Impact of a Novel Digital Therapeutics System on Nonalcoholic Steatohepatitis: The NASH App Clinical Trial.

INTRODUCTION: Management of nonalcoholic steatohepatitis (NASH) is a currently unmet clinical need. Digital therapeutics (DTx) is an emerging class of medicine that delivers evidence-based therapeutic interventions. This study was aimed at investigating the efficacy of DTx in patients with NASH. METHODS: We conducted a multicenter, single-arm, 48-week trial in 19 patients with biopsy-confirmed NASH. All patients received a DTx intervention with a newly developed smartphone application. The primary endpoint was change in the nonalcoholic fatty liver disease activity score (NAS) without worsening of liver fibrosis. The secondary endpoints included improvement of the NAS by ≥2 points without worsening of liver fibrosis, change in the body weight, and regression of fibrosis. RESULTS: After the 48-week DTx intervention, improvement of the NAS was observed in 68.4% (13/19) of patients. The mean change in the NAS from baseline to the end of the intervention was -2.05 ± 1.96 ( P < 0.001 when compared with the threshold of -0.7). A decrease in the NAS by ≥ 2 points was achieved in 11 (57.9%). The average weight loss at the end of the intervention was 8.3% ( P < 0.001). Reduction of the fibrosis stage was observed in 58.3% when the analysis was limited to patients with stage F2/3 fibrosis. There were no serious adverse events that could be considered as being related to the DTx intervention. DISCUSSION: DTx for NASH was found to be highly efficacious and well-tolerated. Further evaluation of the DTx intervention for NASH in a phase 3 trial is warranted.

Prevalence of hepatitis C virus infection among men who have sex with men with human immunodeficiency virus-1 infection between 2010 and 2020 in Japan: A single-center retrospective cohort study.

INTRODUCTION: The high prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) is an important health issue. The purpose of this study is to investigate the actual prevalence of HCV infection among HIV-positive MSM in Japan. METHODS: This study is a single-center retrospective cohort study. We collected data of HIV-infected MSM who visited our hospital from January 2010 to December 2020, and evaluated HCV prevalence, course of HCV infection, and direct-acting antiviral (DAA) treatment efficacy in HIV-infected MSM. RESULTS: Overall, 1135 HIV-infected MSM had HCV antibody (Ab) tests during the observation period. The first anti-HCV Ab positive rate in HIV-infected MSM was 4% (45/1135), and the seroconversion rate of HCV antibody was 3.6% (39/1090). Treponema pallidum hemagglutination antigen positivity (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.9 to 10.5) and intravenous drug injection (OR, 19; 95% CI, 3.4 to 149) were identified as factors associated with HCV Ab positivity. Spontaneous elimination of HCV infection was observed in 17.9% (7/39) of patients. DAA treatment was performed in 43 cases, and the overall sustained virologic response 12 (SVR12) rate for DAA treatment was 93% (40/43). CONCLUSION: A high HCV infection rate among HIV-infected MSM was observed in Japan. The DAA treatment response rate in patients with HIV/HCV co-infection was the high response rate.

WIND1 induces dynamic metabolomic reprogramming during regeneration in Brassica napus.

Plants often display a high competence for regeneration under stress conditions. Signals produced in response to various types of stress serve as critical triggers for de novo organogenesis, but the identity of these signaling molecules underlying cellular reprogramming are largely unknown. We previously identified an AP2/ERF transcription factor, WOUND INDUCED DEDIFFERENTIATION1 (WIND1), as a key regulator involved in wound-induced cellular reprogramming in Arabidopsis. In this study, we found that activation of Arabidopsis WIND1 (AtWIND1) in hypocotyl explants of Brassica napus (B. napus) enhances callus formation and subsequent organ regeneration. Gene expression analyses revealed that AtWIND1 enhances expression of B. napus homologs of ENHANCER OF SHOOT REGENERATION1/DORNRÖSCHEN (ESR1/DRN), which is a direct target of WIND1 in Arabidopsis. Further, time-course hormonal analyses showed that an altered balance of endogenous auxin/cytokinin exists in AtWIND1-activated B. napus explants. Our mass spectrometry analyses, in addition, uncovered dynamic metabolomic reprogramming in AtWIND1-activated explants, including accumulation of several compounds, e.g. proline, gamma aminobutyric acid (GABA), and putrescine, that have historically been utilized as additives to enhance plant cell reprogramming in tissue culture. Our findings thus provide new insights into how WIND1 functions to promote cell reprogramming.

