Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile d...Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role of Escherichia coli (E. coli, the most prevalent organism isolated in women with UTI) as a trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses implicating PBC-specific autoantigens and E. coli mimics have been clearly demonstrated, adding support to the notion that E. coli is a potential infectious inducer of PBC in susceptible individuals. One of the major limitations in proving the E. coli/PBC association was the lack of reliable E. coli-infected animal models of PBC. This review provides an overview of the evidence linking this infectious agent with PBC and discusses the pros and cons of a recently developed E. coli-infected animal model of PBC.
Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to...Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBeAg-positive, 26 HBeAg-negative, and 60 healthy control children. Results. Thirteen microRNAs showed aberrant plasma expressions in HBeAg-positive children and targeted liver-specific genes. In particular, three microRNAs were upregulated and one was downregulated in HBeAg-positive children compared to HBeAg-negative and healthy control children, which showed equal levels. Conclusion. The identified microRNAs might impact the progression of CHB in children. Functional studies are warranted, however, to elucidate the microRNAs' role in the immunopathogenesis of childhood CHB.
Miyamura T, Kanda T, Nakamoto S
… +12 more, Arai M, Nakamura M, Wu S, Jiang X, Sasaki R, Haga Y, Yasui S, Ooka Y, Chiba T, Imazeki F, Mikami S, Yokosuka O
Aim. Eradication of hepatitis C virus (HCV) is still challenging even if interferon- (IFN-) free regimens with direct-acting antiviral agents (DAAs) for HCV-infected individuals are available in clinical practice. IFNL4...Aim. Eradication of hepatitis C virus (HCV) is still challenging even if interferon- (IFN-) free regimens with direct-acting antiviral agents (DAAs) for HCV-infected individuals are available in clinical practice. IFNL4 is a newly described protein, associated with human antiviral defenses. We investigated whether IFNL4 ss469415590 variant has an effect on the prediction of treatment response in HCV-infected patients treated with IFN-including regimens. Patients and Methods. In all, 185 patients infected with HCV genotype 1 treated with peg-IFN plus ribavirin, with or without telaprevir, were genotyped for IFNL4 ss469415590. We retrospectively investigated whether the role of IFNL4 ss469415590 variant and other factors could predict sustained virological response (SVR) in Japanese patients infected with HCV genotype 1. Results. There were 65.7%, 31.5%, and 2.8% patients in the IFNL4 ss469415590 TT/TT, TT/-G, and -G/-G groups, respectively. SVR rates were 82.1% or 49.3% in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. IFNL4 ss469415590 variant and HCV viral loads or IFNL4 ss469415590 variant and early virological response were better predictors of SVR in patients treated with peg-IFN plus ribavirin with or without telaprevir, respectively. Conclusion. In the era of DAAs, measurement of IFNL4 ss469415590 variant could help the prediction of SVR in Japanese HCV genotype 1 infected individuals treated with IFN-including regimens.
Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or...Background and Aims. Minimal hepatic encephalopathy (MHE) is diagnosed using neuropsychometric tests or neurophysiological tests that are either inapplicable to illiterate patient population in resource-poor settings or require sophisticated and expensive equipment. The available tests assess discrete domains of mental impairment. Our aim was (a) to design a neuropsychometric test that measures all domains of mental impairment in MHE using one metric; (b) to evaluate its sensitivity, specificity, and reproducibility. Methods. The mind and liver test (MALT), a psychometric test assessing cognition, memory, and psychometric impairment, each on a scale of 20, was designed keeping in mind the requirements of a universal test. 40 cirrhotics and 36 controls were subjected to critical flicker frequency (CFF) and MALT in same sitting. ROC curve was plotted for MALT using CFF as gold standard. Bland-Altman plot was used to find test-retest agreement. Results. CFF values and MALT scores varied significantly between the cases and the controls (P < 0.05). MALT was 94% sensitive and 83% specific. Using ROC with CFF as gold standard, the AUC for diagnosis of MHE using MALT score was 0.89. Test-retest agreement was high (ICC = 0.89). Conclusion. In this pilot study, MALT proved to be highly sensitive, specific, inexpensive, and reproducible.
