Liver regeneration of living donor after liver donation for transplantation: Disparity in the left and right remnant liver.

Donor safety is crucial for living donor liver transplantation (LDLT), and sufficient liver regeneration significantly affects outcomes of living donors. This study aimed to investigate clinical factors associated with liver regeneration in living donors. The study retrospectively reviewed 380 living donors who underwent liver donation at Chang Gung Memorial Hospital in Linkou. The clinical characteristics and medical parameters of donors were analyzed and compared according to liver donation graft type. There were 355 donors (93.4%) with right hemi-liver donations and 25 donors (6.6%) with left hemi-liver donations. Left hemi-liver donors had a higher body mass index (BMI) and a larger ratio of remnant liver volume (RLV) to total liver volume (TLV). However, the 2 groups showed no significant difference in the liver regeneration ratio. The type of remnant liver (P < .001), RLV/body weight (P = .027), RLV/TLV (P < .001), serum albumin on postoperative day 7 and total bilirubin levels on postoperative day 30 were the most significant factors affecting liver regeneration in living donors. In conclusion, adequate liver regeneration is essential for donor outcome after liver donation. The remnant liver could eventually regenerate to an adequate volume similar to the initial TLV before liver donation. However, the remnant left hemi-liver had a faster growth rate than the remnant right hemi-liver in donors.

Recurrence Pattern Is an Independent Surgical Prognostic Factor for Long-Term Oncological Outcomes in Patients with Hepatocellular Carcinoma.

BACKGROUND: The perioperative outcomes of a partial hepatectomy for hepatocellular carcinoma (HCC) have improved. However, high recurrence rates after a curative hepatectomy for HCC is still an issue. This study aimed to analyze the difference between various recurrence patterns. METHODS: We retrospectively reviewed 754 patients with HCC who underwent a curative hepatectomy between January 2012 and March 2021. Patients with recurrent events were categorized into three types: regional recurrence (type I), multiple intrahepatic recurrence (type II), or presence of any distant metastasis (type III). RESULTS: The median follow-up period was 51.2 months. Regarding recurrence, 375 (49.7%) patients developed recurrence, with 244 (32.4%), 51 (6.8%), and 80 (10.6%) patients having type I, II, and III recurrence, respectively. Type III recurrence appeared to be more common in male patients and those with major liver resection, vascular invasion, a large tumor size (>5 cm), a higher tumor grade, and higher levels of AST and AFP (p < 0.05). Patients who had distant metastasis at recurrence had the shortest recurrence time and the worst overall survival (p < 0.001 and p < 0.001). CONCLUSIONS: our study demonstrated that recurrence with distant metastasis occurred earliest and had the worst outcome compared to regional or multiple intrahepatic recurrences.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy.

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

Development of hybrid 3D printing approach for fabrication of high-strength hydroxyapatite bioscaffold using FDM and DLP techniques.

This study develops a hybrid 3D printing approach that combines fused deposition modeling (FDM) and digital light processing (DLP) techniques for fabricating bioscaffolds, enabling rapid mass production. The FDM technique fabricates outer molds, while DLP prints struts for creating penetrating channels. By combining these components, hydroxyapatite (HA) bioscaffolds with different channel sizes (600, 800, and 1000µm) and designed porosities (10%, 12.5%, and 15%) are fabricated using the slurry casting method with centrifugal vacuum defoaming for significant densification. This innovative method produces high-strength bioscaffolds with an overall porosity of 32%-37%, featuring tightly bound HA grains and a layered surface structure, resulting in remarkable cell viability and adhesion, along with minimal degradation rates and superior calcium phosphate deposition. The HA scaffolds show hardness ranging from 1.43 to 1.87 GPa, with increasing compressive strength as the designed porosity and channel size decrease. Compared to human cancellous bone at a similar porosity range of 30%-40%, exhibiting compressive strengths of 13-70 MPa and moduli of 0.8-8 GPa, the HA scaffolds demonstrate robust strengths ranging from 40 to 73 MPa, paired with lower moduli of 0.7-1.23 GPa. These attributes make them well-suited for cancellous bone repair, effectively mitigating issues like stress shielding and bone atrophy.

