Risk Factors of Proteinuria in Patients with Hepatocellular Carcinoma Receiving Lenvatinib.

Proteinuria is one of the most frequently reported adverse events leading to the discontinuation of lenvatinib treatment in patients with advanced hepatocellular carcinoma (HCC). However, there are no reports regarding the risk factors of proteinuria in patients with HCC or patients receiving lenvatinib. We retrospectively reviewed the medical records of patients with HCC receiving lenvatinib at the Kobe City Medical Center General Hospital between April 2018 and December 2020. The severity of proteinuria was graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A multivariate Cox proportional hazards model was employed to identify the risk factors of developing grade ≥2 proteinuria. Among the 37 patients included, 3 patients had grade-1 proteinuria at baseline and 10 patients had estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline. Grades 1, 2, and 3 proteinuria were observed in 15 (40.5%), 10 (27.0%), and 2 (5.4%) patients, respectively, during lenvatinib treatment. The median value of eGFR was significantly lower in patients who developed grade ≥2 proteinuria than those with grade ≤1 proteinuria (59.6 vs. 78.1 mL/min/1.73 m2, p = 0.045). Multivariate analysis revealed that pre-existing proteinuria at baseline (hazard ratio (HR), 9.72; 95% confidence interval (CI), 1.29-52.21; p = 0.030), and eGFR <60 mL/min/1.73 m2 at baseline (HR, 4.49; 95% CI, 1.32-16.07; p = 0.017) were significantly associated with developing grade ≥2 proteinuria. These patients should be monitored carefully, and our preliminary data should be confirmed by further studies.

CD68-Positive Cells in Hepatic Angiomyolipoma.

Four resected specimens of hepatic angiomyolipoma in which uptake of Sonazoid was observed in the postvascular phase of Sonazoid-enhanced ultrasonography were analyzed. Macrophage localization in the tumor was revealed pathologically by immunohistochemical staining for CD68. CD68-positive cells were observed in the tumor in all cases. The density of CD68-positive cells was 100/mm2, and the ratio of CD68-positive cell density in the tumor to that in the surrounding parenchyma was 32-171%. These results suggested that the uptake of the contrast agent Sonazoid was related to the density of CD68-positive cells.

Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C.

BACKGROUND: Recent genome-wide association studies demonstrated that 2 single nucleotide polymorphisms (SNPs), upstream of the interferon-λ (IFNL) 3 gene, are associated with the spontaneous clearance of hepatitis C virus (HCV) in symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs, rs8099917 and rs12979860, have established their significant roles in the innate immunity response to spontaneously clear HCV in patients with AHC, the detailed mechanisms of their roles remain largely unknown. AIM: This study is aimed at clarifying the factors affecting IFNL3 production and assessing the roles of IFNL3 in AHC. MATERIALS AND METHODS: A total of 21 AHC patients who visited the hospital within 10 days after symptom onset were assessed. As controls, 23 healthy volunteers (HVs) were examined. Serum IFNL3 levels were quantified using an in-house, IFNL3-specific chemiluminescence enzyme immunoassay (CLEIA) kit. Serum IFNL1, IFN-α, IFN-ß, and IFN-γ induced protein-10 (IP-10) levels were assayed using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: At baseline, serum IFNL3 levels were higher in AHC patients than in HVs (p < 0.0001). The higher levels in AHC patients did not differ between patients with the rs8099917 TT genotype and those with the non-TT (TG/GG) genotype (p = 0.546). Serial measurement of serum IFNL3 levels did not predict the outcome of conventional AHC. However, serum IFNL3 levels at baseline correlated positively with the HCV RNA levels (p = 0.005). Following HCV eradication, serum IFNL3 levels reduced to within the range obtained for HVs. Baseline serum IFNL1 levels did not differ significantly between AHC patients and HVs (p = 0.284). Serum levels of IFNL1 and IFNL3 at baseline also showed no correlative power (p = 0.288). Serum IFN-α and IFN-ß were detected together with remarkably high serum IFNL3 levels in only one patient who progressed to acute liver failure (ALF). CONCLUSION: These findings indicate that serum IFNL3 levels at baseline are higher in AHC patients regardless of the rs8099917 polymorphism, and primary HCV infection triggers the production of IFNL3. As a first line of defense in the innate immune system against invading HCV, increased IFNL3 levels play an important role, but serum IFNL3 levels are not the principal determinant of the clinical course of conventional AHC.