Concomitant steatosis in chronic hepatitis C is associated with fibrosis and unfavorable treatment outcome. Central zone injury in nonalcoholic steatohepatitis (NASH) manifests as central portalization, with centrizonal...Concomitant steatosis in chronic hepatitis C is associated with fibrosis and unfavorable treatment outcome. Central zone injury in nonalcoholic steatohepatitis (NASH) manifests as central portalization, with centrizonal microvessels and ductular reaction. We investigated whether central portalization in steatotic HCV biopsies would identify patients with metabolic risk factors for NASH. Liver biopsies with chronic hepatitis C and >10% steatosis (n = 65) were evaluated for the degree of steatosis, zonation of steatosis, fibrosis, and nonalcoholic fatty liver disease (NAFLD) activity score. The presence of centrizonal microvessels, sinusoidal capillarization, ductular reaction, and CK7 positive intermediate-phenotype hepatocytes were evaluated by CD34 and CK7 immunostain. The degree of steatosis and fibrosis showed a positive correlation. Additional positive correlations were noted between centrizonal angiogenesis and NAFLD activity score and central portalization and fibrosis. However, neither central portalization nor zonation of steatosis identified patients with metabolic risk factors for NASH. Therefore, central portalization cannot be used as a surrogate marker to identify patients with metabolic risk factors for NASH in steatotic HCV biopsies. The mechanism of centrizonal injury in steatotic HCV hepatitis is not solely attributable to the metabolic risk factors for NASH.
Background. Information regarding the progression of acute hepatitis B virus (HBV) infection to chronic infection in adults is scarce. Methods. Twenty-five adult patients with acute HBV infection (14 men and 11 women, 18...Background. Information regarding the progression of acute hepatitis B virus (HBV) infection to chronic infection in adults is scarce. Methods. Twenty-five adult patients with acute HBV infection (14 men and 11 women, 18-84 years old), whose clinical features progressed to those of chronic infection (group A) or did not (group B), were studied retrospectively. Results. There were 3 and 22 patients in groups A and B, respectively. Two of the 3 patients of group A lacked the typical symptoms of acute hepatitis. No differences were found between groups with respect to age, sex, or HBV genotypes. However, total bilirubin and alanine aminotransaminase levels were significantly lower in group A. Conclusions. Three of the 25 adult patients with acute HBV infection progressed to chronic infection. Hepatitis was mild in these patients. Patients with mild acute hepatitis B or unapparent HBV infection may have a higher risk of progressing to chronic infection.
In preclinical studies of fructose-induced NAFLD, endotoxin appears to play an important role. We retrospectively examined samples from three pediatric cohorts (1) to investigate whether endotoxemia is associated with th...In preclinical studies of fructose-induced NAFLD, endotoxin appears to play an important role. We retrospectively examined samples from three pediatric cohorts (1) to investigate whether endotoxemia is associated with the presence of hepatic steatosis; (2) to evaluate postprandial endotoxin levels in response to fructose beverage in an acute 24-hour feeding challenge, and (3) to determine the change of fasting endotoxin amounts in a 4-week randomized controlled trial comparing fructose to glucose beverages in NAFLD. We found that adolescents with hepatic steatosis had elevated endotoxin levels compared to obese controls and that the endotoxin level correlated with insulin resistance and several inflammatory cytokines. In a 24-hour feeding study, endotoxin levels in NAFLD adolescents increased after fructose beverages (consumed with meals) as compared to healthy children. Similarly, endotoxin was significantly increased after adolescents consumed fructose beverages for 2 weeks and remained high although not significantly at 4 weeks. In conclusion, these data provide support for the concept of low level endotoxemia contributing to pediatric NAFLD and the possible role of fructose in this process. Further studies are needed to determine if manipulation of the microbiome or other methods of endotoxin reduction would be useful as a therapy for pediatric NAFLD.
IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer a...IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer are often accompanied by significant IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10-producing cells that directly induce IgG4 reactions. Moreover, IgG4-related disease is a high-risk factor for cancer development; IgG4-related sclerosing cholangitis (IgG4-SC) cases associated with cholangiocarcinoma or its precursor lesion biliary intraepithelial neoplasia (BilIN) have been reported. IgG4-positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from cholangiocarcinoma remains important.
Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exer...Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic role mainly in the liver. The prevalence is variable, but most are rare pathologies. We review the pathophysiology of such diseases and the diagnostic contribution of laboratory tests, focusing on the role of molecular genetics. In fact, thanks to recent advances in genetics, molecular analysis permits early and specific diagnosis for most disorders and helps to reduce the invasive approach of liver biopsy.
Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication in cirrhotic patients with ascites. Although identifying the pathogen(s) plays a major role in the management of infectious diseases, ascitic...Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication in cirrhotic patients with ascites. Although identifying the pathogen(s) plays a major role in the management of infectious diseases, ascitic fluid cultures often show negative results in patients with clinical signs and symptoms of SBP, and ascitic fluid cell analyses are the gold standard method for diagnosing SBP. SBP is generally diagnosed based on an increased number of polymorphonuclear neutrophils in the ascitic fluid (>250/mm(3)), and the identification of the causal pathogen may not be given consideration. We newly developed an in situ hybridization (ISH) method to provide early and direct evidence of bacterial infection in ascites in patients with SBP. This paper will review the diagnosis of SBP, including our novel approach with ISH method to detect bacterial DNA in SBP ascitic fluid.
Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary...Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas. IPNBs display a spectrum of premalignant lesion towards invasive cholangiocarcinoma. The most common radiologic findings for IPNB are bile duct dilatation and intraductal masses. The major treatment of IPNB is surgical resection. Ultrasonography, computed tomography, magnetic resonance image, and cholangiography are usually performed to assess tumor location and extension. Cholangioscopy can confirm the histology and assess the extent of the tumor including superficial spreading along the biliary epithelium. However, pathologic diagnosis by preoperative biopsy cannot always reflect the maximum degree of atypia, because IPNBs are often composed of varying degrees of cytoarchitectural atypia. IPNBs are microscopically classified into four epithelial subtypes, such as pancreatobiliary, intestinal, gastric, and oncocytic types. Most cases of IPNB are IPN with high-grade intraepithelial neoplasia or with an associated invasive carcinoma. The histologic types of invasive lesions are either tubular adenocarcinoma or mucinous carcinoma. Although several authors have investigated molecular genetic changes during the development and progression of IPNB, these are still poorly characterized and controversial.
It is known that the interleukin-4 receptor α (IL-4R α ) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4R α -lytic hybrid peptide composed of binding peptide to IL-4R α...It is known that the interleukin-4 receptor α (IL-4R α ) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4R α -lytic hybrid peptide composed of binding peptide to IL-4R α and cell-lytic peptide and reported that the designed IL-4R α -lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4R α . Here, we evaluated the antitumor activity of the IL-4R α -lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4R α -lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5 μ M. We also showed that IL-4R α -lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4R α -lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4R α -lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.
Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a si...Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also in vivo in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.
Cholangiocarcinoma (CC) is divided into distal, perihilar, and intrahepatic CCs (ICCS), and are further subdivided into large bile duct ICC and peripheral ICC. In distal and perihilar CC and large duct ICC, biliary intra...Cholangiocarcinoma (CC) is divided into distal, perihilar, and intrahepatic CCs (ICCS), and are further subdivided into large bile duct ICC and peripheral ICC. In distal and perihilar CC and large duct ICC, biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm (IPN) have been proposed as precursor lesions. Peripheral ICC, bile duct adenoma (BDA), biliary adenofibroma (BAF), and von Meyenburg complexes (VMCs) are reportedly followed by development of ICCs. Herein, we surveyed these candidate precursor lesions in the background liver of 37 cases of peripheral ICC and controls (perihilar CC, 34 cases; hepatocellular carcinoma, 34 cases and combined hepatocellular cholangiocarcinoma, 25 cases). In the background liver of peripheral ICC, BDA and BAF were not found, but there were not infrequently foci of BDA-like lesions and atypical bile duct lesions involving small bile ducts (32.4% and 10.8%, resp.). VMCs were equally found in peripheral CCs and also control CCs. In conclusion, BDA, BAF, and VMCs are a possible precursor lesion of a minority of peripheral CCs, and BDA-like lesions and atypical bile duct lesions involving small bile ducts may also be related to the development of peripheral ICC. Further pathologic studies on these lesions are warranted for analysis of development of peripheral ICCs.
Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar/perihilar and extrahepatic cholangiocarcinoma. BilIN represents the process of multistep cholangiocarcinogenesis and is the biliary counterpart of...Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar/perihilar and extrahepatic cholangiocarcinoma. BilIN represents the process of multistep cholangiocarcinogenesis and is the biliary counterpart of pancreatic intraepithelial neoplasia (PanIN). This study was performed to clarify the histological characteristics of BilIN in relation to PanIN. Using paraffin-embedded tissue sections of surgically resected specimens of cholangiocarcinoma associated with BilIN and pancreatic ductal adenocarcinoma associated with PanIN, immunohistochemical staining was performed using primary antibodies against MUC1, MUC2, MUC5AC, cyclin D1, p21, p53, and S100P. For mucin staining, Alcian blue pH 2.5 was used. Most of the molecules examined here showed similar expression patterns in BilIN and PanIN, in which their expression tended to increase along with the increase in atypia of the epithelial lesions. Significant differences were observed in the increase in mucin production and the expression of S100P in PanIN-1 and the expression of p53 in PanIN-3, when compared with those in BilIN of a corresponding grade. These results suggest that cholangiocarcinoma and pancreatic ductal adenocarcinoma share, at least in part, a common carcinogenic process and further confirm that BilIN can be regarded as the biliary counterpart of PanIN.
