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We herein report two cases of locally advanced unresectable hepatocellular carcinoma (u-HCC) that were resected after achieving a radiological complete response to initially administered lenvatinib followed by transcatheter arterial chemoembolization (LEN-TACE sequential therapy). A 78-year-old woman and an 80-year-old man with HCC of Barcelona Clinic Liver Cancer classification stage C were treated for 15 and 14 months with lenvatinib, respectively. Both patients were subsequently treated with TACE, resulting in complete remission on imaging. The α-fetoprotein level in the woman and man decreased markedly from 9370 ng/ml to 46 ng/ml and from 6380 ng/ml to 3 ng/ml, respectively, leading to hepatectomy. A histopathological examination showed coagulative necrosis of the entire HCC in one case, while the other showed a small population of viable HCC cells. The results showed that LEN-TACE sequential therapy has a synergic effect and could be a promising option for locally advanced u-HCC.

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

Objective Pleomorphic adenomas have risks of malignant transformation and post operate recurrence. Therefor it is important that diagnosing pleomorphic adenomas or Warthin tumors before an operation. We evaluated the usefulness of contrast‐enhanced ultrasonography (CEUS) with Sonazoid for making differential diagnoses between pleomorphic adenomas and Warthin tumors. Methods CEUS was performed the day before surgery in 39 patients. We compared the time‐intensity curve and capillary density rate of 14 pleomorphic adenomas and 13 Warthin tumors. Results Pleomorphic adenomas demonstrated a significantly longer time to peak intensity and lower maximum curve gradient of wash‐in than Warthin tumors. The capillary density rate of Warthin tumors tended to be greater than that of pleomorphic adenomas. Conclusions CEUS and capillary density rate analysis using Sonazoid is helpful for the differential diagnosis of pleomorphic adenomas and Warthin tumors. Level of Evidence 3b., We evaluated the usefulness of contrast‐enhanced ultrasonography (CEUS) for making differential diagnoses between pleomorphic adenomas and Warthin tumors. Pleomorphic adenomas demonstrated a significantly longer time to peak intensity and lower maximum curve gradient of wash‐in than Warthin tumors. The capillary density rate of Warthin tumors tended to be greater than that of pleomorphic adenomas

Two-dimensional shear wave elastography (2D-SWE) is used in the clinical setting for observation of the liver. Unfortunately, a wide spectrum of artifactual images are frequently encountered in 2D-SWE, the precise mechanisms of which remain incompletely understood. This review was designed to present many of the artifactual images seen in 2D-SWE of the liver and to analyze them by computer simulation models that support clinical observations. Our computer simulations yielded the following suggestions: (1) When performing 2D-SWE in patients with chronic hepatic disease, especially liver cirrhosis, it is recommended to measure shear wave values through the least irregular hepatic surface; (2) The most useful 2D-SWE in patients with focal lesion will detect lesions that are poorly visible on B-mode ultrasound and will differentiate true tumors from pseudo-tumors (e.g., irregular fatty change); and (3) Measurement of shear wave values in the area posterior to a focal lesion must be avoided.

535 Background: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. Tumor shrinkage is achieved, and cancer- and treatment-free status is possible in many cases using curative conversion with resection, ablation, or selective transarterial chemoembolization (TACE). This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter study was conducted to clarify the value of curative conversion in intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. Cancer-free rate, treatment-free rate, time to cancer-free status, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, recurrence-free survival (RFS), and overall survival (OS) were assessed in patients who achieved cancer-free status using resection, ablation, selective TACE, or atezolizumab plus bevacizumab alone. Results: Cancer-free status was achieved in 38 patients (35%) (median observation period: 17. 7 months). The modalities of curative conversion were as follows: resection, 7; ablation (including patients who underwent ablation after TACE), 13; and selective TACE (including lenvatinib-TACE sequential therapy), 15. Three patients achieved cancer-free status with only atezolizumab plus bevacizumab therapy. Among the 38 cancer-free patients, 24 achieved treatment-free status. RF5 was 31.8 months (95% confidence interval, 30.5-33.0), and two patients experienced recurrence after reaching cancer-free status. Regarding OS, there were no deaths in any of the groups, and excellent outcomes were obtained. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved cancer-free status, five achieved treatment-free status. Conclusions: The curative conversion rate (cancer-free rate) in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 22% of patients achieved treatment-free status. Thus, achieving cancer-free and/or treatment-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread. Clinical trial information: NCT03434379 .