[A Case of Bladder Urothelial Carcinoma with Hepatic Metastasis Achieving Histologically Complete Response by Multimodal Treatment Including Pembrolizumab].

A 70s man underwent transurethral resection of the bladder tumor(TURBT)at a previous hospital. The pathological diagnosis was urothelial carcinoma pT1. Nine months later, recurrence appeared in the bladder and he underwent repeated TURBT. The pathological diagnosis was also pT1 and he was administered 8 courses of intravesical BCG therapy. Fourteen months after the first operation, computed tomography scans showed new lesions in the liver. Therefore, he was referred to our hospital. Because biopsy from the hepatic lesion confirmed the diagnosis of metastatic urothelial carcinoma, he received 10 courses of gemcitabine plus cisplatin(GC)and radiofrequency ablation. However, daughter nodule and enlargement of the main tumor were revealed on MRI 33 months after the initial TURBT. After 5 courses of pembrolizumab that limited the potential for hepatic metastases, he had no evidence of other metastatic sites and underwent laparoscopic right hepatectomy. There was no viable carcinoma in the pathological specimens of the hepatic lesions. Six months after hepatectomy, the patient has a high quality of life without any recurrence.

WIND1-based acquisition of regeneration competency in Arabidopsis and rapeseed.

Callus formation and de novo organogenesis often occur in the wounded tissues of plants. Although this regenerative capacity of plant cells has been utilized for many years, molecular basis for the wound-induced acquisition of regeneration competency is yet to be elucidated. Here we find that wounding treatment is essential for shoot regeneration from roots in the conventional tissue culture of Arabidopsis thaliana. Furthermore, we show that an AP2/ERF transcription factor WOUND INDUCED DEDIFFERENTIATION1 (WIND1) plays a pivotal role for the acquisition of regeneration competency in the culture system. Ectopic expression of WIND1 can bypass both wounding and auxin pre-treatment and increase de novo shoot regeneration from root explants cultured on shoot-regeneration promoting media. In Brassica napus, activation of Arabidopsis WIND1 also greatly enhances de novo shoot regeneration, further corroborating the role of WIND1 in conferring cellular regenerative capacity. Our data also show that sequential activation of WIND1 and an embryonic regulator LEAFY COTYLEDON2 enhances generation of embryonic callus, suggesting that combining WIND1 with other transcription factors promote efficient and organ-specific regeneration. Our findings in the model plant and crop plant point to a possible way to efficiently induce callus formation and regeneration by utilizing transcription factors as a molecular switch.

Endoscopic features of lymphoid follicles in Helicobacter pylori-associated chronic gastritis.

BACKGROUND AND AIM: Small, round, yellowish-white nodules (YWN) are frequently observed in Helicobacter pylori-associated gastritis. The aim of the present study was to investigate the clinical significance of these YWN. METHODS: Participants comprised 211 patients with H. pylori-associated gastritis, ranging in age from 23 to 86 years. RESULTS: YWN were detected in 23% of participants, more frequently in women (33%) than in men (12%; P < 0.01). YWN were observed on the antral mucosa in 4.7% of cases, lesser curvature of the corpus mucosa in 20%, greater curvature of the corpus mucosa in 0.9%, and fundic mucosa in 12%. Most YWN located on the antral mucosa showed nodular type, and most YWN located on the corpus mucosa and fundic mucosa showed flat type. On magnifying endoscopy with narrow-band imaging, YWN appeared as round whitish lesions with radial or branching microvessels on the surface and hypovascular globe structures just beneath the surface of the mucosa. Targeted biopsies of YWN revealed lymphoid follicles with lymphocyte infiltration or intense inflammatory cell infiltration. CONCLUSION: The endoscopic finding of YWN could be observed at any site of the gastric mucosa in H. pylori-associated gastritis, and represented histological lymphoid follicles.

