Turbulence structure of open channel flows over permeable and impermeable beds : A comparative study

Peer reviewedPublisher PD

Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B

BACKGROUND—The effect of hepatitis delta virus (HDV) infection on the clinical course of cirrhosis type B is poorly defined.
AIMS—To investigate the impact of HDV status on morbidity and mortality in cirrhosis type B.
PATIENTS/METHODS—Retrospective cohort study of 200 Western European patients with compensated cirrhosis type B followed for a median period of 6.6( )years.
RESULTS—At diagnosis, 20% of patients had antibodies to HDV (anti-HDV); median age was lower in anti-HDV positive cirrhotics (34 v 48 years respectively). Kaplan-Meier five year probability of hepatocellular carcinoma (HCC) was 6, 10, and 9% in anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 22, 16, and 19% and for survival they were 92, 89, and 83% respectively. Cox regression analysis identified age, albumin concentration, γ-globulin concentration, and HDV status as significant independent prognostic variables. After adjustment for clinical and serological differences at baseline, the risk (95% confidence interval) for HCC, decompensation, and mortality was increased by a factor of 3.2 (1.0 to 10), 2.2 (0.8( )to 5.7), and 2.0 (0.7 to 5.7) respectively in anti-HDV positive relative to HDV negative cirrhotic patients. The adjusted estimated five year risk for HCC was 13, 4, and 2% for anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 18, 8, and 14% and for survival 90, 95, and 93% respectively.
CONCLUSIONS—HDV infection increases the risk for HCC threefold and for mortality twofold in patients with cirrhosis type B.


Keywords: delta hepatitis; prognosis; hepatocellular carcinoma; decompensation; surviva

Turbulent friction in flows over permeable walls

Peer reviewedPublisher PD

Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action

In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage

Natural history of hepatitis B virus infection and disease

The natural history of hepatitis B virus (HBV) infection is complex and variable and is greatly influenced by the age at infection \u2013the younger the age the higher the probability of chronicity\u2013 the level of HBV replication and host immune status. Chronic hepatitis B is usually characterized by an early replicative phase with hepatitis B e antigen (HBeAg)positivity, high serum HBV-DNA levels (> 105 copies/ml) and normal serum alanine aminotransferase (ALT) (HBeAg-positive chronic hepatitis in the \u201cimmunotolerant\u201d phase) or raised serum ALT and active hepatitis (HBeAg-positive chronic hepatitis in the \u201cimmunoactive\u201d phase) and a late inactive phase with HBeAg seroconversion, low or undetectable serum HBV-DNA, and liver disease remission (inactive carrier state). Another form of chronic hepatitis B is characterized by HBeAg negativity, detectable serum HBV-DNA levels (suggested threshold > 104 copies/ml) and active hepatitis due to HBV variants not expressing HBeAg (HBeAg-negative chronic hepatitis). HBeAg-negative chronic hepatitis represents a late phase of chronic HBV infection and its prevalence is increasing throughout the world. Chronic hepatitis B is associated with serious complications, including cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). The incidence of cirrhosis ranges from 0.5 per 100 person years in HBeAg-positive chronic hepatitis in the immunotolerant phase to 2 to 5 per 100 person years in HBeAg-positive chronic hepatitis in the immunoactive phase, but may be as high as 8 to 10 in HBeAg-negative chronic hepatitis. The incidence of HCC appears to vary geographically and increases with the severity of liver disease (0.02 to 1.0 per 100 person years in carriers without cirrhosis at baseline to 2 to 3 per 100 person years in cirrhotic patients). The five-year mortality rate is about 15% for patients with compensated cirrhosis and 65% to 85% following decompensation. HCC and liver failure are the main causes of death. Viral-related factors (level and persistence of HBV replication, emergence of viral mutants, HBV genotype, viral coinfections), host-related factors (sex, age at infection, age at diagnosis, stage of liver disease at presentation, recurrent hepatitis flares, sustained aminotransferase normalization), and environmental factors (alcohol abuse, smoking and dietary carcinogens) may all be important determinants of the outcome of the diseas

Hepatocellularcarcinoma in cirrhosis: incidence and risk factors.

Emerging data indicate that the mortality rate of hepatocellular carcinoma (HCC) associated with cirrhosis is rising in some developed countries,whereas mortality from non- HCC complications of cirrhosis is decreasing or is stable. Cohort studies indicate that HCC is currently the major cause of liver-related death in patients with compensated cirrhosis. Hepatitis C virus (HCV) infection is associated with the highest HCC incidence in persons with cirrhosis, occurring twice as commonly in Japan than in the West (5-year cumulative incidence,30% and 17%,respectively), followed by hereditary hemochromatosis (5-year cumulative incidence,21%). In hepatitis B virus (HBV)-related cirrhosis, the 5-year cumulative HCC risk is 15% in high endemic areas and 10% in the West. In the absence of HCV and HBV infection,the HCC incidence is lower in alcoholic cirrhotics (5-year cumulative risk,8%) and subjects with advanced biliary cirrhosis (5-year cumulative risk,4%). There are limited data on HCC risk in cirrhosis of other causes. Older age,male sex,severity of compensated cirrhosis at presentation,and sustained activity of liver disease are important predictors of HCC,independent of etiology of cirrhosis. In viral-related cirrhosis,HBV/HCV and HBV/HDV coinfections increase the HCC risk (2- to 6-fold relative to each infection alone) as does alcohol abuse (2- to 4-fold relative to alcohol abstinence). Reducing HBV replication lowers the risk of HCC in HBV-related cirrhosis. Further studies are needed to investigate other viral factors (eg HBV genotype/mutant,occult HBV,HIV coinfection) and preventable or treatable comorbidities (eg,obesity,diabetes) in the HCC risk in cirrhosis

Hepatocellular carcinoma in cirrhosis: Incidence and risk factors

Emerging data indicate that the mortality rate of hepatocellular carcinoma (HCC) associated with cirrhosis is rising in some developed countries, whereas mortality from non- HCC complications of cirrhosis is decreasing or is stable. Cohort studies indicate that HCC is currently the major cause of liver-related death in patients with compensated cirrhosis. Hepatitis C virus (HCV) infection is associated with the highest HCC incidence in persons with cirrhosis, occurring twice as commonly in Japan than in the West (5-year cumulative incidence, 30% and 17%, respectively), followed by hereditary hemochromatosis (5-year cumulative incidence, 21%). In hepatitis B virus (HBV)-related cirrhosis, the 5-year cumulative HCC risk is 15% in high endemic areas and 10% in the West. In the absence of HCV and HBV infection, the HCC incidence is lower in alcoholic cirrhotics (5-year cumulative risk, 8%) and subjects with advanced biliary cirrhosis (5-year cumulative risk, 4%). There are limited data on HCC risk in cirrhosis of other causes. Older age, male sex, severity of compensated cirrhosis at presentation, and sustained activity of liver disease are important predictors of HCC, independent of etiology of cirrhosis. In viral-related cirrhosis, HBV/HCV and HBV/HDV coinfections increase the HCC risk (2- to 6-fold relative to each infection alone) as does alcohol abuse (2- to 4-fold relative to alcohol abstinence). Sustained reduction of HBV replication lowers the risk of HCC in HBV-related cirrhosis. Further studies are needed to investigate other viral factors (eg, HBV genotype/mutant, occult HBV, HIV coinfection) and preventable or treatable comorbidities (eg, obesity, diabetes) in the HCC risk in cirrhosis