Hypophosphatemia in patients with hepatitis B virus infection undergoing long-term adefovir dipivoxil therapy.

AIM: The purpose of this study was to clarify the frequency of hypophosphatemia and other clinical features in patients with hepatitis B undergoing long-term therapy with adefovir dipivoxil (ADF). METHODS: Seventeen hepatitis B patients treated with a combination of lamivudine and ADF were analyzed. They were divided into two groups: patients who developed hypophosphatemia (P < 2.5 mg/dL) (group A) and those who did not (group B). The frequency of hypophosphatemia and other clinical features were retrospectively analyzed. RESULTS: There were six patients (35.3%) in group A. The treatment period was 57.3 ± 15.6 and 61.8 ± 25.7 months in groups A and B, respectively. No differences were found between the groups prior to treatment. Among the six patients in group A, osteomalacia was observed in two, while a pathological fracture of the scapula was found in one. Decreases in phosphate (96 weeks after starting ADF), estimated glomerular filtration rate (eGFR) (48 weeks) and uric acid (24 weeks) levels, and increases in creatinine and alkaline phosphatase were noted in group A. CONCLUSION: Hypophosphatemia occurred in 35% of the patients under the long-term treatment with ADF. Although it was not possible to predict the decrease in phosphate before ADF therapy, decreases in uric acid and eGFR may be the early events relating to low phosphatemia.

Real-time tissue elastography: non-invasive evaluation of liver fibrosis in chronic liver disease due to HCV.

BACKGROUND/AIMS: We evaluated the diagnostic efficacy for advanced fibrosis of real-time tissue elastography (RTE), is a newly introduced non-invasive method, in hepatitis C virus (HCV) patients. METHODOLOGY: Sixty-six chronic liver diseases with HCV (CLD-HCV) were evaluated by RTE, FIB-4, and APRI, as well as biopsy or hepatectomy findings. Seventeen healthy volunteers, and 1 with elevation of transaminase and 5 with liver tumors within their normal liver were enrolled for normal controls. Severe fibrosis was defined as METAVIR score 3 or 4. The tissue elasticity value was expressed by LF-index created by the program incorporated in the ultrasound device. The percentage of fibrosis area in each specimen (%FA) was determined with a personal computer. A receiver operating characteristic curve (ROC) was calculated for each non-invasive method of estimation of fibrosis. RESULTS: The values for the area under the ROC for LF-index, APRI, and FIB-4 were 0.88, 0.81, and 0.84, respectively. Accuracy, sensitivity, and specificity for prediction of LF-index (>2.8) for severe fibrosis were 86.5%, 78.6%, and 93.6%, respectively, which were better than those of FIB-4 and APRI. LF-index showed a good relationship to %FA (r=0.276, P=0.020). CONCLUSION: RTE is an effective method for predicting severe fibrosis in CLD-HCV.

Importance of screening for synchronous malignant neoplasms in patients with hepatocellular carcinoma: impact of FDG PET/CT.

BACKGROUND & AIM: Synchronous neoplasms (SNs) are occasionally found in hepatocellular carcinoma (HCC). We examined such cases and the efficacy of 18-fluoro-2-deoxyglucose positron-emission tomography computed tomography (PET/CT), retrospectively. MATERIALS AND METHODS: We investigated 687 naïve HCC, who were admitted to our hospitals, encountered from October 2006 to December 2010 and evaluated the clinical backgrounds. All study protocols, was approved by our Institutional Ethics Committee. The usefulness of detecting SNs by PET/CT was evaluated in 234 patients who underwent PET/CT (PET group) and in 453 (non-PET group) examined in the same period. We noted the presence of SNs, defined as primary extrahepatic malignant neoplasms within 1 year of diagnosis of HCC. RESULTS: SNs were observed in 48 of 687 patients (54 tumours, 7.0%). SNs were detected by PET/CT in 18, which was 7.7% of PET group. The detection rate for SNs, were increased to 11.1% (26/234) in PET group by using together with upper gastrointestinal endoscopy and routine enhanced CT for HCC, which was greater than that of non-PET group (22/453, 4.9%) (P < 0.001). CONCLUSION: SNs were pointed out more frequently in PET group than non-PET group (11.1% vs. 4.9%). FDG PET/CT can enhance the detection ability for SNs in naïve HCC.

Recent trends of Japanese hepatocellular carcinoma due to HCV in aging society.

BACKGROUND/AIMS: The mean age of hepatocellular carcinoma (HCC) patients has increased (=65 years old). We want to identify the recent trend of the clinical features of HCC patients due to hepatitis C virus (HCV) (HCV-HCC). METHODOLOGY: From 2000 to 2009, 855 naive HCC patients were admitted. HCV-HCC patients were divided into two groups, first period group (2000-04, n=270) and second period group (2005-09, n=343) and the clinical features of HCV-HCC were investigated. RESULTS: There was no difference in gender, TNM stage and percentages of HCV-HCC between the periods. On the other hand, the ratio of HCV-HCC patients with worse liver function (Child-Pugh B or C), elderly (=75 years old) and the population of patients treated with low invasive radiofrequency ablation were increased (30.0% to 42.0%, 17.2% to 35.8% and 25.1% to 36.2%, respectively; p<0.01). The 1y-, 3y- and 5y-survival rate of HCV-HCC did not show differences (82.1%, 60.5% and 44.7% vs. 81.8%, 56.9% and 37.7%, respectively; p=0.219). CONCLUSIONS: The ratio of aged HCV-HCC as well as HCV-HCC patients with worse liver function was increased. The less invasive treatment for HCC in these patients and the quick anti-viral treatment for HCV patients should be considered to avoid occurrence of HCC in Japan.

