MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

BACKGROUND: We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC). METHODS: The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24 weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR. RESULTS: Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI). CONCLUSIONS: The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.

A Case of Adult-onset Still's Disease (AOSD) with Gastrointestinal Lesions.

A 51-year-old woman with fever was admitted to our hospital. A computed tomography (CT) scan showed thickened colonic walls. Colonoscopy revealed erosion in the ileum and colon. Adult-onset Still's disease (AOSD) was diagnosed due to a subsequent sore throat and skin rash. Following AOSD treatment, methylprednisolone pulse therapy, followed by prednisolone and cyclosporine, was initiated. Despite achieving a temporary improvement, relapse occurred with fever, abdominal pain, with worsening CT and endoscopic findings. The reappearance of a skin rash confirmed an exacerbation of AOSD. Tocilizumab treatment alleviated the symptoms and improved the endoscopic findings. Considering their correlation with the symptoms and endoscopic findings, the observed gastrointestinal lesions may be linked to AOSD.

Prognostic nutritional index after introduction of atezolizumab with bevacizumab predicts prognosis in advanced hepatocellular carcinoma: A multicenter study.

INTRODUCTION: Atezolizumab plus bevacizumab (Atez/Bev) is the preferred treatment for advanced hepatocellular carcinoma (HCC). However, biomarkers of therapeutic efficacy have remained unclear. We took a retrospective approach to explore the role of prognostic nutritional index (PNI) for predicting the outcomes of Atez/Bev treatment. METHODS: One hundred twenty-five HCC patients were enlisted; these patients received Atez/Bev treatment and underwent dynamic computerized tomography/magnetic resonance imaging to determine the treatment response on at least one occasion between October 2020 and January 2023, and their PNI before treatment and at the beginning of the second cycle (PNI-2c) was evaluated. RESULTS: During the initial evaluation, 2 (2%), 28 (22%), 70 (56%), and 25 (20%) patients exhibited a complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively. Patients with non-PD tended to have higher PNI at baseline and PNI-2c than those with PD (p = 0.245 and 0.122, respectively), with optimal baseline PNI and PNI-2c cut-off values of 42.6 and 40.4, respectively. PNI at baseline could not be used to predict overall survival (OS) or progression-free survival (PFS). However, PNI-2c predicted OS and PFS (PNI-2c ≥ 40.4 vs. < 40.4: 25.3 vs. 16.2 months, P = 0.008 for OS; 12.7 vs. 8.4 months, P = 0.036 for PFS). A multivariate analysis showed a significant association between PNI-2c and OS. CONCLUSIONS: PNI-2c is a predictor of prognosis in HCC patients treated with Atez/Bev therapy.

Serum angiopoietin-2 levels predict the development of hepatocellular carcinoma following hepatitis C virus eradication using direct-acting antiviral agents.

INTRODUCTION: Our previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. METHODS: We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline and with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥ 2.0 C.O.I. RESULTS: Multivariate analyses revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; P = 0.003). This result was reproduced in individuals without history of HCC and with advanced liver fibrosis (M2BPGi level ≥ 3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at the EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥ 2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, P < 0.001). CONCLUSIONS: At the EOT24W, serum Ang-2 level predicts the likelihood of developing HCC following SVR to DAA therapy.

Serum inducible protein 10 kDa/C-X-C motif chemokine 10 levels predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

AIM: It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitis C virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10 kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy. METHODS: The study participants were recruited from a historical cohort of 116 chronically hepatitis C virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2 years after the end of treatment (EOT) as the regression (n = 71) and non-regression (n = 45) groups, respectively. RESULTS: Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24 weeks after the EOT, and serum IP-10 change from baseline to 24 weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline. CONCLUSIONS: Serum IP-10 change from baseline to 24 weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.

Serum CXCL10 levels at the start of the second course of atezolizumab plus bevacizumab therapy predict therapeutic efficacy in patients with advanced BCLC stage C hepatocellular carcinoma: A multicenter analysis.

