BACKGROUND AND AIM:Alpha-fetoprotein (AFP) is widely used in hepatocellular carcinoma (HCC) surveillance, but its performance may vary with etiology and tumor stage. We assessed etiology-specific AFP and des-gamma-carboxyprothrombin (DCP) positivity at HCC diagnosis, focusing on early-stage disease. METHODS:We retrospectively enrolled consecutive adults with newly diagnosed, treatment-naïve HCC at two tertiary centers in Japan (2007-2023). AFP (cutoff ≥ 10 ng/mL) and DCP (≥ 40 mAU/mL) at diagnosis were analyzed overall and by etiology (Hepatitis B virus (HBV), Hepatitis C virus (HCV), sustained virological response [SVR], and non-B/non-C [NBNC]). Early stage was defined as Barcelona Clinic Liver Cancer (BCLC) 0/A and Union for International Cancer Control tumor-node-metastasis (UICC) T1a. RESULTS:Among 1396 patients, 760 (54.4%) had BCLC 0/A and 278 (19.9%) had T1a tumors. AFP positivity differed by etiology in BCLC 0/A disease (HBV 50.0%, HCV 64.6%, SVR-related 39.0%, NBNC 39.7%; p < 0.001), and in T1a tumors (48.1%, 60.3%, 39.0%, and 34.5%, respectively; p = 0.002). DCP (n = 1364) positivity in BCLC 0/A showed less variability (40.6%, 47.8%, 40.8%, and 58.4%, respectively; p = 0.005). Either-marker positivity in BCLC 0/A increased (64.1%, 80.0%, 59.2%, and 70.6%, respectively); the incremental yield from DCP alone among AFP-negative cases was 21.1% in SVR-related and 30.5% in NBNC early-stage HCC. CONCLUSION:AFP positivity at diagnosis was substantially lower in early-stage SVR-related and NBNC HCC than in HCV-related HCC. Adding DCP provides complementary detection, supporting an etiology-aware dual-marker strategy at diagnosis.

A 78-year-old man came to our department because of obstructive jaundice, and was diagnosed as pancreatic head cancer. He underwent chemoradiation therapy. A metal stent was inserted into the common bile duct and the patient was followed up on an outpatient basis. The patient visited our emergency department 46 days after stent insertion due to abdominal pain. The patient was diagnosed with ruptured pseudoaneurysm of the superior pancreaticoduodenal artery by angiography and treated with coil embolization. He died due to sudden deterioration the next day. Pathological autopsy revealed that the cause of the ruptured pseudoaneurysm appeared to be vasculopathy due to radiation therapy.

Background: Studies investigating the prevalence of celiac disease (CD) in persons with elevated aminotransferases have yielded conflicting results.It raises the question, whether clinicians should consider including celiac serology in initial evaluation of patients with abnormal liver tests.Elevated ALT in asymptomatic patients is commonly encountered in practice and a common reason for referral to gastroenterologists or hepatologists.The aim of our study is to determine the prevalence of CD in a large nationwide sample representative of the general population in the U.S. Methods: This study included 16,975 persons aged 6 years or older from the National Health and Nutrition Examination Survey (NHANES), which collects nationally representative data in the U.S. civilian population.Data from 2009-2012 were combined for this study.Upper limit of normal for ALT was ≥29 in men and ≥ 22 for women (Ruhl et al, Hepatol 2012).CD was defined as having positive tissue transglutaminase plus endomysial IgA Abs or a reported clinical diagnosis (reported diagnosis of CD by a doctor or a health-care professional and being on gluten-free diet).Primary study outcome was proportions of patients with CD in individuals with normal ALT and elevated ALT.Sample weights were used to determine weighted prevalence of CD.Results:The median age of the entire cohort was 36 years (range 6-80, IQR 16-57).Close to half (49.6%) were male with similar distribution between those with normal and elevated ALT.Overall, 38% were Non-Hispanic White, 22.9% were Non-Hispanic Blacks, 27.7% were Hispanic, and 11.4% had other races.Elevated ALT was seen in 29.1% of the cohort.Among the 3,725 individuals with elevated ALT, 41.5% were Non-Hispanic Whites, 16.9% were Non-Hispanic Blacks, 31.5% were Hispanic, and 10.1% were other races.CD was found in 56 individuals out of 16,975 (0.61%, 95%CI 0.43%-0.79%):20 with elevated ALT (0.80%, 95% CI 0.42%-1.2%)and 29 with normal ALT (0.61%, 95% CI 0.30%-0.91%)(Table 1).CD prevalence was highest in non-Hispanic White with both normal and elevated ALT at 0.87% (95% CI, 0.40%-1.3%)and 1.12% (95% CI, 0.58%-1.65%),respectively.Overall, CD prevalence was much lower in other races: 0.09% (95% CI 0%-0.2%) for Non-Hispanic Blacks, 0.12% (95% CI 0%-0.24%) in Hispanic, and 0.05% (95% CI, 0%-0.1%) in other races, and these were also similar among individuals with normal and elevated ALT (Table 1).Conclusion: Interestingly, the prevalence of CD in individuals with elevated ALT is similar to that seen in individuals with normal liver enzymes in U.S. and was approximately 1% or less in both populations.CD prevalence is particularly low in non-White individuals.Based on our results, we do not advocate routine testing with celiac serology to determine if CD is the cause of abnormal liver enzymes, especially in asymptomatic non-White patients.

