[Change in intraperitoneal shunt after DAA treatment for hepatitis C].

Improvement and worsening of portal hypertension after direct acting antiviral agent (DAA) treatment for hepatitis C virus-related cirrhosis have been reported, and a consensus remains elusive. In this study, we underscored on the intraperitoneal shunt formed via portal hypertension and examined how the shunt system confirmed by computed tomography (CT) changes before and after treatment in cases in which sustained virological response (SVR) was attained with DAAs. Of the cases in which we achieved an SVR of 24 with DAA treatment for hepatitis C virus-related cirrhosis at our hospital, 83 cases in which CT images were taken before and after treatment were investigated. If the intraperitoneal shunt diameter changed by 20% or more, it was analyzed as an increase or decrease. In 29 patients, intraperitoneal shunt enlargement was noted. When examining factors related to the increase, multivariate analysis detected the FIB4 index at the end of the DAA treatment. Conversely, only four cases were observed in which the size decreased. At the end of treatment, the FIB4 index was the most important factor in increasing the intraperitoneal shunt after DAA treatment for hepatitis C virus-related cirrhosis, and fibrosis was believed to be an influencing factor.

Clinical effects and emerging issues of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma from Japanese real-world practice.

BACKGROUND: Although the efficacy of atezolizumab has been demonstrated in randomized controlled trials, its long-term efficacy and association with adverse events in real-world practice are unknown. This study was designed to shed light on these issues. METHODS: In this multicenter retrospective study, data were collected from patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab in seven institutions in Japan. The authors focused on the efficacy and adverse events related to vascular endothelial growth factor (VEGF) inhibition. RESULTS: A total of 123 patients were enrolled in this study. The median progression-free survival (PFS) for the first-line treatment group was 8.0 months (95% confidence interval [CI], 6.1-9.9), whereas the median PFS for the second- or later-line treatment group was 4.1 months (95% CI, 2.6-5.7), which was significantly worse than that of the first-line treatment group (p = .005). Twenty-seven patients had interrupted bevacizumab treatment. Proteinuria accounted for the largest proportion of bevacizumab treatment interruptions. The cumulative incidence rate of bevacizumab interruption due to anti-VEGF-related adverse events was significantly higher in patients with hypertension and/or diabetes mellitus than in those without (p = .026). The landmark analysis showed that patients experienced bevacizumab interruption by 24 weeks from treatment initiation had poorer PFS than those who did not (p = .013). CONCLUSIONS: The PFS of atezolizumab plus bevacizumab as first-line treatment mostly replicates that of a global phase 3 trial. Interrupted bevacizumab treatment was more common in patients with hypertension and/or diabetes mellitus, which may be associated with worsening long-term PFS. PLAIN LANGUAGE SUMMARY: Atezolizumab plus bevacizumab has been the standard front line systemic therapy for advanced hepatocellular carcinoma. With the growing incidence of fatty liver due to metabolic syndrome as a background liver disease for hepatocellular carcinoma, the rate of comorbid hypertension and diabetes mellitus has been increasing accordingly. The present study demonstrated the cumulative incidence rate of bevacizumab interruption due to anti-VEGF-related adverse events was significantly higher in patients with hypertension and/or diabetes mellitus. The landmark analysis clarified that interruption of bevacizumab might be a risk of impaired efficacy of atezolizumab plus bevacizumab over the long term in patients with advanced hepatocellular carcinoma.

Hypophosphatemia predicts a failure to recover from adefovir-related renal injury after dose reduction in lamivudine-resistant hepatitis B patients.

AIM: In chronic hepatitis B patients receiving 10 mg adefovir, dose reduction is recommended when renal injury appears. However, recovery is not always achieved and markers that recommend switching to another antiviral agent are unknown. We investigated adefovir-related renal injury, recovery after dose reduction, and their predictors. METHODS: The renal injury in 77 chronic hepatitis B patients receiving 10 mg adefovir and recovery after dose reduction to alternate day administration in those with adefovir-related renal injury were assessed. The predictors for >20% estimated glomerular filtration rate (eGFR) decline following treatment with 10 mg adefovir and for >20% eGFR recovery after dose reduction were investigated. RESULTS: The adefovir dose was reduced in 26 patients (34%) at 59 ± 30 (mean ± standard deviation) months of 10 mg adefovir treatment because of decreases in eGFR (cumulative incidence 27%), serum phosphorus (9%), and uric acid (16%) levels, and increases in alkaline phosphatase (20%), bone type alkaline phosphatase (18%), urinary α1-microglobulin (18%), and urinary N-acetyl-ß-D-glucosaminidase (18%) levels. The only significant predictor for >20% eGFR decline was age ≥50 years at the start of 10 mg adefovir treatment. The cumulative eGFR recovery rate was 42% at 42 ± 27 months after dose reduction, and ≥2.5 mg/dL serum phosphorus level at dose reduction was the only significant predictor for >20% eGFR recovery after dose reduction. CONCLUSION: Patients aged ≥50 years are predisposed to adefovir-related renal injury and switching to another antiviral agent rather than adefovir dose reduction is recommended when hypophosphatemia is observed.