BACKGROUND & AIMS: Relationships of serum C-C motif chemokine ligand 5 (CCL5) and C-X-C motif chemokine ligand 10 (CXCL10) levels with hot immune features have been reported in patients with hepatocellular carcinoma (HCC). Therefore, we examined the utility of their levels for predicting the efficacy of atezolizumab plus bevacizumab (Atez/Bev) in patients with HCC. DESIGN: In total, 98 patients with HCC treated with Atez/Bev were enrolled, and their initial responses were evaluated at least once via dynamic computed tomography or magnetic resonance imaging. Serum CCL5 and CXCL10 levels were assessed by enzyme-linked immunosorbent assay before treatment and at the start of the second course of Atez/Bev therapy, and their relationships with treatment efficacy were determined. RESULTS: No analyzed factor was associated with the initial therapeutic response. Among the 56 patients with Barcelona Clinic Liver Cancer (BCLC) stage C, serum CXCL10 levels at the beginning of course two (CXCL10-2c) tended to be higher in responders than in non-responders in the initial evaluation, and its optimal cutoff level of 690 pg/mL could be used to stratify patients regarding overall survival (OS; high vs. low: not reached vs. 17.6 months, p = 0.034) and progression-free survival (high vs. low: 13.6 vs. 5.1 months, p = 0.014). In multivariate analysis, high CXCL10 levels and neutrophil-to-lymphocyte ratios at the start of course two and Child-Pugh stage A at baseline were independent predictive factors of improved OS. CONCLUSIONS: Serum CXCL10-2c levels were predictive of Atez/Bev efficacy in patients with BCLC stage C HCC.

The neutrophil-to-lymphocyte ratio at the start of the second course during atezolizumab plus bevacizumab therapy predicts therapeutic efficacy in patients with advanced hepatocellular carcinoma: A multicenter analysis.

AIM: Atezolizumab plus bevacizumab (Atez/Bev) therapy is expected to have good therapeutic efficacy for patients with advanced hepatocellular carcinoma (HCC). However, the clinical indicators that predict therapeutic efficacy have not been established. We retrospectively investigated whether the neutrophil-to-lymphocyte ratio (NLR) during Atez/Bev therapy could predict therapeutic efficacy. METHOD: In total, 110 patients with HCC were enrolled; they were treated with Atez/Bev therapy and evaluated for their initial response by dynamic CT or MRI at least once between October 2020 and July 2022. RESULTS: Of the 110 patients with HCC at the initial evaluation, two (2%) showed a complete response (CR), 22 (20%) partial response (PR), 62 (56%) stable disease (SD), and 24 (21%) progressive disease (PD). The NLR at the start of the second course (NLR-2c) increased from CR + PR to SD to PD. There was no significant association between the baseline NLR and the initial therapeutic response. Patients with CR + PR had lower NLR-2c values than those with SD + PD (p < 0.001) and the optimal cut-off value of NLR-2c was 1.97. Patients with NLR-2c <1.97 had better overall survival and progression-free survival (PFS) than those with NLR-2c ≥1.97 (p = 0.005 for overall survival; p < 0.001 for PFS). A multivariate analysis showed that female sex, higher PIVKA-II levels at baseline, and higher values of NLR-2c were significantly associated with poorer PFS. CONCLUSIONS: The NLR-2c value predicts the initial therapeutic response and prognosis of patients with HCC treated with Atez/Bev therapy.

Outcome of nucleos(t)ide analog cessation in patients with treatment for prevention of or against hepatitis B virus reactivation.

AIM: We retrospectively investigated patients with administration of nucleos(t)ide analogs (NAs) for prevention of or against hepatitis B virus (HBV) reactivation, and their clinical outcomes after cessation of the NA. METHODS: We enrolled 180 patients who were positive for HBsAg when they started immunosuppressive therapy or chemotherapy and an NA was administered to prevent HBV reactivation (HBV carrier group), and 82 patients with resolved HBV infection who started administration of an NA after HBV reactivation (de novo HBV group). Cessation of the NA depended on each physician's judgment without definite criteria. RESULTS: A total of 27 patients in the HBV carrier group and 22 in the de novo HBV group stopped NA therapy. In the HBV carrier group, 16 patients experienced virological relapse, which was defined as HBV DNA levels ≥20 IU/ml, and one with hematological disease had an alanine aminotransferase flare after cessation of NA. Of the 16 patients, the NA was reintroduced in three, whereas, the remaining 13 had low levels of HBV DNA and no alanine aminotransferase flare. In the de novo HBV group, virological relapse occurred in six patients, and one with hematological disease had an alanine aminotransferase flare after cessation of the NA. The NA was reintroduced in four of the six patients. CONCLUSIONS: We may be able to consider to cease NA therapy proactively in HBV carriers and resolved patients with non-hematological disease, if their primary diseases are under remission after completion of immunosuppressive therapy or chemotherapy. However, careful follow up is necessary after stopping NA therapy.