Background/Aims. Spontaneous bacterial peritonitis (SBP) is one of the leading causes of morbidity and mortality in patients with cirrhosis. This study aims to determine the microbial agents of SBP and the pattern of ant...Background/Aims. Spontaneous bacterial peritonitis (SBP) is one of the leading causes of morbidity and mortality in patients with cirrhosis. This study aims to determine the microbial agents of SBP and the pattern of antibiotic resistance, in a large number of ascitic samples. Methodology. In a cross-sectional, single center, hospital based study, 1981 consecutive ascitic fluid samples were recruited from 2005 to 2011. Samples were dichotomized into three-year periods, in order to assess the trend of resistance to the first-line empirical antibiotics. Results. SBP was found in 482 (24.33%) of samples, of which 314 (65.15%) were culture positive. The most prevalent isolated pathogen was E. coli (33.8%), followed by staphylococcus aureus (8.9%) and Enterococcus (8.6%). No significant changes in the proportion of gram-negative/gram-positive infections occurred during this period. A percentage of resistant strains to cefotaxime (62.5%, 85.7%), ceftazidim (73%, 82.1%), ciprofloxacin (30, 59.8%), ofloxacin (36.8%, 50%), and oxacilin (35%, 51.6%) were significantly increased. E. coli was most sensitive to imipenem, piperacillin-tazobactam, amikacin, ceftizoxime, and gentamicin. Conclusions. The microbial aetiology of SBP remains relatively constant. However, the resistance rate especially to the first-line recommended antibiotics was significantly increased. This pattern must be watched closely and taken into account in empirical antibiotic treatment.
Objective. To identify the risk factors for HCV infection within married couples in Egypt. Methods. In 2008 Egypt conducted its first nationally representative survey of HCV prevalence. 11126 of the 12780 individuals age...Objective. To identify the risk factors for HCV infection within married couples in Egypt. Methods. In 2008 Egypt conducted its first nationally representative survey of HCV prevalence. 11126 of the 12780 individuals aged 15-59 year who were sampled agreed to participate and provided information via a questionnaire about demographic and behavioural characteristics and blood for HCV antibody and RNA analysis. We assessed the risk factors for HCV infection in a subsample of 5182 married individuals via multivariate logistic regression. Results. Overall HCV antibody prevalence in the married couples was 18.2% (95% CI, 16.8-19.6). HCV antibody prevalence was higher in the husbands (23.7%) than the wives (12.1%; P < 0.001). Having a spouse who was infected with HCV was an independent risk factor for HCV infection with odds ratios of 2.1 (95% CI, 1.6-2.9) and 2.2 (95% CI, 1.6-3.1) for women and men, respectively. Husbands whose wives had experienced female genital cutting (FGC) had a higher prevalence of HCV and this relationship was driven by a strong association in urban areas. Amongst the women there was no association between FGC and HCV overall but in urban areas only women who had experienced FGC were HCV infected. Conclusions. This study provides additional evidence of the importance of intrafamilial transmission of HCV in Egypt.
Platelet-rich plasma (PRP) has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth fa...Platelet-rich plasma (PRP) has been of great concern to the scientists and doctors who are involved in wound healing and regenerative medicine which focuses on repairing and replacing damaged cells and tissues. Growth factors of platelet-rich plasma are cost-effective, available, and is more stable than recombinant human growth factors. Given these valuable properties, we decided to assess the effect of PRP on CCl4-induced hepatotoxicity on rats. The rats received CCl4 (1 mL/kg, i.p. 1 : 1 in olive oil) twice per week for 8 weeks. Five weeks after CCl4 injection, the rats also received PRP (0.5 mL/kg, s.c.) two days a week for three weeks. Twenty-four hours after last CCl4 injection, the animals bled and their livers dissected for biochemical and histopathological studies. Blood analysis was performed to evaluate enzyme activity. The results showed that PRP itself was not toxic for liver and could protect the liver from CCl4-induced histological damages and attenuated oxidative stress by increase in glutathione content and decrease in lipid peroxidative marker of liver tissue. The results of the present study lend support to our beliefs in hepatoprotective effects of PRP.
Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the associati...Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis. Methods. Steatosis severity was defined according to Hamaguchi's echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2 α , soluble NOX2-derived peptide, and adiponectin were measured. Results. Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5) μ IU/mL in mild, moderate, and severe steatosis, respectively; P < 0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2 α , soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchi's score, urinary 8-iso-PGF2 α , and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjusted R (2) = 0.36). Conclusion. We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.
Bai F, Yano Y, Fukumoto T
… +13 more, Takebe A, Tanaka M, Kuramitsu K, Anggorowati N, Rinonce HT, Widasari DI, Saito M, Hirano H, Hayakumo T, Seo Y, Azuma T, Ku Y, Hayashi Y
Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persiste...Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P < 0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.