Liver transplantation for advanced hepatocellular carcinoma

There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future

Porphyra-334, a mycosporine-like amino acid, attenuates UV-induced apoptosis in HaCaT cells

The main aim of the current research was to study the effect of porphyra-334, one of mycosporine-like amino acids (MAAs), well known as UV-absorbing compounds, on UV-induced apoptosis in human immortalized keratinocyte (HaCaT) cells. Due to their UV-screening capacity and ability to prevent UV-induced DNA damage, MAAs have recently attracted considerable attention in both industry and research in pharmacology. Herein, human HaCaT cells were used to determine the biological activities of porphyra-334 by various in vitro assays, including proliferation, apoptosis and Western blot assays. The proliferation rate of UV-irradiated HaCaT cells was significantly decreased compared to the control group. Pretreatment with porphyra-334 markedly attenuated the inhibitory effect of UV and induced a dramatic decrease in the apoptotic rate. Expression of active caspase-3 protein was increased in response to UV irradiation, while caspase-3 levels were similar between cells treated with porphyra-334 and the non-irradiated control group. Taken together, our data suggest that porphyra-334 inhibits UV-induced apoptosis in HaCaT cells through attenuation of the caspase pathway

An Antiproteinase lnhibits High Carbohydrate-Diet Induced Gallstone Formation in Hamsters

High carbohydrate(CHO) diet plays a role in pigment gallstone formation, though the mechanism is not yet clarified. We postulated that high CHO diet induces gallstone formation through a mechanism whereby high CHO diet poorly stimulates cholecystokinin(CCK) release and causes relative bile stasis. The purpose of our study was to examine whether camostat mesilate(camostat), oral antiproteinase increasing CCK release, inhibits gallstone formation from high CHO diet in hamsters. Fifty six hamsters were divided into 3 groups(G): I(n = 18) was fed normal rat chow(43% CHO), lI(n = 19) was fed a high CHO diet(65% CHO), III(n = 19) was fed 0.2% camostat high CHO diet. The animals were sacrificed after 8 weeks. Stones were checked grossly and gallbladder bile was analysed. Gallstones had developed in 11.1% of G-I, 84.2% of G-II, and 26.3% of GIII( p < 0.05: II vs III). Concentrations of cholesterol, phospholipid, calcium, bilirubin and bile acid were low in G-III. Pancreatic weight, reflecting chronic status of CCK level, of G-II1 was greater than other groups and that of G-II was smaller than that of G-I. In conclusion, camostat inhibits high CHO diet induced gallstone formation in hamsters and the possible mechanism is that camostat recovers the low CCK release by high CHO diet. This study suggests that high CHO diet is associated with pigment stone formation through the mechanism that high CHO diet causes poor CCK release

Does living liver donors’ underestimation about surgical outcomes impact on their health-related quality of life after donation?: a descriptive cross-sectional study

In South Korea, the number of living-donor liver transplantations in 2019 was 1,188. Living liver donors (LLDs) undergo surgery and the postoperative recovery process for altruistic purposes. This study explored LLDs’ unmet expectations about surgical outcomes and examined their impact on the donors’ health-related quality of life (HRQOL). This descriptive cross-sectional study utilized a self-reported survey. Data were collected at a university hospital in Seoul, South Korea. Among the 535 LLDs who underwent surgery for donation between January 2011 and March 2021, 124 participated in this study. The Korean version of the 12-item Short Form Health Survey version 2 (SF-12v2) was used to measure the HRQOL of LLDs. Unmet expectations regarding surgical outcomes were measured using four items: pain, length of hospital stay, speed of recovery, and complications. Logistic regression model was applied to determine whether the unmet expectations influence HRQOL in LLDs. Odds ratios with 95% confidence interval were used. The percentage of the participants who reported that their actual experiences for pain, speed of recovery, hospital stay, and complications were worse than expected were 34.7%, 22.6%, 9.7%, and 7.3%, respectively. Unmet expectations about surgical outcomes were significantly associated with physical and mental HRQOL after controlling for age, sex, education level, income, postoperative complications, recipients’ death, time since donation, and satisfaction with the decision to donate. LLDs should be supported in obtaining more accurate and realistic information about surgical outcomes to decrease unmet expectations, which may help improve their quality of life

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

Background/AimsThe dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT

High dose therapy followed by autologous peripheral blood stem cell transplantation as a first line treatment for multiple myeloma: a Korean Multicenter Study.

