Multivariable Quantitative US Parameters for Assessing Hepatic Steatosis.

Background Because of the global increase in the incidence of nonalcoholic fatty liver disease, the development of noninvasive, widely available, and highly accurate methods for assessing hepatic steatosis is necessary. Purpose To evaluate the performance of models with different combinations of quantitative US parameters for their ability to predict at least 5% steatosis in patients with chronic liver disease (CLD) as defined using MRI proton density fat fraction (PDFF). Materials and Methods Patients with CLD were enrolled in this prospective multicenter study between February 2020 and April 2021. Integrated backscatter coefficient (IBSC), signal-to-noise ratio (SNR), and US-guided attenuation parameter (UGAP) were measured in all participants. Participant MRI PDFF value was used to define at least 5% steatosis. Four models based on different combinations of US parameters were created: model 1 (UGAP alone), model 2 (UGAP with IBSC), model 3 (UGAP with SNR), and model 4 (UGAP with IBSC and SNR). Diagnostic performance of all models was assessed using area under the receiver operating characteristic curve (AUC). The model was internally validated using 1000 bootstrap samples. Results A total of 582 participants were included in this study (median age, 64 years; IQR, 52-72 years; 274 female participants). There were 364 participants in the steatosis group and 218 in the nonsteatosis group. The AUC values for steatosis diagnosis in models 1-4 were 0.92, 0.93, 0.95, and 0.96, respectively. The C-indexes of models adjusted by the bootstrap method were 0.92, 0.93, 0.95, and 0.96, respectively. Compared with other models, models 3 and 4 demonstrated improved discrimination of at least 5% steatosis (P < .01). Conclusion A model built using the quantitative US parameters UGAP, IBSC, and SNR could accurately discriminate at least 5% steatosis in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Han in this issue.

Human SOD1 is secreted via a conventional secretion pathway in Saccharomyces cerevisiae.

Soluble proteins sorted through the secretory pathway contain an N-terminal signal peptide that induces their translocation into the endoplasmic reticulum (ER) from the cytosol. However, a few proteins that lack a signal peptide are still translocated into the ER, such as SOD1. SOD1 is a causative gene of amyotrophic lateral sclerosis (ALS). A relationship has been suggested between the secretion of SOD1 and the pathogenesis of ALS; however, the transport mechanism of SOD1 remains unclear. We herein report that SOD1 was translocated into the ER lumen through the translocon Sec61 and was then secreted extracellularly. The present results indicate the potential of suppressing the secretion of SOD1 as a therapeutic target for ALS.

Diagnostic accuracy of ultrasound-guided attenuation parameter as a noninvasive test for steatosis in non-alcoholic fatty liver disease.

The purpose of this study was to evaluate the diagnostic accuracy of the ultrasound-guided attenuation parameter (UGAP) using the LOGEQ E10 for hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and directly compare UGAP with attenuation imaging (ATI) and controlled attenuation parameter (CAP). We prospectively analyzed 105 consecutive patients with NAFLD who underwent UGAP, ATI, CAP, and liver biopsy on the same day between October 2019 and April 2021. The diagnostic ability of the UGAP-determined attenuation coefficient (AC) was evaluated using receiver operating characteristic (ROC) curve analysis, and its correlation with ATI-determined AC values or CAP values was investigated. The success rate of UGAP was 100%. The median IQR/med obtained by UGAP was 4.0%, which was lower than that of ATI and CAP (P < 0.0001). The median ACs obtained by UGAP for grades S0 (control), S1, S2, and S3 were 0.590, 0.670, 0.750, and 0.845 dB/cm/MHz, respectively, demonstrating a stepwise increase with increasing hepatic steatosis severity (P < 0.0001). The areas under the ROC curve of UGAP for identifying ≥ S1, ≥ S2, and S3 were 0.890, 0.906, and 0.912, respectively, which were significantly better than the results obtained with CAP for identifying S3. Furthermore, the correlation coefficient between UGAP-AC and ATI-AC values was 0.803 (P < 0.0001), indicating a strong relationship. Our results indicate that UGAP has high diagnostic accuracy for detecting and grading hepatic steatosis in patients with NAFLD.