Effectiveness of Chemotherapy on Long-Term Survival in a Case of Advanced Juvenile Hepatocellular Carcinoma Without Viral Hepatitis Infection.

Hepatocellular carcinoma (HCC) usually occurs in settings of cirrhosis and chronic hepatitis B or C virus (HBV and HCV, respectively) infection; it is extremely rare in patients <40 years of age since viral- or alcohol-induced chronic hepatitis develops over a prolonged period. Juvenile HCC is mostly associated with persistent HBV infection; cases unrelated to HBV or HCV infection (non-B, non-C juvenile HCC) are sporadic and treated in the same way as classical HCC. A woman in her late 30s was diagnosed with HCC in a healthy liver; her imaging findings were typical of HCC with bone metastasis. She was administered a combination of tyrosine kinase inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors. Throughout chemotherapy, the liver reserve was Grade A on the Child-Pugh classification and tumor markers remained under control without marked elevation. Our patient is the first reported long-term survivor of unresectable non-B, non-C juvenile HCC following chemotherapeutic treatment.

Stem Cell Growth Factor-ß as a Predictive Biomarker of Response to Chemotherapy and Prognosis in Patients with Advanced-Stage Hepatocellular Carcinoma: A Retrospective Study.

In this retrospective study, we investigated the potential application of serum stem cell growth factor beta (SCGF-ß) as a biomarker for predicting the therapeutic response and prognosis in patients with hepatocellular carcinoma (HCC) undergoing atezolizumab and bevacizumab (Atz/Bev) combination therapy. Pre- and post-treatment serum SCGF-ß levels were measured and analyzed in relation to treatment outcomes and overall survival (OS). Pretreatment SCGF-ß levels were associated with treatment response. Patients with SCGF-ß levels exceeding the 163,295 pg/mL cutoff experienced significantly reduced OS, with a median OS of 12.03 months, compared to 28.87 months in those with SCGF-ß levels at or below this threshold. These findings suggest that SCGF-ß can serve as a predictive marker for clinical outcomes in HCC treatment, highlighting the need for prospective studies to further validate these results and clarify the mechanisms underlying SCGF-ß-related therapeutic resistance.

Alpha-fetoprotein-producing gastric cancer with ruptured liver metastasis mimicking hepatocellular carcinoma.

Alpha-fetoprotein (AFP)-producing gastric cancer is a rare subtype of gastric cancer known for its aggressive nature. We present an uncommon case of a 60s male with multiple liver tumors, initially suggested as hepatocellular carcinoma (HCC) by imaging. However, a subsequent gastric biopsy revealed a poorly differentiated adenocarcinoma with hepatoid features, and liver biopsy mirrored these findings. The disease progressed swiftly, with the patient representing owing to the spontaneous rupture of a metastatic liver tumor, an extremely rare occurrence, especially in metastatic liver cancers. Such ruptures in AFP-producing gastric cancer may be attributed to the tumor's rich blood flow. Distinctly differentiating this subtype from HCC is pivotal for apt management, as was evident in our case. The diagnosis was particularly challenging due to the similarities in imaging presentations between AFP-producing gastric cancer liver metastasis and HCC. This case underscores the need for vigilant diagnosis, emphasizing the importance of liver biopsy, especially in the absence of chronic liver disease. It also highlights the potential complications, like spontaneous rupture, associated with this rare form of gastric cancer.

