Takayoshi Oikawa

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 × 109 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.

Liver stiffness measured by acoustic radiation force impulse elastography reflects the severity of liver damage and prognosis in patients with acute liver failure

We measured liver stiffness (LS) in patients with acute liver failure (ALF) using acoustic radiation force impulse (ARFI) elastography and investigated the usefulness of measuring LS for predicting the prognosis of ALF patients.

Bimodal peaks of liver stiffness in a case of drug‐induced liver injury

A 69‐year‐old male complained of general fatigue and presented with elevation of liver enzymes without any cause of liver injury. We diagnosed him with hepatocellular drug‐induced liver injury (DILI). Liver stiffness, which was evaluated according to the shear wave velocity (SWV) using virtual touch tissue quantification, was serially observed during hospitalization. A fast SWV was noted on the date of admission, indicating a “hard” degree of liver stiffness. The SWV gradually decreased until the 20th hospital day. However, the patients liver enzymes again became elevated on the 20th hospital day, and the SWV simultaneously increased in association with a rise in the total bilirubin level. The laboratory data for the second peak of the SWV indicated mixed‐type DILI; therefore, the patients pathological state transitioned from the hepatocellular type to the mixed type. A liver biopsy performed before discharge revealed a state of recovery from acute inflammation without fibrotic changes. We conclude that the second peak of the SWV may be affected by the presence of intrahepatic cholestasis. We herein report the occurrence of bimodal peaks of liver stiffness in a patient with DILI. In such cases, each peak of liver stiffness may be the result of a different pathological mechanism, namely acute inflammation versus acute intrahepatic cholestasis. Although the detailed mechanisms underlying the development of liver stiffness due to intrahepatic cholestasis remain unclear, this case presented a limitation of virtual touch tissue quantification for evaluation of liver stiffness as fibrosis marker in the liver with intrahepatic cholestasis.

The impact of portal vein thrombosis on the prognosis and liver function of nonmalignant cirrhotic patients

Abstract Objectives: The clinical impact of portal vein thrombosis (PVT) in cirrhotic patients remains unclear. The aim of the study is whether recanalization of acute PVT in nonmalignant cirrhotic patients is associated with their prognosis. Materials and methods: We identified subject with PVT in cirrhotic patients from institutional database. Patients with ≥50% reduction in thrombus size were classified into the improved group and those with ≤49% reduction in thrombus size, or thrombus development in other branches were classified into the deteriorated group. We compared the cumulative survival rate, event-free survival rate (EFS), and liver function (albumin-to-bilirubin (ALBI) and model for end-stage liver disease XI (MELD-XI) between the two groups. Results: Twenty-seven patients were enrolled in this retrospective study. Sixteen patients were classified into the improved group, and 11 were classified into the deteriorated group. In the improved group, the ALBI grade and MELD-XI measured before the onset of PVT and at one year after the onset of PVT were not significantly different. In contrast, MELD-XI was significantly aggravated in deteriorated group (MELD-XI [p = .02]). The cumulative survival of the two groups did not differ significantly; however, the EFS of the deteriorated group was significantly lower (p = .049). Conclusions: Residual thrombosis of PVT in cirrhotic patients increased the incidence of liver-related events and was associated with the deterioration of the liver function.

Hepatic Angiomyolipoma Staining in the Post-vascular Phase of Contrast-enhanced Ultrasound Due to the Presence of Macrophages

A 47-year-old Japanese man was referred to hospital after the detection of a liver tumor. Dynamic computed tomography and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging were consistent with a diagnosis of hepatocellular carcinoma (HCC). No perfusion defect was observed in the post-vascular phase of contrast-enhanced ultrasound (CEUS). Histopathological staining of the tumor cells was positive for antibodies against HMB-45 and cluster of differentiation (CD) 68, confirming the diagnosis of hepatic angiomyolipoma (HAML). These findings indicated the presence of macrophages in HAML. We herein report a case of HAML explain how macrophages that are present within the tumor affect the staining characteristics in the post-vascular phase of CEUS.

