Autoimmune Hepatic Failure Following Acute Hepatitis A is Accompanied by Inflammatory Conversion of Regulatory T Cells

To evaluate the pathophysiology of autoimmune hepatitis (AIH) following acute hepatitis A (AHA) in immunologic aspects, we performed multi-color flow cytometry with peripheral blood mononuclear cells of a patient who underwent liver transplantation due to AIH-induced liver failure. Unlike general AHA patients, the proportion of tumor necrosis factor-α-producing Treg cells remained high for 6 months after diagnosis of AHA until she underwent a liver transplantation. The conversion of Treg cells into mediators of inflammation may have played a role in the autoimmune pathogenesis following AHA.ope

Assessment of fibrotic burden among chronic hepatitis B virus-infected patients with normal transaminase level

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Impact of COVID-19 on Gastroenterology Fellowship Training

Background/aims: The coronavirus disease 2019 (COVID-19) outbreak caused numerous social and cultural changes, but few studies focused on their effects on gastroenterology (GI) fellowship training. This study evaluated the impact of COVID-19 on GI fellowship training. Methods: A web-based questionnaire was sent out to GI fellows in Korea between 15 February and 15 March 2021. The questionnaire included questions regarding the characteristics of GI fellows, perception of COVID-19 outbreak, impact of COVID-19 outbreak, and telemedicine on the education of a GI fellowship. Results: Among 111 answers, 94 respondents were analyzed. The GI fellows were provided with sufficient information about the COVID-19 outbreak (74.7%), well educated, and provided with personal protective equipment use (74.7% and 83.9%, respectively). On the other hand, outpatient schedule and volume decreased in 25.5% and 37.8% of respondents, respectively. Moreover, endoscopy sessions and volume decreased in 51.1% and 65.6% of respondents, respectively. As a result, 78.9% of respondents were concerned that the COVID-19 outbreak adversely affected their education. Telemedicine utilization was introduced during the COVID-19 outbreak, but only 20.0% and 10.6% of respondents agreed that telemedicine has benefits from the patient's and doctor's perspectives, respectively. In addition, only 25.9% of respondents were willing to continue telemedicine if adequately reimbursed, and 68.2% of respondents were concerned that it adversely affected their education. Conclusions: The COVID-19 outbreak has adversely affected GI fellowship training in Korea for outpatient clinics, gastrointestinal endoscopy, educational conferences, and telemedicine. This study highlights that GI fellowship training needs more attention in the COVID-19 outbreak.ope

Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein level predicts recurrence of hepatitis B virus-related hepatocellular carcinoma after curative resection

BACKGROUND/AIMS: To investigate whether serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) can predict the recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. METHODS: Patients with chronic hepatitis B (CHB) who underwent curative resection for HCC between 2004 and 2015 were eligible for the study. Recurrence was sub-classified as early (<2 years) or late (≥2 years). RESULTS: A total of 170 patients with CHB were selected. During the follow-up period (median, 22.6 months), 64 (37.6%) patients developed recurrence. In multivariate analyses, WFA+-M2BP level was an independent predictor of overall (hazard ratio [HR]=1.490), early (HR=1.667), and late recurrence (HR=1.416), together with male sex, des-gamma carboxyprothrombin level, maximal tumor size, portal vein invasion, and satellite nodules (all P2.14 experienced recurrence more frequently than those with a WFA+-M2BP level ≤2.14 (P=0.011 by log-rank test), and had poorer postoperative outcomes than those with a WFA+-M2BP level ≤2.14 in terms of overall recurrence (56.0 vs. 34.5%, P=0.047) and early recurrence (52.0 vs. 20.7%, P=0.001). CONCLUSION: WFA+-M2BP level is an independent predictive factor of HBV-related HCC recurrence after curative resection. Further studies should investigate incorporation of WFA+-M2BP level into tailored postoperative surveillance strategies for patients with CHB.ope

Risk of Hepatocellular Carcinoma With Tenofovir vs Entecavir Treatment for Chronic Hepatitis B Virus: A Reconstructed Individual Patient Data Meta-analysis

