Deteriorated outcome of recent patients with acute liver failure and late‐onset hepatic failure caused by infection with hepatitis A virus: A subanalysis of patients seen between 1998 and 2015 and enrolled in nationwide surveys in Japan

Abstract

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.

Late-Onset Hepatic Failure in Children: Risk Factors that Determine the Outcome

“…Tandon et al [1] reported a mortality rate of 72%, and two-third of them died within 6 months of illness. Similar high rate of mortality (81%) was described in a study by Gimson et al [4] In a recent Japanese survey, mortality associated with hepatitis A related LOHF was shown to be on the rise, increasing from 21% before 2003 to 44% thereafter [3]. A quarter of our patients recovered spontaneously including complete normalization of liver function tests with conservative treatment only with longest duration of 24 months.…”

“…Consensus statements from various societies currently agree that features of advanced liver dysfunction in ALF and ACLF present within first 3-4 weeks of illness [13][14][15][16]. There are different viewpoints regarding the duration of illness in LOHF in the definitions proposed by various authors [3][4][5][6][7]. By and large, most agree that late-onset, sub-fulminant, or late-onset liver failures (terminologies interchangeably used) have delayed presentation after 4th week of illness [16,17].…”

“…Despite the considerable confusion and overlap in assessment, this entity should be clearly distinguished from acute on chronic liver failure (ACLF) which has a different outcome. Recent surveys in Japan have shown that LOHF especially with hepatitis A continues to have a major impact on intractable liver diseases [2,3]. The disease has a smouldering course with most of the adult studies showing poor survival [4][5][6][7].…”

Difference in seroprevalence of IgG antibodies against hepatitis A virus on general population in 1998 and 2019 in Iwate Prefecture, Japan

“…Japanese healthcare workers are also reported to be at risk of occupational HAV infection because their immunity to HAV will have decreased with age [11]. Older people without anti-HAV IgG-related immunity may contract a more serious infection [12]. Furthermore, international travel to Japan can also bring foreigners from HAV endemic areas to the country; likewise for Japanese people who have travelled to areas where HAV is endemic.…”

Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease

“…A Japanese nationwide survey of ALF and late-onset hepatic failure (LOHF) caused by HAV infection suggested that diabetic mellitus was more common among deceased patients than among rescued patients (29% vs. 8%; p < 0.05), excluding patients with liver transplantations, and that diabetic mellitus was independently associated with the outcome [ 24 ]. Patients with diabetes are at risk of developing severe hepatitis [ 25 ].…”