Case of primary hepatic gastrinoma: Diagnostic usefulness of the selective arterial calcium injection test.

Gastrinomas mainly occur in the duodenum and pancreas. Primary hepatic gastrinoma is rare and difficult to diagnose because the liver is a frequent site of metastatic gastrinomas. Clinical factors were assessed in a 28-year-old man with diarrhea and heartburn who was hospitalized for recurrent duodenal ulcers. Abdominal ultrasound, endoscopic ultrasound and computed tomography (CT) could not detect a tumor in the duodenum or pancreas. His gastrin level was 846 pg/mL and magnetic resonance imaging showed a mass 12 mm in diameter in the right robe of the liver. A selective intra-arterial calcium injection (SACI) test and 68-gallium edotreotide positron emission tomography CT (Ga-DOTATOC PET-CT) were therefore performed. Calcium gluconate injection into the proper hepatic artery resulted in a marked increase in serum gastrin concentration in the right hepatic vein, with Ga-DOTATOC PET-CT showing uptake only by the liver mass. Following a diagnosis of primary hepatic gastrinoma, the tumor was resected. A histopathological examination indicated gastrinoma. Six months postoperatively, he has no symptoms, is not taking proton-pump inhibitors and his gastrin level remains within the normal range. The SACI test and the clinical course of this patient strongly suggest that the tumor was a primary hepatic gastrinoma. The SACI test is helpful in the diagnosis of primary hepatic gastrinoma.

Outcomes and Prognostic Factors in Patients with Spontaneously Ruptured Hepatocellular Carcinoma.

BACKGROUND/AIMS: Spontaneous rupture is a life-threatening complication of hepatocellular carcinoma (HCC). Although hemostasis can be achieved by transarterial embolization (TAE), the prognosis remains poor. The aims of this study were to evaluate the effectiveness of emergent TAE for ruptured HCC and to clarify the prognostic factors. METHODOLOGY: Thirty-six patients with spontaneously ruptured HCC were retrospectively analyzed. Prognostic factors of short-term (57 days) and long-term (>7 days) survival after HCC rupture were investigated by univariate and multivariate analyses. RESULTS: Emergent TAE was performed in 22 patients and conservative treatment was applied in 14. The hemostasis rate of TAE was 86.4%, and median survival time in patients with TAE was significantly longer than that in patients with conservative treatment (142 days vs. 5 days, p = 0.0006). In multivariate analysis, high serum creatinine (p = 0.036) was a significant independent predictor of poor 7-day survival, and low serum albumin (p = 0.050) and absence of emergent TAE (p = 0.061) tended to be associated with poor 7-day survival. HCC treatment within the past 12 months (p = 0.048) and, high serum total bilirubin (p = 0.016) were predictors of poor long-term survival. Conclusions: We identified some survival predictors after HCC rupture. Emergent TAE appears to be effective for improving short-term oroLnosis after HCC ruoture.

[A case of jejunal ectopic pancreatic cancer: the diagnostic usefulness of MRI].

A 70-year-old man was referred to our hospital because of elevated CA19-9. Magnetic resonance imaging revealed a jejunal tumor having duct and retention cyst-like structures, which suggested ectopic pancreatic cancer. We resected that part of the jejunum and the lymph nodes around the tumor. Pathological examination revealed an adenocarcinoma originating from a Heinrich type I ectopic pancreas in the jejunum. Adjuvant chemotherapy with gemcitabine was performed for half a year. After 8 months, CA19-9 remained elevated, and liver metastasis occurred. We began treatment with tegafur/gimeracil/oteracil potassium (S-1) and particle beam therapy. After 7 months, CA19-9 was normal, and the patient has remained in partial remission with S-1 treatment. Ectopic pancreas tissues typically occur in the stomach and duodenum and rarely become cancerous. Here, we report the features of a rare and illustrative case of jejunal ectopic pancreatic cancer.

