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A 70-year-old woman was admitted to our hospital on suspicion of liver tumor on regular abdominal ultrasonography. The abdominal ultrasonography identified a solitary, low-echoic lesion measuring 17mm in diameter in S7. This lesion was not enhanced in any phase of contrast-enhanced computed tomography (CT), and thus we performed a liver biopsy. Histopathological examination revealed a caseating granuloma. The chest CT showed pulmonary nodules, and Mycobacterium intracellulare was cultured from the bronchoalveolar lavage fluid. We diagnosed the individual with a Mycobacterium avium complex infection, and suspected that this was the cause of the solitary liver lesion.

Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. [ABSTRACT FROM AUTHOR]

Sakamoto S, Kasahara M, Fukuda A, Tanaka H, Kakiuchi T, Karaki C, Kanazawa H, Kamei K, Ito S, Nakazawa A. Pediatric liver-kidney transplantation for hepatorenal fibrocystic disease from a living donor. Pediatr Transplantation 2012: 16: 99-102. © 2011 John Wiley & Sons A/S. Abstract: The indications for and the timing of LT and/or KT for the patients with HRFCD are based on the severity of liver and kidney involvement. Most organs come from living donors, because the number of deceased donors is extremely low in Japan. Therefore, patients with HRFCD may need two organs from living donors. Four patients with HRFCD underwent living donor LT and KT from a single donor. The type of transplantation included combined LKT in one case, sequential LKT in two cases, and sequential KLT in one case. Although the case of combined LKT died because of sepsis, the other cases were doing well. Sequential LKT was successfully performed at the proper timing for each transplant; however, both of the donors suffered from a gastroduodenal ulcer after liver donation because of the psychological burden related to the relatively short period between two donations. In conclusion, living donation for LKT with cautious surgical procedures is not harmful for donors and recipients. However, changes in the allocation system established for deceased donors for HRFCD should be considered to avoid the need for two organ donations from the same living donor. [ABSTRACT FROM AUTHOR]

To clarify the impact of visceral fat on chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and hepatitis C, we investigated the effects of lifestyle modifications on the amount of visceral fat, liver biochemistry and serum ferritin levels in patients with liver disease. Eighty-two patients (NAFLD, n = 37; hepatitis C, n = 45) were advised to adopt lifestyle modifications, including dietary changes and exercise, and these were maintained for 6 months. Bodyweight, percentage of body fat, visceral fat area (VFA) and serum alanine aminotransferase (ALT) and ferritin were measured before and after intervention. In NAFLD, the mean VFA of 134.5 cm was significantly reduced to 125.3 cm after 6 months ( P < 0.001). ALT levels improved significantly between the values measured before and after intervention ( P = 0.039). The VFA prior to intervention was 100 cm in hepatitis C patients and it was reduced significantly after 6 months to 95.6 cm ( P < 0.001). ALT levels also improved significantly in the hepatitis C patients ( P < 0.001). The serum ferritin levels also reduced in these patients. Improvements in serum ALT and ferritin levels correlated with the amount of visceral fat reduction in both groups ( P = 0.046, P = 0.008, respectively). These findings demonstrate that restriction of calorie and iron intake results in reduction of visceral fat, liver enzymes and ferritin in patients with chronic liver disease. Visceral fat may be a central target for future interventions, not only in NAFLD but also in hepatitis C. [ABSTRACT FROM AUTHOR]

Aims: Ascites, which often complicates liver cirrhosis, is reported to be a factor that worsens the outcome. The aims of this study were to quantify body water compartment changes in cirrhotic patients, with and without ascites, and to elucidate the value of body water analysis for predicting the development of ascites. Methods: A total of 109 cirrhotic patients, with and without ascites, and 65 controls were studied. Intra- and extracellular water (ECW) in the whole body and in the arm, leg and trunk were measured using the recently developed 8-electrodes multiple-frequency bioelectrical impedance analyzer. Furthermore, patients without ascites were followed to an episode of ascites or death. Results: Patients with liver cirrhosis had significantly higher ECW ratios than controls. ECW ratios were increased in cirrhotic patients with moderate and severe disease. The ECW ratio of the trunk showed highly significant changes in cirrhotic patients with ascites. The ECW ratio correlated with age, serum albumin, and prothrombin time. A relative expansion of ECW and low albumin were predictive of further episodes of ascites (log-rank 6.94, P < 0.01). In multivariate analysis, the ECW ratio was independently associated with the development of ascites. Conclusion: Liver cirrhosis was characterized by a redistribution of body water. The ECW ratio is a reliable tool for quantification of redistribution of body water and can predict the development of ascites. [ABSTRACT FROM AUTHOR]

