Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

Long-term outcomes of drug-induced autoimmune-like hepatitis after pulse steroid therapy.

AIM: Pulse steroid therapy occasionally causes drug-induced autoimmune-like hepatitis (DI-ALH), but the long-term outcome of treated patients is not well known. In this study, we investigated the long-term outcomes of DI-ALH due to pulse steroid therapy. METHODS: We retrospectively reviewed the medical records of 405 patients treated with pulse high-dose methylprednisolone in Kurashiki Central Hospital. The frequency and clinicopathological characteristics of acute liver injury that occurred within 3 months after the therapy were analyzed. The diagnosis of DI-ALH was made according to the revised international autoimmune hepatitis group criteria. RESULTS: Among the 405 patients treated with methylprednisolone, 61 (15.1%) had acute liver injury after the pulse steroid therapy, and DI-ALH was diagnosed in five patients (1.2%). Absence of oral prednisolone tapering after the pulse steroid therapy was a significant risk factor for the subsequent development of DI-ALH (odds ratio 11.9; p = 0.017). One patient was treated with 3 days of intravenous methylprednisolone followed by oral prednisolone. Two patients were treated with glycyrrhizin followed by oral prednisolone due to ineffectiveness of glycyrrhizin. Remission was achieved with glycyrrhizin alone, and spontaneous remission without drug therapy occurred in one patient each. During the median follow-up period of 34 months, no relapse was evident in all the patients without maintenance therapy. CONCLUSIONS: Pulse steroid therapy can cause DI-ALH, especially when subsequent prednisolone is not tapered. Prednisolone is effective for DI-ALH due to pulse steroid therapy, and can be safely withdrawn once remission is achieved.

Changes in Liver and Spleen Stiffness by Virtual Touch Quantification Technique after Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices and Exacerbation of Esophageal Varices: A Preliminary Study.

PURPOSE: To assess liver stiffness (LS) and spleen stiffness (SS) values measured by virtual touch quantification (VTQ) technique in the monitoring of portal pressure and their usefulness for the prediction of the exacerbation of esophageal varices (EV) in patients with gastric varices undergoing balloon-occluded retrograde transvenous obliteration (B-RTO). MATERIALS AND METHODS: The LS, SS, and hepatic venous pressure gradient (HVPG) were measured in 20 patients both before and after B-RTO. The change in each parameter between the two groups (EV exacerbation and non-exacerbation groups) was compared by analysis of variance. The efficacy of the parameters for the prediction of the exacerbation of EV was analyzed using a receiver operating characteristic (ROC) curve analysis. RESULTS: 9 patients (40.9 %) exhibited an exacerbation of EV within 24 months after B-RTO. Significant changes were observed in the HVPG and SS after B-RTO between the two groups (EV exacerbation group vs. non-exacerbation group: HVPG before 12.7 ±â€Š4.4 mmHg vs. 11.0 ±â€Š4.4 mmHg; HVPG after 19.6 ±â€Š6.0 mmHg vs. 13.6 ±â€Š3.1 mmHg P = 0.003; SS before 3.40 ±â€Š0.50 m/s vs. 3.20 ±â€Š0.51 m/s; SS after 3.74 ± 0.53 m/s vs. 3.34 ±â€Š0.43 m/s P = 0.016). However, no significant changes in LS were observed between the two groups. The area under the ROC curves of elevation in HVPG and SS for the prediction of the exacerbation of EV after B-RTO were 0.833 and 0.818, respectively. CONCLUSION: Elevation of the HVPG and SS measured by VTQ after B-RTO was useful for the prediction of the exacerbation of EV.

Measurement of Spleen Stiffness With Acoustic Radiation Force Impulse Imaging Predicts Mortality and Hepatic Decompensation in Patients With Liver Cirrhosis.

