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Background: The Japanese guidelines for the treatment of cirrhosis suggest zinc supplementation to prevent hepatic encephalopathy in patients with cirrhosis and zinc deficiency, although the factors that are associated with therapeutic efficacy remain unknown. Method: A total of 159 patients with chronic liver diseases but without previous zinc supplementation were analyzed. Factors associated with serum zinc levels as well as the therapeutic efficacy of zinc supplementation were evaluated. Result: Serum zinc levels decreased with the progression of liver diseases. A multiple linear regression analysis revealed that the serum levels of albumin and cholinesterase and the daily furosemide dose were independently associated with the serum zinc levels. The optimal furosemide cut‐off dosage for patients with zinc deficiency (<60 μg/dl) was 5 mg/day. Among 34 patients receiving zinc acetate hydrate, overt hepatic encephalopathy occurred in 12 patients (35.4%). A multivariate analysis identified a minimal serum zinc level of 50 μg/dl after more than 12 weeks of zinc supplementation as a factor associated with overt encephalopathy development, while furosemide use was not associated. The Child‐Pugh score at baseline was the only factor associated with the maintenance of sufficient serum zinc levels. Conclusion: Although the furosemide dose was negatively correlated with the serum zinc level in patients with chronic liver diseases, furosemide use was not associated with the occurrence of overt encephalopathy in those receiving zinc supplementation. Serum zinc levels of ≥50 μg/dl were required to prevent overt encephalopathy development during zinc supplementation in both patients with and those without furosemide administration. [ABSTRACT FROM AUTHOR]

Aim: To optimize the therapeutic strategy for cirrhotic patients manifesting hepatic encephalopathy, factors affecting the outcome of patients receiving rifaximin were evaluated. Methods: The subjects were 95 patients receiving rifaximin. Serum ammonia levels were measured serially during rifaximin treatment. Factors associated with long‐term outcomes and cumulative survival rates were evaluated. Results: Serum ammonia levels were decreased at 4 weeks after rifaximin treatment compared to the levels at baseline even in patients receiving rifaximin as an add‐on therapy with lactitol hydrate (P < 0.001) and reduction values were negatively correlated with the maximal diameter of portosystemic shunts (r = −0.275, P = 0.009). Overt encephalopathy occurred in 37 patients (38.9%) during rifaximin treatment, and the hazard function analysis identified 90 days as a high‐risk term for developing the first‐time overt encephalopathy. Thus, the long‐term outcome was judged as favorable in 77 patients (81.1%) in whom overt encephalopathy was absent for at least 90 days during rifaximin initiation. A multivariate analysis revealed that furosemide, especially at daily doses of ≥20 mg both at baseline and during rifaximin treatment, was a significant factor associated with unfavorable outcome (P = 0.009 and P = 0.022, respectively) as well as occurrence and recurrence of overt encephalopathy (P = 0.012). Moreover, furosemide treatment significantly deteriorated the cumulative survival rate of patients receiving rifaximin (P = 0.026). Conclusion: Furosemide contributed to the deteriorated outcome of patients receiving rifaximin. Consequently, rifaximin should be given before increasing the furosemide dose, and the furosemide dose should not be increased during rifaximin treatment. [ABSTRACT FROM AUTHOR]

Aim: A nationwide survey of acute liver failure (ALF) and late‐onset hepatic failure (LOHF) has revealed that the outcomes of recent patients whose diseases were caused by infection with hepatitis A virus (HAV) have worsened, compared with those of previously reported patients. The factors associated with this deterioration were evaluated. Methods: A total of 83 patients with HAV infection seen between 1998 and 2015 were enrolled. All the patients had a prothrombin time–international normalized ratio of 1.5 or more and hepatic encephalopathy of grade 2 or more severe. The demographic and clinical features of 45 patients seen prior to 2003 (cohort 1) and 38 patients seen during 2004 and thereafter (cohort 2) were compared. Results: Three and four patients in cohort 1 and cohort 2, respectively, received liver transplantations; the survival rates among the remaining patients were 56% for cohort 2 and 79% for cohort 1 (P < 0.05). The mean age (±standard deviation) of the patients was higher in cohort 2 than in cohort 1 (58 ± 11 vs. 48 ± 13 years; P < 0.01). The percentages of patients with underlying metabolic diseases were 22% in cohort 1 and 61% in cohort 2 (P < 0.01). Diabetic mellitus was more common among deceased patients than among rescued patients (29% vs. 8%; P < 0.05) among patients who did not receive liver transplantations, and a multivariate analysis revealed that patient age and disease type were significantly and independently associated with the outcome. Conclusion: The outcomes of recent patients with ALF or LOHF caused by HAV infection have recently worsened mainly because of an increase in underlying metabolic diseases as a consequence of aging. [ABSTRACT FROM AUTHOR]

Background: A nationwide survey was performed to clarify the recent status of acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan.Methods: Two-step surveys for patients with ALF and LOHF meeting the Japanese diagnostic criteria were performed annually in 782 hospitals. The clinical features of the patients were then compared to those reported in previous surveys.Results: In total, 1554 and 49 patients with ALF and LOHF, respectively, who were seen between 2010 and 2015 were enrolled. The subjects were classified into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323 patients without hepatitis (190 non-comatose and 133 comatose). Compared with patients seen between 1998 and 2009, an older patient age and a higher percentage of underlying extrahepatic disease were observed. Although hepatitis virus infection was the most frequent etiology, the percentage of patients with this etiology had decreased, compared with previous cohorts, while the percentages of patients with drug-induced liver injuries, autoimmune hepatitis, and an indeterminate etiology had increased. Liver transplantation was performed in 170 patients (10.6%), whereas artificial liver support with plasmapheresis and/or hemodiafiltration were performed for most of the comatose patients. The outcomes of comatose patients were unfavorable, similar to previous surveys, especially the outcomes of hepatitis B virus carriers, including those with de novo hepatitis B (survival rate of 5.4% without liver transplantation).Conclusion: Although the clinical features, including the etiologies, of patients with ALF and LOHF have changed, the outcomes of patients have not improved in recent years. [ABSTRACT FROM AUTHOR]