Background/Aims: Photodynamic therapy (PDT) has a promising effect on nonresectable cholangiocarcinoma (CC) but its long term data are not available. This study examined the long term outcome and factors associated with increased survival after PDT for hilar cholangiocarcinoma. Methods: A list of 393 patients with a diagnosis of hilar CC was retrieved from the data base of Soonchunhyang University Hospital (Seoul, Korea) from January 1, 2001, to April 1, 2010. We retrospectively reviewed the records of 74 patients who underwent PDT in addition to biliary stenting with/without chemoradiation. Results: The median overall survival from the date of diagnosis to death or the last follow-up was 11.7months (range, 2.2-78.4) respectively. After PDT on negative bile duct biopsy specimens, a complete remission was observed in 1.3% (1/74) of the patients who had superficial tumor depth without lymph node involvement. In multivariate analysis with Cox regression model, increasing the time to treatment after diagnosis was statistically significant predictors of shorter survival after PDT. [Odds ratio, 3.25; 95% confidence interval (CI), 1.90-4.71, p= 0.034] Conclusion: The early treatment of PDT after diagnosis showed the survival benefit in advanced hilar CC.

confined to the cytoplasm of the hepatocytes inside the regenerative nodules and in the periphery of the fibrotic bands.Control animals, for each group had normal liver histology and SA-βgal was negative.The expression of p16, p21, and p53, was positive since early stages, with a significant increase of p16 from 15% in-group 1 to 70% in-group 3 that declined after withdrawal of TAA to 16%.No significant changes were noted in p21 and p53 labeling indexes.Conclusions: This study provides evidence that cellular senescence applies to liver cirrhosis and carries a risk of cell cycle checkpoints alterations that may affect liver regeneration at the cirrhotic stage.The selective loss of p16 after withdrawal of TAA may allow clonal expansion of hepatocytes, which may be relevant to understanding hepatocarcinogenesis This work was supported in part by grants UNAM, PAPIIT IN-208107, and CONACyT Salud 2004-CO1-175.

TNM stage (P=.025) and high CTP class (P=.022) were independently correlated to early mortality in HCC-CC group.When comparing only AJCC stage I of each disease, the TTR and the OS of patients with HCC-CC were significantly shorter than HCC (P<.001 and P= .015,respectively) or CC (P<.001 and P=.034, respectively).Conclusions: In this study, we found that male sex and high TNM stage were independent risk factors for early recurrence; and old age, high TNM stage and high CTP class were independent risk factors for early mortality in the HCC-CC group.Furthermore, HCC-CC showed poorer prognosis with earlier recurrence and shorter survival, which was significantly worse than HCC and CC, in the patients after curative resection in AJCC stage I of each disease.Close follow-up may be needed in the HCC-CC patients after curative resection with these risk factors, even in the early stage.

