Hisato Jomura

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Nonalcoholic steatohepatitis/nonalcoholic fatty liver disease is considered to be a hepatic manifestation of various metabolic disorders. However, its precise pathogenic mechanism is obscure. Oxidative stress and consequent lipid peroxidation seem to play a pivotal role in disease progression. In this study, we analyzed the localization of oxidized phosphatidylcholine (oxPC), a lipid peroxide that serves as a ligand for scavenger receptors, in livers of patients with this steatotic disorder. Specimens of non‐alcoholic fatty liver disease (15 autopsy livers with simple steatosis and 32 biopsy livers with steatohepatitis) were examined via immunohistochemistry and immunoelectron microscopy using a specific antibody against oxPC. In addition, scavenger receptor expression, hepatocyte apoptosis, iron deposition, and inflammatory cell infiltration in the diseased livers were also assessed. Oxidized phosphatidylcholine was mainly localized to steatotic hepatocytes and some macrophages/Kupffer cells. A few degenerative or apoptotic hepatocytes were also positive for oxPC. Immunoelectron microscopy showed oxPC localized to cytoplasmic/intracytoplasmic membranes including lipid droplets. Steatotic livers showed enhanced expression of scavenger receptors. The number of oxPC cells was correlated with disease severity and the number of myeloperoxidase‐positive neutrophils, but not with the degree of iron deposition. In conclusion, distinct localization of oxPC in liver tissues suggest that neutrophil myeloperoxidase‐derived oxidative stress may be crucial in the formation of oxPC and the progression of steatotic liver disease. (HEPATOLOGY 2006;43:506–514.)

Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors

We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma.FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV.The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the α-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC.

Interferon-β plus ribavirin for patients with hepatitis C virus genotype 1: a randomised pilot trial

The rate of sustained eradication of hepatitis C virus (HCV) in response to a combination of interferon-α and ribavirin remains unsatisfactory in patients with genotype 1 infection.1 No effective alternative treatment is currently available for non-responders. Interferon-β is also a type I interferon commonly used to treat chronic HCV infection in Japan. A previous study showed that a 24 week course of therapy with interferon-β plus ribavirin resulted in sustained loss of HCV in three of nine patients with chronic hepatitis C.2 However, the efficacy and safety of interferon-β combined with ribavirin has yet to be fully evaluated. We report the results of a randomised pilot trial comparing interferon-β plus ribavirin with interferon-α plus ribavirin in patients with HCV genotype 1 who poorly responded to interferon-α plus ribavirin. A total of 28 patients with HCV genotype 1 were given 6 MU of recombinant interferon-α2b (Schering-Plough, Kenilworth, New Jersey, USA) by intramuscular injection …

Two cases of focal nodular hyperplasia of the liver : Value of scintigraphy with Tc-99m GSA and positron emission tomography with FDG

Focal nodular hyperplasia (FNH) of the liver is relatively rare, and can be difficult to differentiate from other benign tumors arising in the liver. We describe a 23-year-old woman and a 25-year-old man with FNH. They were hospitalized for further evaluation of a space-occupying lesion in the liver. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) revealed increased radioactivity in the tumor in one patient and radioactivity similar to that in the normal part of liver in the other. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed uptake similar to that of the normal liver in both patients. FNH was diagnosed on the basis of angiographic findings and histological findings in liver biopsy specimens. Our results show that scintigraphy with Tc-99m GSA and FDG-PET may provide information helpful in the diagnosis of FNH.

Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C

Purpose. Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention. Methods. The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-α or 10 MIU of recombinant human IFN-α 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy. Results. Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 × 104/mm2 in the group with hemorrhage and 16.6 × 104/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 × 104/mm3 in the group with hemorrhage and 9.5 × 104/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 × 104/mm3 in the group with cotton-wool spots and 9.7 × 104/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036). Conclusions. Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C.

Hepatocellular carcinoma monitored by F-18 fluorodeoxyglucose positron emission tomography after laparoscopic microwave coagulation therapy

A 46-year-old woman was hospitalized for treatment of hepatocellular carcinoma. On admission, positron emission tomography with F-18 fluorodeoxyglucose (FDG PET) showed a hot spot that coincided with the tumor; its standardized uptake value (SUV) was 5.47. Two weeks and 6 months after laparoscopic microwave coagulation therapy, FDG PET showed a reduction in radioactive uptake to less than the background level, and the SUVs were 0.46 and 0.50, respectively. FDG PET performed 18 months after treatment showed a hot spot on the abdominal side of the site treated previously, and the SUV was 3.19. However, CT and MRI showed no evidence of recurrence. Our findings indicate that FDG PET is useful for evaluating the response to treatment and disease recurrence in patients with hepatocellular carcinoma.

Combined hepatocellular carcinoma and cholangiocarcinoma with high F-18 fluorodeoxyglucose positron emission tomographic uptake

A 34-year-old woman was hospitalized for further evaluation of a space-occupying lesion in the liver. Ga-67 SPECT showed increased accumulation of isotope in the tumor periphery. Fluorine-18 Fluorodeoxygluclose (F-18 FDG) positron emission tomography (PET) revealed a ring-like accumulation of isotop

Optimal duration of additional therapy after biochemical and virological responses to lamivudine in patients with HBeAg-negative chronic hepatitis B: a randomized trial.

Aim:  The endpoint of treatment with nucleoside analogs remains unclear for patients with hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B. We report the results of a randomized trial to determine the optimal duration of additional therapy after response to lamivudine in HBeAg‐negative patients.

Hepatitis C virus relapse was suppressed by long-term self-injection of low-dose interferon in patients with chronic hepatitis C after pegylated interferon plus ribavirin treatment.

The recommended treatment for chronic hepatitis C is a combination of pegylated interferon (PEG IFN) plus ribavirin (RBV). However, the sustained virological response (SVR) rate of PEG IFN‐RBV therapy was approximately 50% in patients with genotype 1b and a high viral load. Thus, we compared the efficiencies and side‐effects of PEG IFN‐RBV and self‐injected low‐dose natural (n) IFN‐α in patients with hepatitis C virus (HCV).