Evaluation of the Long-term Administration of Rifaximin for More than Three Years in the Treatment of Repeated and Recurrent Overt Hepatic Encephalopathy.

The patient was a 65-year-old man with alcoholic liver cirrhosis who had been admitted to hospital 5 times for repeated and recurrent overt hepatic encephalopathy (HE) despite numerous therapies, including disaccharide, branched-chain amino acid (BCAA) formula, L-carnitine and zinc. After the additional administration of rifaximin (1,200 mg/day orally), his consciousness level was well controlled for 3 years without any adverse effects. The long-term administration of rifaximin may be useful and safe for managing recurrent overt HE, although the maintenance dosage and duration of rifaximin and safety should be evaluated in patients with ameliorated HE.

Comparing the Safety and Efficacy of Microwave Ablation Using ThermosphereTM Technology versus Radiofrequency Ablation for Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

There is limited information regarding the oncological benefits of microwave ablation using ThermosphereTM technology for hepatocellular carcinoma. This study compared the overall survival and recurrence-free survival outcomes among patients with hepatocellular carcinoma after microwave ablation using ThermosphereTM technology and after radiofrequency ablation. Between December 2017 and August 2020, 410 patients with hepatocellular carcinoma (a single lesion that was ≤5 cm or ≤3 lesions that were ≤3 cm) underwent ablation at our institution. Propensity score matching identified 150 matched pairs of patients with well-balanced characteristics. The microwave ablation and radiofrequency ablation groups had similar overall survival rates at 1 year (99.3% vs. 98.2%) and at 2 years (88.4% vs. 87.5%) (p = 0.728), as well as similar recurrence-free survival rates at 1 year (81.1% vs. 76.2%) and at 2 years (60.5% vs. 62.1%) (p = 0.492). However, the microwave ablation group had a significantly lower mean number of total insertions (1.22 ± 0.49 vs. 1.59 ± 0.94; p < 0.0001). This retrospective study revealed no significant differences in the overall survival and recurrence-free survival outcomes after microwave ablation or radiofrequency ablation. However, we recommend microwave ablation for hepatocellular carcinoma tumors with a diameter of >2 cm based on the lower number of insertions.

Two-dimensional shear wave elastography and ultrasound-guided attenuation parameter for progressive non-alcoholic steatohepatitis.

BACKGROUND AND AIMS: We investigated the usefulness of combining two-dimensional shear wave elastography and the ultrasound-guided attenuation parameter for assessing the risk of progressive non-alcoholic steatohepatitis, defined as non-alcoholic steatohepatitis with a non-alcoholic fatty liver disease activity score of ≥4 and a fibrosis stage of ≥2. METHODS: This prospective study included 202 patients with non-alcoholic fatty liver disease who underwent two-dimensional shear wave elastography, ultrasound-guided attenuation parameter, vibration-controlled transient elastography, the controlled attenuation parameter, and liver biopsy on the same day. Patients were grouped according to liver stiffness measurement using two-dimensional shear wave elastography and the attenuation coefficient, assessed using the ultrasound-guided attenuation parameter: A, low liver stiffness measurement/low attenuation coefficient; B, low liver stiffness measurement/high attenuation coefficient; C, high liver stiffness measurement/low attenuation coefficient; and D, high liver stiffness measurement/high attenuation coefficient. RESULTS: Two-dimensional shear wave elastography and vibration-controlled transient elastography had equivalent diagnostic performance for fibrosis. The areas under the curve of the ultrasound-guided attenuation parameter for identifying steatosis grades ≥S1, ≥S2, and S3 were 0.89, 0.91, and 0.92, respectively, which were significantly better than those of the controlled attenuation parameter (P<0.05). The percentages of progressive non-alcoholic steatohepatitis in Groups A, B, C, and D were 0.0%, 7.7%, 35.7%, and 50.0%, respectively (P<0.001). The prediction model was established as logit (p) = 0.5414 × liver stiffness measurement (kPa) + 7.791 × attenuation coefficient (dB/cm/MHz)-8.401, with area under the receiver operating characteristic curve, sensitivity, and specificity values of 0.832, 80.9%, and 74.6%, respectively; there was no significant difference from the FibroScan-aspartate aminotransferase score. CONCLUSION: Combined assessment by two-dimensional shear wave elastography and the ultrasound-guided attenuation parameter is useful for risk stratification of progressive non-alcoholic steatohepatitis and may be convenient for evaluating the necessity of specialist referral and liver biopsy.