The gross classification of hepatocellular carcinoma: usefulness of contrast-enhanced US.

BACKGROUND: This study investigated the usefulness of postvascular images of contrast-enhanced ultrasonography (CE-US) in the gross classification of hepatocellular carcinoma (HCC) in comparison with contrast-enhanced CT (CE-CT) findings. METHODS: This is a prospective study with consecutive HCC patients who had both CE-US and CE-CT prior to surgical resection. Fifty-one patients (32 men, 19 women; mean age, 68.9 years) with 61 HCCs were enrolled. The maximal diameters of all tumors ranged from 1.0 to 5.0 cm (mean ± SD, 2.5 cm ± 1.1). Weighted kappa statistics were used to assess the agreement of the sonographic or CT findings versus the results of macroscopic configurations. RESULTS: Thirty-nine tumors were macroscopically diagnosed as simple nodule type; 19 tumors were macroscopically diagnosed as simple nodular type with extranodular growth, and 3 were macroscopically diagnosed as confluent multinodular type from the resected specimen. The diagnostic accuracy was 86.9% (53/61) for CE-US and 65.6% (40/61) for CE-CT. The differences in accuracy between CE-US and CE-CT were statistically significant (McNemar; p = 0.007). Agreement analysis between gross classification using CE-US and final macroscopic results gave a kappa value of 0.74 (95% CI: 0.65­0.82), which was considered a good agreement. On the other hand, kappa coefficient value was 0.38 (95% CI: 0.28­0.48) between gross classification using CE-CT and final macroscopic results. CONCLUSIONS: CE-US is a more reliable tool than CE-CT to evaluate the gross type of HCC than CE-CT. Accurate gross classification using imaging is considered to be essential for the determination of the correct treatment strategy and the estimates of the patients' prognosis.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus: A case report.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a major global health concern that leads to liver fibrosis, cirrhosis, and cancer. Regimens containing direct-acting antivirals (DAAs) have become the mainstay of HCV treatment, achieving a high sustained virological response (SVR) with minimal adverse events. CASE SUMMARY: A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir, and sofosbuvir for 12 wk and achieved SVR. Twenty-four weeks after treatment completion, the liver enzyme and serum IgG levels increased, and antinuclear antibody became positive without HCV viremia, suggesting the development of autoimmune hepatitis (AIH). After liver biopsy indicated AIH, a definite AIH diagnosis was made and prednisolone was initiated. The treatment was effective, and the liver enzyme and serum IgG levels normalized. However, multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR, which were consistent with primary sclerosing cholangitis. CONCLUSION: The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

Autoimmune hepatitis and immunoglobulin G4-associated autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a disease that is characterized by the presence of autoantibodies and elevated levels of serum immunoglobulin G (IgG) and hepatic enzymes. Its characteristic findings in the liver include interface hepatitis, infiltration of lymphocytes and plasma cells, and rosette formation, and is treated with immunosuppressive drugs. Autoimmune pancreatitis, a pancreatic disease caused by an autoimmune mechanism, is associated with elevated levels of serum IgG4 and the infiltration of IgG4-positive cells into the pancreatic parenchyma, and it is occasionally accompanied by systemic features. This systemic inflammatory disease characterized by the infiltration of IgG4-positive plasma cells and elevated serum IgG4 levels was recently classified as an IgG4-related disease. A few studies have reported AIH cases with infiltrated IgG4-positive plasma cells in the liver, suggesting the involvement of IgG4 in the pathogenesis of AIH. This feature was called IgG4-associated AIH and only two studies have been published. However, the diagnostic criteria of IgG4-associated AIH has not been defined and the epidemiology and clinical features remain uncertain. The degree of IgG4-positive plasma cell infiltration in the liver was different in each article. The serum IgG4 level was not elevated in one study, whereas it was severely elevated in the other. Corticosteroid therapy normalized liver enzymes in both studies. Further studies are needed to define the epidemiological features or diagnostic criteria.