Hepatic resection assisted by ablative therapy for advanced hepatocellular carcinoma.

BACKGROUND/AIMS: We attempted combinations of resection and ablative therapies (ethanol injection (EI) or radiofrequency therapy (RFA)) in hepatocellular carcinoma (HCC) patients. METHODOLOGY: Thirty-one patients with naive HCC treated from January 2000 to June 2010 were enrolled. All were tumor node metastasis stage III and the number of tumors was countable (< or = 5). Twelve were treated with resection assisted with an ablative therapy (combination group) and 19 with resection only (resection group). Clinical backgrounds and prognosis were investigated. RESULTS: The total scores for up-to-seven criteria were larger in the combination group than in the resection group (p=0.01), while other clinical background findings were not significantly different between the groups. In the combination group, 10 cases underwent resection combined with RFA and 2 with EI. The 1- and 3-year survival rates were not significantly different between the groups (combination group, 88.2% and 88.2%, respectively; resection group, 90.9% and 80.8%, respectively). There were no severe complications. CONCLUSION: Our results indicate that combination therapy is a therapeutic option for cases with countable HCCs who are difficult to treat by resection only.

Diagnostic value of sonazoid for hepatic metastasis: comparison with FDG PET/CT.

BACKGROUND/AIMS: This study was conducted to evaluate the diagnostic efficacy of contrast enhanced ultrasonography (CEUS) with perflubutane (Sonazoid) for hepatic metastasis and compared it with that of 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT). METHODOLOGY: From January 2007 to July 2009, 109 Japanese patients with gastrointestinal tract cancer were enrolled, of whom 4 had esophageal cancer, 28 gastric cancer, 1 duodenal cancer, and 76 colorectal cancer. After a bolus injection with Sonazoid (0.5 ml/body), the liver was scanned in both arterial and Kupffer phases. The results of PET/CT and other abdominal imaging examinations were not shown to the CEUS operators. We compared diagnostic efficacy between CEUS and PET/CT. RESULTS: Average values for age, body mass index, and maximum diameter of the hepatic metastasis were 68.7 +/- 11.0 years, 21.2 +/- 4.2, and 29.2 +/- 20.5mm, respectively. Hepatic metastasis were suspected in 31 patients based on PET/CT findings and 32 by CEUS. Finally, hepatic metastasis was diagnosed in 30 patients. The sensitivity, specificity, and accuracy rates for CEUS and PET/CT were similar (100% vs. 100%, 97.5% vs. 98.7%, and 95.5% vs. 93.6%, respectively). CONCLUSION: CEUS had a diagnostic value similar to that of PET/CT for hepatic metastasis.

Hepatitis B virus reactivation induced by infliximab administration in a patient with Crohn's disease.

A 47-year-old man diagnosed with Crohn's disease was treated with infliximab. He tested negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) but positive for anti-HB core antibody (anti-HBc). He tested positive for hepatitis B virus (HBV-) DNA 3 months after treatment and was administered entecavir. HBV-DNA test showed negative results 1 month later. ALT was persistently within the normal range, and HBV-DNA was persistently negative thereafter despite the continuation of infliximab every 8 weeks. In our hospital, 14 patients with inflammatory bowel disease, who tested negative for HBsAg, were treated with infliximab; 2 of them tested positive for anti-HBs and/or anti-HBc, and HBV reactivation was observed in 1 patient (the present patient). The present case and these findings highlight that careful follow-up is needed in patients with inflammatory bowel disease treated with infliximab who test positive for anti-HBc and/or anti-HBs.

Colonic intussusception caused by anisakiasis: a case report and review of the literature.

A 67-year-old woman presented with periumbilical pain. Contrast-enhanced computed tomography findings indicated intussusception of the ascending colon without ischemia or necrosis, and we performed successful colonoscopy to treat the condition. Furthermore, an edematous area caused by anisakis was detected in the ascending colon and the anisakis was removed. The patient noted that she had eaten raw fish one day before the symptoms developed. Although colonic intussusception caused by anisakiasis is extremely rare, colonoscopy should be performed in colonic intussusception patients suspected of having anisakiasis in order to avoid invasive resection.

An adult patient with acute infection with hepatitis B virus genotype C that progressed to chronic infection.

