Effect of sofosbuvir and velpatasvir therapy on clinical outcome in hepatitis C virus patients with decompensated cirrhosis.

AIM: To determine the impact of direct-acting antiviral therapy on the long-term prognosis of decompensated cirrhotic patients. METHODS: A total of 37 patients with hepatitis C virus-induced decompensated cirrhosis treated with sofosbuvir and velpatasvir (SOF/VEL group) were prospectively enrolled. For historical control, 65 hepatitis C virus-positive decompensated cirrhotic patients who did not receive direct-acting antiviral therapy were included (control group). The incidence rates of hepatocellular carcinoma (HCC), decompensated events with hospitalization, and overall survival were compared between both groups. RESULTS: A total of 41 patients experienced decompensated events during 15.0 months in the control group, and six patients during 21.6 months in the SOF/VEL group. The cumulative incidence rates of decompensated events after 2 years were significantly higher in the control group (53.1%) than in the SOF/VEL group (14.5%; p < 0.001). A total of 27 patients died within 22.0 months in the control group, and three patients died within 25.6 months in the SOF/VEL group. The overall survival rates after 2 years were significantly lower in the control group (67.6%) than in the SOF/VEL group (91.3%; p = 0.010). A total of 13 patients in the control group developed HCC during 15.8 months, and 10 patients during 17.3 months in the SOF/VEL group. The HCC incidence rates after 2 years were 20.3% and 29.6% in the control and SOF/VEL groups, respectively, with no significant difference (p = 0.327). CONCLUSIONS: SOF/VEL therapy may suppress the development of decompensated events and improve the prognosis in decompensated cirrhotic patients; however, the incidence of HCC remains prevalent in these patients irrespective of SOF/VEL therapy.

Risk of hepatocellular carcinoma after sustained virologic response in hepatitis C virus patients without advanced liver fibrosis.

AIM: Hepatocellular carcinoma (HCC) after sustained virologic response (SVR) has been observed even in hepatitis C virus (HCV) patients without advanced liver fibrosis. Identifying predictors for HCC incidence in patients without advanced liver fibrosis will enable efficient post-SVR HCC surveillance. This study aimed to develop a scoring system to predict the incidence of HCC after SVR in HCV patients without advanced liver fibrosis. METHODS: A total of 1682 HCV patients without advanced liver fibrosis (defined as Fibrosis-4 index <3.25) with no history of HCC who initiated direct-acting antiviral treatment between September 2014 and October 2020 at 26 institutions, and achieved SVR24, were included. We divided 1682 patients into training (1122) and validation (560) cohorts. RESULTS: In the multivariate analysis, baseline age ≥ 65 years (p = 0.030), alanine aminotransferase (ALT) levels at SVR24 ≥ 30 U/l (p = 0.001), and α-fetoprotein (AFP) levels at SVR24 ≥ 5.0 ng/ml (p = 0.001) were independent predictors for HCC incidence in the training cohort. We developed a scoring system to predict HCC incidence after SVR24 using these three factors (1 point was added for each factor). The cumulative HCC incidence rates at 5 years were 7.1% in patients who scored 2 or 3, and no patients developed HCC in those who scored 0 in the validation cohort. CONCLUSIONS: Our scoring system using the three factors of baseline age, ALT levels at SVR, and AFP levels at SVR is useful for post-SVR HCC surveillance of patients without advanced liver fibrosis.

Lower Serum Sodium Levels Are Associated with the Therapeutic Effect of Sorafenib on Hepatocellular Carcinoma.