Usefulness of combination of imaging modalities in the diagnosis of hepatocellular carcinoma using Sonazoid®-enhanced ultrasound, gadolinium diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging, and contrast-enhanced computed tomography.

OBJECTIVE: To clarify the diagnostic ability of combining imaging methods to diagnose hepatocellular carcinoma (HCC) using Sonazoid®-enhanced ultrasound (US), gadolinium diethylene-triamine-pentaacetic acid-enhanced (Gd-EOB-DTPA) magnetic resonance imaging (MRI), and contrast-enhanced computed tomography (CECT). METHODS: A total of 32 patients who underwent surgical resection for HCC were studied. Sonazoid-enhanced US, Gd-EOB-DTPA MRI, CECT, and intraoperative contrast-enhanced ultrasonography were done for all patients. The definitive diagnosis of HCC in those patients was based on histopathological confirmation. RESULTS: A total of 50 histologically proven HCCs were obtained from 32 patients; their mean (± SD) age was 68.3 years ± 8.1. The mean (± SD) nodule size was 2.6 cm ± 1.9. Twenty percent were well-differentiated HCC, 64% were moderately differentiated HCC, 10% were poorly differentiated HCC, 4% were combined HCC and CCC, and 2% were HCC with severe necrosis. The overall diagnostic sensitivity of CEUS, CECT, and Gd-EOB-DTPA MRI was 72, 74, and 86%, respectively; however, there was no significant difference between the three imaging modalities in diagnosing typical HCC (p = 0.092). When combining the diagnostic ability of the different imaging modalities, the diagnostic sensitivity of Sonazoid-enhanced US and Gd-EOB-DTPA MRI was 90%, while addition of Sonazoid-enhanced US to CECT and CECT to Gd-EOB-DTPA MRI had a sensitivity of 82 and 88%, respectively. There was no significant difference between the three imaging combinations (p = 0.970). CONCLUSION: Sonazoid-enhanced US and Gd-EOB-DTPA MRI can be confidently used in daily clinical practice for the management of HCC.

Oral branched-chain amino acid granules reduce the incidence of hepatocellular carcinoma and improve event-free survival in patients with liver cirrhosis.

BACKGROUND: It has been reported that branched-chain amino acid (BCAA) supplementation can improve nutritional status and prevent liver-related complications in patients with decompensated cirrhosis. We investigated the effects of oral BCAA supplementation on the incidence of hepatocellular carcinoma (HCC) and liver-related events in patients with compensated and decompensated cirrhosis. METHODS: We enrolled 211 patients with cirrhosis including 152 patients with Child-Pugh A cirrhosis, but no history of HCC. Of these, 56 received oral administration of 12 g/day BCAA for ≥6 months (BCAA group), and 155 were followed-up without BCAA treatment (control group). The HCC occurrence and event-free survival rates were compared between the two groups. We used a propensity score analysis to overcome selection bias of this retrospective analysis. RESULTS: The HCC occurrence rate was significantly lower and event-free survival rate was significantly higher in the BCAA group than in the control group. Multivariate analyses showed BCAA supplementation was significantly associated with reduced incidence of HCC (hazard ratio (HR) 0.416, 95% confidence interval (CI) 0.216-0.800, p = 0.0085). BCAA supplementation also reduced the incidence of liver-related events in patients with Child-Pugh A cirrhosis, although the difference did not reach statistical significance (HR 0.585, 95% CI 0.336-1.017, p = 0.0575). CONCLUSIONS: Oral BCAA supplementation is associated with reduced incidence of HCC in patients with cirrhosis and seems to prevent liver-related events in patients with Child-Pugh A cirrhosis.