BACKGROUND & AIMS: Hepatic venous pressure gradient can predict mortality and hepatic decompensation in patients with cirrhosis. Measurement of hepatic venous pressure gradient requires an invasive procedure; therefore, prognostic markers are needed that do not require invasive procedures. We investigated whether measurements of spleen stiffness, made by acoustic radiation force impulse (ARFI) imaging, associated with mortality and decompensation in patients with cirrhosis, compared with liver stiffness and other markers. METHODS: We measured spleen stiffness in 393 patients diagnosed with cirrhosis (based on histologic or physical, laboratory, and radiologic findings) at a hospital in Japan from September 2010 through August 2013 (280 patients with compensated and 113 patients with decompensated cirrhosis). Patients underwent biochemical, ARFI, ultrasonography, and endoscopy evaluations every 3 or 6 months to screen for liver-related complications until their death, liver transplantation, or the end of the study period (October 2015). The primary outcome was the accuracy of spleen stiffness in predicting mortality and decompensation, measured by Cox proportional hazards model analysis. We compared spleen stiffness with other noninvasive parameters using the Harrell's C-index analysis. RESULTS: During a median follow-up period of 44.6 months, 67 patients died and 35 patients developed hepatic decompensation. In the multivariate analysis, spleen stiffness was an independent parameter associated with mortality, after adjustment for levels of alanine aminotransferase and serum sodium, and the model for end-stage liver disease score (P < .001). Spleen stiffness was associated independently with decompensation after adjustment for Child-Pugh score and model for end-stage liver disease score (P < .001). Spleen stiffness predicted mortality and decompensation with greater accuracy than other parameters (C-indexes for predicting mortality and decompensation were 0.824 and 0.843, respectively). A spleen stiffness cut-off value of 3.43 m/s identified the death of patients with a 95.3% negative predictive value and 75.8% accuracy. A spleen stiffness cut-off value of 3.25 m/s identified patients with decompensation with a 98.8% negative predictive value and 68.9% accuracy. CONCLUSIONS: Spleen stiffness, measured by ARFI imaging, can predict death of patients with cirrhosis with almost 76% accuracy and hepatic decompensation with almost 70% accuracy. It might be a useful noninvasive test to predict patient outcome. UMIN Clinical Trials Registry no. UMIN000004363.

Portal Hypertension in Patients with Liver Cirrhosis: Diagnostic Accuracy of Spleen Stiffness.

PURPOSE: To evaluate the accuracy of spleen stiffness (SS) and liver stiffness (LS) measured by using acoustic radiation force impulse imaging in the diagnosis of portal hypertension in patients with liver cirrhosis, with the hepatic venous pressure gradient (HVPG) as a reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this prospective single-center study. From February 2012 to August 2013, 60 patients with liver cirrhosis (mean age, 70.8 years; age range, 34-88 years; 34 men, 26 women) with HVPG, LS, and SS measurements and gastrointestinal endoscopy and laboratory data were included if they met the following criteria: no recent episodes of gastrointestinal bleeding, no history of splenectomy, no history of partial splenic embolization, no history of ß-blocker therapy, and absence of portal thrombosis. The efficacy of the parameters for the evaluation of portal hypertension was analyzed by using the Spearman rank-order correlation coefficient and receiver operating characteristic (ROC) curve analysis. RESULTS: The correlation coefficient between SS and HVPG (r = 0.876) was significantly better than that between LS and HVPG (r = 0.609, P < .0001). The areas under the ROC curve of SS for the identification of clinically important portal hypertension (HVPG ≥ 10 mm Hg), severe portal hypertension (HVPG ≥ 12 mm Hg), esophageal varices (EVs), and high-risk EVs were significantly higher (0.943, 0.963, 0.937, and 0.955, respectively) than those of LS, spleen diameter, platelet count, and platelet count to spleen diameter ratio (P < .05 for all). SS could be used to accurately rule out the presence of clinically important portal hypertension, severe portal hypertension, EVs, and high-risk EVs (negative likelihood ratios, 0.051, 0.056, 0.054, and 0.074, respectively). CONCLUSION: SS is reliable and has better diagnostic performance than LS for identifying portal hypertension in liver cirrhosis.