BACKGROUND:Extrahepatic metastasis of hepatocellular carcinoma (HCC) is of growing importance as the survival of patients has been improved owing to advances in treatments to intrahepatic lesions. METHODS:To elucidate the incidence and risk factors of extrahepatic metastasis of HCC, we enrolled 1573 (1131 treatment-naïve and 442 previously treated on referral) patients with HCC without extrahepatic tumour spread treated at the authors' department between 1990 and 2003. Patients received medical treatment including percutaneous ablation and transcatheter arterial chemoembolization, and followed by dynamic computed tomography (CT) or magnetic resonance imaging (MRI) and tumour markers every 3-4 months. Extrahepatic metastasis was diagnosed by plain X-ray, CT, MRI and scintigraphy. Clinical parameters at the time of treatment to intrahepatic lesions were evaluated as a predictor of subsequent extrahepatic metastasis among the 1131 treatment-naïve patients by Cox's proportional hazard model. RESULTS:During the average observation period of 3.9 years, extrahepatic metastasis was diagnosed in 123 in the treatment-naïve and 53 in the patients treated previously. The incidence rate of extrahepatic metastasis, as detected during the lifetime after medical treatment of HCC, was approximately 13% at 5 years. Multivariate analysis with Cox proportional hazard model revealed that positivity for viral markers, lager tumour diameter, multiple tumour nodules, presence of vascular tumour invasion and elevated tumour markers were associated with the development of extrahepatic metastasis. CONCLUSION:The incidence of extrahepatic metastasis of HCC diagnosed during clinical course was not frequent. Advanced intrahepatic lesions, presence of vascular tumour invasion, elevated tumour markers and presence of viral hepatitis were risk factors for extrahepatic metastasis.

Intrahepatic cholangiocarcinoma (ICC) is well known to have a very poor prognosis. Aggressive surgical strategies in the treatment of ICC, including major hepatectomy, have been reported to afford patients the best chance for significant survival. Recent advancements in surgical techniques concerning live donor liver transplantation have dramatically improved the results of major hepatectomy. However, surgical treatment of biliary malignancy is complex and is known to increase the likelihood of blood transfusion. We describe a Jehovah's Witness patient with ICC and concomitant bile duct invasion who had a successful right trisectionectomy with bile duct resection, lymph node dissection, and Rouxen-Y hepatico-jejunostomy without blood transfusion. A multidisciplinary preparation was crucial in obtaining this positive outcome. Importantly, bloodless liver transection techniques with inflow clamping, meticulous dissection, and hemostasis should be utilized for major hepatectomy in a Jehovah's Witness. The success of this case may alert clinicians to consider a hepatectomy as a possible option in the treatment of ICC in a Jehovah's Witness.

Background/Aims: It is not known whether the putative etiologic factors and clinical and pathological features of hepatocellular carcinoma differ between young adults and older patients. Therefore this study aims to evaluate whether the clinicopathological features in young patients with HCC significantly differ from those of elderly patients. Methodology: A total of 1014 consecutive patients with HCC were divided into two groups based on age. Among them, 73 patients younger than 50 years of age comprised the first group and 941 patients 50 years and older made up the second. Clinical, laboratory, and pathological characteristics were compared between the two age groups. Results: The male: female ratio and the incidence of positive hepatitis B surface antigen were significantly higher in young patients than in elderly patients. Tumor size, pathological grading of the tumor, and the severity of liver disease did not differ between the two groups. Especially in those patients demonstrating positive antibody to hepatitis C virus, alanine aminotransferase was higher in the younger, and platelet count was lower. Younger patients also had a higher ratio of alcohol consumption compared to elderly patients. Conclusions: There were age-related differences in the clinicopathological characteristics of HCC patients. Concerning hepatocarcinogenesis, male and HBsAg positive patients were at high risk in young. Of the HCV-related HCC patients, heavy drinking may accelerate the progression from chronic hepatitis to cirrhosis and HCC.

Congenital absence of the portal vein is an extremely rare anomaly, in which enteric blood bypasses the liver and drains into the inferior vena cava. A 16-year-old girl was referred to our hospital presenting with liver tumor. Although she had suffered from galactosemia soon after birth, the galactosemia had improved spontaneously 1 year later. Between the ages of 8 and 12 years, chronic hepatitis with a mild elevation of aspartate transaminase (AST) and alanine transaminase (ALT) was observed, but liver tumor had not been detected on computed tomography (CT) in regular medical examinations. However, at age 16, liver tumors, 10 cm in diameter, were found. Abdominal angiography indicated complete absence of the portal vein, suggesting that enteric blood was bypassing the liver and draining into the inferior vena cava. In biopsy specimens obtained under ultrasonographic guidance, liver tumors were confirmed histologically as hyperplastic nodules. In addition to this case report, the clinical features of 25 reported cases of congenital absence of the portal vein are reviewed.