A combination of locoregional treatment with systemic therapy after atezolizumab plus bevacizumab failure for unresectable hepatocellular carcinoma provides survival benefit.

Atezolizumab plus bevacizumab (A+B) is used to treat unresectable hepatocellular carcinoma (HCC), but the optimal rescue therapy after A+B remains unclear. Combining locoregional therapy (LRT) with systemic treatment has been shown to improve tumor control, but the role in patients who fail A+B is unknown. We retrospectively enrolled patients who experienced radiological progression after A+B. Objective response rate (ORR), disease control rate (DCR), post progression survival (PPS), and secondary progression-free survival (PFS) were evaluated by modified RECIST. Inverse probability weighting (IPW) was used to balance baseline clinical features. A total of 61 patients were enrolled with a median age of 60.7 years, 83.6% male, 88.5% viral hepatitis-related, and 60.7% without prior systemic treatment before A+B. Patients receiving sequential therapies had significantly longer PPS than supportive care (10.5 vs. 2.3 months, P<0.0001). Among 37 patients received sequential systemic treatment, 18 received combined LRT. The median follow-up after post A+B failure was 6.6 months. The combined LRT group had higher ORR (27.8 vs. 0%, P=0.0197) and DCR (72.2 vs. 26.3%, P=0.0052) than systemic alone group. The median PPS and secondary PFS were significantly longer in combined LRT group (PPS: 12.2 vs. 5.8 months, P=0.0070; PFS: 5.0 vs. 2.6 months, P=0.0134) than systemic alone group. After IPW analysis, patients with combined LRT had superior PPS and secondary PFS. The incidence rates of AEs were higher in LRT combination compared to systemic alone (any grade AEs: 94.4 vs. 63.2%, P=0.0422; severe AEs: 33.3 vs. 5.3%, P=0.0422). No significant albumin-bilirubin index changed in the first 3 months in combined LRT group (0.966 [0.647-1.443], P=0.867) though a trend of deterioration in systemic alone group. In conclusion, sequential systemic therapy provides survival benefits after A+B failure. Furthermore, combining LRT with systemic treatment could provide better tumor responses and survival benefits with acceptable toxicity than systemic therapy alone.

The effect of a helmet type, home-use low-level light therapy device for chemotherapy-induced alopecia: study protocol for a randomized controlled trial.

BACKGROUND: Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient's self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations. Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial. METHODS: One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored. The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire. DISCUSSION: This study improves cancer patients' quality of life and provides clinical evidence. TRIAL REGISTRATION: Registered at ClinicalTrials.gov- NCT05397457 on 1 June 2022.

Adding nutritional status to the original BCLC stage improves mortality prediction for hepatocellular carcinoma patients in HBV-endemic regions.

Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte ratio (NLR), and Albumin-Bilirubin (ALBI) score in predicting short-term mortality (one- and two-year) and (ii) develop a novel model with improved accuracy compared to the conventional models. This study enrolled 298 consecutive HCC patients from our hepatology department. The prognostic values for mortality were assessed by area under the receiver operating characteristic curve (AUROC) analysis. A novel model was established and internally validated using 5-fold cross-validation, followed by external validation in a cohort of 100 patients. The primary etiology of cirrhosis was hepatitis B virus (HBV), with 81.2% of HCC patients having preserved liver function. Significant differences were observed in hemoglobin (Hb) and serum albumin levels, which reflect patients' nutrition status, between patients who survived for one year and those who died. BCLC exhibited superior predictive accuracy compared to NLR but had borderline superiority to the ALBI score. Therefore, a novel model incorporating BCLC, Hb, and serum albumin was developed, internally and externally validated, as well as subgroup sensitivity analysis. The model exhibited significantly higher predictive accuracy for one- and two-year mortality than conventional prognostic predictors, with AUROC values of 0.841 and 0.805, respectively. The novel "BCLC-Nutrition Model", which incorporates BCLC, Hb, and serum albumin, may provide improved predictive accuracy for short-term mortality in HCC patients compared to commonly used prognostic scores. This emphasizes the importance of nutrition in the management of HCC patients.

Characterization and Crystal Structures of a Cubebol-Producing Sesquiterpene Synthase from Antrodia cinnamomea.