Contrast-Enhanced Ultrasonography-Based Hepatic Perfusion for Early Prediction of Prognosis in Acute Liver Failure.

BACKGROUND AND AIMS: Acute liver failure (ALF) is a rare but dramatic clinical syndrome characterized by massive hepatic necrosis leading to multiorgan failure. It is difficult to predict the outcomes in patients with ALF using existing prognostic models. We aimed to analyze hepatic perfusion using contrast-enhanced ultrasound and Doppler ultrasound in patients with ALF and investigate its utility as a prognostic biomarker. APPROACH AND RESULTS: In this prospective observational study, 208 patients with acute liver injury/ALF were enrolled from 2015 to 2019. We evaluated 50 consecutive patients with ALF with Doppler ultrasound and contrast-enhanced ultrasound performed on admission. The cases were divided into the following two groups: survivors (recovered without surgical intervention) and nonsurvivors (died of ALF or underwent liver transplantation). The time to peak and peak intensity of hepatic artery, portal vein, hepatic vein, and liver parenchyma were calculated using the time-intensity curve analysis. The hepatic artery (HA) resistive index was calculated using the fast Fourier transform analysis of Doppler ultrasound. The time interval (TI) between the time to peak of HA and liver parenchyma (LP) was significantly shorter in the nonsurvivors than in the survivors (P < 0.0001). The area under the receiver operating curve values for TI (HA, LP), Japanese scoring system, HE prediction model, Model for End-Stage Liver Disease score, and King's College Hospital criteria for the prediction of poor prognosis were 0.953, 0.914, 0.861, 0.816, and 0.731, respectively. The most appropriate cutoff value of TI (HA, LP) was 6.897 seconds; the sensitivity, specificity, positive and negative predictive values were 94.4%, 90.6%, 85.0%, and 96.7%, respectively. CONCLUSIONS: TI (HA, LP) accurately predicts the outcome in patients with ALF and may be useful in clinical decision making.

Impact of Grip Strength in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib.

Although sarcopenia is characterized by a loss of muscle strength and skeletal muscle mass, few studies have evaluated the effect of muscle strength on hepatocellular carcinoma (HCC) patients. We evaluated the impact of sarcopenia-related factors (grip strength (GS) and the skeletal muscle index (SMI)) on the survival among lenvatinib-treated unresectable HCC (u-HCC) patients. This single-center cohort study was conducted at a university hospital. The study population included 63 lenvatinib-treated u-HCC patients managed between April 2018 and April 2020. A decreased GS and decreased SMI were found in 21 (33.3%) and 22 (34.9%) patients, respectively. The overall survival (OS) of the normal GS group was significantly higher than that of the decreased GS group, while that of the normal and decreased SMI groups did not differ markedly. There were no significant differences in the progression-free survival between the normal GS and decreased GS groups or the normal SMI and decreased SMI groups. A multivariate Cox proportional hazards model showed that modified albumin-bilirubin-grade (mALBI) 2b (hazard ratio (HR) 4.39) and a decreased GS (HR 3.55) were independently associated with an increased risk of poor prognosis. In addition to the hepatic functional reserve, a decreased GS was a poor prognostic factor in lenvatinib-treated u-HCC patients.