Safety and tolerability of OP-724 in patients with haemophilia and liver cirrhosis due to HIV/HCV coinfection: an investigator-initiated, open-label, non-randomised, single-centre, phase I study.

OBJECTIVE: Patients with haemophilia and HIV who acquire hepatitis C virus (HCV) after receiving contaminated blood products can experience accelerated progression of liver fibrosis and a poor prognosis, making liver disease a prominent cause of mortality among these patients. In the current study, we aimed to evaluate the safety and tolerability of the potential antifibrotic agent OP-724-a CREB-binding protein/ß-catenin inhibitor-in this patient subset. DESIGN: In this single-centre, open-label, non-randomised, phase I trial, we sequentially enrolled patients with cirrhosis following HIV/HCV coinfection classified as Child-Pugh (CP) class A or B. Five patients received an intravenous infusion of OP-724 at doses of 140 or 280 mg/m2 for 4 hours two times weekly over 12 weeks. The primary endpoint was the incidence of serious adverse events (SAEs). Secondary endpoints included the incidence of AEs and improved liver stiffness measure (LSM), as determined by vibration-controlled transient elastography. This study was registered at ClinicalTrials.gov (NCT04688034). RESULTS: Between 9 February 2021 and 5 July 2022, five patients (median age: 51 years) were enrolled. All five patients completed 12 cycles of treatment. SAEs were not observed. The most common AEs were fever (60%) and gastrointestinal symptoms (diarrhoea: 20%, enterocolitis: 20%). Improvements in LSM and serum albumin levels were also observed. CONCLUSION: In this preliminary assessment, intravenous administration of 140 or 280 mg/m2/4 hours OP-724 over 12 weeks was well tolerated by patients with haemophilia combined with cirrhosis due to HIV/HCV coinfection. Hence, the antifibrotic effects of OP-724 warrant further assessment in patients with cirrhosis. TRIAL REGISTRATION NUMBER: NCT04688034.

Rapidly Progressing Sarcomatoid Hepatocellular Carcinoma after Needle Biopsy and Radiofrequency Ablation.

BACKGROUND Sarcomatoid hepatocellular carcinoma is a rare, primary malignant liver cancer. Its pathogenesis is unknown, but it often occurs in patients who have undergone repeated antitumor therapies for hepatocellular carcinoma. Sarcomatoid hepatocellular carcinoma is more likely to recur and has a worse prognosis than that of hepatocellular carcinoma. As no specific features have been identified in the symptoms, serological findings, or imaging findings, it is difficult to accurately diagnose the disease before surgical resection or autopsy. CASE REPORT An 83-year-old woman was diagnosed with hepatocellular carcinoma 20 years ago. Radiofrequency ablation was initially performed. Thereafter, invasive, non-surgical treatments were repeated. The most recent treatment was 4 years ago, during which computed tomography suggested recurrent hepatocellular carcinoma. However, upon needle biopsy, histological examination revealed spindle-shaped tumor cells and actively mitotic cells. Immunohistochemical analysis showed negative results for Arginase-1, HepPar1, and Glypican3 and positive results for AE1/AE3, CK7, and vimentin. Therefore, sarcomatoid hepatocellular carcinoma was diagnosed, which was treated with radiofrequency ablation but progressed rapidly thereafter. Considering the rapid disease progression, the patient was treated conservatively. However, the patient's general condition gradually deteriorated, resulting in death. CONCLUSIONS Compared with hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma is more prone to recurrence and has a poorer prognosis. Therefore, aggressive surgical resection seems to be the most appropriate treatment for sarcomatoid hepatocellular carcinoma at present. Additional hepatic resection or follow-up imaging in a short period should be considered at the time of diagnosis of sarcomatoid hepatocellular carcinoma by biopsy, considering the risk of seeding or recurrence.

Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice.

