Outcome of untreated low-level viremia versus antiviral therapy-induced or spontaneous undetectable HBV-DNA in compensated cirrhosis.

BACKGROUND: Comparative outcomes of HBV-infected compensated cirrhosis with low-level viremia (LLV) versus maintained virological response (MVR) are unclear. We conducted a large, multiethnic, multicenter study to examine the natural history of LLV versus MVR in compensated cirrhosis. PATIENTS AND METHODS: We enrolled patients with HBV-infected compensated cirrhosis (n=2316) from 19 hospitals in South Korea, Singapore, and Japan. We defined the LLV group as untreated patients with ≥1 detectable serum HBV-DNA (20-2000 IU/mL), Spontaneous-MVR group as untreated patients with spontaneously achieved MVR, and antiviral therapy (AVT)-MVR group as patients achieving AVT-induced MVR. Study end points were HCC or hepatic decompensation. RESULTS: The annual HCC incidence was 2.7/100 person-years (PYs), 2.6/100 PYs, and 3.3/100 PYs for LLV (n=742), Spontaneous-MVR (n=333), and AVT-MVR (n=1241) groups, respectively ( p = 0.81 between LLV vs. Spontaneous-MVR groups and p = 0.37 between LLV vs. AVT-MVR groups). Similarly, the annual decompensation incidence was 1.6/100 PYs, 1.9/100 PYs, and 1.6/100 PYs for LLV, Spontaneous-MVR, and AVT-MVR groups, respectively ( p = 0.40 between LLV vs. Spontaneous-MVR groups and p = 0.83 between LLV vs. AVT-MVR groups). Multivariable analyses determined that HCC and decompensation risks in the LLV group were comparable to those with Spontaneous-MVR and AVT-MVR groups (all p >0.05). Propensity score matching also reproduced similar results for HCC and decompensation risks (all p >0.05 between LLV vs. Spontaneous-MVR groups and between LLV vs. AVT-MVR groups). CONCLUSIONS: Untreated LLV in HBV-infected compensated cirrhosis is not associated with increased risk of disease progression compared with Spontaneous-MVR and AVT-MVR. These data have important implications for practice and further research.

Treatment response to durvalumab plus tremelimumab after progression with previous immune checkpoint inhibitor in unresectable hepatocellular carcinoma.

Although immune checkpoint inhibitors (ICI) are used for unresectable hepatocellular carcinoma (HCC), it is unclear whether sequential ICI treatment-durvalumab plus tremelimumab (DT) after progression on atezolizumab plus bevacizumab (AB)-is effective for HCC. In this nationwide multicenter study, we aimed to investigate the effect of DT treatment based on the timing of treatment. A total of 85 patients receiving DT treatment were enrolled. The primary endpoint is treatment response at week 8 among patients receiving first-line DT treatment, those receiving second-line or later treatment without prior AB therapy, and those receiving second-line or later treatment with prior AB therapy. Objective response rates (ORRs) in patients with first-line treatment, second-line treatment without AB, and second-line treatment with prior AB were 44%, 54%, and 5%, respectively (p < 0.001). Similarly, disease control rates (DCRs) were 69%, 91%, and 26%, respectively (p < 0.001). ORR and DCR were significantly lower in patients with prior AB treatment. Progression free survival (PFS) was significantly shortened in patients receiving second-line therapy following prior AB treatment and an adjusted hazard ratio (95% confidence interval) in those patients for PFS, using first-line therapy as a reference, was 2.35 (1.1-5.1, p = 0.03). In conclusion, the impact of DT sequencing following AB treatment was limited. However, even after second-line treatment, the treatment effect can be equivalent to that of first-line treatment in cases with no history of AB treatment. Thus, prior treatment history should be taken into account when initiating DT treatment.

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B.

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin-bilirubin (ALBI) score was significantly improved by NA therapy (-0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03-15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.

Clinical role of radiofrequency ablation for early-stage hepatocellular carcinoma in an advanced aging society.