The serial transverse enteroplasty (STEP) procedure is a safe and successful way to lengthen the small bowel in patients with short bowel syndrome. However, postoperative dilatation of the intestine may occur, which induces bacterial overgrowth and malabsorption leading to liver failure. We describe the case of an infant boy with short bowel syndrome caused by jejunal atresia requiring the STEP procedure twice. The first STEP improved the liver function, and the second STEP allowed 80% of the total calorie intake to be tolerated enterally. One should not hesitate to perform a second STEP if after the initial bowel lengthening procedure the patient develops small bowel dilatation that interferes with enteral nutrition. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to determine the clinical relevance of hepcidin, a recently identified key iron regulatory hormone, in patients with chronic hepatitis C virus (C-HCV). Methods: Serum hepcidin levels were measured in 9 C-HCV patients by surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS), and compared to those of healthy controls. Sequential changes of hepcidin were also investigated during phlebotomy. Results: Serum hepcidin and ferritin were significantly higher in C-HCV than in controls ( P = 0.0002), these two variables were strongly related to each other ( r = 0.658; P < 0.01), and phlebotomy significantly decreased serum hepcidin in C-HCV ( P = 0.0007); all these results recollect the hepcidin response to iron signal. Hepcidin/ferritin ratio, an index of the appropriateness of hepcidin expression relative to iron overload, was significantly lower in C-HCV than in controls (0.33 ± 0.41 vs. 0.73 ± 0.36, P = 0.0068). This relative impairment of hepcidin expression was not reversible after phlebotomy ( P = NS). Conclusions: Although the hepcidin expression responds to iron conditions in C-HCV, this response is relatively limited. This relative impairment of hepcidin expression may be relevant to disease progression, and thus correction of its regulation may be beneficial for these iron-overloaded C-HCV patients. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (HE) is associated with poorer quality of life and increased work disability. Recently, low-grade cerebral edema has been implicated in chronic liver disease. METHODS: We measured the apparent diffusion coefficient (ADC) of water in various regions of the brains of patients with cirrhosis, and elucidated the significance of the evaluation of ADC in quantifying low-grade HE and predicting overt HE and survival. Forty patients with cirrhosis and 24 controls underwent diffusion-weighted imaging, and patients were followed up every month. RESULTS: The mean ADC values were increased in cirrhotic patients with minimal HE versus no HE or controls. Minimal HE patients separated from no HE patients with a sensitivity of 70∼90% and a specificity of 85∼90%. ADC values correlated with individual neuropsychological tests. ADC values of white matter, such as the frontal (log-rank test 4.35, P < 0.05) and parietal (log-rank test 5.98, P < 0.05) white matter, was predictive of further bouts of overt HE. CONCLUSIONS: ADC is a reliable tool for quantification of low-grade HE, and could predict the development of overt HE. [ABSTRACT FROM AUTHOR]

We performed indirect immunogold electron microscopy (EM) for immunological identification and characterization of hepatitis C virus (HCV). To clarify the morphology of HCV, an indirect immunogold EM of two plasma samples from patients with high HCV RNA titers was carried out using antibodies specific for the putative HCV envelope protein (E) 1. Spherical virus particles 55–65 nm in diameter with delicate spike projections were detected in the 1.14–1.16 g/ml fractions after sucrose density gradient centrifugation. Polyclonal and monoclonal antibodies to the putative HCV E1 specifically recognized these particles. In addition, immunogold EM of the samples was also performed to uncover the morphology of HCV core particles. Spherical particles 33–40 nm in diameter (average, 37 nm) were detected in the 1.22- to 1.25-g/ml fractions by conventional EM after sucrose density gradient centrifugation. Immunogold EM using rabbit polyclonal antibody (RR8) specific for the putative HCV core protein and colloidal gold-labeled goat antirabbit IgG showed binding of the gold particles with RR8. Some of the HCV core particles showed icosahedric morphology. Optical rotation technique showed that the HCV core particles exhibit sixfold symmetry and that the length of the regular hexagon side is approximately 20 nm, suggesting that they have an icosahedric structure. Further, the detection limit of the indirect immunogold EM was evaluated in 11 plasma samples from chronic hepatitis B patients with different degrees of hepatitis B virus (HBV) DNA titers using antihepatitis B surface antigen antibody. The study showed that the detection limit of virus using this method is 107 virions/ml. [ABSTRACT FROM AUTHOR]