Utility of Prediction Scores for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Treated with Nucleos(t)ide Analogues.

OBJECTIVE: The utility of risk scores to predict the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogue (NA) remains to be elucidated. METHODS: CU-HCC (The Chinese University of Hong Kong-HCC) and GAG-HCC (Guide with Age, Gender, HBV DNA, Core promoter mutations and Cirrhosis) scores of 225 Japanese patients treated with NAs for at least 2 years were calculated before and 2 years after the NA treatment. According to the cutoff values, the patients were categorized into high-score or low-score groups. RESULTS: Sixteen of 225 patients developed HCC. Patients with a high score before the NA treatment showed a significantly higher HCC incidence than those with a low score using both score models (p < 0.001). Time-dependent receiver operating characteristic analyses based on scores before and 2 years after the NA treatment showed that both models exhibited moderate accuracy in predicting HCC development. The HCC incidence was significantly lower in the patients whose scores decreased below the cutoff values in response to the NA treatment than in those whose scores remained high using both models (p < 0.01). CONCLUSIONS: The predictive performance of the CU-HCC and GAG-HCC scores in the CHB patients treated with NAs is comparable to that in the NA-naive patients. The patients with sustained high scores after the NA treatment showed a higher incidence of HCC development.

Sustained virologic response achieved after curative treatment of hepatitis C virus-related hepatocellular carcinoma as an independent prognostic factor.

BACKGROUND AND AIM: Whether an antiviral interferon (IFN)-based therapy (IBT) after curative treatment of hepatocellular carcinoma (HCC) improves the prognosis in patients with hepatitis C virus (HCV)-related HCC remains to be elucidated. METHODS: A total of 178 patients within the Milan criteria underwent curative treatment for HCV-related HCC. Both the time to beyond the Milan criteria (TTBMC) and overall survival (OS) were compared between the sustained virologic response (SVR) (IFN with SVR, n = 22), non-SVR (IFN without SVR, n = 19), and non-IBT (control, n = 82) groups using propensity score matching analysis. Prognostic factors to predict survival were also determined by the Cox proportional-hazards model. RESULTS: TTBMC in the IFN with SVR group was significantly longer than those in the control and IFN without SVR groups (P < 0.001 and P = 0.006, respectively), although no significant difference existed between the IFN without SVR and control groups. Similarly, OS of the IFN with SVR group was significantly longer than that of the control and IFN without SVR groups (P < 0.001 and P = 0.029, respectively), although no significant difference existed between the IFN without SVR and control groups. The Cox proportional-hazards model identified SVR as an independent prognostic factor in these patients. The IFN with SVR group showed a 0.096-fold decrease in mortality risk compared with the control group (95% confidence intervals = 0.023-0.405; P = 0.001). CONCLUSION: Elimination of HCV after curative treatment of patients with HCC within the Milan criteria inhibits recurrence and contributes to a preferential prognosis.

Effect of previous interferon-based therapy on recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma.

Previous reports have shown that interferon (IFN)-based therapy decreases the risk of development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection. However, it remains to be fully elucidated whether elimination of HCV by IFN-based therapy inhibits HCC recurrence after curative treatment, such as surgical resection and local ablation therapies. In this study, we aimed to clarify the influence of a sustained virological response (SVR) after IFN-based therapy on recurrence and survival after curative treatment of HCC. Fifty-one patients who underwent curative treatment of HCV-related HCC after receiving IFN-based therapy were analyzed retrospectively. They were classified into SVR (N = 14) and non-SVR groups (N = 37). In the SVR group, serum levels of aspartate aminotransferase and alanine aminotransferase, the indocyanine green retention rate at 15 min, and the percentages of patients with liver cirrhosis and HCV serotype 1 were significantly lower, whereas serum albumin level and platelet count were significantly higher upon HCC occurrence. Recurrence-free survival (RFS) for the first recurrence was significantly higher in the SVR group (P < 0.01). Multivariate analysis showed that SVR at initial HCC treatment (P < 0.01) and multiple tumors (P < 0.01) are prognostic factors for RFS. Moreover, RFS for the second recurrence showed a similar trend to that for the first recurrence. In conclusion, patients who underwent IFN-based therapy before initial curative treatment of HCC had a favorable clinical outcome compared with non-SVR patients.

Efficacy of lamivudine or entecavir against virological rebound after achieving HBV DNA negativity in chronic hepatitis B patients.