Des-γ-carboxyprothrombin may be a promising biomarker to determine the therapeutic efficacy of sorafenib for hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to evaluate the role of des-γ-carboxyprothrombin (DCP) as a marker for the efficacy of sorafenib therapy for hepatocellular carcinoma (HCC). METHODS: Patients with advanced HCC treated with sorafenib were retrospectively evaluated, focusing on DCP levels and clinical characteristics. RESULTS: 50 patients with advanced HCC were treated with sorafenib alone. In 25 of these patients, the serum levels of DCP were evaluated twice (pretreatment and within 2 weeks after starting therapy). The time to progression was significantly longer in patients in whom the DCP level at 2 weeks after starting sorafenib was ≥2-fold higher than the pretreatment levels, as compared with patients without an increase in DCP (p = 0.0296). CONCLUSIONS: The serum level of DCP is a surrogate marker for tissue hypoxia and can be a predictive marker to assess the tumor response to sorafenib therapy.

Association of interleukin-28B and hepatitis C genotype 1 with a high viral load and response to pegylated interferon plus ribavirin therapy.

BACKGROUND: Pegylated interferon (PEG-IFN) plus ribavirin therapy is the current standard treatment for chronic hepatitis C (CHC) genotype 1 with high viral load. A common genetic variation near the IL28B gene has been found to affect the response to PEG-IFN plus ribavirin therapy for CHC. The aims of this study were to analyze the association between the rs8099917 genotype and treatment response in a cohort study of CHC. METHODS: This study evaluated clinical and laboratory parameters retrospectively in a cohort of 122 patients with chronic hepatitis C with genotype 1 and a high viral load who received PEG-IFN plus ribavirin therapy. We carried out univariate and multivariate statistical analyses of parameters and clinical responses. RESULTS: Sixty-three of 122 patients (51.6%) had sustained virological responses (SVRs). Patients with the rs8099917 genotype TT achieved significantly higher SVR rates (p < 0.01). Univariate analysis revealed that SVRs were associated with BMI, fibrosis, albumin, total cholesterol, PEG-IFN dose, ribavirin dose and the rs8099917 genotype. Multivariate analysis revealed that the rs8099917 genotype (odds ratio 7.434, 95% CI 2.278-24.257, p = 0.001) and total PEG-IFN dose (odds ratio 7.162, 95% CI 1.565-18.15, p = 0.007) were significant factors. CONCLUSIONS: The rs8099917 genotype and total PEG-IFN dose were associated with SVR in patients with hepatitis C virus genotype 1.

Hepatitis C virus core protein induces homotolerance and cross-tolerance to Toll-like receptor ligands by activation of Toll-like receptor 2.

BACKGROUND: Hepatitis C virus (HCV) activates host innate immune responses mediated by retinoic acid inducing gene-I (RIG-I) and Toll-like receptors (TLRs). Although the nonstructural protein 3/4A (NS3/4A) of HCV disrupts interferon responses by inhibiting RIG-I signaling, the effects of TLR activation by HCV-associated proteins on host innate immune responses are poorly understood. METHODS: Proinflammatory cytokine responses to various TLR ligands in human antigen-presenting cells (APCs) were examined either with or without prestimulation by HCV core protein. RESULTS: TLR2 activation by the HCV core protein leads to a decrease in interleukin 6 (IL-6) production by human APCs after subsequent stimulation with TLR2 (homotolerance) ligands and TLR4 (cross-tolerance) ligands. This hyporesponsiveness induced by preexposure to the HCV core protein was partially mediated by the negative regulation of nuclear factor-kappaB activation by the induction of IRAK-M. TLR ligand-induced IL-6 production was significantly reduced in peripheral blood monocytes isolated from HCV-infected patients, compared with those of healthy control subjects. Alloantigen presentation by monocytes isolated from HCV-infected patients results in impaired production of interleukin 17 by naive CD4(+) T cells in the presence of TLR ligands. CONCLUSIONS: Chronic stimulation of APCs with HCV core protein is associated with hyporesponsiveness in TLR-mediated innate immunity.

Contrast-enhanced ultrasound techniques for guiding and assessing response to locoregional treatments for hepatocellular carcinoma.

Most hepatocellular carcinomas (HCC) are diagnosed in patients with cirrhosis and/or when tumor burden is too advanced for surgical treatment. In many of these cases the only suitable therapy is locoregional, percutaneous and/or intraarterial treatment. Moreover, the best way to guide and assess response to locoregional HCC treatment are two issues under discussion today. First-generation and subsequent second-generation microbubble contrast agents, together with contrast-enhanced ultrasound (US) imaging, have expanded the role of US techniques in HCC treatments. In this review our purpose is to illustrate the advantages, limits and potential of contrast-enhanced US application for locoregional HCC treatment.