We conducted a phase II multicenter trial to estimate the response and survival of patients with newly diagnosed multiple myeloma to high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation. Eligible patients who had undergone induction with vincristine, adriamycin and dexamethasone (VAD) should have adequate cardiac, pulmonary and renal function (creatinine <2 mg/dL). Melphalan at 200 mg/m2 was used as a conditioning regimen. Eighty patients were enrolled from 13 centers. The median age of the patients was 53 yr (range; 20 to 68 yr). The initial stage was IA/IIA/IIB/IIIA/IIIB in 3/8/1/54/14 patients, respectively. Beta2-microglobulin, CRP and LDH were increased in 74, 42 and 34% of the patients examined. Cytogenetic data were available in 30 patients, and 6 patients showed numeric or structural abnormalities. Two therapy-related mortalities occurred from infection. Among the 78 evaluable patients, CR/PR/MR/NC/PD were achieved in 48/26/2/1/1 patients, respectively. After a median follow-up of 30 months, the median overall and event-free survivals were 66 months (95% CI: 20-112) and 24 months (95% CI: 18-29), respectively. This study verifies the efficacy and feasibility of high dose melphalan therapy with autologous stem cell transplantation in newly diagnosed multiple myeloma

CD160 serves as a negative regulator of NKT cells in acute hepatic injury

[EN] CD160 and BTLA both bind to herpes virus entry mediator. Although a negative regulatory function of BTLA in natural killer T (NKT) cell activation has been reported, whether CD160 is also involved is unclear. By analyzing CD160−/− mice and mixed bone marrow chimeras, we show that CD160 is not essential for NKT cell development. However, CD160−/− mice exhibit severe liver injury after in vivo challenge with α-galactosylceramide (α-GalCer). Moreover, CD160−/− mice are more susceptible to Concanavalin A challenge, and display elevated serum AST and ALT levels, hyperactivation of NKT cells, and enhanced IFN-γ, TNF, and IL-4 production. Lastly, inhibition of BTLA by anti-BTLA mAb aggravates α-GalCer-induced hepatic injury in CD160−/− mice, suggesting that both CD160 and BTLA serve as non-overlapping negative regulators of NKT cells. Our data thus implicate CD160 as a co-inhibitory receptor that delivers antigen-dependent signals in NKT cells to dampen cytokine production during early innate immune activationSIWe thank the NIH Tetramer Core Facility for providing PBS 57 ligand loaded CD1d Tetramers. Further, we thank the staffs of Gyerim Experimental Animal Resource Center for animal care and technical assistance. K.-M. Lee was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future planning (NRF-2016M3A9B6948342, NRF- 2017R1A2B3004828, and NRF-2018M3A9D3079288). S.-J. Kim was supported by the Korea Health Industry Development Institute (KHIDI-HI14C2640) grant funded by Korea Government. S.-J. Ha was supported by a grant from the NRF (NRF- 2018R1A2A1A05076997). T.-J. Kim was additionally supported by a grant from the NRF (NRF-2016R1A6A3A04009698

Hepatocellular carcinoma in liver transplantation candidates: detection with gadobenate dimeglumine-enhanced MRI

The purpose of this study was to retrospectively evaluate the diagnostic performance of dynamic gadobenate dimeglumine-enhanced MRI with explant pathologic correlation in the detection of hepatocellular carcinoma (HCC) in patients undergoing liver transplantation. MATERIALS AND METHODS: Forty-seven patients (28 men, 19 women; mean age, 49 years) underwent dynamic gadobenate dimeglumine-enhanced MRI within 3 months before primary liver transplantation. Dynamic imaging was performed before (unenhanced) and after (hepatic arterial, portal venous, equilibrium, and 1-hour delayed phases) IV bolus administration of gadobenate dimeglumine at 0.1 mmol/kg body weight. Retrospective image analysis to detect HCC nodules was performed independently by two abdominal radiologists who had no pathologic information. On a per-nodule basis, the sensitivity and positive predictive value were calculated for the two observers. Sensitivity and specificity in the diagnosis of HCC also were evaluated. Fisher's exact test was performed to determine whether there was a detection difference between HCC nodules 1 cm in diameter or larger and nodules smaller than 1 cm and to evaluate the differences in causes of false-positive MRI findings based on lesion size (>or= 1 cm vs < 1 cm). RESULTS: Twenty-seven patients had 41 HCCs. In HCC detection, gadobenate dimeglumine-enhanced MRI had a sensitivity of 85% (35 of 41 HCCs) and a positive predictive value of 66% (35 of 53 readings) for observer 1 and a sensitivity of 80% (33 of 41 HCCs) and a positive predictive value of 65% (34 of 52 readings) for observer 2. For both observers, sensitivity in the detection of HCCs 1 cm in diameter and larger (91-94%) was significantly different (p < 0.05) from that in detection of HCCs smaller than 1 cm (29-43%). Nonneoplastic arterial hypervascular lesions more often caused false-positive diagnoses of lesions smaller than 1 cm in diameter (80-86%) on MR images than of those 1 cm in diameter and larger (0-25%). The difference was statistically significant (p < 0.05) for both observers. In diagnosis, gadobenate dimeglumine-enhanced MRI had a sensitivity of 87% (20 of 23 patients) and a specificity of 79% (19 of 24 patients) for both observers. CONCLUSION: Dynamic gadobenate dimeglumine-enhanced MRI has a sensitivity of 80-85% and a positive predictive value of 65-66% in the detection of HCC. The technique, however, is of limited value for detecting and characterizing lesions smaller than 1 cm in diameter