BACKGROUND AND AIM: Although the serum sodium level has been reported to be a prognostic and predictive marker for the therapeutic effects of lung cancer and renal cell carcinoma treated with molecular targeted therapy, the serum sodium level has not been investigated in hepatocellular carcinoma (HCC) patients treated with sorafenib. The aim of our analysis was to assess the prognostic role of serum sodium levels in these patients. METHODS: We retrospectively analyzed 341 HCC patients treated with sorafenib between 2009 and 2012 in our hospital and other related institutions. RESULTS: A total of 178 patients were enrolled in this study. The median age was 72 years (44-88), and 148 patients (83%) were male. The median overall survival (OS) was 12.9 months, and the median time to progression (TTP) was 3.1 months. Hyponatremia (hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.26-2.52), a lower sodium level (HR 1.57, 95% CI 1.07-2.80), and a high level of α-fetoprotein (AFP) (≥ 200 ng/mL) (HR 1.78, 95% CI 1.26-2.52) were independent prognostic factors for TTP. We also categorized the patients into three groups according to serum sodium and AFP levels: Group A (n = 39) (serum sodium > 140 mEq/L, AFP < 200 ng/mL), Group C (n = 58) (serum sodium ≤ 140 mEq/L, AFP ≥ 200 ng/mL), and Group B (n = 81) (other patients). Significantly longer TTP and OS were observed in the following order: Groups A, C, and B. CONCLUSION: Serum sodium levels are associated with the effectiveness of sorafenib. The serum sodium level can predict the therapeutic effect of sorafenib in advanced HCC patients.

[Anaphylactic shock secondary to the use of macrogol 4000 as a bowel cleanser:a case report].

A 44-year-old man was administered Niflec® containing macrogol 4000 as a bowel cleanser for colonoscopic examination. Immediately after ingestion, he experienced oral cavity discomfort and nasal congestion, followed by acute urticaria and presyncope. His systolic blood pressure and peripheral capillary oxygen saturation dropped to 66mmHg and 89%, respectively. Fluid infusion, as well as steroid and epinephrine administration, improved his symptoms. Skin prick tests were then performed using Niflec®, macrogol 4000, and Actosin® ointment (containing macrogol 4000), all of which were positive. Therefore, the patient was diagnosed with anaphylactic shock caused by macrogol 4000 included in Niflec®. Macrogol present in bowel cleansers used for colonoscopy rarely causes anaphylactic shock. However, clinicians need to be mindful of this risk. Prompt and appropriate treatment is needed should this condition occur.

Quick and stable parallel puncture of hepatic tumors using a double-barreled needle direction system for ultrasound-guided bipolar radiofrequency ablation.

AIM: In bipolar radiofrequency ablation (RFA) therapy, insertion of multiple needles at appropriate points on a target is difficult. The aim of our study was to evaluate a simplified method for multi-electrode insertion using a newly developed double-barreled needle guidance system for percutaneous RFA of hepatic tumors. METHODS: RFA using two bipolar electrodes was performed in 15 consecutive patients (nine men, six women; mean age, 72.0 ± 8.2 years) with a solitary small (≤3 cm) hepatic tumor. The first five nodules were treated using the conventional puncture method with the standard attachment, then 10 nodules were ablated using the parallel puncture method with the double-barreled attachment. The times required for double-needle placement and the shapes of the ablated areas were compared between the two puncture methods. RESULTS: The parallel puncture method required a shorter time for double-needle placement than the conventional method (12 s [range, 8-24] vs 96 s [range, 50-240]; P = 0.0003), and allowed continuous observation of the tip of all needles and the size of the ablated area as it increased until completion of the ablation. The method also provided a stable ellipsoidal ablated area. The median height, width and thickness were 30 mm (range, 22-34), 30 mm (range, 21-33) and 20 mm (range, 7-25), respectively, using 20-mm electrodes, and 34 mm (range, 32-41), 36 mm (range, 35-38) and 24 mm (range, 23-24), respectively, using 30-mm electrodes. CONCLUSION: The parallel puncture method may be a feasible procedure for multi-needle RFA therapy.

Impact of branched-chain amino acid supplementation on survival in patients with advanced hepatocellular carcinoma treated with sorafenib: A multicenter retrospective cohort study.

