a real clinical setting. METHODS: A total of 273 patients who received LDV/SOF therapy between May 2016 and February 2021 were consecutively enrolled and analyzed. A per-protocol analysis was performed to evaluate the virologic response. RESULTS: Seventy-five percent were infected with genotype 1, and 25% were infected with genotype 2. A hundred eightyone (66.3%) patients had chronic hepatitis, 74 (27.1%) had compensated cirrhosis, eight (2.9%) had decompensated cirrhosis, and 10 (3.7%) had undergone liver transplantation. Undetectable HCV RNA at week 4 was achieved in 90.2% (231/256) of patients, 99.2% (250/252) achieved the end of treatment response, and 98.1% (202/206) achieved sustained virologic response at 12 weeks post-treatment (SVR12). According to liver function, the SVR12 rates were 99.3% (135/136) in chronic hepatitis, 96.4% (53/55) in compensated cirrhosis, and 100% (6/6) in decompensated cirrhosis. The SVR12 rates according to the genotype were 98.2% (167/170) for genotype 1 and 97.2% (35/36) for genotype 2. An 8-week LDV/SOF treatment in treatment-naïve chronic hepatitis patients with HCV RNA < 6,000,000 IU/mL at baseline resulted in 100% (23/23) SVR12 rates. Overall, LDV/SOF was tolerated well, with a 0.7% (2/273) discontinuation rate due to adverse events that were unrelated to LDV/SOF. CONCLUSION: LDV/SOF is effective and safe for treating HCV-infected Korean patients with high SVR12 rates.

Intraindividual Changes in Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Performed in Korean Subjects.

BACKGROUND: Limited data are available regarding intraindividual changes in the Mac-2 binding protein glycosylation isomer (M2BPGi), a liver fibrosis biomarker, performed for health checkups in Korean subjects. METHODS: Through a laboratory information system, we retrospectively investigated longitudinally measured M2BPGi to assess intraindividual changes in M2BPGi test results. RESULTS: During a 38-month study period, 526 test results from 246 Korean subjects undergoing general health checkups were requested from 13 local clinics and hospitals. Among all 246 subjects, 190 (77.2%) exhibited negative M2BPGi (< 1.0 C.O.I.) during the initial measurement. Among all 246 subjects, 210 (85.4%) did not experience any changes in qualitative results during a follow-up. Among 42 subjects with initially 1+ positive results for M2BPGi, 17 (40.5%) changed to a negative M2BPGi result at least once during follow-up. No subjects with initially negative results or 1+ positive (1.0 ≤ C.O.I. < 3.0) results changed to 2+ positive (≥ 3.0 C.O.I.) results during the 38-month follow-up period. CONCLUSIONS: Some subjects exhibited qualitative changes in M2BPGi during follow-up health examinations. Future studies are needed to clarify the clinical implication of such changes.

Systematic Review of Reciprocal Changes after Spinal Reconstruction Surgery : Do Not Miss the Forest for the Trees.

The purpose of this review was to synthesize the research on global spinal alignment and reciprocal changes following cervical or thoracolumbar reconstruction surgery. We carried out a search of PubMed, EMBASE, and Cochrane Library for studies through May 2020, and ultimately included 11 articles. The optimal goal of a truly balanced spine is to maintain the head over the femoral heads. When spinal imbalance occurs, the human body reacts through various compensatory mechanisms to maintain the head over the pelvis and to retain a horizontal gaze. Historically, deformity correction has focused on correcting scoliosis and preventing scoliotic curve progression. Following substantial correction of a spinal deformity, reciprocal changes take place in the flexible segments proximal and distal to the area of correction. Restoration of lumbar lordosis following surgery to correct a thoracolumbar deformity induces reciprocal changes in T1 slope, cervical lordosis, pelvic shift, and lower extremity parameters. Patients with cervical kyphosis exhibit different patterns of reciprocal changes depending on whether they have head-balanced or trunk-balanced kyphosis. These reciprocal changes should be considered to in order to prevent secondary spine disorders. We emphasize the importance of evaluating the global spinal alignment to assess postoperative changes.