AIM: It is unclear whether prognosis differs by age for early-stage hepatocellular carcinoma (HCC). We aimed to examine prognosis and recurrence after radiofrequency ablation (RFA) for early-stage HCC and to determine its prognostic factors for different age groups. METHODS: This retrospective study enrolled 1079 patients with initial early-stage HCC treated with RFA at two institutions. All patients in this study were divided into four groups: <70 years old (group1, n = 483), 70-74 years old (group2, n = 198), 75-79 years old (group3, n = 201), and ≥80 years old (group4, n = 197). Prognostic factors were evaluated by comparing survival and recurrence rates between each group. RESULTS: The median survival time and 5-year survival rates for each group were 113 months and 70.8% in group1, 99.2 months and 71.5% in group2, 91.3 months and 66.5% in group3, and 71 months and 52.6% in group 4, respectively. Group4 had a significantly shorter survival than the other groups (p < 0.05). There were no significant differences in recurrence-free survival among the groups. In group4, the most common cause of death was nonliver-related disease (69.4%). In all groups, modified albumin-bilirubin index grade was a factor contributing to prolonged prognosis, but only in group4 performance status (PS) was a significant factor (hazard ratio, 2.46; 95% confidence interval, 1.16-3.00; p = 0.009). CONCLUSION: For early-stage HCC in the elderly, preoperative evaluation of PS and management of other diseases could contribute to a prolonged prognosis.

Usefulness of neutrophil-to-lymphocyte ratio in predicting progression and survival outcomes after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

AIM: We investigated pretreatment neutrophil-to-lymphocyte ratio (NLR) for predicting survival outcomes of atezolizumab plus bevacizumab therapy for hepatocellular carcinoma (HCC) and determined the predictive ability of combined liver reserve-NLR. METHODS: This retrospective, multicenter study enrolled 242 patients receiving atezolizumab plus bevacizumab for unresectable HCC. Pretreatment NLR <2.56 was designated as the "low group" and NLR ≥2.56 as the "high group" (120 and 122 patients, respectively). Propensity score-matched analysis was undertaken between the low and high groups. RESULTS: In this cohort, the objective response and disease control rates were 20% and 72.5%, respectively, in the low group and 19.6% and 72.9%, respectively, in the high group. After matching, median progression-free survival (PFS) time was 283 and 167 days in the low and high groups, respectively (p = 0.022). Neutrophil-to-lymphocyte ratio ≥2.56 (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.05-2.28; p = 0.028), modified albumin-bilirubin index (mALBI) grade 2b or 3 (HR 1.55; 95% CI, 1.05-2.29; p = 0.025), and protein induced by vitamin K absence or antagonist-II ≥ 400 (HR 2.03; 95% CI, 1.36-3.02; p = 0.001) were significantly associated with PFS in univariate analysis using the Cox proportional hazards model. In cases involving mALBI grade 1 or 2a (n = 131), the median PFS time was not reached in the low group, whereas it was 210 days in the high group (p = 0.037). CONCLUSIONS: Pretreatment NLR is a simple tool for routine measurement in clinical practice. It can predict PFS in patients with unresectable HCC treated with atezolizumab plus bevacizumab, especially mALBI grade 1 or 2a.

Efficacy of hepatitis C virus eradication after curative treatment for hepatocellular carcinoma in patients with advanced hepatocellular carcinoma and decreased hepatic functional reserve: A nationwide, multicentre study by the Japanese Red Cross Liver Study Group.

Improvements in the hepatocellular carcinoma (HCC) recurrence rate and survival have been frequently reported following virus eradication after hepatitis C virus (HCV)-related HCC cure. However, the efficacy of direct-acting antiviral (DAA) therapy in patients who included those with advanced HCC and decreased hepatic functional reserve is unknown. A comparative examination was retrospectively conducted of 141 patients with hepatitis C who started DAA therapy within 1 year after undergoing curative HCC treatment and showed a sustained viral response (SVR) and 327 patients who underwent curative treatment for HCV-related HCC and did not subsequently receive antiviral therapy. Whether DAA therapy was given was identified as an independent factor related to both HCC recurrence and survival. Both the recurrence and survival rates improved significantly with DAA therapy in Child-Pugh (CP)-A, whereas no difference in the recurrence rate was seen with DAA therapy in CP-B. However, the survival rate was significantly higher in the DAA group in this class. Similarly, dividing the patients by the Milan criteria showed significant improvements in the recurrence rate and survival with DAA therapy in patients within the Milan criteria. Patients with HCC beyond the Milan criteria showed no difference in recurrence rates, but the DAA group tended to have higher survival rates. Thus, DAA after curative therapy for HCC can be expected to improve survival in patients with advanced HCC or decreased hepatic functional reserve. HCV should be aggressively eradicated in all patients eligible for curative treatment of HCC.

Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Alpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment. In this prospective multicenter study, we aimed to investigate an optimal threshold of AFP response in Atez/Bev treatment. Out of 284 patients with unresectable HCC who were treated with Atez/Bev, 91 patients with AFP ≥ 10 ng/ml were enrolled in the multicenter study. We investigated the relationship between various AFP response thresholds (relative decline ≥ 20%, ≥ 50%, and ≥ 75%) and treatment response and progression-free survival (PFS). An AFP relative decrease of ≥ 50% was associated with an overall response rate (ORR) with an odds ratio (95% confidence interval [CI]) of 5.7 (1.9-17). Disease control rate (DCR) was associated with an AFP relative decrease of ≥ 20%, with a 100% positive predictive value and a 52.0% sensitivity. AFP relative decreases of ≥ 50% and ≥ 20% were significantly associated with PFS with a hazard ratio (HR) of 5.60 (95% CI: 1.6-19, p = 0.006) and a HR of 4.44 (95% CI: 1.9-10, p < 0.001), respectively. AFP response of ≥ 50% and ≥ 20% were related to ORR and DCR, respectively, and both of these responses were also associated with PFS. AFP can be used as a real-time monitor during Atez/Bev treatment and is helpful for treatment optimization.

Real-world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group.

AIM: The present study aimed to determine the real-world efficacy and safety of the non-structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection. METHODS: This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post-treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study. RESULTS: Treatment outcomes for EBR/GZR were good in direct-acting antiviral (DAA)-naïve patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A-L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A-L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A-Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91-16 940; P < 0.0001) was identified as an independent predictor of treatment failure. No serious adverse events were observed with EBR/GZR therapy. CONCLUSIONS: The SVR rate of EBR/GZR would have been 100% in patients without either a history of DAA therapy or double mutation. This combination of drugs could be safely given and is, thus, considered a highly useful first-line treatment for DAA-naïve patients with HCV.

Effects of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma: survey findings of the Japanese Red Cross Liver Study Group.

AIM: To investigate, in a large number of cases at multiple institutions, the effects and limitations of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma (HCC) in clinical practice. METHODS: Retrospective analysis was performed of 112 patients who had received interferon (IFN) for treating hepatitis C following treatment of HCC and were registered with the Japanese Red Cross Liver Study Group. Factors that may influence recurrence and survival rates were investigated. RESULTS: Factors involved in prevention of recurrence were: surgical resection as HCC treatment, platelet and α-fetoprotein (AFP) levels prior to IFN administration, IFN adherence and post-IFN AFP level. Multivariate analysis showed post-IFN AFP level to be an independent factor. Factors involved in prolonging survival were: IFN adherence, IFN response (sustained viral response), pre-IFN alanine aminotransferase and AFP levels, post-IFN AFP level and absence of recurrence. Multivariate analysis showed absence of recurrence to be an independent factor. Although IFN adherence was involved in recurrence and survival, ribavirin adherence was not. IFN was suggested to be involved in preventing recurrence and improving survival due not only to its anti-viral effect, but also its antitumor effect. CONCLUSION: Although complete prevention of HCC recurrence is difficult, the most important factor affecting first recurrence is the AFP level at 6 months after the conclusion of antiviral treatment. The survival rate improves dramatically if the hepatitis C virus is eliminated, but the most important factor for improving survival is absence of recurrence.

Glut-1-Negative Choroidal Malignant Melanoma with Liver Metastasis Recurrence 12 Years after Surgery without FDG Accumulation in a Recurrent Lesion on FDG-PET/CT: a Case Report.