Change in arterial tumor perfusion is an early biomarker of lenvatinib efficacy in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma (HCC). In the present study, we evaluated the potential of early changes in the time-intensity curve (TIC) of arterial phase on contrast-enhanced ultrasound (CEUS) as early imaging biomarkers of lenvatinib efficacy. AIM: To evaluate the potential of the early changes in the TIC of CEUS as early imaging biomarkers of lenvatinib efficacy in patients with unresectable HCC. METHODS: We analyzed 20 consecutive patients with unresectable HCC treated with lenvatinib from March to November 2018. Tumor response at 8 wk was assessed by computed tomography using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). CEUS was performed at baseline before treatment (Day 0) and on day 7 (Day 7), and the images were analyzed in the arterial phase for 20 seconds after the contrast agent arrived at the target tumor. Three perfusion parameters were extracted from the TICs: the slope of wash-in (Slope), time to peak (TTP) intensity, and the total area under the curve (AUC) during wash-in. The rate of change in the TIC parameters between Day 0 and Day 7 was compared between treatment responders and non-responders based on mRECIST. RESULTS: The rate of change for all TIC parameters showed significant differences between the responders (n = 9) and non-responders (n = 11) (Slope, P = 0.025; TTP, P = 0.004; and AUC, P = 0.0003). The area under the receiver operating curve values for slope, TTP, and AUC for the prediction of responders were 0.805, 0.869, and 0.939, respectively. CONCLUSION: CEUS may be useful for the early prediction of tumor response to lenvatinib therapy in patients with unresectable HCC.

Caspase-independent hepatocyte death: A result of the decrease of lysophosphatidylcholine acyltransferase 3 in non-alcoholic steatohepatitis.

BACKGROUND AND AIMS: Lipotoxicity causes liver inflammation, which leads to non-alcoholic steatohepatitis (NASH). Lysophosphatidylcholine (LPC) is a causal agent of lipotoxicity. Recently, lysophosphatidylcholine acyltransferase (LPCAT) was identified as an enzyme that catalyzes the esterification of LPC, which potentially decreases LPC levels. However, the effect of LPCAT in lipotoxicity of the liver is not fully understood. Our aim was to determine whether LPCAT attenuates lipotoxicity in the liver. METHODS: Mice fed a high-fat diet with sucrose (HFDS) or high-fat diet without sucrose, and Huh-7 cells treated with palmitate were used. RESULTS: Mice-fed HFDS showed advanced liver fibrosis as compared with mice-fed high-fat diet or normal chow. Lysophosphatidylcholine acyltransferase 3 (LPCAT3) mRNA expression in the liver was significantly decreased in the HFDS liver, and LPC content in the HFDS liver was significantly increased as compared with the other groups. When Huh-7 cells with short hairpin RNA-mediated knockdown of LPCAT3 (shLPCAT3 cells) were treated with palmitate, the intracellular LPC concentration and cell death were significantly higher than those in wild-type Huh-7 cells. Palmitate-induced cell death in shLPCAT3 was attenuated by a combination of receptor-interacting protein kinase 1 inhibitor with pan-caspase inhibitor. In contrast, intracellular LPC and palmitate-induced cell death were significantly lower in LPCAT3-overexpressing Huh-7 cells than in wild-type cells. CONCLUSION: Depletion of LPCAT3 in a mouse model of NASH leads to caspase-independent cell death, and LPCAT3 is a potential therapeutic target in NASH.

Occurrence of hepatocellular carcinoma 24 years after successful interferon therapy in a patient with chronic hepatitis C: a case report.

An 82-year-old man presented with hepatocellular carcinomas (HCCs) 24 years after achieving a sustained virological response (SVR) to an interferon for hepatitis C. His hepatic fibrosis stage was F1 when he was treated at 58 years. He was followed-up by annual blood tests and abdominal ultrasonography or computed tomography. After the IFN treatment, he had drunk approximately 100 g of ethanol. Serum aspartate aminotransferase and gamma-glutamyl transpeptidase levels had been elevated since 2012. To investigate the possible factors that affect hepatocarcinogenesis over 10 years after achieving an SVR, we reviewed the literature. Of 39 reported patients, 26, as well as ours, had one or more lifestyle-related factors, including body mass index ≥ 25 kg/m2, diabetes mellitus, impaired glucose tolerance, hepatosteatosis, or alcohol consumption. In our patient, aging and daily alcohol consumption might have triggered the development of HCCs.

Efficacy of combination therapy with transcatheter arterial chemoembolization and radiofrequency ablation for intermediate-stage hepatocellular carcinoma.