The Role of Urinary N-Acetyl-ß-d-glucosaminidase in Cirrhotic Patients with Acute Kidney Injury: Multicenter, Prospective Cohort Study.

BACKGROUND AND AIMS: Currently, it is difficult to predict the reversibility of renal function and to discriminate renal parenchymal injury in cirrhotic patients with acute kidney injury (AKI). The aim of this study is to evaluate whether urine N-acetyl-ß-d-Glucosaminidase (NAG) can predict the survival and response to terlipressin in cirrhotic patients with AKI. METHODS: Two hundred sixty-two cirrhotic consecutive patients who developed AKI were prospectively enrolled from 11 tertiary medical centers in Korea between 2016 to 2019. AKI was defined as an increase in serum Cr (SCr) of 0.3 mg/dL or a 50% increase in baseline SCr. Patients diagnosed with hepatorenal syndrome (HRS-AKI) were treated with terlipressin plus albumin. RESULTS: The patients were 58.8 ± 12.9 years old on average and were predominantly male (72.5%). The mean MELD score was 25.3 ± 9.1. When classified according to the AKI phenotype, there were 119 pre-renal, 52 acute tubular necrosis, 18 miscellaneous, and 73 HRS-AKI patients. However, the urine NAG was not effective at discriminating AKI phenotypes, except for HRS-AKI. The baseline urine NAG increased as the baseline AKI stage increased (p < 0.001). In addition, within the same AKI stage, the urine NAG values were significantly lower in the AKI-resolved group than in the unresolved group. The urine NAG level was significantly lower in living patients compared with those who died or who underwent a liver transplant within 3 months (p = 0.005). In the multivariate analysis, the increased urine NAG was a significant risk factor for the 3-month transplant-free survival (TFS) rate, especially in patients with Child-Pugh class ≤ B or MELD < 24. The urine NAG did not predict the response to terlipressin treatment in patients with HRS. CONCLUSIONS: Urine NAG is strongly associated with the severity of AKI in patients with liver cirrhosis and is useful for predicting the 3-month TFS.

Comparative Analysis of Lenvatinib and Hepatic Arterial Infusion Chemotherapy in Unresectable Hepatocellular Carcinoma: A Multi-Center, Propensity Score Study.

The comparative efficacy and safety between lenvatinib and hepatic artery infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC) is still unclear. This multicenter historical cohort study enrolled 244 patients who were treated with HAIC (n = 173) or lenvatinib (n = 71) between 2012 and 2020. Propensity score matching (PSM) was performed, and 52 patients were selected per group. Clinical outcomes and safety were compared. Objective response rate (ORR) was not different between the two groups (26.0% vs. 23.1%, p = 0.736). Before PSM, the HAIC group had a higher proportion of Child-Pugh B and portal vein tumor, whereas the lenvatinib group had more patients with extrahepatic metastases, which was adjusted after PSM. There were no differences in progression-free survival (PFS) and overall survival (OS) after PSM (HAIC vs. lenvatinib, median PFS, 3.6 vs. 4.0 months, p = 0.706; median OS 10.8 vs. 7.9 months, p = 0.106). Multivariate Cox-regression showed that alpha-fetoprotein ≤1000 ng/mL was only an associated factor for OS after PSM in all patients (hazard ratio = 0.421, p = 0.011). Subgroup analysis for patients with a high tumor burden beyond the REFLECT eligibility criteria revealed that the HAIC group (n = 29) had a significantly longer OS than did the lenvatinib group (n = 30) (10.0 vs. 5.4 months, p = 0.004). More patients in the HAIC group achieved better liver function than those in the lenvatinib group at the time of best responses. There was no difference in the incidence of grade 3 and 4 adverse events between the two groups. Therefore, lenvatinib is comparable to HAIC in terms of ORR and OS in unresectable HCC meeting REFLECT eligibility criteria.