Choroidal malignant melanoma is a rare malignant tumor that develops in adult eyeballs. It causes early lymph node and distant metastasis. Fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (CT) is widely used for screening malignant melanoma metastases. We encountered a 58-year-old man with choroidal malignant melanoma in whom liver metastasis recurred 12 years after surgery, without any observable FDG accumulation. Immunostaining revealed the absence of glucose transporter type 1 (GLUT-1) expression, crucial for intracellular FDG uptake. The lack of FDG accumulation in the lesion could be attributed to the diminished cellular FDG uptake due to the absence of GLUT-1 expression.

Change in Liver Function in Durvalumab Plus Tremelimumab Treatment for Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: Maintaining liver function throughout the treatment of hepatocellular carcinoma (HCC) is crucial, yet the impact of durvalumab plus tremelimumab (DT) treatment on liver function is not well understood. This multicenter study aimed to examine the changes in liver function during DT treatment. PATIENTS AND METHODS: This nationwide multicenter study included 80 patients who received DT treatment for unresectable HCC. The primary outcome was changes in albumin-bilirubin (ALBI) scores at baseline, week 8, week 12, and at the time of progressive disease (PD). RESULTS: The median (interquartile range) ALBI scores at baseline, week 8, week 12, and the time of PD were -2.24 (-2.49 to -1.94), -2.13 (-2.51 to -1.86), -2.23 (-2.51 to - 1.77), and -2.06 (-2.53 to -1.72), respectively. No significant differences were observed at 8 weeks (p=0.06), at 12 weeks (p=0.4), and at PD (p=0.8) compared to baseline. Subgroup analyses were conducted for patients with an ALBI grade of 2 at baseline and for those who received DT treatment as a second-line or later treatment. No deterioration in liver function was observed at any time point in both analyses. CONCLUSION: DT treatment can maintain liver function throughout the treatment period. Maintaining liver function is crucial in managing HCC, and this is an advantage of using DT treatment as a first-line treatment for unresectable HCC.

Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study.

Background and aim: In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. Methods: This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. Results: The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). Conclusion: GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.

Ribavirin regulates hepatitis C virus replication through enhancing interferon-stimulated genes and interleukin 8.

BACKGROUND: The manner in which ribavirin (RBV) enhances the antiviral effects of interferon (IFN) against hepatitis C virus (HCV) remains unknown. We investigated whether RBV modifies IFN-stimulated genes (ISGs) in vivo and in vitro. METHODS: We measured the messenger RNA (mRNA) levels of ISGs in T lymphocytes from patients with HCV infection who were receiving IFN-α therapy with or without RBV. We added RBV and/or IFN-α to a plasmid-based HCV replication system containing a full-length HCV genotype 1a sequence in HepG2 and Huh7 cell lines and the JFH-1 HCV genotype 2a sequence in Huh7 cell lines and measured levels of ISGs and autocrine IFN-ß. RESULTS: The expression of protein kinase R and myxovirus resistance A mRNA was enhanced more with IFN-α and RBV than by IFN-α alone in assays in vivo and in vitro. Such enhancement depended on autocrine IFN-ß being enhanced by RBV. RBV upregulated interleukin 8 (IL-8) in the absence of IFN-α. The IL-8 upregulation induced by RBV was responsible for the activation of activator protein 1 (AP-1). CONCLUSIONS: Ribavirin augments the anti-HCV effects of IFN-α induced by ISGs through enhancing autocrine IFN-ß. Moreover, RBV can enhance IL-8 through activating AP-1. Improved understanding of ISG modulation by RBV would help to establish a means of eliminating HCV.

Metastasis from Renal Cell Carcinoma to Ectopic Pancreas Diagnosed after Resection.

We herein report a 68-year-old man who underwent nephrectomy for right renal cell carcinoma 10 years prior. He remained under regular medical observation, and abdominal computed tomography showed tumors in the head and tail of the pancreas. He was diagnosed with pancreatic metastasis from renal cell carcinoma. He underwent surgical excision. The pathologic diagnosis proved that the pancreatic tumors were metastases from renal cell carcinoma and clarified that an ectopic pancreas in the duodenum had metastases as well. To our knowledge, this is the first case of metastasis to an ectopic pancreas.