Efficacy of minocycline hydrochloride aspiration sclerotherapy with additional monoethanolamine oleate aspiration sclerotherapy for symptomatic hepatic cysts.

AIM: Minocycline hydrochloride (MINO) aspiration sclerotherapy (AS) has been widely used for treating hepatic cysts (HC). However, cyst recurrence remains problematic. Information on monoethanolamine oleate (EO) AS, another effective HC treatment, is currently limited. We investigated the efficacy of EO on ineffective MINO treatments, and the relationship between MINO AS and cyst fluid pH. METHODS: A total of 22 cases with symptomatic HC underwent AS with 500 mg of MINO from January 2016 to June 2021. Cyst fluid pH was measured before and after MINO injection. Cyst volume ratio (CVR, %) after 2 weeks was calculated as follows:cyst volume 2 weeks after MINO injection / pre-treatment cyst volume × 100. Treatment was completed if CVR after 2 weeks was ≤35% (MINO-group). For patients with CVR >35%, 2 g of EO was added (MINO/EO-group). Cyst volume ratio was measured every 12 months thereafter. RESULTS: There were no recurrence symptoms in any of the patients during follow-up. Of the 22 cases, 21 had CVR ≤20% after 12 months. The MINO/EO-group (n = 8) tended to have smaller CVRs after 12 months than the MINO-group (n = 14). Cyst volume ratio after 2 weeks was correlated to pH change (p = 0.012) and was larger in patients whose pH decreased by <1.5 (p = 0.015). All adverse events were mild, including in elderly patients. CONCLUSION: Adding EO is an effective and safe treatment for symptomatic HC when MINO AS alone is insufficient. Patients with pH decreases of <1.5 should be considered for additional EO treatment.

Serum angiopoietin-2 levels predict regression of Mac-2 binding protein glycosylation isomer-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.

AIM: It is desirable to identify predictors of regression of liver fibrosis after achieving a sustained virologic response (SVR) by direct-acting antiviral agents (DAAs) to antihepatitis C virus (HCV) therapy. Here, we retrospectively investigated the serum angiopoietin-2 (Ang-2) level as a predictive indicator of regression of liver fibrosis after successful HCV eradication by DAA therapy. METHODS: The study subjects were recruited from a historical cohort of 109 chronically HCV-infected patients who had achieved SVR by DAA therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAA therapy) were ≥2.0 the cut-off index (COI). We defined patients with M2BPGi levels <1.76 and ≥1.76 COI at 2 years after the end of treatment (EOT) as the regression (R, n = 69) and nonregression (NR, n = 40) groups, respectively. RESULTS: Multivariate analyses revealed that the Ang-2 level at baseline and the Ang-2 level, albumin-bilirubin score, and FIB-4 index at 24 weeks after the EOT were significantly associated with regression of M2BPGi-based liver fibrosis. Receiver operating characteristic curve analyses showed that the Ang-2 level at 24 weeks after the EOT had the largest area under the curve values (0.859). The same results were obtained even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 COI at baseline. CONCLUSIONS: The serum Ang-2 level at 24 weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving SVR by DAA therapy.

Primary Sclerosing Cholangitis and Autoimmune Hepatitis Overlapping Syndrome Complicated by Ulcerative Colitis.

The case of a 28-year-old man who had primary sclerosing cholangitis and autoimmune hepatitis overlapping syndrome (PSC-AIH OS) complicated by ulcerative colitis (UC) is reported. First, he was diagnosed with PSC complicated by UC and initially treated with ursodeoxycholic acid and mesalazine. Twenty-four months later, liver damage reappeared, and we performed a liver biopsy, which showed the features of AIH. We eventually diagnosed him with PSC-AIH OS complicated by UC. If liver damage worsens in PSC patients, PSC-AIH OS should be considered. The optimum management approach for PSC-AIH OS should be established.

Serum miR-192-5p levels predict the efficacy of pegylated interferon therapy for chronic hepatitis B.

We examined the association between serum miRNA (-192-5p, -122-3p, -320a and -6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24-weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor (Odds 4.5, P = 0.041). Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.

Long-term outcomes of nasogastric tube with Gastrografin for adhesive small bowel obstruction.