Antrodia cinnamomea is an endemic species found in Taiwan, known for its medicinal properties in treating various discomforts, including inflammation, diarrhea, abdominal pain, and other diseases. A. cinnamomea contains terpenoids that exhibit numerous bioactivities, making them potential food additives. This discovery piqued our interest in uncovering their biosynthetic pathway. Herein, we conducted functional and structural characterization of a sesquiterpene synthase Cop4 from A. cinnamomea (AcCop4). Through gas chromatography-mass spectrometry analysis, we observed that AcCop4 catalyzes the cyclization of farnesyl pyrophosphate (FPP), primarily producing cubebol. Cubebol is widely used as a long-lasting cooling and refreshing agent in the food industry. The structure of AcCop4, complexed with pyrophosphate and magnesium ions, revealed the closure of the active site facilitated by R311. Interestingly, binding of pyrophosphate and magnesium ions did not cause any significant conformational change in the G1/2 helix of AcCop4, indicating that the apo form is not fully open. This high-resolution structure serves as a solid basis for understanding the biosynthetic mechanism of AcCop4 and supports further production and modification of cubebol for its applications in the food industry.

A Validated Composite Score Demonstrates Potential Superiority to MELD-Based Systems in Predicting Short-Term Survival in Patients with Liver Cirrhosis and Spontaneous Bacterial Peritonitis-A Preliminary Study.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhosis patients with ascites, leading to high mortality rates if not promptly treated. However, specific prediction models for SBP are lacking. AIMS: This study aimed to compare commonly used cirrhotic prediction models (CTP score, MELD, MELD-Na, iMELD, and MELD 3.0) for short-term mortality prediction and develop a novel model to improve mortality prediction. METHODS: Patients with the first episode of SBP were included. Prognostic values for mortality were assessed using AUROC analysis. A novel prediction model was developed and validated. RESULTS: In total, 327 SBP patients were analyzed, with HBV infection as the main etiologies. MELD 3.0 demonstrated the highest AUROC among the traditional models. The novel model, incorporating HRS, exhibited superior predictive accuracy for in-hospital in all patients and 3-month mortality in HBV-cirrhosis, with AUROC values of 0.827 and 0.813 respectively, surpassing 0.8. CONCLUSIONS: MELD 3.0 score outperformed the CTP score and showed a non-significant improvement compared to other MELD-based scores, while the novel SBP model demonstrated impressive accuracy. Internal validation and an HBV-related cirrhosis subgroup sensitivity analysis supported these findings, highlighting the need for a specific prognostic model for SBP and the importance of preventing HRS development to improve SBP prognosis.

Bioinspired, Non-Enzymatic, Aqueous Synthesis of Size-Tunable CdS Quantum Dots for Sustainable Optoelectronic Applications.

The enzymatic production of hydrogen sulfide (H2S) from cysteine in various metabolic processes has been exploited as an intrinsically "green" and sustainable mode for the aqueous biomineralization of functional metal sulfide quantum dots (QDs). Yet, the reliance on proteinaceous enzymes tends to limit the efficacy of the synthesis to physiological temperature and pH, with implications for QD functionality, stability, and tunability (i.e., particle size and composition). Inspired by a secondary non-enzymatic biochemical cycle that is responsible for basal H2S production in mammalian systems, we establish how iron(III)- and vitamin B6 (pyridoxal phosphate, PLP)-catalyzed decomposition of cysteine can be harnessed for the aqueous synthesis of size-tunable QDs, demonstrated here for CdS, within an expanded temperature, pH, and compositional space. Rates of H2S production by this non-enzymatic biochemical process are sufficient for the nucleation and growth of CdS QDs within buffered solutions of cadmium acetate. Ultimately, the simplicity, demonstrated robustness, and tunability of the previously unexploited H2S-producing biochemical cycle help establish its promise as a versatile platform for the benign, sustainable synthesis of an even wider range of functional metal sulfide nanomaterials for optoelectronic applications.

Daily Aspirin Reduced the Incidence of Hepatocellular Carcinoma and Overall Mortality in Patients with Cirrhosis.