Ultrasound-guided attenuation parameter (UGAP) is recently developed for noninvasive evaluation of steatosis. However, reports on its usefulness in clinical practice are limited. This prospective multicenter study analyzed the diagnostic accuracy of grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), a noninvasive method with high accuracy, in a large cohort.Altogether, 1010 patients with chronic liver disease who underwent MRI-PDFF and UGAP were recruited and prospectively enrolled from 6 Japanese liver centers. Linearity was evaluated using intraclass correlation coefficients between MRI-PDFF and UGAP values. Bias, defined as the mean difference between MRI-PDFF and UGAP values, was assessed by Bland-Altman analysis. UGAP cutoffs for pairwise MRI-PDFF-based steatosis grade were determined using area under the receiver-operating characteristic curve (AUROC) analyses.UGAP values were shown to be normally distributed. However, because PDFF values were not normally distributed, they were log-transformed (MRI-logPDFF). UGAP values significantly correlated with MRI-logPDFF (intraclass correlation coefficient = 0.768). Additionally, Bland-Altman analysis showed good agreement between MRI-logPDFF and UGAP with a mean bias of 0.0002% and a narrow range of agreement (95% confidence interval [CI], -0.015 to 0.015). The AUROCs for distinguishing steatosis grade ≥1 (MRI-PDFF ≥5.2%), ≥2 (MRI-PDFF ≥11.3%), and 3 (MRI-PDFF ≥17.1%) were 0.910 (95% CI, 0.891-0.928), 0.912 (95% CI, 0.894-0.929), and 0.894 (95% CI, 0.873-0.916), respectively.UGAP has excellent diagnostic accuracy for grading steatosis with reference to MRI-PDFF. Additionally, UGAP has good linearity and negligible bias, suggesting that UGAP has excellent technical performance characteristics that can be widely used in clinical trials and patient care. (UMIN Clinical Trials Registry, Number: UMIN000041196).

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

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 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.

Background: Ultrasound-guided attenuation parameter (UGAP) is a tool recently developed for noninvasive evaluation of hepatic steatosis. However, there are still few reports on its usefulness in clinical practice. This prospective multicenter study analyzed the diagnostic accuracy of grading hepatic steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) in a large cohort of patients with chronic liver disease. Methods: A total of 1010 patients with chronic liver disease were prospectively enrolled from six Japanese liver centers. MRI-PDFF and UGAP values were analyzed to examine whether the distribution was normal using a normal probability plot. Linearity was evaluated using intra-class correlation coefficients (ICCs) between MRI-PDFF and UGAP values. Bias, defined as the mean difference between MRI-PDFF and UGAP values, was assessed by Bland–Altman analysis. UGAP cutoffs for pairwise MRI-PDFF-based hepatic steatosis grade were determined using area under the receiver operating characteristics curve (AUROC) analyses. Findings: UGAP values were shown to be normally distributed. In contrast, since PDFF values were not normally distributed, they were log-transformed (MRI-logPDFF). UGAP values were significantly correlated with MRI-logPDFF (ICC=0·768). Additionally, Bland–Altman analysis showed good agreement between MRI-logPDFF and UGAP with a mean bias of 0·0002% and a narrow range of agreement (95% CI: -0·015–0·015). The AUROCs for distinguishing ≥S1 (MRI-PDFF>5·2%), ≥S2 (MRI-PDFF>11·3%), and S3 (MRI-PDFF>17·1%) were 0·910 (95% CI: 0·891–0·928), 0·912 (95% CI: 0·894–0·929), and 0·894 (95% CI: 0·873–0·916), respectively. Clinical Trial: This study was registered in the UMIN Clinical Trials Registry (UMIN000041196). Interpretation: UGAP has an excellent diagnostic accuracy for grading hepatic steatosis with reference to MRI-PDFF. Additionally, UGAP has good linearity and negligible bias, suggesting that UGAP has excellent technical performance characteristics that can be widely used in clinical trials and patient care. Funding: GE Healthcare and JSPS KAKENHI [grant number JP 21K07987]. Declaration of Interest: Kento Imajo, Hidenori Toyoda, Satoshi Yasuda, Yasuaki Suzuki, Katsutoshi Sugimoto, Hidekatsu Kuroda, Tomoyuki Akita, Junko Tanaka, Yutaka Yasui, Masayuki Kurosaki, Namiki Izumi, Atsushi Nakajima, and Takashi Kumada have no competing interests to disclose. Ethical Approval: This study was approved by the Ogaki Municipal Hospital and by the local research ethics committee at each center.