OBJECTIVES: Transcatheter arterial chemoembolization (TACE) is the standard therapy for patients with intermediate-stage hepatocellular carcinoma (HCC). This study aimed to determine whether combination therapy with radiofrequency ablation (RFA) and TACE was superior to TACE monotherapy for intermediate-stage HCC and identify cases in which this technique was the most effective. MATERIALS AND METHODS: We selected patients with intermediate HCC who met the following eligibility criteria: (1) ≥ 20 years of age, (2) receiving initial therapy, (3) ≤7 tumors, and (4) maximum tumor diameter <5 cm. We performed propensity score matching (PSM) using potential confounding factors. We retrospectively compared the cumulative overall survival rate and recurrence-free survival rate between the TACE + RFA and TACE groups. Additionally, a sub-group analysis was performed for preoperative factors. RESULTS: Among the 103 patients, 92 were selected using PSM. The cumulative overall survival rates at 1, 3, and 5 years for the TACE + RFA group were 97.4%, 70.4%, and 60.4%, respectively, which were significantly higher than those for the TACE group (92.7%, 55.7%, and 22.8%, respectively, p = .045). The recurrence-free survival rates at 0.5, 1, and 2 years for the TACE + RFA group were 80.0%, 58.6%, and 33.3%, respectively, which were significantly higher than those for the TACE group (34.5%, 8.8%, and 2.9%, respectively, p < .01). For the sub-group with α-fetoprotein (AFP) <100 ng/mL, the TACE + RFA group demonstrated a significantly improved prognosis than the TACE group (p = .036). CONCLUSIONS: The addition of RFA to TACE improved cumulative overall and recurrence-free survival in patients with intermediate-stage HCC, especially in patients with AFP <100.

The B-Mode Image-Guided Ultrasound Attenuation Parameter Accurately Detects Hepatic Steatosis in Chronic Liver Disease.

The purpose of our study was to evaluate the diagnostic accuracy of the ultrasound-guided attenuation parameter (UGAP) for the detection of hepatic steatosis in comparison with the controlled attenuation parameter (CAP), using histopathology as the reference standard. We prospectively analyzed 163 consecutive chronic liver disease patients who underwent UGAP, CAP, computed tomography and a liver biopsy on the same day between April 2016 and July 2017. Radiofrequency signals corresponding to the images were compensated by the reference signal previously measured from the uniform phantom with known attenuation (0.44 dB/cm/MHz). The attenuation coefficient was calculated from the signals' decay slope. The median attenuation coefficient values in patients with S0 (n = 62), S1 (n = 63), S2 (n = 23) and S3 grade (n = 15) were 0.485, 0.560, 0.660 and 0.720, respectively. Significant correlations were found between attenuation coefficient and percentage steatosis, CAP values and liver-to-spleen computed tomography attenuation ratio (p < 0.001). The areas under the receiver operating characteristic curve of UGAP for identifying ≥S1, ≥S2 and ≥S3 were 0.900, 0.953 and 0.959, respectively, which were significantly better than the results obtained with CAP for identifying ≥S2 and ≥S3. In conclusion, UGAP had high diagnostic accuracy for detecting hepatic steatosis in patients with chronic liver disease.

Evaluation of ballooned hepatocytes as a risk factor for future progression of fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased. Non-alcoholic steatohepatitis (NASH) shows progression of liver fibrosis in NAFLD. It remains unclear which patients with NAFLD will show progression of liver fibrosis. Therefore, we aimed to investigate the risk factor associated with the progression of liver fibrosis among patients with NAFLD. METHODS: This observational study enrolled 157 patients with biopsy-proven NAFLD. Thirty-two patients were excluded because of lack of data. The accuracy of the formulae for estimating liver fibrosis, i.e., the FIB-4 index, APRI, and Forns index, was compared. Using serial changes of the best formula for liver fibrosis, we identified factors associated with the progression of liver fibrosis. Histological liver fibrosis was quantified using the Brunt stage. RESULTS: Sixty-three patients were diagnosed as having NASH. The FIB-4 index provided the best diagnostic accuracy for liver fibrosis [Brunt stage 0 versus 1-4, areas under the curve (AUC) 0.74; 0-1 versus 2-4, AUC 0.77; 0-2 versus 3-4, AUC 0.78; and 1-3 versus 4, AUC 0.87]. The association between body mass index, sex, observation period, and histological findings (liver fat content, bridging fibrosis, and hepatocyte ballooning) with the change in the FIB-4 index was evaluated among patients with NASH, using multivariate analysis. Among these factors, hepatocyte ballooning was associated with an increase in the FIB-4 index. CONCLUSION: The FIB-4 index was the best formula for estimating liver fibrosis in patients with biopsy-proven NAFLD, and the presence of ballooned hepatocytes was a risk factor for the progression of liver fibrosis.