Nucleos(t)ide analogues (NAs) lead to viral suppression and undetectable hepatitis B virus (HBV) DNA in some individuals infected with HBV, but the rate of virological rebound has been unknown in such patients. We examined the prevalence of virological rebound of HBV DNA among NA-treated patients with undetectable HBV DNA. We retrospectively analyzed 303 consecutive patients [158 entecavir (ETV)- and 145 lamivudine (LAM)-treated] who achieved HBV DNA negativity, defined as HBV DNA < 3.7 log IU/mL for at least 3 months. They were followed up and their features, including their rates of viral breakthrough, were determined. Viral rebound after HBV DNA negativity was not observed in the ETV-group. Viral rebound after HBV DNA negativity occurred in 38.7% of 62 HBe antigen-positive patients in the LAM-group. On multivariate analysis, age was an independent factor for viral breakthrough among these patients (P = 0.035). Viral rebound after HBV DNA negativity occurred in 29.1% of 79 HBe antigen-negative patients in the LAM-group. Differently from LAM, ETV could inhibit HBV replication once HBV DNA negativity was achieved. In contrast, LAM could not inhibit HBV replication even if HBV negativity was achieved in the early phase. Attention should be paid to these features in clinical practice.

Hiatal Hernia with Prolapse of the Pancreas Causing Bile Duct Stricture and Liver Function Disorders: A Case Report and Literature Review.

Hiatal hernia is a common condition in elderly patients, but the additional presence of prolapse of the pancreas is extremely rare. We herein report an 89-year-old woman who presented with liver function disorders and abdominal pain. Her laboratory tests revealed cholestasis, and imaging examinations showed stenosis of the common bile duct pulled toward the hernia sac. She was diagnosed with a common bile duct stricture due to pancreatic herniation and underwent laparoscopic surgery. Our review of the literature identified three types of pancreatic herniations: asymptomatic, bile duct complication, and acute pancreatitis. Pancreatic head herniation tends to induce bile duct complications.

Efficacy of lamivudine or entecavir on acute exacerbation of chronic hepatitis B.

BACKGROUND/AIMS: Spontaneous acute exacerbation of chronic hepatitis B virus (HBV) infection occasionally occurs in its natural history, sometimes leading rapidly to fatal hepatic failure. We compared the effects of lamivudine (LAM) with those of entecavir (ETV) treatments in acute exacerbation of chronic hepatitis B with 500 IU/L or higher alanine aminotransferase (ALT) levels. METHODS: Thirty-four patients with acute exacerbation were consecutively treated with LAM /ETV. Their clinical improvements were compared. RESULTS: Among LAM-treated and ETV-treated patients, none showed a reduction of <1 log IU/mL in HBV DNA after 1 or 3 months of treatment. Initial virological response, defined as a reduction of 4 log IU/mL in HBV DNA at 6 months, with LAM and ETV, respectively, was 83.3% and 100%. One LAM patient developed hepatic encephalopathy, but all patients in both groups survived. Twelve months after treatment, 41.6% of 24 LAM group patients switched to another drug or added adefovir to their treatment due to the emergence of LAM-resistant mutants. On the other hand, patients receiving ETV did not need to change drugs. CONCLUSIONS: ETV appears to be as effective as LAM in the treatment of patients with acute exacerbation of chronic hepatitis B. Clinicians should carefully start to treat these patients as soon as possible.

Bowel Obstruction due to Shiitake Mushrooms: Diagnostic Features on Computed Tomography.

Shiitake mushrooms are edible mushrooms popular in East Asian cuisine. We herein report a 69-year-old man with abdominal distension and vomiting after ingesting several pieces of sautéed Shiitake mushrooms. Abdominal computed tomography (CT) revealed ring-shaped and crescent-shaped low-density objects (-100 to -300 Hounsfield units) in the ileum. Based on the specific shapes and CT numbers of the foreign bodies, he was diagnosed with small bowel obstruction due to Shiitake mushrooms. After conservative treatment, he passed four pieces of Shiitake mushrooms. Despite the rarity, the condition can be diagnosed before exploratory surgery by careful and detailed interpretation of CT findings.

Japanese patient preferences regarding intermediate to advanced hepatocellular carcinoma treatments.