It has been reported that histological activity index and piecemeal necrosis are good factors to evaluate the prognosis in patients with chronic hepatitis C (CHC). Thus, there is a need for simple and noninvasive means to assess disease activity and piecemeal necrosis in patients with CHC. In this study, we measured the serum concentrations of large splice variants of tenascin-C (cTN-C) in patients with CHC, and examined their correlation with the degree of inflammatory activity and fibrosis as evaluated in liver biopsy specimens. Methods: The serum levels of cTN-C in 150 patients with CHC and 50 healthy volunteers were measured by enzyme-linked immunosorbent. The histology of liver biopsy specimens was also evaluated following the Desmet's grading/staging system and the Ishak's classification. Liver specimens obtained by biopsy were also immunohistochemically evaluated with anti-human tenascin-C antibodies. Results: Serum cTN-C concentrations were significantly higher in CHC patients than in healthy volunteers ( P<0.0001). The levels of cTN-C showed no significant difference among the fibrosis stages as assessed by the Desmet's grading/staging system and Ishak's classification scores. However, the concentration of cTN-C was significantly correlated with the grade of activity. According to the Ishak's classification, the concentration of cTN-C was increased in proportion to the degree of piecemeal necrosis. Specific immunostaining of cTN-C was observed in limited areas of piecemeal necrosis but not in fibrotic areas. Conclusion: The measurement of serum levels of cTN-C is a useful marker of the activity of CHC, in particular of the degree of piecemeal necrosis. [ABSTRACT FROM AUTHOR]

Iron accumulation has been reported to be associated with progression of liver injury. The mechanism of iron accumulation in the liver is not known. In the present study, hepatic messenger RNA (mRNA) expression oftransferrin receptor(TfR)1,TfR2, andferroportin(FP)1was measured in patients with chronic hepatitis (CH).Eleven patients with CH-B and 43 patients with CH-C were enrolled. All patients underwent liver biopsy. Hepatic expression ofTfR1,TfR2andFP1mRNA was analyzed using a real-time polymerase chain reaction. Total hepatic iron score (THIS) was evaluated by Prussian blue staining.Serum ferritin concentration is significantly higher in CH-C than in CH-B. Values of THIS of≥5 were observed only in CH-C patients (44% of CH-C patients). The expression level ofTfR2mRNA was 10–26-fold higher than theTfR1mRNA expression level. TheTfR2andFP1mRNA expression was significantly higher in CH-C than in CH-B patients. Hepatic expression ofTfR2andFP1mRNA was well correlated with THIS.Hepatic iron accumulation is more severe in patients with CH-C. Upregulation of hepatic iron transporters may contribute to the hepatic iron accumulation in CH-C. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Iron reduction therapy by phlebotomy reduces lipid peroxidation and oxidative stress in patients with chronic hepatitis C" in the previous issue of "Journal of Gastroenterology."

Background/Aims: Earlier studies have suggested involvement of tenascin-C (TN-C) in liver fibrosis. Here, we examined expression of TN-C variants and types of alternatively spliced fibronectin-type III (FNIII) repeats in chronic hepatitis. Methods: Using three monoclonal antibodies against TN-C variants, immunohistochemical staining was performed and the correlation with histological parameters of chronic hepatitis C was examined. The cellular source was also determined and variant expression and their types were tested using isolated rat hepatic stellate cells (HSCs), liver myofibroblasts, and/or LI90 cells. Results: Large variants were not expressed in normal liver, but were up-regulated in chronic hepatitis, especially at sites of interface hepatitis and confluent necrosis, showing stronger correlations between staining intensity and these than with other parameters or fibrosis. TN-C deposition was closely correlated with increase in the number of α-smooth muscle actin-positive cells, i.e. activated HSCs/myofibroblasts, and in situ hybridization showed TN-C mRNA signals in the cells. Activated HSCs and myofibroblasts in culture highly expressed large variants of TN-C. In LI90 cells, sequencing of large variants revealed that the FNIII repeats D and A1/A4, followed by B, were preferentially included. Conclusions: TN-C and its variants are produced by HSCs/myofibroblasts, suggesting important roles in liver fibrogenesis. [Copyright &y& Elsevier]

Background/Aims: Nucleic acid damage by reactive nitrogen and oxygen species may contribute to inflammation-related carcinogenesis. To investigate the extent of nucleic acid damage in hepatitis C virus infection and its change after interferon treatment, we measured 8-nitroguanine and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the liver of patients with chronic hepatitis C (CHC) before and after interferon therapy. Methods: Hepatic accumulation of 8-nitroguanine and 8-OHdG was immunohistochemically evaluated in 20 CHC patients and 7 control patients with non-alcoholic fatty liver. Results: Immunoreactivities of 8-nitroguanine and 8-OHdG were strongly detected in the liver from patients with CHC, but not in control livers. 8-Nitroguanine accumulation was found not only in infiltrating inflammatory cells, but also hepatocytes particularly in the periportal area. The accumulation of 8-nitroguanine and 8-OHdG increased with inflammatory grade (8-nitroguanine; P=0.0019, 8-OHdG; P=0.0009). In the sustained virological responder group after interferon therapy, 8-nitroguanine and 8-OHdG accumulation were markedly decreased in the liver (8-nitroguanine; P=0.018, 8-OHdG; P=0.018). Conclusions: In this study, we demonstrated for the first time that 8-nitroguanine accumulated in the liver of patients with CHC. 8-Nitroguanine is a useful biomarker to evaluate the severity of HCV-induced chronic inflammation in relation to hepatocellular carcinoma. [Copyright &y& Elsevier]