Over 3-Years Follow-Up of a Case of Primary Biliary Cholangitis With Autoimmune Hyperthyroidism: Factors Associated With Liver Dysfunction.

We present a rare case of a 50-year-old woman with simultaneous primary biliary cholangitis (PBC) and autoimmune hyperthyroidism in which the factors associated with liver dysfunction were evaluated over a 3-year follow-up period. Although serum thyroid hormone levels improved after the administration of thiamazole, thyroid dysfunction was not directly associated with liver dysfunction. During the follow-up period, anti-hyperlipidemic drug therapy and eradication therapy for Helicobacter pylori (HP) infection caused transient elevation of serum transaminase levels. It should be recognized that serum liver enzyme levels might be affected by various factors, including the therapies for the many complications of PBC.

A 51-Year-Old Woman with Drug-Induced Hypersensitivity Syndrome Associated with Carbamazepine, Reactivation of Human Herpesvirus 6, and Acute Liver Failure: A Case Report.

BACKGROUND Infection with human herpesvirus 6 (HHV-6) is a recognized risk factor for the development of drug-induced hypersensitivity syndrome (DIHS). DIHS is a systemic autoimmune condition that presents with mucocutaneous lesions of varying severity and comprises 3 subtypes: toxic epidermal necrolysis, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS). Here, we describe the case of a 51-year-old woman with a diagnosis of DIHS associated with carbamazepine, reactivation of HHV-6, and acute liver failure, which was consistent with DRESS. CASE REPORT We present the case of a 51-year-old Japanese woman who had been taking carbamazepine for epilepsy for the past 3 weeks. She presented with a fever, liver dysfunction, eosinophilia, and the sudden appearance of a skin rash. Steroid therapy was started for suspected drug-induced liver injury. The skin eruption disappeared, and liver dysfunction showed an improving trend. However, after stopping steroid, the pyrexia and eosinophilia reappeared. Therefore, prednisolone was re-administrated. HHV-6 DNA was detected, so HHV-6 reactivation was confirmed. Carbamazepine was stopped, and the clinical manifestations improved. She was ultimately diagnosed with DIHS, consistent with DRESS, associated with carbamazepine and HHV-6 reactivation, and liver dysfunction was assessed histologically. Therefore, the drug-related hepatotoxicity of carbamazepine played a role in causing liver damage rather than HHV-6 infection at that time. CONCLUSIONS We describe a case of DIHS that was also associated with acute liver failure, consistent with DRESS. The case highlights the importance of making the correct diagnosis, as well as the management of mucocutaneous lesions and other systemic conditions (including acute liver failure).

Asymptomatic acute hepatitis E in a female patient with ulcerative colitis.

We present a 60-year-old female patient with asymptomatic acute hepatitis E that was fortuitously detected during the course of ulcerative colitis (UC). She was admitted to hospital on October 30, 2015. Endoscopy and histological examination of the colon showed typical findings of UC. All parameters of liver function tests were normal on this date. Combination therapy with oral prednisolone and mesalazine was started and intravenous administration of infliximab once every 8 weeks was added later. Her symptoms gradually improved after these treatments, and she was discharged on February 7, 2016. In a periodic check-up on July 7, 2016, high levels of serum transaminases were detected in liver function tests. Although drug-induced liver injury was first suspected, anti-hepatitis E virus (HEV) immunoglobulin A was positive. The genotype and subgenotype of this HEV are 3 and 3a, respectively, although the infectious route of the HEV was unclear. Within 2 weeks after the onset of acute liver injury, the HEV viremia disappeared and her liver function tests improved. Examination of serum anti-HEV immunoglobulin A should be added at the time of abnormal liver function tests in patients with UC receiving immunosuppressive and biological drugs.

Clinical and molecular analyses of sporadic acute hepatitis A and E and the specific viral genotypes isolated in Iwate and three neighboring prefectures in the northern part of Honshu, Japan, between 2004 and 2013.

AIM: To examine the prevalence and characteristics of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in the northern part of Honshu, Japan, during the last decade. METHODS: Using the registration system of a prospective cohort study for acute liver injury (ALI) in Iwate and three neighboring prefectures, we examined the prevalence of sporadic acute hepatitis (AH) with HAV (AH-A) and HEV (AH-E) and the distribution of viral genotypes in 487 patients diagnosed with ALI between 2004 and 2013. RESULTS: Among all 487 patients, 135 (28%) had ALI with viral infection. In the cases with viral ALI, the prevalence of hepatitis B virus-related AH was highest (55.6%). AH-E was seen in 23 patients (17.0%) and its prevalence was higher than that of AH-A (10 patients, 7.4%). There were no appreciable differences in the prevalence of AH-A and AH-E between 2004-2008 and 2009-2013. However, subgenotype IIIA HAV homologous to Korean strains has recently emerged, and the number of AH-E cases seems to be increasing. HEV genotype 3 was predominant throughout the observation period, but HEV genotype 4 was found in three patients after 2010. The transmission routes of HAV and HEV infections were unknown in approximately 60% of the patients. CONCLUSION: In the northern part of Honshu, Japan, HEV has been more frequently implicated in the development of AH than HAV, and HEV genotype 4 has been recently increasing. To provide an effective prophylactic management for HAV and HEV infections, further clarification of the transmission routes is needed.