BACKGROUND: We had previously reported that the administration of Gastrografin through a nasogastric tube (NGT-G) followed by long tube (LT) strategy could be a novel standard treatment for adhesive small bowel obstruction (ASBO); however, the long-term outcomes after initial improvement remain unknown. This study aimed to analyze the long-term outcomes of first-line NGT-G. METHODS: Enrolled patients with ASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018. Thereafter, the cumulative surgery rate, cumulative recurrence rate, and overall survival (OS) rate were analyzed. In addition, subset analysis was conducted to determine the cumulative recurrence rate according to colonic contrast with Gastrografin at 24 h. RESULTS: A total of 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed over a median follow-up duration of 550 days. The cumulative 1-year surgery rates, cumulative 1-year recurrence rates, and 1-year OS rates in the LT and NGT-G groups were 18.8% and 18.1%, 30.0% and 31.7%, and 99.1% and 96.6%, respectively; no significant differences were observed between both groups. In the NGT-G group, a negative colonic contrast at 24 h demonstrated a higher tendency for future recurrence compared with a positive colonic contrast at 24 h (1-year recurrence rate: negative contrast, 46.9% vs positive contrast, 27.6%). CONCLUSIONS: Gastrografin through a nasogastric tube followed by LT can be a promising treatment strategy for ASBO, with long-term efficacies equivalent to initial LT placement.

Development of hepatocellular carcinoma from various phases of chronic hepatitis B virus infection.

BACKGROUND & AIMS: There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period. DESIGN: We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA　 (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups. RESULTS: Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients. CONCLUSIONS: HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words).

Complex structural variations in non-human primate hepatitis B virus.

BACKGROUND: Recent genome sequence technology has revealed a novel type of genetic rearrangement referred to as complex structural variations (SVs). Previous studies have elucidated the complex SVs in human hepatitis B viruses (HBVs). In this study, we investigated the existence of complex SVs in HBVs from non-human primates (NHPs). METHODS: Searches for nucleotide sequences of NHP HBV were conducted using the PubMed, and genetic sequences were retrieved from databases. The candidate genetic sequences harboring complex SVs were analyzed using the CLUSTALW program and MAFFT. Additional bioinformatical analyses were performed to determine strains with complex SVs and to elucidate characteristics of NHP HBV strains. RESULTS: One hundred and fifty-four HBV strains from NHPs were identified from databases. SVs and complex SVs were observed in 11 (7.1%) strains. Three gibbon HBV (GiHBV) strains showed complex SVs consisting of an insertion and a deletion in the pre-S1 region. One GiHBV strain possessed a 6-nt insertion, which are normally specific to human HBV genotype A (HBV/A) in the Core region, and further analyses clarified that the 6-nt insertion was not caused by recombination, but rather by simple insertion. Another chimpanzee HBV strain showed complex SVs in the pre-S1 region, which were composed of human HBV/E, G-specific polymorphic SV, and an additional 6-nt insertion. CONCLUSIONS: In this study, complex SVs were observed in HBV strains from NHPs, in addition to human HBV strains, as shown in previous studies. These data suggest that complex SVs could also be found in other members of hepadnaviruses, and may play a role in their genetic diversity.

A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C.

Evaluating liver fibrosis is crucial for disease severity assessment, treatment decisions, and hepatocarcinogenic risk prediction among patients with chronic hepatitis C. In this retrospective multicenter study, we aimed to construct a novel model formula to predict cirrhosis. A total of 749 patients were randomly allocated to training and validation sets at a ratio of 2:1. Liver stiffness measurement (LSM) was made via transient elastography using FibroScan. Patients with LSM ≥12.5 kPa were regarded as having cirrhosis. The best model formula for predicting cirrhosis was constructed based on factors significantly and independently associated with LSM (≥12.5 kPa) using multivariate regression analysis. Among the 749 patients, 198 (26.4%) had LSM ≥12.5 kPa. In the training set, multivariate analysis identified logarithm natural (ln) type IV collagen 7S, ln hyaluronic acid, and ln Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-Mac-2 BP) as the factors that were significantly and independently associated with LSM ≥12.5 kPa. Thus, the formula was constructed as follows: score = -6.154 + 1.166 × ln type IV collagen 7S + 0.526 × ln hyaluronic acid + 1.069 × WFA+-Mac-2 BP. The novel formula yielded the highest area under the curve (0.882; optimal cutoff, -0.381), specificity (81.5%), positive predictive values (62.6%), and predictive accuracy (81.6%) for predicting LSM ≥12.5 kPa among fibrosis markers and indices. These results were almost similar to those in the validated set, indicating the reproducibility and validity of the novel formula. The novel formula scores were significantly, strongly, and positively correlated with LSM values in both the training and validation data sets (correlation coefficient, 0.721 and 0.762; p = 2.67 × 10-81 and 1.88 × 10-48, respectively). In conclusion, the novel formula was highly capable of diagnosing cirrhosis in patients with chronic hepatitis C and exhibited better diagnostic performance compared to conventional fibrosis markers and indices.