AIM: The therapeutic efficacy of branched-chain amino acid (BCAA) when added to sorafenib has not been fully assessed in patients with advanced hepatocellular carcinoma (HCC). This multicenter study investigated whether BCAA supplementation improves prognosis in patients with advanced HCC who underwent sorafenib treatment. METHODS: This retrospective analysis included 256 patients with advanced HCC treated with sorafenib, including 55 who did and 201 who did not receive BCAA supplementation. Clinical characteristics and outcomes in relation to Child-Pugh classification were compared in the two groups. Statistical analyses of univariate, multivariate and propensity score-based procedures were used for this study. RESULTS: Assessment of 216 Child-Pugh A patients showed that median overall survival was significantly longer in patients with BCAA supplementation than in those without it (440 vs 299 days, P = 0.023). Multivariate analysis showed that BCAA supplementation (P = 0.023), low α-fetoprotein (<100 ng/mL) (P < 0.001), less progressive Barcelona Clinic Liver Cancer stage (A and B) (P = 0.007) and male sex (P = 0.018) were significant independent contributors to better overall survival. The significantly longer overall survival by BCAA supplementation was verified in the analysis using the propensity score in combination with the inverse probability of treatment weighted adjustment (P = 0.026). Assessment of the 40 Child-Pugh B patients showed no significant differences in overall survival between patients with and without BCAA supplementation. CONCLUSION: BCAA supplementation may be a valuable adjunctive therapy for improving prognosis in sorafenib-treated Child-Pugh A patients with advanced HCC.

Phase I study of combination chemotherapy using sorafenib and transcatheter arterial infusion with cisplatin for advanced hepatocellular carcinoma.

The aims of this study were to evaluate the frequency of dose-limiting toxicities and to find the recommended dose of combination chemotherapy with sorafenib and transcatheter arterial infusion (TAI) using cisplatin for patients with advanced hepatocellular carcinoma (HCC), for whom surgical resection, local ablation therapy, or transcatheter arterial chemoembolization were not indicated. Patients received 800 mg sorafenib daily. Cisplatin was given at one of three dosages (level 1, 35 mg/m(2) /cycle; level 2, 50 mg/m(2) /cycle; and level 3, 65 mg/m(2) /cycle) from feeding arteries to the HCC. The treatment was repeated every 4-6 weeks up to a maximum of six cycles, until there were signs of tumor progression or unacceptable toxicity. The dose-limiting toxicities experienced by the 20 enrolled patients were grade 4 increased aspartate aminotransferase at level 1, grade 3 gastrointestinal hemorrhaging at level 1, and grade 3 hypertension at level 3. The common drug-related adverse events that were of severity grade 3 or 4 included the elevation of aspartate aminotransferase (30%), alanine aminotransferase (20%), amylase (30%), and lipase (30%). Partial response was seen in four patients (20%), and 13 patients (65%) had stable disease. The median overall survival and progression-free survival were 9.1 and 3.3 months, respectively. The combination of sorafenib at 800 mg/day with TAI of cisplatin at 65 mg/m(2) /cycle was determined to be the recommended regimen. A randomized phase II trial of sorafenib alone versus sorafenib plus TAI of cisplatin is currently underway. This study was registered at UMIN as trial number UMIN000001496.

Three-dimensional registration of images obtained before and after radiofrequency ablation of hepatocellular carcinoma to assess treatment adequacy.

OBJECTIVE: The aim of our study was to evaluate the value of 3D registration images reconstructed by fusion of pre- and posttreatment CT or MRI for the assessment of ablative margins after percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From January 2007 to May 2011, we performed RFA in 84 patients to treat 139 HCC nodules, the margins of which had been assessed by comparing pre- and postablation images side by side. The same nodules were retrospectively assessed again with 3D registration images after classification into four margin grades. We analyzed the cumulative local recurrence rate for each grade and reviewed the origin of recurrence. RESULTS: Three-dimensional registration images predicted local recurrences more accurately than did the conventional side-by-side method (area under the curve, 0.678 and 0.536, respectively; p = 0.0144). The cumulative rates of local recurrence were significantly different among the margin grades assessed with 3D registration images (p = 0.0088). Three-dimensional registration images detected that the major origins of recurrence (n = 22) were residuals (n = 13) and sites of no margin (n = 6), especially proximate to blood vessels more than 3 mm in diameter. CONCLUSION: Three-dimensional registration of pre- and postablation CT or MRI more accurately assesses the ablative margin than the conventional method. It can predict a proclivity for local recurrence after RFA according to margin grade. It also indicated that residuals and sites of no margin proximate to blood vessels that are more than 3 mm in diameter are high-risk locations for local recurrence after ablation.

Computed tomography during hepatic arteriography pattern may predict hepatocellular carcinoma recurrence following transarterial chemoembolization.