Septic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs. To evaluate our hypothesis, we utilized a mouse model of SE induced by intraperitoneal injection of lipopolysaccharide (0.3 mg per mouse) and administered noninvasive, high-frequency ultrasound VNS. To assess the efficacy of ultrasound VNS, we measured inflammation-related molecules, including the α7 nicotinic acetylcholine receptor (α7nAChR) expression in peritoneal macrophages and plasma interleukin 1ß (IL-1ß) levels. Consistent with our hypothesis, SE mice exhibited reduced α7nAChR expression in macrophages and elevated IL-1ß levels in the blood. Remarkably, VNS in SE mice restored α7nAChR expression and IL-1ß levels to those observed in control mice. Furthermore, we evaluated the effects of VNS on survival rate, body temperature, and locomotor activity. SE mice subjected to VNS demonstrated a modest, yet significant, improvement in survival rate, recovery from hypothermia, and increased locomotor activity. To investigate the impact on the brain, we examined the hippocampus of SE mice. In control mice, VNS increased the expression of c-fos, a marker of neuronal electrical excitability, in the hippocampus. In SE mice, VNS led to the restoration of aberrant firing patterns in hippocampal neurons. Additionally, proteomic analysis of hippocampal tissue in SE mice revealed abnormal increases in two proteins, tissue factor (TF) and acyl-CoA dehydrogenase family member 9 (ACAD9), which returned to control levels following VNS. Collectively, our findings support the value of exploring the beneficial effects of ultrasound VNS on SE.

Safety, tolerability, and anti-fibrotic efficacy of the CBP/ß-catenin inhibitor PRI-724 in patients with hepatitis C and B virus-induced liver cirrhosis: An investigator-initiated, open-label, non-randomised, multicentre, phase 1/2a study.

BACKGROUND: We conducted an exploratory study to assess the safety tolerability, and anti-fibrotic effects of PRI-724, a CBP/ß-catenin inhibitor, in patients with hepatitis C virus (HCV)- and hepatitis B virus (HBV)-induced cirrhosis. METHODS: This multicentre, open-label, non-randomised, non-placebo-controlled phase 1/2a trial was conducted at three hospitals in Japan. Between July 27, 2018, and July 13, 2021, we enrolled patients with HCV- and HBV-induced cirrhosis classified as Child-Pugh (CP) class A or B. In phase 1, 15 patients received intravenous infusions of PRI-724 at escalating doses of 140, 280, and 380 mg/m2/4 h twice weekly for 12 weeks. In phase 2a, 12 patients received the recommended PRI-724 dose. The primary endpoints of phases 1 and 2a were the frequency and severity of adverse events and efficacy in treating cirrhosis based on liver biopsy. This study was registered at ClinicalTrials.gov (no. NCT03620474). FINDINGS: Three patients from phase 1 who received the recommended PRI-724 dose were evaluated to obtain efficacy and safety data in phase 2a. Serious adverse events occurred in three patients, one of which was possibly related to PRI-724. The most common adverse events were diarrhoea and nausea. PRI-724 did not decrease hepatic fibrosis with any statistical significance, either by ordinal scoring or measurement of collagen proportionate area at 12 weeks; however, we observed statistically significant improvements in liver stiffness, Model for End-stage Liver Disease score, and serum albumin level. INTERPRETATION: Intravenous administration of 280 mg/m2/4 h PRI-724 over 12 weeks was preliminarily assessed to be well tolerated; however, further evaluation of anti-fibrotic effects in patients with cirrhosis is warranted. FUNDING: AMED, Ohara Pharmaceutical.

Inhibition of CBP/ß-catenin signaling ameliorated fibrosis in cholestatic liver disease.