The aim of this study was to examine the predictive scoring system of advanced liver fibrosis in severely obese Japanese patients. Seventy-two patients underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies. We classified these patients into two groups: Brunt stage ≥ 2 (advanced fibrosis) and 0/1 (none/mild fibrosis). A logistic regression analysis was performed to identify the predictors of advanced fibrosis. Sixteen patients had advanced fibrosis, while 56 had no/mild fibrosis. The prevalence of type 2 diabetes mellitus (T2DM) in advanced fibrosis group was significantly higher than in none/mild fibrosis. An univariate analysis of the factors predicting advanced fibrosis showed significant differences in AST/ALT ratio, serum insulin levels, HOMA-IR, and type IV collagen 7S in the T2DM group. According to a multivariate analysis, type IV collagen 7S was an independent predictor and the cutoff value was 5.6 ng/mL. We created a flow chart; high risk (T2DM and type IV collagen 7S ≥ 5.6 ng/mL), moderate risk (T2DM and type IV collagen 7S

Hereditary hemorrhagic telangiectasia (HHT) is a multiorgan genetic angiodysplastic affection characterized by visceral vascular malformations. It affects mainly the brains, lungs, gastrointestinal tract, and nasal mucosa. Unlike those organs, hepatic involvement, although very frequently occurring, is insufficiently recognized, mainly because of the complex vascular structure of this organ. Thus, treating HHT patients requires a solid understanding of these hepatic anomalies. It is especially important for any general clinicians to be able to recognize clinical findings in HHT, which leads to a high suspicion of HHT and have an index of suspicion for liver abnormalities of HHT. For this purpose, keen awareness of clinical as well as hepatic sonographic (US) findings is paramount. The aim of this review is to summarize previously reported findings on the hepatic US through a thorough analysis of related articles, and to (a) determine the role of US in the diagnosis of hepatic involvement in HHT patients and (b) propose the most simple and easy way to detect HHT-related abnormalities during routine US examinations. Hepatic US serves to diagnose the detailed complex hepatic changes typical of HHT, and contributes to increased diagnostic confidence of hepatic changes in HHT patients, with the most simple way not to overlook HHT-related abnormalities being to find hepatic artery dilatation.

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. 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. 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. 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.

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 (p0.001). 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.

Background and aim Acute liver failure (ALF) is defined as acute liver injury (ALI) associated with coagulopathy. A follow-up strategy for ALI and characterization of ALI patients with a risk of progressing to ALF have never been established. To establish predictive markers for progression from ALI to ALF, this study compared the clinical characteristics and laboratory data on the day of registration to data from a regional referral system of patients with ALI. Methods This prospective, observational study enrolled 365 consecutive patients with ALI/ALF between 2007 and 2016. We evaluated 109 ALI patients, 27 of whom satisfied the ALF criteria during observation and another 82 patients who recovered without progression to ALF. Results Four patients died; all were in the ALF group. The variables of age, incidence of autoimmune hepatitis, model of end-stage liver disease score, values for total bilirubin and prothrombin time (PT)-international ratio, and Japan Hepatic Encephalopathy Prediction Model (JHEPM) probability at registration were significantly higher in ALF patients than in ALI patients. In multivariate analysis, PT and JHEPM were identified as risk factors for progression to ALF. The cut-off values of 13%, 4.9%, 65%, and 1.32% for the model of end-stage liver disease score, JHEPM probability, PT, and PT-international ratio values, respectively, had high negative predictive values. Furthermore, among patients whose JHEPM was underestimated, none died due to ALF. Conclusion The JHEPM probability is a predictive parameter that can be used to decide a follow-up treatment strategy for ALI patients.