In 2008, a 28-year-old woman consulted our hospital due to general fatigue. Her ALT level was within normal range but she was positive for hepatitis B surface antigen (HBsAg). Her ALT level was nearly within normal range thereafter and she was consistently positive for HBeAg. Later, it was proven that she was negative for HBsAg in 1999. She had been a sex worker in 2007-2008. Complete genome sequencing revealed that her HBV was genotype C. The present case may indicate that it is possible for acute infection with HBV genotype C to progress to chronic infection in adults.

Huge pancreatic acinar cell carcinoma with high levels of AFP and fucosylated AFP (AFP-L3).

A 25-year-old Japanese woman with a large abdominal tumor (10 cm in diameter) and high level of serum alpha-fetoprotein (AFP, 1,222.4 ng/mL) was introduced and admitted to our hospital in January 2011. Pre-operative imaging modalities could not identify the tumor origin. There was no chronic hepatic viral disease, however, the elevated level of fucosylated AFP (87.8%) and connection with the left hepatic lobe led us to diagnose the tumor as a hepatocellular carcinoma. Surgical resection was performed in February. Histological findings revealed a pancreatic acinar cell carcinoma (ACC). Herein, we provide details of this difficulty to diagnose a case of ACC.

Clinical features and hepatitis B virus (HBV) genotypes in pregnant women chronically infected with HBV.

OBJECTIVE: The purpose of this study was to clarify the clinical features and hepatitis B virus (HBV) genotypes in pregnant women chronically infected with HBV. METHODS: Among 1,489 pregnant women who visited our hospital in 2010, 26 were positive for hepatitis B surface antigens (HBsAg). Of these subjects, 21 from whom informed consent was obtained were included in this study. The clinical features and HBV markers, including genotypes, were investigated. RESULTS: No adverse events were observed in the subjects or the neonates during pregnancy or the perinatal period. The HBV genotypes were C in 14 cases, D in six cases, and undetermined in one case. Hepatitis B e antigens and a high viral load (>7.0 log copies/mL) were found in four and six subjects with genotype C, respectively, and in none of subjects with genotype D. The alanine aminotransferase (ALT) levels and platelet counts were within the normal ranges during pregnancy in all subjects except two and three subjects with genotype C, respectively. Three subjects with genotype C showed transient elevations of ALT after delivery. CONCLUSION: The majority of subjects were anti-HBe-positive with normal ALT levels; however, some subjects with genotype C showed a high viral load, elevated ALT levels and/or low platelet counts. The pregnancies and deliveries were safe; however, transient elevations of ALT after delivery were observed in some subjects with genotype C.

Hepatocellular carcinoma in a case of Wilson's disease treated with radiofrequency ablation therapy.

A 37-year-old Japanese man was diagnosed with liver cirrhosis due to Wilson's disease in 2001 and treated with D-penicillamine. Thereafter, he was admitted to our hospital for further examination of a space occupying lesion in the liver. The patient was diagnosed with hepatocellular carcinoma (HCC) (7th segment, 2.5 cm in diameter) in May 2010 and treated with radiofrequency ablation therapy. Biopsy findings from a non-cancerous area revealed a fatty liver, though cirrhotic nodules were not found. Long-term treatment for Wilson's disease may improve hepatic fibrosis, and careful screening for HCC by abdominal imaging is needed in such cases.

Malignant pheochromocytoma with liver metastasis treated by transcatheter arterial chemo-embolization (TACE).

Multiple liver metastatic lesions were shown by computed tomography and scintigraphy with 123I- metaiodobenzylguanidine (MIBG) in a 76-year-old woman 2 years after resection of a pheochromocytoma of the right adrenal gland. Transcatheter arterial chemo-embolization (TACE) was performed for the liver metastasis, with blood pressure strictly controlled by administration of doxazosin and phentolamine for the prevention of hypertensive crisis after TACE. There were no severe adverse events associated with the treatment, and the number and size of the lesions were decreased. TACE with strict blood pressure control was an effective and safe therapy for multiple liver metastatic lesions related to malignant pheochromocytoma.

Amino acid imbalance in patients with chronic liver diseases.

AIM: The aim of this study is to clarify the amino acid imbalance in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). METHODS: We assayed total branched-chain amino acids (BCAA), tyrosine (Tyr) levels and their ratio (BTR) in sera of 101 patients with CH (37 in fibrosis stage F1, 23 in F2, 21 in F3) and 20 with LC (F4) who were diagnosed by liver biopsy. Their levels in relation to the staging of liver fibrosis were analyzed. RESULTS: The percentage of patients whose BTR was less than the normal range was 32.1% in CH and 75.0% in LC. The levels of BTR and BCAA were significantly lower (P < 0.001, P < 0.05, respectively) and that of Tyr was significantly higher (P < 0.001) in patients with LC than those in CH. The levels of BTR decreased according to the staging. The levels of Tyr increased according the staging, whereas the levels of BCAA deceased prominently in F4 (487 +/- 103 in F1, 483 +/- 122 in F2, 487 +/- 111 in F3 and 423 +/- 94 in F4). CONCLUSION: A considerable number of patients not only with LC but also with CH showed lower levels of BTR. It has been clarified that amino acid imbalance of Tyr was found in the early stage of liver disease, whereas decrease of BCAA was found mainly in F4 stage.