Chronic cholestatic liver diseases are characterized by injury of the bile ducts and hepatocytes caused by accumulated bile acids (BAs) and inflammation. Wnt/ß-catenin signaling is implicated in organ fibrosis; however, its role in cholestatic liver fibrosis remains unclear. Therefore, we explored the effect of a selective cAMP response element-binding protein-binding protein (CBP)/ß-catenin inhibitor, PRI-724, on murine cholestatic liver fibrosis. PRI-724 suppressed liver fibrosis induced by multidrug resistance protein 2 knockout (KO), bile duct ligation, or a 3.5-diethoxycarbonyl-1.4-dihydrocollidine (DDC) diet; it also suppressed BA synthesis and macrophage infiltration. The expression of early growth response-1 (Egr-1), which plays a key role in BA synthesis, was increased in the hepatocytes of patients with cholestatic liver disease. PRI-724 inhibited Egr-1 expression induced by cholestasis, and adenoviral shEgr-1-mediated Egr-1 knockdown suppressed BA synthesis and fibrosis in DDC diet-fed mice, suggesting that PRI-724 exerts its effects, at least in part, by suppressing Egr-1 expression in hepatocytes. Hepatocyte-specific CBP KO in mice suppressed BA synthesis, liver injury, and fibrosis, whereas hepatocyte-specific KO of P300, a CBP homolog, exacerbated DDC-induced fibrosis. Intrahepatic Egr-1 expression was also decreased in hepatocyte-specific CBP-KO mice and increased in P300-KO mice, indicating that Egr-1 is located downstream of CBP/ß-catenin signaling. Conclusion: PRI-724 inhibits cholestatic liver injury and fibrosis by inhibiting BA synthesis in hepatocytes. These results highlight the therapeutic effect of CBP/ß-catenin inhibition in cholestatic liver diseases.

Feasibility, safety and tolerability of the CREB-binding protein/ß-catenin inhibitor OP-724 in patients with advanced primary biliary cholangitis: an investigator-initiated, open-label, non-randomised, two-centre, phase 1 study.

OBJECTIVE: This study aimed to evaluate the safety and tolerability of OP-724, a CREB-binding protein/ß-catenin inhibitor, in patients with advanced primary biliary cholangitis (PBC). DESIGN: An open-label, non-randomised, phase 1 trial was conducted at two hospitals in Japan. Patients with advanced PBC classified as stage III or higher according to the Scheuer classification by liver biopsy between 4 September 2019 and 21 September 2021 were enrolled. Seven patients received intravenous OP-724 infusions at escalating dosages of 280 and 380 mg/m2/4 hours two times weekly for 12 weeks. The primary endpoint was the incidence of serious adverse events (SAEs). The secondary endpoints were the incidence of AEs and the improvement in the modified Histological Activity Index (mHAI) score. RESULTS: Seven patients (median age, 68 years) were enrolled. Of these seven patients, five completed twelve cycles of treatment, one discontinued prematurely for personal reasons in the 280 mg/m2/4 hours cohort, and one in the 380 mg/m2/4 hours cohort was withdrawn from the study due to drug-induced liver injury (grade 2). Consequently, the recommended dosage was determined to be 280 mg/m2/4 hours. SAEs did not occur. The most common AEs were abdominal discomfort (29%) and abnormal hepatic function (43%). OP-724 treatment was associated with histological improvements in the fibrosis stage (2/5 (40%)) and mHAI score (3/5 (60%)) on histological analysis. CONCLUSION: Administration of intravenous OP-724 infusion at a dosage of 280 mg/m2/4 hours two times weekly for 12 weeks was well tolerated by patients with advanced PBC. However, further evaluation of antifibrotic effects in patients with PBC is warranted. TRIAL REGISTRATION NUMBER: NCT04047160.

Indocyanine green fluorescence navigation for hepatocellular carcinoma with bile duct tumor thrombus: a case report.