Measurement of spleen stiffness by acoustic radiation force impulse imaging identifies cirrhotic patients with esophageal varices.

BACKGROUND & AIMS: We evaluated whether spleen stiffness (SS), measured by acoustic radiation force impulse imaging, can identify patients who have esophageal varices (EVs); those without EVs would not require endoscopic examination. METHODS: In a prospective study, we measured SS and liver stiffness (LS) in 340 patients with cirrhosis undergoing endoscopic screening for EVs and 16 healthy volunteers (controls) at the Kurashiki Central Hospital in Okayama, Japan. The diagnostic accuracy of SS for the presence of EVs was compared with that of other noninvasive parameters (LS, spleen diameter, and platelet count). Optimal cutoff values of SS were chosen to confidently rule out the presence of varices. RESULTS: Patients with cirrhosis had significantly higher SS and LS values than controls (P < .0001 and P < .0001, respectively). Levels of SS were higher among patients with EVs (n = 132) than controls, and values were highest among patients with high-risk EVs (n = 87). SS had the greatest diagnostic accuracy for the identification of patients with EVs or high-risk EVs compared with other noninvasive parameters, independent of the etiology of cirrhosis. An SS cutoff value of 3.18 m/s identified patients with EVs with a 98.4% negative predictive value, 98.5% sensitivity, 75.0% accuracy, and 0.025 negative likelihood ratio. An SS cutoff value of 3.30 m/s identified patients with high-risk EVs with a 99.4% negative predictive value, 98.9% sensitivity, 72.1% accuracy, and 0.018 negative likelihood ratio. SS values less than 3.3 m/s ruled out the presence of high-risk varices in patients with compensated or decompensated cirrhosis. SS could not be measured in 16 patients (4.5%). CONCLUSIONS: Measurements of SS can be used to identify patients with cirrhosis with EVs or high-risk EVs. A cutoff SS was identified that could rule out the presence of varices and could be used as an initial noninvasive screening test; UMIN Clinical Trials Registry number, UMIN000004363.

Comparison of combined transcatheter arterial chemoembolization and radiofrequency ablation with surgical resection by using propensity score matching in patients with hepatocellular carcinoma within Milan criteria.

PURPOSE: To retrospectively compare the outcome of combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) with that of surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within the Milan criteria. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. From January 2000 to December 2010, 154 patients (mean age, 69.9 years; age range, 50-89 years; 107 men, 47 women) underwent TACE-RFA, and 176 patients (mean age, 66.9 years; age range, 29-83 years; 128 men, 48 women) underwent SR. Patients with HCC who underwent TACE-RFA or SR were enrolled if they met the following inclusion criteria: no previous HCC treatment, one HCC lesion no larger than 5 cm or up to three nodules smaller than 3 cm without vascular invasion or extrahepatic metastasis, and Child-Pugh class A or B disease. Cumulative overall survival (OS) and disease-free survival (DFS) rates were compared after adjustment with propensity score matching. RESULTS: After this adjustment, OS rates were comparable between the groups (P = .393), but DFS was superior in the SR group (P < .048). Among patients with very early stage HCC (lesions <2 cm in diameter), OS and DFS rates in the SR group were significantly higher than those in the TACE-RFA group (P < .001 and P = .008, respectively). However, adjustment with propensity score matching yielded comparable OS and DFS rates between the two groups (P = .348 and P = .614, respectively). CONCLUSION: TACE-RFA may be a viable alternative treatment for early-stage HCC when SR is not feasible.

[Radiofrequency ablation for hepatocellular carcinoma in elderly patients].

The efficacy and safety of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) were compared between elderly (age≥75 years, n=82) and non-elderly groups (age<75 years, n=158). No significant differences were observed in complications between the two groups. Elderly patients had a lower survival rate compared to the non-elderly patients. Multivariate analysis showed that age was not a significant factor for survival on tumor recurrence. Matching by propensity score revealed no significant differences were observed in survival on tumor recurrence rate. The prognosis of elderly patients undergoing RFA might be considered poorer than that of non-elderly patients. However, when considering the clinical background, RFA might be safe and effective in elderly patients, as well as non-elderly patients.

Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.

Several vaccines have been developed for coronavirus disease 2019 (COVID-19) and are used worldwide. Here we report a case of severe acute hepatitis induced by COVID-19 vaccination. A 54-year-old woman received two doses of the Pfizer-BioNTech COVID-19 mRNA vaccine and an additional dose of the Moderna COVID-19 mRNA vaccine. Seven days after the third dose, she noticed fatigue, appetite loss and dark urine. Laboratory tests were consistent with severe liver injury and jaundice. Anti-smooth muscle antibody and HLA-DR4 were positive; thus, we suspected that she had autoimmune hepatitis (AIH). Intravenous methylprednisolone followed by oral prednisolone were administered. Because remission was not achieved, we performed percutaneous liver biopsy. Histologically, pan-lobular inflammation with moderate infiltration of lymphocytes and macrophages, interface hepatitis, and rosette formation were present. We regarded these findings as confirmation of the diagnosis of AIH. As she had not responded to corticosteroids, we added azathioprine. Liver biochemistry tests gradually improved, and prednisolone could be tapered without relapse of AIH. Dozens of cases of AIH after COVID-19 vaccination have been reported. Corticosteroids were effective in most cases, but some patients have died from liver failure after vaccination. This case illustrates the efficacy of azathioprine for steroid-refractory AIH induced by COVID-19 vaccination.

Real-world efficacy of antibiotic prophylaxis for upper gastrointestinal bleeding in cirrhotic patients in Japan.

BACKGROUND AND AIMS: Antibiotic prophylaxis is recommended for cirrhotic patients with upper gastrointestinal bleeding (UGIB). However, the frequency of bacterial infection in such patients has remarkably decreased over the decades, which has reduced the necessity for prophylaxis. Therefore, here we investigated the real-world adherence and effectiveness of antibiotic prophylaxis in cirrhotic patients with UGIB in Japan. METHODS: This population-based study was conducted with a Japanese real-world database of the Health, Clinic, and Education Information Evaluation Institute. We enrolled cirrhotic patients who were hospitalized for UGIB between April 2010 and March 2020. After those who died within 24 h and who had aspiration pneumonia at admission were excluded, 1232 patients were analyzed. Rates of 6-week mortality, in-hospital bacterial infection, 30-day readmission, and length of hospital stay were evaluated. RESULTS: Prophylactic antibiotics were prescribed in 142 (11.5%) patients. Multivariate analysis revealed that antibiotic prophylaxis was not significantly associated with either 6-week mortality or bacterial infection. After propensity score matching, the rates of 6-week mortality (7.2% vs. 8.4%, P = 0.810), bacterial infection (9.6% vs. 4.2%, P = 0.082), and 30-day unexpected readmission (7.2% vs. 7.8%, P = 1.000) were similar in patients with and without prophylaxis, whereas the median length of hospital stay was significantly longer in patients with prophylaxis (17 days vs. 13 days, P = 0.013). CONCLUSIONS: Under current real-world circumstances in Japan, prophylactic antibiotics were prescribed in only 11.5% of cirrhotic patients with UGIB and were not associated with better clinical outcomes.