Background: Histological findings of the liver in acute liver injury are basically affected by degree of liver damage. However, the differences in liver histology between acute self-limiting hepatitis A (AH-A) and hepatitis E (AH-E) have not yet been clarified. This study aimed to clarify the differences in histological findings of the liver between AH-A and AH-E.

Aim We prospectively screened patients treated with direct-acting antivirals (DAA) in order to detect and analyze serum markers that are present prior to the development of drug-induced liver injury (DILI). Methods The levels of various serum markers among DILI, non-DILI and control groups were compared. The DILI group consisted of eight patients whose alanine aminotransferase (ALT) levels exceeded 32 IU/L during the DAA treatment. Eight patients without DILI were selected for the non-DILI group via a matched-group design based on age, sex and disease severity. Additionally, eight healthy volunteers were employed as the controls. Serum measurements of cytokines/chemokines, cytokeratin-18 fragment (CK-18F) and super oxidase dismutase-2 (SOD2) were evaluated on the date at which hepatitis C virus RNA was absent (baseline). For patients with DILI, serum measurements taken before treatment, 1 week before pronounced transaminase elevation (prominence-1 W) and on the date at which pronounced elevation of transaminase occurred (prominence) were also evaluated. Results All patients treated with DAA had normalized transaminase levels at baseline. In patients with DILI, interferon-inducible protein-10 (IP-10) levels were higher at prominence-1 W than at baseline. Those patients also had significantly higher levels of SOD2 and CK-18F at prominence-1 W than at baseline. Conclusion Elevated IP-10 may be a preconditioning chemokine for DAA-induced liver injury, and damage markers associated with cell death and mitochondrial dysfunction are potential predictive serum markers for DILI.

Aim Acute liver injury (ALI) has a favorable prognosis, whereas acute liver failure (ALF) leads to organ failure and thus has an unfavorable prognosis. The effect of each etiology on the clinical course of ALI remains unclear. This study aimed to determine how each etiology and glucocorticoid on the unfavorable etiology affects the clinical course of ALI. Methods This prospective observational study enrolled 522 patients with ALI/ALF from 2004 and 2017. To evaluate the influence of etiology on prognosis, decision tree analysis was carried out using age, disease type, etiology, and the presence of hepatic encephalopathy. Results Of 522 patients, 398 patients satisfied the ALI criteria at registration in this study. The ALI etiologies were as follows: viral hepatitis through oral infection (n = 54), acute hepatitis B virus (HBV) infection (n = 24), acute exacerbation of HBV infection (n = 30), de novo hepatitis due to HBV (n = 5), autoimmune hepatitis (n = 59), drug-induced liver injury (DILI; n = 85), other viruses (n = 12), and undetermined (n = 129). ALI in 46 patients progressed to ALF after registration. Of 11 patients (age >52 years) with ALF due to acute exacerbation of HBV infection or DILI, seven patients (63.6%) died. Whether glucocorticoid affected the clinical course of ALI due to acute exacerbation of HBV infection or DILI was evaluated using propensity score matching (age, sex, alanine aminotransferase, total bilirubin, and prothrombin time-international normalized ratio). Glucocorticoid did not improve the prognosis of ALI patients due to the two etiologies. Conclusions Progression of ALI due to DILI or acute exacerbation of HBV infection to ALF showed a poor prognosis.

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 &lt, 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 &gt, 2 cm based on the lower number of insertions.