BACKGROUND: Bile duct tumor thrombus (BDTT) is one of the features of advanced hepatocellular carcinoma (HCC). In the resection of HCC with BDTT, it is important to detect the BDTT tip to decide the appropriate point of bile duct division. In this regard, the efficacy of indocyanine green (ICG) fluorescence navigation has been confirmed for the detection of HCC, whereas its utility for BDTT has not yet been reported. Herein, we describe our experience with right hepatectomy for HCC with BDTT using ICG fluorescence navigation. CASE PRESENTATION: A 72-year-old woman had experienced local recurrences of HCC after radiofrequency ablation, with BDTT reaching the confluence of the right anterior branch and posterior branch. Right hepatectomy was planned, and 2.5 mg of ICG was injected one day before surgery. After transection of the liver parenchyma, the right liver was connected with only the right hepatic duct. ICG fluorescence imaging visualized the tip of BDTT in the bile duct with clear contrast; the proximal side (hepatic side) of the right hepatic duct showed stronger fluorescence than the distal side (duodenal side). The bile duct was divided at the distal side of the BDTT border, and the tip of BDTT was recognized into the resected right hepatic duct without laceration. The patient had an uneventful postoperative course and currently lives without recurrences for 6 months. CONCLUSIONS: ICG fluorescence navigation assisted in the precise resection of the bile duct in HCC with BDTT.

A resected case of ruptured peritoneal metastasis of hepatocellular carcinoma.

Peritoneal metastases of hepatocellular carcinoma (HCC) are occasionally observed, but rupture of such metastases is rare. We report a resected case with a single ruptured peritoneal HCC metastasis. A 57-year-old man with chronic hepatitis C underwent hepatic resection twice for hepatocellular carcinoma. Recurrence in S3 was found, and the tumor was treated by radiofrequency ablation therapy (RFA). One month after RFA, plane computed tomography (CT) showed a nodule with a diameter of 5 cm near the upper pole of the spleen, and the serum alpha-fetoprotein (AFP) level remained high. The patient was admitted to hospital, with a chief complaint of abdominal pain 4 days after the CT scan, and diagnosed with intra-abdominal hemorrhage caused by a ruptured peritoneal HCC metastatic nodule. We performed semi-urgent surgery, including splenectomy and peritoneal metastasis resection, and the patient was discharged on the 10th postoperative day. Histopathological examination of the nodule confirmed HCC metastasis. The patient is alive with no evidence of recurrence as of 1 year and 6 months after the operation, with AFP levels remaining within the normal range.

Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography.

UNLABELLED: Liver stiffness, noninvasively measured by transient elastography, correlates well with liver fibrosis stage. The aim of this prospective study was to evaluate the liver stiffness measurement (LSM) as a predictor of hepatocellular carcinoma (HCC) development among patients with chronic hepatitis C. Between December 2004 and June 2005, a total of 984 HCV-RNA positive patients, without HCC or a past history of it, visited the University of Tokyo Hospital. LSM was performed successfully in 866 patients, who gave informed consent. During the follow-up period (mean, 3.0 years), HCC developed in 77 patients (2.9% per 1 person-year). The cumulative incidence rates of HCC at 1, 2, and 3 years were 2.4%, 6.0%, and 8.9%, respectively. Adjusting for other significant factors for HCC development, patients with higher LSM were revealed to be at a significantly higher risk, with a hazard ratio, as compared to LSM < or =10 kPa, of 16.7 (95% confidence interval [CI], 3.71-75.2; P < 0.001) when LSM 10.1-15 kPa, 20.9 (95% CI, 4.43-98.8; P < 0.001) when LSM 15.1-20 kPa, 25.6 (95%CI, 5.21-126.1; P < 0.001) when LSM 20.1-25 kPa, and 45.5 (95% CI, 9.75-212.3; P < 0.001) when LSM >25 kPa. CONCLUSIONS: This prospective study has shown the association between LSM and the risk of HCC development in patients with hepatitis C. The utility of LSM is not limited to a surrogate for liver biopsy but can be applied as an indicator of the wide range of the risk of HCC development.