Viral decline over 48h and HCV amino acid mutations are related to efficacy of PEG-IFN/ribavirin.

BACKGROUND/AIMS: The relationship between mutations and HCV dynamics has not been fully studied in terms of the efficacy of PEG-IFN/Rib combination treatment. Here we aimed to systematically examine HCV dynamics during PEG-IFN/Rib treatment and evaluate the association between amino acid (aa) substitutions in HCV and efficacy of PEG-IFN/Rib treatment. METHODOLOGY: Patients (n=36) having HCV genotype 1b infection and high viral loads with PEG-IFN/Rib for 48 weeks were treated. HCV RNA levels were quantified every 24h from 0-144h after initial injection of PEGIFN and every month thereafter. The aa substitutions in HCV core region (CoreR) and interferon sensitivity determining region (ISDR) were determined at baseline. On the basis of treatment response, we divided patients into 3 groups: sustained virological response (SVR: n=18), transient response (TR: n=9) and no response (NR: n=9). RESULTS: Patients with double wild type (DW) in CoreR had higher SVR rate as compared to patients with non-double wild type (NDW) in CoreR (58% vs. 33%). Patients with =2 aa substitutions in ISDR had significantly higher SVR rate compared with patients with =1 aa substitution in ISDR (71% vs. 36%). Further, 68% patients who exhibited =2-log decline in HCV-RNA levels within the initial 48h of treatment achieved SVR, and only 18% patients who reached <2 log declines did not achieve SVR. Patients who reached =2 log declines in HCV-RNA levels within the initial 48h of treatment with DW in CoreR or =2 aa substitutions in ISDR could achieve SVR and those with NDW in CoreR or =1 aa substitution in ISDR could not achieve SVR. CONCLUSIONS: The combination of the apparent =2-log decline in HCV RNA level within the initial 48h and aa substitutions in CoreR and ISDR may be useful predictors of PEG-IFN/Rib treatment.

A male patient with severe acute hepatitis who was domestically infected with a genotype H hepatitis B virus in Iwate, Japan.

Although all eight genotypes of hepatitis B virus (HBV) strains are circulating in Japan, no cases of acute hepatitis with foreign HBV strains of genotype H have thus far been reported in Japan. Here, we report a 35-year-old Japanese patient with severe acute hepatitis who was domestically infected with genotype H HBV. On admission, he had a high HBV load of 1.0 x 10(9) copies/ml, elevated levels of total bilirubin (7.0 mg/dl) and alanine aminotransferase (3606 IU/l), and reduced prothrombin activity of 39.0%. The HB-JAIW05 isolate obtained in the present study was composed of 3215 nucleotides and had the highest similarity of 99.7% with the reported genotype H HBV isolate recovered from a Japanese blood donor. The HB-JAIW05 isolate had neither precore (A1896) nor core promoter (T1762/A1764) mutations. However, upon comparison with the consensus sequence of ten reported HBV isolates of the same genotype, the HB-JAIW05 isolate had 17 nucleotide substitutions including five missense mutations in the P gene, which may be related to vigorous replication of HBV in this case. He had no history of traveling abroad, but had had extramarital sexual contact with two Japanese women living in Iwate, Japan, 2 weeks and 2 months before the disease onset, respectively. Our results suggest that rare HBV genotypes such as H may be spreading in Japan via sexual contact. Further molecular epidemiological studies on HBV to clarify the exact changing profiles of de novo HBV infection in Japan in relation to genotype and genomic variability are warranted.

Epidemiological and clinical study of sporadic acute hepatitis E caused by indigenous strains of hepatitis E virus in Japan compared with acute hepatitis A.

BACKGROUND: We compared acute hepatitis E (AH-E) and acute hepatitis A (AH-A) to investigate the epidemiology, clinical features, and prognosis of AH-E caused by an indigenous hepatitis E virus (HEV) in Japan. METHODS: We enrolled 58 patients diagnosed with AH-A or AH-E (32 men and 26 women; age, 20-72 years) from December 1997 to October 2002. Phylogenetic analysis of the partial 412-nucleotide sequence of open reading frame (ORF) 2 was performed in patients with AH-E. RESULTS: Regarding the geographic distribution of the HEV genotype, genotype III was principally distributed in Honshu Island, and genotype IV in Hokkaido Island ( P = 0.0034). The phylogenetic analysis of the ORF2 region revealed that there were significant geographic differences in the distribution of the HEV strains in Japan, with some strains being widespread and some, localized. In comparison with AH-A patients, those with AH-E were older (56.1 +/- 10.6 vs 45.9 +/- 10.8 years; P = 0.0017). The proportion of males among patients with AH-E was significantly higher ( P = 0.0001). Pyrexia was often observed in AH-A, and malaise in AH-E. Laboratory data indicate that AH-E induces a weak immunological reaction, whereas jaundice appears earlier in AH-E than in AH-A. One patient with AH-E died of acute hepatic failure, but none of those with AH-A died during the study period. CONCLUSIONS: Our results suggest that there are geographical differences between HEV strains in Japan, and that AH-E is more common in males and older patients than AH-A. Laboratory data indicate a weak immunological reaction and early appearance of jaundice in AH-E.