Mycophenolate mofetil for immune checkpoint inhibitor-related hepatotoxicity relapsing during dose reduction of corticosteroid: A report of two cases and literature review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) sometimes cause immune-related liver injury, which can lead to cessation of treatment, hospitalization, and even mortality. Although high-dose corticosteroids are usually effective in treatment of ICI-related liver injury, one fifth of affected patients require additional immunosuppressive therapy. It remains uncertain how best to treat ICI-related liver injury that relapses under corticosteroid therapy after temporary remission. CASE: Here we report two cases of ICI-related liver injury successfully treated with mycophenolate mofetil (MMF). In the first case, a 74-year-old man with stage IIIA lung cancer underwent curative chemoradiotherapy. After the second infusion of durvalumab, grade 3 ICI-related liver injury (mixed pattern) developed. In the second case, a 46-year-old man with stage IVB lung cancer received pembrolizumab-containing chemotherapy. After the first cycle, grade 2 ICI-related hepatitis developed. In the both cases, liver injury improved with high-dose prednisolone but relapsed during tapering of the drug. After liver biopsy was performed to confirm the diagnosis of ICI-related liver injury, MMF (2000 mg/day) was added. MMF was effective for both patients and permitted discontinuation or reduction of prednisolone. CONCLUSION: MMF appears to be an appropriate treatment option for ICI-related liver injury that respond to high-dose corticosteroids but relapse during steroid tapering.

Environmental factors, medical and family history, and comorbidities associated with primary biliary cholangitis in Japan: a multicenter case-control study.

BACKGROUND: Primary biliary cholangitis (PBC) is considered to be caused by the interaction between genetic background and environmental triggers. Previous case-control studies have indicated the associations of environmental factors (tobacco smoking, a history of urinary tract infection, and hair dye) use with PBC. Therefore, we conducted a multicenter case-control study to identify the environmental factors associated with the development of PBC in Japan. METHODS: From 21 participating centers in Japan, we prospectively enrolled 548 patients with PBC (male/female = 78/470, median age 66), and 548 age- and sex-matched controls. These participants completed a questionnaire comprising 121 items with respect to demographic, anthropometric, socioeconomic features, lifestyle, medical/familial history, and reproductive history in female individuals. The association was determined using conditional multivariate logistic regression analysis. RESULTS: The identified factors were vault toilet at home in childhood [odds ratio (OR), 1.63; 95% confidence interval (CI), 1.01-2.62], unpaved roads around the house in childhood (OR, 1.43; 95% CI, 1.07-1.92), ever smoking (OR, 1.70; 95% CI, 1.28-2.25), and hair dye use (OR, 1.57; 95% CI, 1.15-2.14) in the model for lifestyle factors, and a history of any type of autoimmune disease (OR, 8.74; 95% CI, 3.99-19.13), a history of Cesarean section (OR, 0.20; 95% CI, 0.077-0.53), and presence of PBC in first-degree relatives (OR, 21.1; 95% CI, 6.52-68.0) in the model for medical and familial factors. CONCLUSIONS: These results suggest that poor environmental hygiene in childhood (vault toilets and unpaved roads) and chronic exposure to chemicals (smoking and hair dye use) are likely to be risk factors for the development of PBC in Japan.

Outcomes after curative treatment for cryptogenic cirrhosis-associated hepatocellular carcinoma satisfying the Milan criteria.

BACKGROUND AND AIM: The prognosis of cryptogenic cirrhosis-associated hepatocellular carcinoma (CC-HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC-HCC. METHODS: Consecutive 36 curatively treated CC-HCC patients satisfying the Milan Criteria were compared with corresponding 211 HCV-associated HCC (HCV-HCC) patients. The clinical background, tumor recurrence rate, overall survival rate, and prognostic values of the patients were assessed. RESULTS: The size of CC-HCCs was larger than that of HCV-HCCs (P = 0.01). The respective tumor recurrence rates at 1, 3, and 5 years were 11%, 32%, and 46% in the CC-HCC, and 21%, 59%, and 81% in the HCV-HCC. The respective overall survival rates at 1, 3, and 5 years were 94%, 85%, and 80% in the CC-HCC, and 98%, 81%, and 61% in the HCV-HCC. CC-HCC patients had a lower tumor recurrence rate and a higher survival rate compared to the HCV-HCC patients (P = 0.001 and P = 0.02, respectively). Via multivariate analysis, significant factors for high recurrence rate were number of HCCs (P = 0.02) and serum alpha fetoprotein levels (P = 0.03) in CC-HCC, whereas multiple tumors (P < 0.001), large tumor size (P = 0.01), and high alanine aminotransferase (P = 0.04) in HCV-HCC. The factor for survival was albumin in both groups. CONCLUSION: The size of CC-HCC was larger than that of HCV-HCC even in patients who received curative treatment; however, the risk for recurrence and the mortality of the patients with CC-HCC was lower than those with HCV-HCC.

