Positive impact of obesity on the prognosis of liver cirrhosis.

BACKGROUND AND AIM: The study aims to determine the prognostic impact of obesity, sarcopenic obesity, and dynapenic obesity in patients with chronic liver disease. METHODS: This retrospective observational study enrolled patients with chronic hepatitis (n = 746) and liver cirrhosis (n = 434) without hepatocellular carcinoma at entry. The patients were evaluated for sarcopenia and obesity between April 2016 and April 2022. Obesity was defined as a body mass index of ≥ 25 kg/m2. Sarcopenic obesity was defined as low skeletal muscle mass (pre-sarcopenia) with obesity and dynapenic obesity was defined as low muscle strength (dynapenia) with obesity. The effects of obesity on survival were evaluated retrospectively. RESULTS: The mean observation period was 2.5 years. Obesity, sarcopenic obesity, and dynapenic obesity were found in 271 (45.5%), 17 (2.9%), and 21 (3.5%) men, and 261 (44.7%), 59 (10.1%), and 53 (9.1%) women, respectively. A multivariate Cox proportional hazards model revealed that Child-Pugh class, dynapenia (hazard ratio [HR] 3.89), elderly (≥ 65 years old) (HR 2.11), and obesity (HR 0.58) were independently associated with overall survival (OS). However, neither sarcopenic nor dynapenic obesity were associated with OS. In patients with cirrhosis, the OS of the obese group was significantly higher than that of the non-obese group. The effect of obesity on OS was significant in elderly patients, but not in younger patients. CONCLUSIONS: Sarcopenic and dynapenic obesity seem unrelated to the prognosis of patients with chronic liver disease. Obesity has a positive effect on the prognosis of elderly patients with cirrhosis.

Immune checkpoint inhibitor-associated colitis in unresectable hepatocellular carcinoma: two cases of early onset after treatment with durvalumab plus tremelimumab.

The HIMALAYA trial is the first chemotherapeutic trial to demonstrate the efficacy of combined immune checkpoint inhibitors (ICIs) for unresectable hepatocellular carcinoma (u-HCC). The STRIDE regimen used in this trial consists of a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor and programmed cell death ligand 1 (PD-L1) inhibitor. Herein, we report two cases of ICI-colitis that occurred immediately after the initiation of the STRIDE regimen for u-HCC. A 73-year-old man and 75-year-old man with u-HCC were treated with the STRIDE regimen. Both patients developed grade 3 diarrhea (Common Terminology Criteria for Adverse Events, ver. 5.0) within 10 days of treatment initiation. Colonoscopy revealed aphthous erosions and erythema extending from the terminal ileum to the rectum in one case, while the other showed aphthous ulcers in the terminal ileum and shallow ulcers in the colorectum. Histopathological examination of a biopsy specimen revealed epithelial cell apoptosis and neutrophil infiltration bodies, consistent with ICI-colitis. Prednisolone (0.5 mg/kg) was effective in both patients. Our experience suggests the need for both careful monitoring and early endoscopic examination of ICI colitis in patients with unresectable HCC treated with the STRIDE regimen.

Seroprevalence and incidence of hepatitis E virus infection in the general population of Iwate prefecture, Japan: A retrospective cohort study.

AIM: Hepatitis E virus (HEV) causes subclinical or acute self-limiting hepatitis. We surveyed the current seroprevalence and incidence of HEV infection among the general population in Iwate Prefecture, Japan, where the endemic infection is presumed to be low. METHODS: Between 2014 and 2016, we recruited individuals from Iwate Prefecture, Japan, who visited a general medical work-up program. Serum anti-HEV antibody and HEV RNA were measured twice, with an interval of 2 years. Anti-HEV antibody was measured with enzyme-linked immunosorbent assay and HEV RNA with reverse transcription-polymerase chain reaction. RESULTS: Study participants comprised 1284 Japanese (650 men and 634 women) with age ranging 20-89 years. A total of 90 participants were found to be positive for anti-HEV immunoglobulin G on the first visit, with a prevalence of 7.0% (95% confidence interval [CI] 5.6%-8.4%). Seroprevalence was higher in men than in women (10.1% vs. 3.7%, p < 0.001), and in those aged in their 50s-80s than in those aged in their 20s-40s (p = 0.006). Positive seroconversion indicating new HEV infection was found in seven of 1194 seronegative participants (0.59%; 95% CI 0.15%-1.0%), indicating the incidence of HEV infection to be 272 per 100 000 person-years (95% CI 109-561). CONCLUSIONS: Our observations suggest that the incidence of HEV infection is high and that it is a leading cause of hepatitis virus infection in Iwate Prefecture, Japan.

A Case of Autoimmune Hepatitis Complicated by Undiagnosed Factor VII Deficiency: A Pitfall of Coagulopathy.

Prothrombin time (PT) is a key parameter for assessing the severity of liver disease. We present the case of a 37-year-old woman with severe acute liver injury due to autoimmune hepatitis. Although prednisolone drastically improved her hepatocyte function, her PT did not recover to the reference range. A review of her medical records revealed that the patient had normal transaminase levels and prolonged PT 2 years previously. Further examinations of her coagulopathy revealed that she had low factor VII activity, suggesting a diagnosis of factor VII deficiency. Our experience suggests that altered coagulopathy should be considered in cases of liver injury with an extraordinary PT.