BACKGROUND: Cirrhosis is the primary risk factor for hepatocellular carcinoma (HCC) and gastrointestinal bleeding (GI). We aimed to assess the efficacy and safety of daily aspirin on HCC occurrence, overall survival, and GI bleeding in cirrhotic patients. METHODS: A total of 35,898 eligible cases were enrolled for analyses from an initial 40,603 cirrhotic patients without tumor history. Patients continuously treated with aspirin for at least 84 days were in the therapy group, whereas those without treatment were controls. A 1:2 propensity score matching by age, sex, comorbidities, drugs, and significant clinical laboratory tests with covariate assessment was used. RESULTS: Multivariable regression analyses revealed that daily aspirin use was independently associated with a reduced risk of HCC (three-year HR 0.57; 95% CI 0.37-0.87; p = 0.0091; five-year HR 0.63, 95% CI 0.45-0.88; p = 0.0072) inversely correlated with the treatment duration [3-12 months: HR 0.88 (95% CI 0.58-1.34); 12-36 months: HR 0.56 (0.31-0.99); and ≥ 36 months: HR 0.37 (0.18-0.76)]. Overall mortality rates were significantly lower among aspirin users compared with untreated controls [three-year HR 0.43 (0.33-0.57); five-year HR 0.51 (0.42-0.63)]. Consistent results were obtained when the laboratory data were included in the propensity score for matching. CONCLUSIONS: Long-term aspirin use significantly reduced the incidence of HCC and overall mortality without increasing gastrointestinal bleeding in cirrhotic patients.

Converting from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Patients with Hepatitis B Following Liver Transplantation.

BACKGROUND Taiwan has a high prevalence of hepatitis B virus (HBV) infection. HBV-related end-stage liver disease is the leading cause of liver transplantation (LT). Tenofovir alafenamide (TAF) is a recently approved agent for the treatment of chronic HBV infection that improves renal profiles compared with tenofovir disoproxil fumarate (TDF) in phase III trials. This study aimed to assess the outcomes of TAF treatment in LT recipients. MATERIAL AND METHODS This retrospective study analyzed 17 LT recipients who underwent treatment with TDF and TAF. Changes in baseline renal function were compared. RESULTS Seventeen LT recipients received TDF for ≥48 weeks and were switched to TAF. During TDF treatment, estimated glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease [MDRD] formula) decreased significantly at weeks 24 and 48. At week 48, only 2 patients (11.8%) displayed improved renal function, whereas the other patients showed decreased eGFR ranging from 5.48% to 62.84%. After switching to TAF, the median eGFR increased by 3.01% at week 24 and decreased by 0.31% at week 48. Seven patients (47%) showed improved renal function at week 48 after TAF treatment. CONCLUSIONS Switching from TDF to TAF was associated with fewer short-term renal impairment while maintaining the antiviral efficacy in LT recipients.

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

Significance of Physical Status and Liver Function Reserve for Outcome of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib Treatment.

Background: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment. Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed. Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55-3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20-3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32-0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21-0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients. Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.

Elevation of Lipid Metabolites in Deceased Liver Donors Reflects Graft Suffering.

Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver allograft recovery. How to define the damage of liver grafts is unclear. A total of 47 liver donors, 23 deceased and 24 living, were enrolled in this study. All deceased donors had suffered from severe brain damage, and six of them had experienced cardio-pulmonary-cerebral resuscitation (CPR). The exploration of liver graft metabolomics was conducted by liquid chromatography coupled with mass spectrometry. Compared with living donor grafts, the deceased liver grafts expressed higher levels of various diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, oleoylcarnitine and linoleylcarnitine; and lower levels of cardiolipin and phosphatidylcholine. The liver grafts from the donors with CPR had higher levels of cardiolipin, phosphatidic acid, phosphatidylcholine, phatidylethanolamine and amiodarone than the donors without CPR. When focusing on amino acids, the deceased livers had higher levels of histidine, taurine and tryptophan than the living donor livers. In conclusion, the deceased donors had suffered from cardio-circulation instability, and their lipid metabolites were increased. The elevation of lipid metabolites can be employed as an indicator of liver graft suffering.

Determinants of Antibody Response to SARS-CoV-2 Vaccines in Liver Transplant Recipients: The Role of Immunosuppression Reduction.