Radiofrequency ablation for hepatocellular carcinoma: assistant techniques for difficult cases.

PURPOSE: To confirm the safety and effectiveness of techniques to assist radiofrequency ablation (RFA) for difficult cases, we retrospectively evaluated successful treatment rates, early complications and local tumor progressions. PATIENTS AND METHODS: Between June 1999 and April 2009, a total of 341 patients with 535 nodules were treated as difficult cases. Artificial pleural effusion assisted ablation was performed on 64 patients with 82 nodules. Artificial ascites-assisted ablation was performed on 11 patients with 13 nodules. Cooling by endoscopic nasobiliary drainage (ENBD) tube-assisted ablation was performed on 6 patients with 8 nodules. When the tumors were not well visualized with conventional B-mode ultrasonography (US), contrast-enhanced US-assisted ablation with Levovist or Sonazoid or virtual CT sonography-assisted ablation was performed. Contrast-enhanced US-assisted ablation was performed on 139 patients with 224 nodules and virtual CT sonography-assisted ablation was performed on 121 patients with 209 nodules. RESULTS: In total, complete ablation was achieved in 514 of 535 (96%) nodules in difficult cases. For RFA with artificial pleural effusion, artificial ascites and ENBD, complete response was confirmed in all cases. For contrast-enhanced US- and CT sonography-assisted ablation, complete response was 95%. Early complications were recognized in 24 cases (4.5%). All cases recovered with no invasive treatment. Local tumor recurrence was investigated in 377 nodules of 245 patients, and 69 (18%) nodules were positive. Tumor recurrences in each assisted technique were 14.7% in artificial pleural effusion cases, 7% in artificial ascites, 12.5% in ENBD tube cases, 31% in virtual CT sonography, and 8.5% in contrast-enhanced US. CONCLUSION: Although local tumor progression needs to be carefully monitored, assisted techniques of RFA for difficult cases are well tolerated and expand the indications of RFA.

Hepatic arterial infusion chemotherapy using low-dose 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma.

BACKGROUND: Although hepatic arterial infusion chemotherapy (HAIC) using low-dose 5-fluorouracil (5-FU) and cisplatin (low-dose FP) is commonly used for advanced hepatocellular carcinoma (HCC) with vascular invasion in Japan, few reports have investigated the efficacy and safety of this approach. We investigated the efficacy and toxicity of HAIC using low-dose FP for patients with advanced HCC as a phase II trial. METHODS: Low-dose FP consisted of a continuous arterial infusion of 5-FU (250-500 mg/day, 5 days/week, for the first 2 weeks) and cisplatin (10 mg/day, 5 days/week, for the first 2 weeks). Then, 5-FU (1,000 mg/body for 5 h) and cisplatin (10 mg/body) were administered once weekly. RESULTS: In these patients treated with low-dose FP, the response rate was 38.5%, the median time to progression was 4.1 months (95% CI 2.1-6.1 months) and the median survival time was 15.9 months (95% CI 9.8-22.0 months). The most frequent adverse events were myelosuppression such as neutropenia or thrombocytopenia. CONCLUSIONS: HAIC using low-dose FP is an effective treatment option for locally advanced HCC. However, it is not well tolerated hematologically because of potent pancytopenia and poor hepatic reserve. Therefore, this regimen should be performed carefully with regular monitoring of hematological function.