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.

Coincidental items in the definition of metabolic dysfunction-associated fatty liver are useful in identifying patients having significant fibrosis with fatty liver.

AIM: We aimed to establish a method that will identify patients at a high risk for progressive phenotype of fatty liver. METHODS: Patients with fatty liver who underwent liver biopsy between July 2008 and November 2019 were included as cohort 1, and those who underwent abdominal ultrasound screening examination by general physicians between August 2020 and May 2022 served as cohort 2. According to the definition of metabolic dysfunction-associated fatty liver (MAFLD), the subjects were classified by body mass index of ≥23, diabetes mellitus, and coexistence of two or more metabolic risk items. The progressive phenotype of MAFLD is defined by significant fibrosis complicated with either nonalcoholic fatty liver disease activity score ≥4 (BpMAFLD) or steatosis grade ≥2 by ultrasound examination (UpMAFLD). RESULTS: One hundred sixty-eight patients and 233 patients were enrolled in cohorts 1 and 2, respectively. In cohort 1, the prevalence of BpMAFLD was 0% in patients without a complicating factor (n = 10), 13% in those with one complicating factor (n = 67), 32% in those with two (n = 73), and 44% in those with all three complicating factors (n = 36). A logistic regression analysis revealed that factors in the MAFLD definition were significantly associated with BpMAFLD. In cohort 2, a criterion of two or more positive MAFLD definitions was found to have a 97.4% negative predictive value for the diagnosis of UpMAFLD. CONCLUSION: Patients with two or more complicating factors in the MAFLD definition should have further evaluation for liver fibrosis.

Shear wave dispersion to assess liver disease progression in Fontan-associated liver disease.

AIM: We aimed to analyze the dispersion slope (DS) using shear wave dispersion (SWD) in patients with Fontan-associated liver disease (FALD) and to investigate its utility as a biomarker of disease progression. METHODS: This cross-sectional study enrolled 27 adults with FALD who underwent SWD, two-dimensional shear wave elastography (2D-SWE), transthoracic echocardiography, cardiac catheterization, or abdominal computed tomography (CT) from April 2019 to April 2021. According to CT findings, patients were divided into two groups: significant fibrosis and non-significant fibrosis. RESULTS: The median DS in the control (n = 10), non-significant fibrosis (n = 12), and significant fibrosis (n = 15) was 9.35, 12.55, and 17.64 (m/s)/kHz, respectively. The significant fibrosis group showed a significantly higher DS than non-significant fibrosis group (P = 0.003). DS showed a significant correlation with central venous pressure (r = 0.532, P = 0.017) and liver stiffness measurements using 2D-SWE (r = 0.581, P = 0.002). The areas under the receiver operating characteristic curve for the diagnosis of significant fibrosis were 0.903 and 0.734 for SWD and 2D-SWE, respectively (P = 0.043). CONCLUSIONS: DS measured by SWD reflects the severity of liver damage in patients with FALD. SWE may be valuable for the therapeutic management of patients with FALD.

The Concept of Indeterminable NASH Inducted by Preoperative Diet and Metabolic Surgery: Analyses of Histopathological and Clinical Features.

Practitioners routinely perform intraoperative liver biopsies during laparoscopic sleeve gastrectomy (LSG) to evaluate nonalcoholic fatty liver disease (NAFLD). In some patients, hepatocyte ballooning, inflammation, and fibrosis without steatosis are observed, even in the absence of other etiologies. We call this finding indeterminable nonalcoholic steatohepatitis (Ind-NASH). In this study, we clarified the prevalence, as well as histopathological and clinical features, of Ind-NASH through intraoperative liver biopsy in Japanese patients presenting with severe obesity. We enrolled 63 patients who had undergone LSG and intraoperative liver biopsy. In patients diagnosed with histopathological NASH, we performed protocol liver biopsies at 6 and 12 months after LSG. We statistically analyzed these histopathological findings and clinical parameters and found the prevalence rate of Ind-NASH discovered through intraoperative biopsy to be 15.9%. Protocol liver biopsy also revealed that Ind-NASH was an intermediate condition between NASH and normal liver. The clinical features of patients with Ind-NASH are a higher body weight compared to NASH (134.9 kg vs. 114.7 kg; p = 0.0245), stronger insulin resistance compared to nonalcoholic fatty liver (homeostasis model assessment-insulin resistance: 7.1 vs. 4.9; p = 0.0188), and mild liver dysfunction compared to NASH. Patients with Ind-NASH observed positive weight-loss effects from a preoperative diet compared to the postoperative course (percentage total weight loss: 32.0% vs. 26.7%; p < 0.0001). Patients with Ind-NASH may also be good candidates for metabolic surgery owing to their good treatment response; therefore, efforts should be made by specialists in the near future to deeply discuss and define Ind-NASH.

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.

Two hepatectomy cases for initially unresectable hepatocellular carcinoma after achieving a radiological complete response to sequential therapy with lenvatinib and transcatheter arterial chemoembolization.

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.

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.

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.