AIM: This study aimed to determine the role of morphological patterns seen on imaging in predicting hepatocellular carcinoma recurrence following transarterial chemoembolization therapy. METHODS: Forty-seven patients from a single center who underwent transarterial chemoembolization to treat unresectable hepatocellular carcinomas between January 2011 and June 2012 were included in this study. We investigated whether the two pretreatment findings on computed tomography during hepatic arteriography (pattern 1, the single nodule pattern; pattern 2, at least one nodule showing the contiguous multinodular pattern) and other factors (age, sex, etiology, serum total bilirubin, serum albumin, prothrombin time, platelet count, serum level of protein induced by vitamin K absence/antagonist-II, serum α-fetoprotein, number of previous treatments for hepatocellular carcinoma, tumor number and maximum tumor size, presence of hypovascular lesions) could predict post-treatment recurrence. RESULTS: In a univariate analysis using Cox's proportional hazards model, serum total bilirubin, the serum level of protein induced by vitamin K absence/antagonist-II (≤100 vs ≥101 mAU/mL), tumor morphology (pattern 1 vs 2) and tumor number (≤3 vs ≥4) showed statistical significance (≤0.05). In a multivariate analysis of these factors, morphology and tumor number showed significance. According to Kaplan-Meier estimation, the cumulative disease-free survival rates were significantly lower in patients with four or more lesions than in those with three or less lesions and in patients showing pattern 2 than in those showing pattern 1. CONCLUSION: Patients with pattern 2 hepatocellular carcinoma and/or four or more lesions may have a relatively high recurrence rate after transarterial chemoembolization.

Factors related to shift from hepatic borderline lesion to overt HCC diagnosed by CT.

BACKGROUND/AIMS: Factors contributing to the shift from the hepatic borderline lesion to overt hepatocellular carcinoma (HCC) were investigated. METHODOLOGY: Ninety-five borderline nodules from 69 patients were followed-up for 6-55 (median 24) months. The borderline lesion was diagnosed when the CT image demonstrated low density in the portal phase and lacked enhancement in the arterial phase. RESULTS: The shift to overt HCC was seen in 32 nodules from 27 patients. Using multivariate analysis, only size was a significant factor contributing to the shift to overt HCC (p = 0.009). The cumulative incidence of the shift to overt HCC was higher in nodules of ≥13 mm in size than in those of < 13 mm (p = 0.034). Among nodules of ≥13 mm, nodules showing iso density in the arterial phase and low density in the portal phase had a higher cumulative incidence of the shift to overt HCC than those showing low density in the arterial and portal phases on CT (p=0.007). CONCLUSIONS: In hepatic borderline nodules diagnosed by CT, greater size, and iso density in the arterial phase and low density in the portal phase may be risk factors associated with the shift to overt HCC.

Clinical factors associated with the therapeutic efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter prospective observational study.

The treatment efficiency and predictors of atezolizumab plus bevacizumab therapy for unresectable hepatocellular carcinoma in real-world practice have not been established. This study aimed to assess the efficacy and safety of atezolizumab plus bevacizumab and to investigate predictors of progression-free survival and overall survival. Patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab therapy in 19 hospitals were enrolled before treatment and observed prospectively. The outcomes of 222 patients in this cohort were analyzed. The objective response rate and disease control rate were 22.0% and 70.6%, respectively, whereas the median progression-free survival was 5.7 months. Independent risk factors for shortened progression-free survival were younger age (<75 years; 3.9 months vs. 8.6 months), higher number of intrahepatic tumors (≥5; 4.0 months vs. 7.9 months), macrovascular invasion (2.3 months vs. 6.7 months), and higher neutrophil-to-lymphocyte ratio (≥3.03; 3.0 months vs. 7.8 months). The median overall survival was not reached; however, independent risk factors for shortened overall survival were absence of hyperlipidemia, higher number of intrahepatic tumors (≥5), macrovascular invasion, higher α-fetoprotein level (≥400 ng/mL), worse Child-Pugh score (≥6), and higher neutrophil-to-lymphocyte ratio (≥3.03). Severe adverse events (grade ≥3) were observed in 96 patients (36.0%), with proteinuria being the most frequent. In conclusion, patients with older age, lower number of intrahepatic tumors, absent macrovascular invasion, and lower neutrophil-to-lymphocyte ratio are expected to have better progression-free survival with atezolizumab plus bevacizumab therapy for unresectable hepatocellular carcinoma.