Background & aims: The aim of this study was to investigate the clinical characteristics and pathophysiology of drug-induced liver injury (DILI) – acute liver failure (ALF). Methods: The patients with acute liver injury (ALI) including ALF from 2009 to 2014 were analyzed. The hepatic encephalopathy (HE) development rate was compared with the findings from a national survey in Japan. The serum cytokines levels and the findings of a liver function test were evaluated in the DILI patients. Results: The HE development rate substantially decreased for autoimmune hepatitis (AIH) – and undetermined cause-induced ALI owing to the early prediction system, but not in DILI-ALI. Among the DILI-ALF and AIH-ALF cases, the CK-18 fragment (1480.1 U/L, 3945.4 U/L), IL-8 (82.9 pg/mL, 207.5 pg/mL), IP-10 (1379.6 pg/mL, 3731.2 pg/mL) and MIP-1β (1017.7 pg/mL, 2273.3 pg/mL) levels were lower in the DILI-ALF cases. Among the DILI-ALI and DILI-ALF cases, IL-4 (19.8 pg/mL, 25.4 pg/mL) and RANTES (14028.0 pg/mL, 17804.7 pg/mL) were higher in DILI-ALI, and HMGB-1 (397.1 pg/μL, 326.2 pg/μL) and HGF (2.41 ng/mL, 0.55 ng/mL) were higher in DILI-ALF. We observed that HGF independently associated with DLI-ALF development. Conclusions: Despite the low grade apoptosis and inflammation, DILI patients progressed to ALF comparable with that of the AIH patients.

Sclerosing cholangitis (SC) with granulocytic epithelial lesion (GEL) responds well to immunosuppression therapy. We treated a 42-year-old Japanese female with ulcerative colitis, who was admitted for further evaluation of both an elevated alkaline phosphatase level and dilated intrahepatic bile ducts. A liver biopsy on the fourth hospital day revealed the infiltration of neutrophils into the bile duct epithelium, which was diagnosed as GEL. Because her ulcerative colitis was in an active stage, prednisolone (PSL) therapy was started. After the administration of PSL, laboratory data dramatically decreased. A liver biopsy was performed on the 66th hospital day to confirm the lesion around bile ducts in the portal tract. The infiltration of neutrophils into the bile duct epithelium disappeared after PSL administration, and IgG4-positive plasma cells were not found in the liver. Herein, we report a rare case of GEL-positive SC. The present case provides early evidence of treatment-induced histological changes as well as serial changes in biochemical data during the course of immunosuppression therapy.

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.

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.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 diameter5 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.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).The addition of RFA to TACE improved cumulative overall and recurrence-free survival in patients with intermediate-stage HCC, especially in patients with AFP100.

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.

A 52-year-old Japanese woman admitted to our hospital for the treatment of liver dysfunction due to an undetermined cause developed disorientation on the 58th hospital day and was diagnosed with late-onset liver failure. Abdominal ultrasound examinations were performed several times from the admission. Before the disorientation appeared, the results of the examinations revealed that the portal flow decreased, after which the hepatic arterial flow increased and the degree of liver stiffness became elevated. Although the pathophysiology of these changes remains unclear, hemodynamic changes and elevation of liver stiffness might be predictive markers of severe liver tissue damage.

Aim The prognosis of acute-on-chronic liver failure (ACLF) is extremely poor in comparison to acute liver failure (ALF). We aimed to establish methods for the early diagnosis of ACLF and its severity to identify the patients with a poor prognosis. Methods The laboratory data at admission of 30 ACLF and 46 ALF patients were compared. Three established prognosis prediction models (Model for End-Stage Liver Disease [MELD]; MELD modified by serum sodium concentration, [MELD-Na]; and the Japan hepatic encephalopathy prediction model [J-HEPM]) were assessed using area under the receiver-operator curve (AUROC) values. Results No significant difference was found in the laboratory data of the two patient groups. J-HEPM was able to predict the outcome of the ACLF subjects (AUROC = 0.93). Conclusion Although ACLF could not be differentially diagnosed from ALF at admission from the laboratory data alone, the J-HEPM effectively predicted the prognosis of liver failure in patients with ACLF. These findings indicate that ACLF patients with high J-HEPM scores require earlier and more intensive care than ALF patients.

A 47-year-old Japanese man was referred to hospital after the detection of a liver tumor. Dynamic computed tomography and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging were consistent with a diagnosis of hepatocellular carcinoma (HCC). No perfusion defect was observed in the post-vascular phase of contrast-enhanced ultrasound (CEUS). Histopathological staining of the tumor cells was positive for antibodies against HMB-45 and cluster of differentiation (CD) 68, confirming the diagnosis of hepatic angiomyolipoma (HAML). These findings indicated the presence of macrophages in HAML. We herein report a case of HAML explain how macrophages that are present within the tumor affect the staining characteristics in the post-vascular phase of CEUS.