Usefulness of the post-vascular phase of contrast-enhanced ultrasonography with sonazoid in the evaluation of gross types of hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to assess the usefulness of post-vascular phase (PVP) images of contrast-enhanced ultrasonography (CE-US) in the evaluation of the gross types of hepatocellular carcinoma (HCC) that is closely related to the malignant potential of the tumor. METHODS: A total of 29 patients with 40 HCCs of <5 cm in diameter, who underwent hepatic resection, were enrolled. The gross type of the tumor was evaluated using real-time scanning during the PVP of CE-US with Sonazoid prior to surgery. The tumors were classified into three types based on the macroscopic classification of the Liver Cancer Study Group of Japan: single nodular (SN) type, single nodular with extranodular growth (SNEG) type, and confluent multinodular (CMN) type. The ability of CE-US to correctly depict the gross type of HCC was evaluated. RESULTS: 26 tumors were macroscopically diagnosed as the SN type, 11 tumors as the SNEG type, and 3 tumors as the CMN type. The sensitivity, specificity and accuracy of CE-US were 96, 80 and 90%, respectively. CONCLUSION: The PVP image of CE-US with Sonazoid is a useful tool in the evaluation of the gross type of HCC and is considered essential in deciding treatment strategy.

Identification and characterization of IgG4-associated autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) and autoimmune pancreatitis (AIP) share clinical and pathological features such as high serum levels of immunoglobulin (Ig) G and autoantibodies, and lymphoplasmacytic infiltration, suggesting the presence of common immunological abnormalities. However, little is known about the possible involvement of IgG4, a hallmark of AIP, in AIH. AIMS: In this study, we examined whether the IgG4 response contributes to the histopathological and clinical findings in AIH. METHODS: Liver sections from 26 patients with AIH, 10 patients with primary biliary cirrhosis (PBC), three patients with primary sclerosing cholangitis (PSC) and 20 chronic hepatitis patients with hepatitis C virus (HCV) infection were immunostained for IgG4. We investigated the relationship among the histopathology, the responses to steroid therapy and the IgG4 staining. RESULTS: Nine of the 26 liver specimens from patients with AIH showed positive staining for IgG4 whereas none of the 10 samples from patients with PBC, the three samples from patients with PSC or the 20 samples from patients with HCV hepatitis were positive. Patients with IgG4-positive AIH also showed increased serum levels of IgG. The numbers of T cells, B cells and plasma cells were significantly increased in the livers of patients with IgG4-positive AIH as compared with those patients with IgG4-negative AIH. Patients with IgG4-positive AIH also showed a marked response to prednisolone therapy. CONCLUSIONS: AIH may be classified into either an IgG4-associated type or an IgG4 non-associated type with the former showing a marked response to prednisolone treatment.

Radiofrequency ablation guided by contrast harmonic sonography using perfluorocarbon microbubbles (Sonazoid) for hepatic malignancies: an initial experience.

AIM: Conventional contrast harmonic sonography has the technical problem of a short enhancement time during targeting of hepatic malignancies for radiofrequency (RF) ablation. This study investigated the effectiveness of contrast harmonic sonographic guidance using perfluorocarbon microbubbles (Sonazoid) during RF ablation of hepatic malignancies. MATERIALS AND METHODS: Nodules were detected on contrast-enhanced computed tomography, but could not be resolved clearly by B-mode sonography. Sixty-six patients (51 men, 15 women; mean age, 65.8 years) with 108 hepatic malignancies were enrolled. Fifty-one patients with hepatocellular carcinoma and 15 patients with liver metastases were treated by RF ablation guided by contrast harmonic sonography using perfluorocarbon microbubbles for a target lesion identified as a defect image after the administration of contrast medium. RESULTS: The maximal diameters of all tumours ranged from 0.7 to 3.5 cm (mean +/- SD, 1.7 cm +/- 0.9) on sonography. Complete tumour necrosis was achieved by a single session of RF ablation in 62 (94%) of the 66 patients, while two sessions were required for the remaining four (6%) patients. The average number of treatment sessions was 1.1 +/- 0.3. In the post-vascular phase, 105 (97%) of a total of 108 malignant hepatic tumours were depicted as a defect with a margin. Clinical courses have been satisfactory without any signs of local tumour progression during 1-12 months of follow-up (mean, 4.3 months). CONCLUSION: Using perfluorocarbon microbubbles, contrast harmonic sonographic-guided RF ablation is an efficient approach for guiding further ablation of hepatic malignancies that are not clearly demarcated by B-mode sonography.