Plasmablastic lymphoma occurring in ulcerative colitis during treatment with immunosuppressive therapy.

A 53-year-old man who had a history of ulcerative colitis (UC) for 2 years underwent colonoscopy as regular follow-up. The results showed an elevated lesion in the descending colon, which was diagnosed as plasmablastic lymphoma (PBL) based on pathological findings. In situ hybridization for the Epstein-Barr virus-encoded RNA probe was positive. Fluorescence in situ hybridization revealed rearrangement of the MYC gene. He had been taking prednisolone, 5-aminosalicylic acid, azathiopurine, and ustekinumab at the diagnosis of PBL and had multiple prior therapies for UC including infliximab, tacrolimus, and tofacitinib due to steroid dependence. PBL is a rare aggressive B cell lymphoma initially described in the oral cavity of human immunodeficiency virus positive patients and it is suspected to have an association with immunocompromised status of patients. The number of cases of PBL in inflammatory bowel disease (IBD) patients is extremely rare. All these patients were administered immunosuppressive therapy including thiopurines or biologics. IBD patients with immunosuppressive therapy have a higher potential for developing lymphoproliferative disorders. Clinicians should be aware of the risk of lymphoma, including PBL.

Pretreatment with antibiotics is associated with reduced therapeutic response to atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.

AIM: Alterations in microbial composition of gut microbiota due to antibiotics (ATB) may lead to resistance to immune checkpoint inhibitors (ICIs). This study aimed to assess the impact of ATB use on therapeutic response in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab. METHODS: This study retrospectively analyzed 105 patients with HCC treated with atezolizumab plus bevacizumab as a primary systemic therapy from prospectively-registered, multicenter, cohorts. Nineteen patients who received prior ATB were included in the ATB (+) group; 86 patients who did not receive prior ATB were included in the ATB (-) group. The therapeutic outcomes were compared between the two groups. RESULTS: Most of the patients' baseline characteristics were not significantly different between the two groups. The objective response rates according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (30.1% vs. 11.1%; p = 0.143) and modified RECIST (mRECIST) (44.6% vs. 27.8%; p = 0.190) were not significantly different between the ATB (-) and ATB (+) groups. The disease control rates were higher in the ATB (-) group than in the ATB (+) group according to RECIST v1.1 (74.7% vs. 44.4%; p = 0.012) and mRECIST (78.3% vs. 50.0%; p = 0.020). Prior ATB use was found to be independently associated with radiological progressive disease of the first therapeutic assessment. The median progression-free survival according to RECIST v1.1 (9.1 months vs. 3.0 months; p = 0.049) and mRECIST (9.1 months vs. 3.0 months; p = 0.036), and overall survival (not reached vs. 11.4 months; p = 0.015) were longer in the ATB (-) group than in the ATB (+) group. CONCLUSIONS: Prior ATB use was associated with reduced therapeutic responses in patients with HCC receiving atezolizumab plus bevacizumab.

Lipiodol accumulation and transarterial chemoembolization efficacy for HCC patients.

BACKGROUND/AIMS: To elucidate the prognostic factors for hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). METHODOLOGY: We studied 85 TACE-treated HCC patients, including 117 lesions, who fulfilled the Milan criteria. The area of iodized poppy-seed oil (lipiodol) accumulation on CT immediately after TACE was classified into three groups, by comparing with the area of HCC detected by CT during hepatic arteriography; accumulation surrounding the HCC lesion (group I), accumulation involving the entire area of the HCC lesion (group II), and accumulation that covered a portion of the HCC lesion (group III). RESULTS: Among 85 patients, the 1- and 2-year disease free survival (DFS) rates were 67% and 50% in group I, 49% and 29% in group II and 29% and 15% in group III. DFS rate was higher in group I than in groups II and III (p=0.016 and p<0.001). Difference in DFS by lipiodol accumulation pattern was evident in patients aged 75 or younger. CONCLUSIONS: Lipiodol accumulation pattern as evaluated by CT immediately after TACE may be a powerful indicator of the therapeutic efficacy of TACE in HCC patients.

Fucosylated haptoglobin is a novel predictive marker of hepatocellular carcinoma after hepatitis C virus elimination in patients with advanced liver fibrosis.