Importance: Conventional meta-analyses with aggregated study-level data have yielded conflicting results for the comparative effectiveness of tenofovir disoproxil fumarate vs entecavir in reducing hepatocellular carcinoma (HCC) risk among patients with chronic hepatitis B virus. Within-study heterogeneity, between-study heterogeneity, and the inability of conventional meta-analyses to capture time-to-event data were associated with these results. Objective: To perform a reconstructed individual patient data meta-analysis of high-quality propensity score-matched studies to provide robust estimates for comparative HCC risk between groups receiving tenofovir or entecavir. Data sources: Medline and Embase databases were searched from inception to October 6, 2021. Study selection: The initial search yielded 3435 articles. Fourteen studies that used propensity score matching to balance baseline characteristics were included in the final analysis. Data extraction and synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Individual patient data were reconstructed from Kaplan-Meier curves. Risk of HCC was evaluated using random-effects hazard ratios (HRs) via a shared-frailty model and a Cox proportional hazards model stratified by study group. Restricted mean survival time (RMST) analysis was conducted to account for varying estimated treatment effect across time. Main outcomes and measures: The comparative risk of HCC with tenofovir vs entecavir treatment. Results: From analysis of 14 studes with 24 269 patients (10 534 receiving tenofovir and 13 735 receiving entecavir; mean age, 49.86 [95% CI, 48.35-51.36] years; 65.05% [95% CI, 58.60%-71.00%] men), tenofovir was associated with decreased HCC incidence compared with entecavir (stratified Cox HR, 0.85 [95% CI, 0.76-0.94] at 5 years; P = .002). However, there was no significant difference in subanalysis of clinical cohort studies (stratified Cox HR, 0.92 [95% CI, 0.80-1.06] at 5 years; P = .24). Among administrative database studies, proportionality was violated, and HRs could not be obtained via Cox proporational hazards-based models. The mean time to HCC development in RMST analysis was 2.8 (95% CI, 1.8-3.7) weeks longer (P < .001) for tenofovir vs entecavir at 5 years. The RMST analyses for other subgroups revealed either insignificant or minimal differences (<3 weeks) in the mean time to HCC at 5 years. Conclusions and relevance: In this meta-analysis, there was no clinically meaningful difference in the risk of HCC between patients who received entecavir and patients who received tenofovir. There was no difference between tenofovir and entecavir among clinical cohort studies, whereas the mean time to HCC development was less than 3 weeks longer for patients who received tenofovir vs those who received entecavir at year 5 among administrative database studies. The choice between tenofovir or entecavir should be decided based on patient convenience and tolerability.ope

KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic encephalopathy, and related complications

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A Case of Sarcoidosis Presenting as a Rectal Polyp

Sarcoidosis is a multi-systemic syndrome with an unknown etiology that is characterized by the formation of multiple non-caseating granulomas that disrupts the architecture and function of the tissues. A 58-year-old woman was referred for a skin rash and papules. No specific findings were observed on the initial skin biopsy. On gastroscopy and colonoscopy, gastric erosion and rectal polyp were noted. The rectal biopsy revealed non-caseating granulomas without acid-fast bacilli, indicating a differential diagnosis of Crohn's disease and other granulomatous diseases. A repeat skin biopsy of the papular lesion showed non-caseating granulomas that was consistent with sarcoidosis. The chest x-ray and computed tomography (CT) revealed cardiomegaly without hilar lymphadenopathy. The serum angiotensin converting enzyme level was 122 U/L (normal: 8~52 U/L) with normal liver chemistry as well as normal electrolyte, serum calcium and c-reactive protein levels. Finally, the patient was diagnosed with sarcoidosis with rectal involvement. We report this rare case of sarcoidosis that presented as a rectal polyp.ope

How to Optimize the Care Cascade of Hepatitis C Virus Infection

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Pharmacological Inhibition of Sonic Hedgehog Signaling Suppresses Tumor Development in a Murine Model of Intrahepatic Cholangiocarcinoma

Cholangiocarcinoma (CCC) is the second most primary liver cancer with an aggressive biological behavior, and its incidence increases steadily. An aberrant up-regulation of the sonic hedgehog signaling pathway has been reported in a variety of hepatic diseases including hepatic inflammation, fibrosis, as well as cancer. In this study, we determined the effect of a sonic hedgehog inhibitor, vismodegib, on the development of CCC. Through database analyses, we found sonic hedgehog signaling was up-regulated in human CCC, based on overexpression of its target genes, GLI1 and GLI2. Further, human CCC cells were highly sensitive to the treatment with vismodegib in vitro. Based on the data, we investigated the in vivo anti-cancer efficacy of vismodegib in CCC employing a murine model of CCC developed by hydrodynamic tail vein injection method. In the murine model, CCC induced by constitutively active forms of TAZ and PI3K exhibited up-regulated sonic hedgehog signaling. Treatment of vismodegib significantly suppressed tumor development in the murine CCC model, based on comparison of gross morphologies and liver weight/body weight. It is expected that pharmacological inhibition of sonic hedgehog signaling would be an effective molecular target therapy for CCC.ope

Advanced Stage Hepatocellular Carcinoma Successfully Treated with Liver-directed Concurrent Chemoradiotherapy and Sequential Transarterial Radio-embolization

Optimal treatment strategies for patients with advanced hepatocellular carcinoma (HCC) is yet to be determined. Herein, we present a case of advanced HCC with tumor invasion into the right anterior portal vein and right hepatic vein where complete response (CR) was achieved via a multidisciplinary approach. This patient had a 10.5 cm-sized HCC invading segment VI, without extrahepatic spread. Liver function was classified as Child-Pugh class A, and the performance status was good. Transarterial radio-embolization (TARE) was performed 6 weeks after the completion of liver-directed concurrent chemoradiotherapy, and CR was confirmed 3 months post-TARE. Adoptive cell therapies were performed as adjuvant therapy and CR was maintained for over 15 months, until the local recurrence of a 2 cm-sized HCC was found. Therefore, in selected cases with preserved liver function, combination therapies, including LRTs and systemic therapy, can be a useful therapeutic option for advanced HCC.ope