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1−2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.

Modified preoperative score to predict disease-free survival for hepatocellular carcinoma patients with surgical resections.

BACKGROUND: No prognostic models specific to hepatocellular carcinoma patients receiving surgical resection have been considered strong and convincing enough for survival prediction thus far, and there are no models including only preoperative predictors. We derived a nomogram to predict disease-free survival in a previous study. AIM: To simplify our score and compare research outcomes among other scoring systems. METHODS: We retrospectively reviewed data from 1106 patients with hepatocellular carcinoma who underwent liver resection at the Linkou Chang Gung Memorial Hospital between April 2003 and December 2012. Multivariate analyses were conducted to identify the significant survival predictors. Homogeneity, Harrell's C-index, and Akaike information criterion were compared between our score, AJCC 8th edition, Tokyo score, and Taipei Integrated Scoring System (TTV-CTP-AFP model). RESULTS: Among the 1106 patients, 731 (66.1%) had tumor recurrence at a median follow-up of 83.9 mo. Five risk factors were identified: platelet count, albumin level, indocyanine green retention rate, multiplicity, and radiologic total tumor volume. Patients were divided into three risk groups, and the 5-year survival rates were 61.7%, 39%, and 25.7%, respectively. The C-index was 0.617, which was higher than the Tokyo score (0.613) and the Taipei Integrated Scoring System (0.562) and equal to the value of the AJCC 8th edition (0.617). CONCLUSION: The modified score provides an easier method to predict survival. Appropriate treatment can be planned preoperatively by dividing patients into risk groups.

Differential Response to Sorafenib Administration for Advanced Hepatocellular Carcinoma.

Sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). However, there is no evidence for a response of different target lesions to sorafenib administration. Therefore, we aimed to evaluate the effect of sorafenib on various aHCC target lesions. The outcomes of sorafenib treatment on aHCC, i.e., treatment response for all Child A status patients receiving the drug, were analyzed. Of 377 aHCC patients, 73 (19.3%) had complete/partial response to sorafenib, while 134 (35.4%) and 171 (45.2) had a stable or progressive disease, respectively, in the first six months. Of the evaluated metastatic lesions, 149 (39.4%), 48 (12.7%), 123 (32.5%), 98 (25.9%), 83 (22.0%), and 45 (11.9%) were present in liver, bone, lung, portal/hepatic vein thrombus, lymph nodes, and peritoneum, respectively. The overall survival and duration of treatment were 16.9 ± 18.3 and 8.1 ± 10.5 months (with median times of 11.4 and 4.6, respectively). Our analysis showed poor outcomes in macroscopic venous thrombus and bone, higher AFP, and multiple target lesions. ALBI grade A had a better outcome. Sorafenib administration showed good treatment outcomes in selected situations. PD patients with thrombus or multiple metastases should be considered for sorafenib second-line treatment. The ALBI liver function test should be selected as a treatment criterion.

Recurrence Patterns After Hepatectomy With Very Narrow Resection Margins for Hepatocellular Carcinoma.

Background: The extent of hepatic resection In HCC depends on the remnant liver reserve or the proximity of the tumor to major vessels. In this study, we evaluated the effects of very close resection margins on postoperative recurrence. Methods: Consecutive LR for HCC between 2003 and 2009 were studied. Patients were divided into groups with very narrow (≤1 mm) or wider (>1 mm) resection margins. Propensity score matching (PSM) was used to balance demographic, surgical, and pathological factors. Results: 983 patients were included in the study. After PSM, 173 patients were analyzed in each group. 5-year tumor recurrence and survival rates were comparable. Most recurrences were multiple intrahepatic. Section margin recurrences were similar in both groups. By multivariate analysis, tumor size >5 cm was associated with a very narrow resection margin, whereas low platelet count and tumor macrovascular invasion were significant factors related to tumor recurrence. Conclusions: Patients with very narrow surgical margins showed outcomes comparable to those with wider surgical margins. Most recurrences were multiple intrahepatic and associated with the degree of portal hypertension and adverse tumor biology. Although wide surgical margins should be aimed whenever possible, a narrow tumor-free margin resection still represents an effective therapeutic strategy.