Acute liver failure (ALF) is defined as acute liver injury (ALI) associated with coagulopathy. A follow-up strategy for ALI and characterization of ALI patients with a risk of progressing to ALF have never been established. To establish predictive markers for progression from ALI to ALF, this study compared the clinical characteristics and laboratory data on the day of registration to data from a regional referral system of patients with ALI.This prospective, observational study enrolled 365 consecutive patients with ALI/ALF between 2007 and 2016. We evaluated 109 ALI patients, 27 of whom satisfied the ALF criteria during observation and another 82 patients who recovered without progression to ALF.Four patients died; all were in the ALF group. The variables of age, incidence of autoimmune hepatitis, model of end-stage liver disease score, values for total bilirubin and prothrombin time (PT)-international ratio, and Japan Hepatic Encephalopathy Prediction Model (JHEPM) probability at registration were significantly higher in ALF patients than in ALI patients. In multivariate analysis, PT and JHEPM were identified as risk factors for progression to ALF. The cut-off values of 13%, 4.9%, 65%, and 1.32% for the model of end-stage liver disease score, JHEPM probability, PT, and PT-international ratio values, respectively, had high negative predictive values. Furthermore, among patients whose JHEPM was underestimated, none died due to ALF.The JHEPM probability is a predictive parameter that can be used to decide a follow-up treatment strategy for ALI patients.

AIM The optimal conditions for hepatocyte proliferation should be clarified in an attempt to improve the impaired liver regeneration observed in patients with acute liver failure (ALF). In order to evaluate the significance of the serum α-fetoprotein (AFP). level and prothrombin time international normalized ratio (PT-INR) as possible biomarkers of the proliferation of liver stem/progenitor cells (LPC) and mature hepatocytes (MH), respectively, we focused on donors of living donor liver transplantation (LDLT) and patients with acute liver injury (ALI), including ALF. METHODS Seventy-three patients with ALI/ALF and 11 donors for LDLT were evaluated. LPC induction was histologically evaluated using cytokeratin (CK)-7 staining in 45 ALI/ALF patients. RESULTS The AFP level was not apparently elevated during the observation period in any of the LDLT donors, whereas the serum AFP levels were substantially increased in the patients with ALI/ALF and significantly correlated with the number of CK-7 positive LPC in the liver, except for very severe damaged liver. All patients exhibiting an early peak in the AFP level prior to PT-INR elevation died. CONCLUSION The serum AFP level may reflect the induction of LPC in ALI/ALF patients. The substantial and persistent induction of LPC until sufficient regeneration of MH may be needed for a recovery from ALF. We herein demonstrate that the serum AFP level may be a serum marker of LPC in patients with ALI/ALF. A comparison of the serial changes in the AFP levels and PT-INR in our study patients showed impaired proliferation of LPC and delayed recovery of MH in the patients who died.

Aim We measured liver stiffness (LS) in patients with acute liver failure (ALF) using acoustic radiation force impulse (ARFI) elastography and investigated the usefulness of measuring LS for predicting the prognosis of ALF patients. Methods From April 2010 to December 2013, we evaluated 63 patients with acute liver disease. The subjects included 41 patients with acute hepatitis (AH), 16 patients with severe AH (SAH), who had no hepatic encephalopathy despite plasma prothrombin time of 40% or less, and six patients with fulminant hepatitis (FH) diagnosed according to the criteria of the Japanese Study Group. The relationships among shear wave velocity (SWV), clinical diagnosis, liver function tests and prognosis were evaluated. Receiver–operator curve (ROC) analysis was performed to investigate whether ARFI elastography exhibits potential usefulness for the prediction of FH. Results The mean SWV on admission were 1.98 ± 0.55, 2.61 ± 0.58 and 3.66 ± 0.86 m/s in the AH, SAH and FH groups, respectively. The SWV was significantly higher in the FH group than in the other groups (P