Drug-induced lymphocyte stimulation test (DLST) is used for diagnosis of drug induced liver injury (DILI) in Japan. However, it is difficult to interpret the results of single DLST because of low sensitivity and high false positivity. We analyzed eight subjects tested DLST twice from 330 subjects tested DLST from 2009 to 2015 in our hospital.

Twenty-six drugs were applied to DLST. The median interval between first and second DLST was 82 (27-247) days. In second DLST, three drugs (11.5%) turned to be positive, and stimulation index (S.I.) markedly increased in six drugs (23%). On the other hand, S.I. decreased in eight drugs (30.7%). The first DLST demonstrated sensitivity 53.9%, specificity 58.3%, positive predictive value (PPV) 58.3%, and negative predictive value (NPV) 57.1%. The second DLST demonstrated sensitivity 87.5%, specificity 72.2%, PPV 58.3%, and NPV 92.9%. The second DLST improved sensitivity, specificity and NPV.

A 63-year-old man with previous HBV infection was followed up for hypertension, hyperlipidemia and diabetes. He was detected a hepatic tumor by abdominal ultrasonography. A laboratory examination showed the elevated levels of ALT of 43 U/l and tumor marker showed no abnormal findings. CT and MRI scan with contrast media revealed liver tumor and we diagnosed with hepatocellular carcinoma. Hepatic resection of segment 6 was performed and another 4 mm tumor was found by accident near liver tumor detected before the operation. Microscopic examination of the 4 mm tumor was suspicious of infiltration by parasites and the final diagnosis with real-time PCR method was hepatic anisakiasis by Anisakis pegreffii. Hepatic anisakiasis should be considered as a possible diagnosis in patients with hypovascular liver tumor located in the surface of hepatic lobes.

A 71-year-old man without a history of heavy drinking was referred to our hospital for anti-viral treatment against chronic hepatitis C with genotype 1 virus infection, and the therapy with ledipasvir and sofosbuvir was started. Five days after the start of the therapy, he drank approximately 1500 ml of beer. In the early morning of the next day, he suffered high fever and arrhythmia. Elevation of WBC with neutrophilia and slight elevation of CRP were observed without deterioration of liver function tests. Symptoms of high fever and arrhythmia disappeared within one day. The therapy was continued for 12 weeks, and sustained virologic response at 12 week from the end of treatment (SVR12) was achieved. Mechanism of high fever and arrhythmia could not be determined, however, there is a possibility that alcohol intake under the treatment of ledipasvir and sofosbuvir may have some relation with these symptoms.

An 80-year-old female with an asymptomatic, 15-cm diameter, giant simple liver cyst had bruised the right side of her body. Computed tomography performed for her abdominal distension revealed the ruptured liver cyst and ascites. Four days later, this patient was admitted for worsening anemia. Paracentesis showed bloody ascites, and we determined that the bleeding was from the ruptured cyst. Hepatic angiography revealed no extravasation, but stains in the periphery of the right anterior segmental artery and right posterior superior segmental branch were thought to be the bleeding points. Transcatheter arterial embolization (TAE) of those branches was subsequently performed, and the anemia improved. Furthermore, the patency of the large hiatus of the cyst, which had an effect similar to a fenestration for a giant liver cyst, might have decreased the size of the liver cyst. This case indicated that TAE is a nonoperative management option for bleeding from ruptured liver cysts.

A case was 64-year-old Japanese women who was started combined administration of daclatasvir and asunaprevir for the treatment of chronic hepatitis C from February 2015. Although development of fever and elevated level of lactate dehydrogenase were observed approximately 17 days after the start of treatment, administration of daclatasvir and asunaprevir was continued with careful observation. However, she was admitted to the hospital for detailed examination 21 days after the start of treatment, because of being suffered from hyposthenia and of being suspected as having rhabdomyolysis. Administration of both daclatasvir and asunaprevir was discontinued and treatment for rhabdomyolysis with rehydration was started immediately. Afterward, findings of blood examination and subjective symptoms were improved. Moreover, negative of HCV RNA continued and sustained virological response was obtained, in spite of discontinuation of administration of daclatasvir and asunaprevir.

We describe a 92-year-old man who developed acute hepatitis E living in the mountains in Tottori, Japan. He had no history of travel abroad and blood transfusion as well as consumption of animal meat/viscera and raw seafood within three months before the disease onset. However, he had a peculiar habit of drinking diluted bile of dried gall bladders obtained from wild boars. Although leftover bile suspensions were not available, seven (39%) of the 18 stored gall bladders had detectable hepatitis E virus (HEV) RNA at the viral load of up to 4.6×10⁵ copies/ml in 10% bile suspension. The wild boar HEV isolates shared 99.0-99.8% nucleotide sequence identities with a subgenotype 3a HEV strain recovered from the index patient. These results suggest that dried gall bladders obtained from HEV-infected wild boars may have been a source of HEV infection in this patient.

We experienced a case of acute hepatitis E who developed persistent jaundice for as long as six months. The phylogenetic tree analysis indicated that the hepatitis E virus (HEV) isolate obtained from the patient lived in Gifu was included in the HEV subtype 3f (HEV-3f) cluster and the isolate clustered with two HEV-3f isolates previously reported in Japan. Interestingly, our patient and the two others had no history of travel abroad, e.g. to Europa, where HEV-3f strains are endemic. The source and the route of the HEV-3f infection are unknown and the specific symptoms of HEV-3f infection are not well-known in Japan, either. We should reveal the characteristics of HEV-3f infection in Japan by accumulating cases.