Purpose: This study aimed to evaluate Japanese patient preferences regarding features of intermediate or advanced (Progressed) hepatocellular carcinoma (HCC) treatments: transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and oral anti-cancer therapy. Methods: Patients with HCC, recruited from clinical sites and a patient panel in Japan, completed a cross-sectional web-based survey. Preferences were quantified using best-worst scaling, where patients identified the best and worst among 13 treatment features. Direct elicitation was used to identify preference for TACE, HAIC, or oral therapy, including the likelihood of trying each. Additional items asked for the willingness to try an oral medication that delays progression by six months but has an 8% or 21% risk of severe hand-foot skin reaction (HFSR). Results: The sample (N=119; 29 early stage; 90 Progressed) most preferred "oral medication", "artery branches plugged", and "prevents formation of new blood vessels", and least preferred "risk of liver damage" and "risk of catheter-related complications". Overall, 51%, 40%, and 8% preferred oral therapy, TACE, and HAIC, respectively (p<0.05), and the mean likelihood of trying each were 59%, 52%, and 35%, respectively (p<0.001). Patients with sorafenib or TACE experience most preferred what they had received; however, both groups were equally willing to try the other treatment. Patients preferring oral therapy favored "oral medication" over "artery branches plugged", "surgery is repeated as required when the cancer grows again", and "risk of liver damage", compared to those preferring TACE (p<0.05). Sixty-eight percent would probably try therapy with an 8% risk of severe HFSR, compared to 50% with a 21% risk. Conclusion: Treatment type, mode of action, and risks may drive HCC patient preferences. Such features likely should be incorporated into physician-patient interactions regarding treatment decision-making.

Atypical Clinical Presentation of Crohn's Disease with Superior Mesenteric Vein Obstruction and Protein-losing Enteropathy.

We herein report a 44-year-old man suffering from systemic edema due to protein-losing enteropathy (PLE) with superior mesenteric vein (SMV) obstruction and development of collateral veins, which subsequently proved to be a chronic result of thrombosis and a complication of Crohn's disease (CD). PLE was supposedly induced by both intestinal erosion and thrombosis-related lymphangiectasia, which was histologically proven in his surgically-resected ileal stenosis. Elemental diet and anti-TNFα agent improved his hypoalbuminemia after surgery. The rarity of the simultaneous coexistence of SMV obstruction and PLE and the precedence of these complications over typical abdominal symptoms of CD made the clinical course complex.

Nutritional enrichment of larval fish feed with thraustochytrid producing polyunsaturated fatty acids and xanthophylls.

In marine aquaculture, rotifers and Artemia nauplii employed as larval fish feed are often nutritionally enriched with forage such as yeast and algal cells supplemented with polyunsaturated fatty acids and xanthophylls, which are required for normal growth and a high survival ratio of fish larvae. To reduce the enrichment steps, we propose here the use of a marine thraustochytrid strain, Schizochytrium sp. KH105, producing docosahexaenoic acid, docosapentaenoic acid, canthaxanthin, and astaxanthin. The KH105 cells prepared by cultivation under optimized conditions were successfully incorporated by rotifers and Artemia nauplii. The contents of docosahexaenoic acid surpassed the levels required in feed for fish larvae, and the enriched Artemia showed an increased body length. The results demonstrate that we have developed an improved method of increasing the dietary value of larval fish feed.

Utilization of Shochu distillery wastewater for production of polyunsaturated fatty acids and xanthophylls using thraustochytrid.

The industrial production of barley shochu, a distilled alcoholic beverage, results in distillery waste that is currently incinerated or disposed of in landfills, causing environmental pollution. The supernatant of distillery waste contains organic matter such as proteins ( approximately 2.5%) and amino acids ( approximately 0.2%). This study demonstrates that the utilization of distillery wastewater as a sole nitrogen source enables a marine thraustochytrid, Schizochytrium sp. strain KH105, to propagate and accumulate valuable lipids including docosahexaenoic acid (DHA) and astaxanthin. Under optimized culture conditions, the highest DHA and astaxanthin yields were obtained at 3.4 g/l and 7.7 mg/l, respectively, after 4 or 5 d of cultivation in a 3-l jar fermentor. The chemical oxygen demand of the wastewater was reduced by 35%. About 67% of crude protein content and 85% of total free amino acid content also decreased in the culture supernatant. The thraustochytrid therefore serves to upgrade the distillery by-product to one containing value-added lipids for functional foods as well as to regulate the environmental contamination.

Moisturizing Effects of Diglycerol Combined with Glycerol on Human Stratum Corneum.

The water content of the stratum corneum was measured to investigate the skin-moisturizing property of diglycerol in water and in a lotion. The water content of the stratum corneum, to which the diglycerol solution was applied, was lower than that of the glycerol solution for 8 h. However, skin treated with diglycerol in combination with glycerol solution maintained a higher capacitance level compared with that of glycerol solution alone after 8 h. Moreover, the long-term moisturizing effect of the stratum corneum prominently appeared when diglycerol was formulated to the lotion containing glycerol and 1,3-butylene glycol. These studies suggest that diglycerol in combination with glycerol has a long-term moisturizing effect on human skin.

A prognostic score for patients with intermediate-stage hepatocellular carcinoma treated with transarterial chemoembolization.

BACKGROUND: Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE. METHODS: Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child-Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions. RESULTS: The number of lesions and the Child-Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0-7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child-Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0-2 points, 3 points, 4 points, 5 points, and 6-7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001). CONCLUSIONS: The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.