Necessity for surveillance for hepatocellualr carcinoma in older patients with chronic hepatitis C who achieved sustained virological response.

Background and Aim: Hepatocellular carcinoma (HCC) surveillance in low-risk patients (annual incidence <1.5%) is not recommended per the American Association for the Study of Liver Diseases guidelines. Because patients with chronic hepatitis C with non-advanced fibrosis who have achieved sustained virological response (SVR) have a low risk of HCC, HCC surveillance is not recommended for them. However, aging is a risk factor for HCC; threfore, the necessity for HCC surveillance in older patients with non-advanced fibrosis needs to be verified. Methods: This multicenter, prospective study enrolled 4993 patients with SVR (1998 patients with advanced fibrosis and 2995 patients with non-advanced fibrosis). The HCC incidence was examined with particular attention to age. Results: The 3-year incidence of HCC in patients with advanced and non-advanced fibrosis was 9.2% (95% CI: 7.8-10.9) and 2.9% (95% CI: 2.1-3.7), respectively. HCC incidence was significantly higher in patients with advanced fibrosis (P < 0.001). HCC incidence stratified by age and sex was investigated in patients with non-advanced fibrosis. The HCC incidence in the 18-49, 50s, 60s, 70s, and ≥80 age groups were 0.26, 1.3, 1.8, 1.7, and 2.9 per 100 person-years in men, and 0.00, 0.32, 0.58, 0.49, and 0.57 per 100 person-years in women, respectively. Conclusions: Male patients with non-advanced fibrosis aged ≥60 years have a higher risk of developing HCC and, thus, require HCC surveillance.

A case of walled-off necrosis extending into the pelvic cavity successfully treated by endoscopic necrosectomy using a lumen-apposing metal stent.

A 31-year-old man developed massive walled-off necrosis extending into the pelvic cavity following severe acute alcoholic pancreatitis. Endoscopic ultrasound-guided fistula drainage was performed using a lumen-apposing metal stent, but this was insufficiently effective, and endoscopic necrosectomy was also performed, after which the patient improved. Percutaneous drainage and surgery are other options for the treatment of walled-off necrosis extending into the pelvic cavity, but a valuable case in which the patient improved with endoscopic treatment alone is presented.

Direct-acting antivirals improve survival and recurrence rates after treatment of hepatocellular carcinoma within the Milan criteria.

BACKGROUND: The effects of direct-acting antivirals (DAAs) on survival and recurrence rates after curative hepatocellular carcinoma (HCC) treatment in patients with hepatitis C virus (HCV) infection remain controversial. METHODS: This retrospective, multicenter study involved Child-Pugh class A patients within the Milan criteria who had a first diagnosis of HCC and survived 6 months or longer after undergoing hepatectomy or radiofrequency ablation (RFA). The DAA-treated group (DAA group) included 56 patients, and the DAA-untreated group (untreated group) included 261 patients. The study was conducted using the propensity score-matched (1:2) DAA group and untreated group, 56 and 112 patients, respectively. RESULTS: The survival rate at 48 months in the DAA group and the untreated group was 91.0% and 68.7%, respectively, showing significantly better survival in the DAA group (HR: 0.33; 95% CI 0.13-0.84; p = 0.021). The recurrence rate at 48 months was 36.7% and 66.7%, respectively, showing a significantly lower recurrence rate in the DAA group (HR, 0.46; 95% CI 0.27-0.77; p = 0.003). The median albumin-bilirubin (ALBI) score at 3 years post-HCC treatment was - 2.84 in the DAA group and - 2.34 in the untreated group. The ALBI score showed a significant improvement from baseline to 3 years post-HCC treatment (p = 0.001), whereas that in the untreated group showed a significant decline (p = 0.040). CONCLUSIONS: DAAs after HCC treatment prevents deterioration of hepatic functional reserve and significantly improves both recurrence and survival rates.

A rare case of acute pancreatitis caused by Candida Albicans.