P1-098The effectiveness of cisplatin eluting beads TACE for hepatocellular carcinoma

Results: RAS mutations testing of 32 mCRC pts were 15 RAS wild-type(wt) and 17 RAS mutant type(mt) (KRAS exon2 mt: other RAS mt 11:6). The proportion of Rigt side tumor location(cecumtransverse colon) was more in RAS mt(35.3%) than in RAS wt(20.0%).Medical condition of 32 pts was ’fit’condition of 27 pts (RAS wt:mt 14:13) and ’may be unfit’condition of 5 pts (RAS wt:mt 1:4) .Among 14 RAS wt and ’fit’condition pts, 7 pts who assign treatment goal to Cytoreduction were chosen Chemothrapy (CT) doublet plus anti-EGFR and 7 pts who assign treatment goal to Disease control were chosen CT doublet plus Bevacizumab(Bmab) as first-line CT. 13 RAS mt and ’fit’condition pts were all chosen CT doublet plus Bmab as first-line CT. Among 5 ’may be unfit’condition pts, 3 pts were chosen reduced CT doublet, 1 pts fluoropyrmidine(FP)þBmab and 1 pts FP as first-line CT. Regarding first Response Rate evaluation of First-line CT(except discontinued and not evaluated pts), RAS wt and ’fit’condition group was 66.7%, RAS mt and ’fit’condition group was 44.4%,and ’may be unfit’condition group was 25.0%. By undergoing first-lineCT, 4 ’fit’condition pts who assign treatment goal to Cytoreduction became possible for Conversion surgery(RAS wt:mt 3:1).

Predictive biomarkers for diagnosis of minimal hepatic encephalopathy in patients with liver cirrhosis: A preliminary result in a single center study in Japan

Aim: Minimal hepatic encephalopathy (MHE) in liver cirrhosis (LC) is a subclinical abnormality which is only detectable by neuropsychiatric and neurophysiological tests. Reliable predictive biomarkers for diagnosing MHE have not been confirmed. This study examined potential biomarkers to detect MHE in LC patients. Methods: We divided 35 outpatients with LC into two groups based on the presence of MHE according to the results of computer-aided neuropsychiatric testing using four psychometric tests. Differences in clinical and laboratory data were compared between the two groups, and predictive biomarkers for diagnosing MHE were determined using the logistic regression model. Results: The prevalence of MHE in LC was 28.6% (10/35). Clinical features involving Child-Pugh classification and the modified end-stage liver disease score showed no differences between the MHE-positive and MHE-negative patients. Among biochemical parameters, elevated plasma ammonia level (P=0.034), increased creatinine (P=0.008), and low estimated glomerular filtration rate (P=0.042) showed greater significance in MHE-positive patients compared with MHE-negative patients. However, univariate and multivariate analysis showed that ammonia level (odds ratio, 1.023 and 1.031, respectively; 95% confidence interval of coefficient estimate, 1.005-1.041 and 1.006-1.058, respectively) was the only significant independent predictor for the detection of MHE. Conclusion: Plasma ammonia level may be useful as a predictive biomarker to prediagnose the neuropsychiatric test-based diagnosis of MHE. Our results also reinforce previous findings on crucial roles for renal ammonia metabolism and urinary excretion in patients with LC. Correspondence to: Kazuyuki Suzuki, M.D., Ph.D., Department of Nutritional Science, Morioka University, Sunakomi 808, Takizawa, Iwate 020-0694, Japan, Tel: 081-19-688-5555, Fax: 081-19-688-5577; E-mail: kasuzuki@morioka-u.ac.jp

Hypothyroidism Enhanced Portal Hypertension in a Patient with Alcoholic Liver Cirrhosis, Resulting in the Development of Ascites.

A man diagnosed with alcoholic liver cirrhosis complained of abdominal distention due to massive ascites. The ascites did not resolve with diuretic agents. The serum-ascites albumin gradient value of 1.9 g/dL and the total protein level in the ascites of 3.1 g/dL indicated the ascites to have been caused by portal hypertension. Hypothyroidism was detected, and the patient received supplementation with levothyroxine. The ascites dramatically decreased after supplementation with levothyroxine. We herein conclude that the ascites in the present case had thus been strongly influenced by portal hypertension, which was induced by liver dysfunction associated with liver cirrhosis and hypothyroidism.