The first management using intubation of a nasogastric tube with Gastrografin enterography or long tube for non-strangulated acute small bowel obstruction: a multicenter, randomized controlled trial.

BACKGROUND: Gastrointestinal decompression is generally applied to a non-strangulated acute small bowel obstruction (NSASBO). Although long tube (LT) placement and administration of Gastrografin through a nasogastric tube (NGT-G) have shown advantages over NGT alone in previous studies, no studies appear to have compared LT and NGT-G. METHODS: In this multicenter, randomized controlled trial, patients with NSASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018 at 11 Japanese institutions. The primary endpoint was non-inferiority of NGT-G compared to LT for non-surgery rate, and the lower limit of the 95% confidence interval for the non-surgery rate (-15%) was set as the lower margin for inferiority of NGT-G compared to LT. RESULTS: In total, 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed in the present trial. The non-surgery rate was 87.4% in the LT group and 91.1% in the NGT-G group, with a 3.7% difference between NGT-G and LT (95.3%CI - 5.55 to 12.91; non-inferiority P = 0.00002923). On the other hand, the non-surgery rate with pure NGT-G alone (76.8%) that represents non-cross-over NGT-G without subsequent LT was significantly lower than that with LT (P = 0.039). Median procedure time was significantly shorter with NGT-G (1 min) than with LT (25 min; P < 0.001), whereas no significant differences in mortality or hospital stay were noted between groups. CONCLUSION: NGT-G is an effective alternative to LT as a first-line treatment for NSASBO. A sequential strategy comprising NGT-G followed by LT might offer a new standard for NSASBO. CLINICAL TRIALS REGISTRATION: This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (umin.ac.jp/ctr Identifier: UMIN000022669) prior to the start of this trial.

Novel Genetic Rearrangements Termed "Structural Variation Polymorphisms" Contribute to the Genetic Diversity of Orthohepadnaviruses.

The genetic diversity of orthohepadnaviruses is not yet fully understood. This study was conducted to investigate the role of structural variations (SVs) in their diversity. Genetic sequences of orthohepadnaviruses were retrieved from databases. The positions of sequence gaps were investigated, since they were found to be related to SVs, and they were further used to search for SVs. Then, a combination of pair-wise and multiple alignment analyses was performed to analyze the genomic structure. Unique patterns of SVs were observed; genetic sequences at certain genomic positions could be separated into multiple patterns, such as no SV, SV pattern 1, SV pattern 2, and SV pattern 3, which were observed as polymorphic changes. We provisionally referred to these genetic changes as SV polymorphisms. Our data showed that higher frequency of sequence gaps and lower genetic identity were observed in the pre-S1-S2 region of various types of HBVs. Detailed examination of the genetic structure in the pre-S region by a combination of pair-wise and multiple alignment analyses showed that the genetic diversity of orthohepadnaviruses in the pre-S1 region could have been also induced by SV polymorphisms. Our data showed that novel genetic rearrangements provisionally termed SV polymorphisms were observed in various orthohepadnaviruses.

Percutaneous Transhepatic Self-expanding Metallic Stent Placement for the Treatment of Malignant Afferent Loop Obstruction.

We report the case of a 71-year-old man with afferent loop obstruction (ALO) after Roux-en-Y reconstruction due to gastric cancer. Computed tomography showed a distended afferent loop and a dilatated bile duct. We could not reach the stricture site in the afferent loop using a gastroscope. We performed percutaneous transhepatic biliary drainage (PTBD) and placed a self-expanding metallic stent (SEMS) in the duodenal stricture through the PTBD route. Although an endoscopic approach is preferable, when PTBD can be performed, percutaneous transhepatic SEMS placement might be an alternative option for treating ALO in cases in which it is not possible to reach the site of stenosis with an endoscope.