Transarterial embolization for ruptured hepatocellular carcinoma: survival predictors.

BACKGROUND/AIMS: Survival predictors in patients with ruptured hepatocellular carcinoma (HCC) treated by transarterial embolization (TAE), have not been fully investigated. METHODOLOGY: Predictors of short-term (< or = 30 days) and long-term (>30 days) survival were evaluated by using the logistic regression model and the Cox proportional hazard model, respectively. RESULTS: Forty-eight patients treated by emergency TAE were enrolled. The median survival time was 231 days. Although hemostasis was attained by TAE in 44 patients (91.7%), 15 patients (31.3%) died within 30 days. In a multivariate analysis, low serum creatinine level (p=0.018) was the only significant predictor of increased short-term survival. Of the 33 patients who survived more than 30 days after TAE, he patic resection was performed in 8, transarterial chemoembolization or chemotherapy in 8, and conservative treatment in 17. In a multivariate analysis, among the 33 who survived, unilateral location of tumors (p=0.041) and low a-fetoprotein level (p=0.004) were significant predictors of increased long-term survival. CONCLUSIONS: Short-term survival of patients with ruptured HCC who were treated by TAE depended on serum creatinine level on arrival. Long-term survival of patients who survived more than 30 days after TAE, was influenced by tumor location and a-fetoprotein level.

Stereotactic body radiation therapy versus radiofrequency ablation for single small hepatocellular carcinoma: a propensity-score matching analysis of their impact on liver function and clinical outcomes.

BACKGROUND: Stereotactic body radiation therapy (SBRT) has high efficacy for early-stage hepatocellular carcinoma (HCC) and is an accepted alternative to radiofrequency ablation (RFA). However, SBRT for HCC may cause subacute liver injury leading to negative clinical outcomes. In this study, we compared changes of liver function and prognosis after SBRT or RFA in patients with single, small HCC by using a propensity-score matching analysis. METHODS: We reviewed medical records of 140 patients with single ≤3 cm HCC treated with SBRT or RFA at Kurashiki Central Hospital between January 2014 and February 2019. Changes of albumin-bilirubin (ALBI) score, local recurrence, and overall survival were compared between the propensity-score matched groups (31 patients treated with SBRT and 62 treated with RFA). RESULTS: The ALBI score increased modestly but significantly after SBRT, while it was unchanged in the RFA group; the intergroup difference was statistically significant (P=0.004). No local recurrence was identified in the SBRT group, whereas the cumulative recurrence incidence was 9.7% in the RFA group (P=0.023). Overall survival was not significantly different between the two groups (hazard ratio: 1.32, 95% confidence interval: 0.60-2.89, P=0.401). CONCLUSIONS: SBRT had modestly negative impact on liver function but with appraisable local control of HCC. Our findings should contribute to the selection of this modality for treatment of single, small HCC.

Universal antibiotic prophylaxis may no longer be necessary for patients with acute variceal bleeding: A retrospective observational study.