BACKGROUND: Patients with advanced fibrosis are at risk for developing hepatocellular carcinoma (HCC) even after hepatitis C virus (HCV) elimination. We previously reported that serum fucosylated haptoglobin (Fuc-Hp) levels increase as the disease progresses from chronic hepatitis to cirrhosis and then HCC. However, it remains unclear whether serum Fuc-Hp levels can stratify the risk of HCC occurrence after a sustained virological response (SVR) is achieved with direct-acting antivirals (DAAs) in patients with advanced liver fibrosis. METHODS: Among 3,550 patients with chronic hepatitis C treated with DAAs at Osaka University Hospital and related hospitals, the stored sera of 140 patients who were diagnosed with F3 or F4 by liver biopsy before DAA treatment, achieved SVR, and had no history of HCC were available at both baseline and the end of treatment (EOT). We measured the Fuc-Hp levels in these samples. RESULTS: The median serum levels of Fuc-Hp at EOT were significantly lower than those at baseline. During the 54.4-month follow-up period, 16 of 140 patients developed HCC. Multivariate Cox proportional hazards analysis revealed that high Fuc-Hp at EOT, high body mass index (BMI), and low albumin at EOT were independent risk factors for HCC occurrence. Patients with all three factors-high Fuc-Hp, high BMI, and low albumin-had a higher incidence of HCC than patients without these factors. CONCLUSIONS: High serum Fuc-Hp levels at EOT were an independent risk factor for HCC occurrence after SVR. Combined with BMI and albumin, Fuc-Hp can stratify the risk of HCC occurrence among those with advanced fibrosis.

Combined brush cytology and stent placement in a single session for presumed malignant biliary stricture.

BACKGROUND AND AIM: Biliary stricture may be benign or malignant and causes obstructive jaundice. Brush cytology is a simple technique for diagnosing the cause of biliary stricture; however, its sensitivity has been reported to be low. A technique that comprises diagnosing the cause of stricture with a satisfactory sensitivity and relieving jaundice is required. This study was designed to evaluate the diagnostic performance of brush cytology and the feasibility of the subsequent stent placement in a single endoscopic retrograde cholangiopancreatography (ERCP) session performed for presumed malignant biliary strictures. METHODS: Data were collected by reviewing the medical records of 100 consecutive patients with suspected malignant biliary stricture who underwent brush cytology followed by stent placement at our center. Diagnostic performance of brush cytology, completion rate of the whole procedures comprising brush cytology and stent placement, and complications were evaluated. RESULT: Sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of brush cytology were 83%, 100%, 100%, 33% and 84%, respectively. Biliary stent was successfully inserted for all patients (100%) subsequent to brush cytology in a single ERCP session. Eight patients (8%) had complications. CONCLUSION: Brush cytology was performed with much higher sensitivity of 83% than those of previous reports and the subsequent stent placement was successfully completed in all cases. For presumed malignant biliary stricture, brush cytology should be selected as an initial attempt because this technique is simple and enables subsequent stent placement in a single ERCP session.

Renal Dysfunction is an Independent Risk Factor for Rebleeding After Endoscopic Hemostasis in Patients with Peptic Ulcer Bleeding.

BACKGROUND: Despite the progress in endoscopic hemostasis and pharmacological treatment, the mortality rate of peptic ulcer bleeding remains at 5-10%. Rebleeding after peptic ulcer bleeding is believed to be a risk factor for mortality. This study aimed to evaluate whether renal dysfunction is a predictor of rebleeding after endoscopic hemostasis in patients with peptic ulcer bleeding. METHODS: In this retrospective study, consecutive patients with peptic ulcer bleeding who underwent endoscopic hemostasis at our Hospital from January 2010 to December 2018 were enrolled. The relationship between rebleeding within 30 days after endoscopic hemostasis and the patients' admission and endoscopic characteristics were analyzed using univariate and multivariate regression models. RESULTS: Out of 274 patients with peptic ulcer bleeding, 17 (6.2%) patients experienced rebleeding. In the analysis of the patients' admission characteristics, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 was an independent risk factor for rebleeding (odds ratio 4.77, 95% confidence interval 1.168-18.211, p = 0.03). Patients with eGFR < 15 mL/min/1.73 m2 with or without hemodialysis had the highest rebleeding rate at 36.8%. With respect to endoscopic characteristics, the rate of rebleeding was associated with combination therapy (p < 0.0001) and active bleeding (p = 0.03). CONCLUSION: Renal dysfunction might be an independent risk factor for rebleeding after endoscopic hemostasis in patients with peptic ulcer bleeding.