We experienced a rare case of acute pancreatitis caused by Candida infection. A 52-year-old man was admitted to our hospital with a chief complaint of abdominal pain. Blood tests revealed high amylase and hepatobiliary enzyme abnormalities, and the patient was hospitalized for acute pancreatitis. Abdominal computed tomography showed a 15-mm space-occupying lesion at the parenchyma of the pancreatic head. Endoscopic retrograde cholangiopancreatography was performed after conservative treatment, which revealed a cystic lesion with a suspected solid component inside involving both lower bile duct and pancreatic duct. Cytology of collected bile and pancreatic juice revealed innumerous hyphae and spores morphologically consistent with Candida spp., as did endoscopic ultrasound-guided fine needle aspiration biopsy of the tumor site. Empiric therapy with oral fluconazole resulted in reduction of the space-occupying lesion 3 months after discharge. However, acute pancreatitis recurred about 1 year and 6 months after discharge. After conservative treatment was carried out again, the same lesion was fenestrated by endoscopic sphincteroplasty, and its internal solid components were resected using a basket catheter. Pathological analysis confirmed the presence of fungus balls and degenerated substances. Candida Albicans was identified by fungal culture examination. After the excretion of the fungus balls, pancreatitis did not recur thereafter during outpatient follow-up.

Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection.

BACKGROUND: A possible interaction of hepatitis viruses at cellular and molecular levels has been suggested. Eradication of hepatitis C virus (HCV) has been reported to induce activation of hepatitis B virus (HBV)-related liver diseases. MATERIALS AND METHODS: The present study examined association of HBV markers with recurrence of hepatocellular carcinoma (HCC) in patients with resolved HCV infection by direct-acting antiviral (DAA) therapy. In a patient pool of 378 patients with sustained virologic response (SVR) by DAA, the antibody to the hepatitis B surface antigen (anti-HBs), the antibody to the hepatitis B core antigen (anti-HBc), and HBV-DNA levels were estimated before and at the end of DAA therapy. These patients were HBsAg negative. Eighty-nine patients had a history of curative treatment of HCC by resection or radiofrequency ablation. A Cox proportional hazards model was used to identify risk factors for HCC recurrence, including the change ratio of the antibody against HBV proteins. RESULTS: Although 188 patients had resolved HBV infection, no patient showed HBV reactivation, but anti-HBs and anti-HBc levels decreased significantly. No significant difference in the HCC recurrence rate was evident between patients with and without resolved HBV infection. Changes of immune responses to HBV proteins did not affect HCC recurrence after DAA therapy for HCV infection in this cohort. CONCLUSION: The mechanisms underlying diverse roles of DAA-induced SVR of HCV on HBV kinetics need to be resolved in future. HOW TO CITE THIS ARTICLE: Joko K, Mashiba T, Ochi H, et al. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepato-Gastroenterol 2019;9(2):78-83.

Wilms' tumour 1 gene expression is increased in hepatocellular carcinoma and associated with poor prognosis.

BACKGROUND/AIMS: Wilms' tumour 1 gene (WT1) was originally isolated as a tumour-suppressor gene. We investigated the expression of WT1 in hepatocellular carcinoma (HCC; T) and in non-cancerous hepatic tissues (non-tumour: NT) from patients with chronic liver diseases, and then examined the role of WT1 in the carcinogenesis or prognosis of HCC. METHODS: The expression of WT1 in T and NT from 50 patients with HCC was investigated using Western blotting, immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined whether WT1 expression was related to clinicopathological factors in individual patients in addition to prognostic factors in 50 patients with HCC and in 26 without HCC. RESULTS: Western blotting and immunohistochemical staining showed that WT1 was overexpressed in T compared with NT (P<0.001) and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) showed that WT1 mRNA expression was similarly increased. Overexpressed WT1 in HCC was significantly associated with T factors at the TNM stage, and short doubling time of HCC. Univariate and multivariate analyses revealed that WT1 overexpression was an independent prognostic factor for HCC. The disease-free survival period in patients with overexpressed WT1 in NT tissues was significantly reduced. CONCLUSION: The expression of WT1 is increased more in HCC than in non-tumour tissues. Moreover, overexpressed WT1 was associated with tumour growth, and resulted in a worsening prognosis of HCC. Our findings from NT tissues revealed that WT1 overexpression might contribute to oncogenic potential.