A few decades ago, antibiotic prophylaxis for patients with acute variceal bleeding was reported beneficial. However, endoscopic and systemic therapy for variceal bleeding has dramatically improved since then, so the necessity of prophylactic antibiotics can be questioned. In this study, we reevaluated the efficacy of antibiotic prophylaxis in acute variceal bleeding, using the most recent data in our hospital.We retrospectively analyzed the medical records of 150 patients with acute variceal bleeding who were admitted to Kurashiki Central Hospital between January 2012 and December 2016. We compared the rates of bacterial infection, in-hospital mortality, 5-day rebleeding rate, and 30-day emergency readmission between patients treated or not treated with antibiotic prophylaxis.Forty-six patients (30.7%) received antibiotic prophylaxis; 104 (69.3%) did not. The rates of the outcomes in patients with antibiotic prophylaxis were 6.5% (bacterial infection), 4.3% (in-hospital mortality), 2.2% (5-day rebleeding), and 10.9% (30-day emergency readmission) and were not significantly different form the corresponding figures in those without antibiotic prophylaxis (1.9%, 7.7%, 1.9%, and 10.6%, respectively). Moreover, these rates in our patients, even without antibiotic prophylaxis, were much lower than rates reported in past years, perhaps because of improvements in care of patients with variceal hemorrhage.Antibiotic prophylaxis was not associated with significantly better outcomes of bacterial infection, mortality, rebleeding or readmission rate in patients with acute variceal bleeding. Universal antibiotic prophylaxis for patients with acute variceal bleeding should be reconsidered.

Mucin-producing hepatocellular carcinoma without morphological features of biliary differentiation: A case report.

RATIONALE: Hepatocellular carcinoma has been believed not to produce mucin unless it has biliary differentiation. However, some cases of hepatocellular carcinoma with extracellular myxoid change have been reported recently, raising the possibility that, in rare cases, hepatocellular carcinoma cells produce mucin. PATIENT CONCERNS: Here we report a case of hepatocellular carcinoma that contained intracellular and extracellular myxoid matrix without morphological evidence of biliary differentiation, although cells in a portion of the tumor were positive for the epithelial markers cytokeratin 7 and 19. She was brought to our hospital due to abnormal liver tests and a large liver tumor found by ultrasound examination. DIAGNOSES: The liver tumor showed typical imaging findings of hepatocellular carcinoma. INTERVENTIONS: The tumor was resected with negative margins, and pathologically diagnosed as hepatocellular carcinoma with mucin production. OUTCOMES: The patient has been free from recurrence of cancer during two-years' follow-up. LESSONS: Our case suggests that hepatocellular carcinoma cells can produce mucin without or before morphological differentiation to biliary phenotypes, an observation that may help elucidate the mechanism for the development of combined hepatocellular and cholangiocarcinoma.

Nomograms to Predict the Disease-free Survival and Overall Survival after Radiofrequency Ablation for Hepatocellular Carcinoma.

Objective The purpose of this study was to construct nomograms for the disease-free survival (DFS) and overall survival (OS) of post-radiofrequency ablation (RFA) patients with hepatocellular carcinoma (HCC). Furthermore, we compared the prognostic predictive ability of these nomograms for estimating per-patient outcomes with that of traditional staging systems. Methods We retrospectively enrolled 298 patients in the training set and 272 patients in the validation set who underwent RFA for HCC. The nomograms for the DFS and OS were constructed from the training set using the multivariate Cox proportional hazards model. The discriminatory accuracy of the models was compared with traditional staging systems by analyzing the Harrell's C-index. Results The DFS nomogram was developed based on the tumor size, tumor number, aspartate aminotransferase (AST), albumin, age, and α-fetoprotein. The OS nomogram was developed based on the tumor size, the model for end-stage liver disease, AST, and albumin. Our DFS and OS nomograms had good calibration and discriminatory abilities in the training set, with C-indexes of 0.640 and 0.692, respectively, that were greater than those of traditional staging systems. The C-indexes of our DFS and OS nomograms were also greater than those of traditional staging systems in the validation set, with C-indexes of 0.614 and 0.657, respectively. RFA patients were stratified into low- and high-risk groups based on the median nomogram scores. High-risk patients receiving surgical resection (SR) were associated with a better DFS and OS than those undergoing RFA. However, the DFS and OS were similar between the low-risk RFA and SR groups. Conclusion We constructed reliable and useful nomograms that accurately predict the DFS and OS after RFA for early-stage HCC patients. These graphical tools are easy to use and will assist physicians during the therapeutic decision-making process.