Accuracy of 2D shear wave elastography in the diagnosis of liver fibrosis in patients with chronic hepatitis C.

PURPOSE: This prospective study was conducted to assess the diagnostic accuracy of two-dimensional shear wave elastography (2D SWE) in the diagnosis of liver fibrosis in patients with chronic liver disease and hepatitis C virus (HCV) compared with the serum liver fibrosis biomarkers using the results of liver biopsy as the reference standard. METHODS: We analyzed 233 consecutive HCV patients. On the same day, 2D SWE m, biochemical tests, and liver biopsy were performed. We used the METAVIR staging system and receiver operating characteristic curves for the analysis. RESULTS: The success rate of 2D-SWE was 98.7%. The median shear wave velocities (SWVs) of patients in the F0, F1, F2, F3, and F4 stages were 1.35 m/s, 1.42 m/s, 1.58 m/s, 1.83 m/s, and 2.13 m/s, respectively, demonstrating a stepwise increase (P < .0001). The accuracy of 2D-SWE in the prediction of ≥F1, ≥F2, ≥F3, and F4 was .888 (95% CI: .85-.93), .915 (95% CI: .88-095), .940 (95% CI: .91-.97), and .949 (95% CI: .92-.97), respectively. 2D-SWE was significantly superior to serum liver fibrosis biomarkers. CONCLUSION: 2D-SWE was positively correlated with the severity of liver fibrosis and was more useful for to predict all liver fibrosis grades in HCV patients than liver fibrosis biomarkers.

Visualizing the hepatic vascular architecture using superb microvascular imaging in patients with hepatitis C virus: A novel technique.

AIM: To identify the hepatic vascular architecture of patients with hepatitis C virus (HCV) using superb microvascular imaging (SMI) and investigate the use of SMI in the evaluation of liver fibrosis. METHODS: SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees (VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated. RESULTS: There was a significant difference between SMI distribution pattern and fibrosis stage (P < 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic (AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index (r = 0.617, P < 0.0001). CONCLUSION: SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients.

Bismuth heterocycles based on a diphenyl sulfone scaffold: synthesis and substituent effect on the antifungal activity against Saccharomyces cerevisiae.

A series of heterocyclic organobismuth(III) compounds 2 [ClBi(5-R-C6H(3)-2-SO2C6H(4)-1'-): R=Me, Ph, MeO, Cl, H, t-Bu, CF3, F, Me2N] was synthesized in order to study the relative importance of structure and specific substitutions in relation to their lipophilicity and antifungal activity against the yeast Saccharomyces cerevisiae. A clear structure-activity relationship between the size of the inhibition zone and the value of ClogP was found for 2. These results suggest that the higher the lipophilicity, the lower the antifungal activity. Thus, 2e (R=H) and 2h (R=F), which had ClogP values of 1.18 and 1.45, respectively, were most active. In contrast, 2b (R=Ph) and 2f (R=t-Bu) had ClogP values of 3.06 and 3.00, respectively, and exhibited no antifungal activity. Compound 6b ClBi[5-(OH)C6H(3)-2-SO(2)-5'-(OH)C6H(3)-1'-] had an estimated ClogP value of 0.81 but exhibited only low activity in spite of its low ClogP value, suggesting that such a considerable decrease in lipophilicity lowers inhibition activity. Bismuth carboxylate 7b derived from p-nitrobenzoic acid and 2e exhibited inhibition activity comparable to those of 2e and 2h despite its higher lipophilicity (ClogP=2.68).