[Investigation of simplified international diagnostic criteria for autoimmune hepatitis].

The simplified international diagnostic criteria for autoimmune hepatitis (AIH), re-revised by the International AIH Group in 2008, were investigated in 114 patients with AIH from 15 centers in Japan. While applying of the criteria, we had to pay attention to anti-nuclear antibody measurement methods, and liver histology scoring. Definite and probable AIH were diagnosed in 83 and 22 patients, respectively. The criteria were found to be useful for the diagnosis of AIH in Japan. However, 9 patients who did not meet the diagnostic criteria showed normal immunoglobulin G levels or were negative for autoantibodies. As the criteria were unreliable for diagnosing such atypical cases in the present series, we speculated that we should not rely solely on these, criteria and take a more holistic approach to diagnosis in such cases.

Effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis.

AIM: The objective of this study was to elucidate the long-term effects of interferon (IFN)alpha-2b plus ribavirin combination therapy and to clarify whether this therapy can reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. METHODS: A total of 403 patients infected with hepatitis C virus (HCV) were enrolled in a multicenter trial. All patients were treated with a combination of IFN-alpha-2b plus ribavirin therapy. We examined the incidence of HCC after combination therapy and analyzed the risk factors for liver carcinogenesis. RESULTS: A sustained virological response (SVR) was achieved by 139 (34%) of the patients. The cumulative rate of incidence of HCC was significantly lower in SVR patients than in non-SVR patients (P = 0.03), while there was no difference in the cumulative incidence of HCC between the transient response (TR) group and the no response (NR) group. Cox's regression analysis indicated the following risk factors as independently significant in relation to the development of HCC: age being > 60 years (P = 0.006), advanced histological staging (P = 0.033), non-SVR to IFN therapy (P = 0.044). The cumulative incidence rate of HCC was significantly lower in patients who had average serum alanine aminotransferase (ALT) levels of < 40 IU/L than in those who showed average serum ALT levels of >== 40 IU/L after the combination therapy (P = 0.021). CONCLUSIONS: These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development.

Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to 2003.

BACKGROUND: Japan has the highest incidence rate of primary liver cancer attributed to chronic hepatitis C virus (HCV) infection among developed countries. Molecular clock analysis of HCV sequences revealed that the spread of HCV took place earlier in Japan than in other countries. This might influence recent temporal trends in hepatocellular carcinoma (HCC) incidence. OBJECTIVE: To characterize the contribution of HCV-related hepatocellular carcinoma (HCC) to recent changes in HCC incidence in Osaka, Japan. DESIGN: Population-based survey. SETTING: Osaka Cancer Registry and 10 hospitals in Osaka. PARTICIPANTS: 63,862 patients with HCC that was diagnosed between 1981 and 2003 in Osaka Prefecture, including 5253 HCV-seropositive patients with HCC that was diagnosed between 1990 and 2003 at 10 hospitals. MEASUREMENTS: Incidence of HCC and estimated incidence rate of HCV-related HCC, measured by multiplying the prevalence of anti-HCV by the corresponding HCC incidence rate. RESULTS: Between 1981 and 2003, peak incidence of HCC among men age 50 to 59 years, 60 to 69 years, and 70 to 79 years occurred in 1986, 1995, and 2000, respectively, with marked downward trends thereafter (average annual change, -7.9, -22.3, and -12.4 per 100,000 persons, respectively). Similar trends were observed in women. Estimated sex- and age-specific incidence of HCV-related HCC (per 100,000 persons) decreased from 255 to 92 cases at the maximum in men age 60 to 69 years and from 61 to 34 cases in women age 60 to 69 years, whereas estimated incidence of non-HCV-related HCC did not change between 1990 and 2003. LIMITATION: Infection was determined only by HCV seropositivity. CONCLUSION: The incidence of HCC in Osaka started to decrease by 2000, mainly because of decreased HCV-related HCC.