Objectives-To describe prospectively the evolution of liver abnormalities in cystic fibrosis (CF), and to assess their impact on nutritional status. Study design-124 children (61 boys) with CF (median age, 5.4 years; range, 0.1-13.9) were followed longitudinally for a median of four years. Annual clinical examination, biochemistry, and ultrasound assessment were performed. Chrispin-Norman score, anthropometry, and bacterial colonisation of airway secretions were measured at each assessment. Results-At initial assessment, 45% of the patients had no liver abnormalities, 42% had biochemical abnormality, 35% ultrasound abnormality, and 6% had clinical abnormality of the liver. In this cross sectional analysis, abnormal biochemistry was present in 40% of children with ultrasound or clinical abnormalities, but when longitudinal follow up data were analysed, abnormal biochemistry preceded or coincided with abnormal ultrasound or clinical hepatosplenomegaly in three quarters of 53 children developing new abnormalities. Eighty four of 124 children (68%) showed ultrasound or clinical evidence of liver abnormality at some point during the four years of follow up. No association was found between liver disease and nutritional status. Conclusions-Hepatic abnormality was common in this group of children with CF, was often predicted by intermittent biochemical abnormalities, and was not associated with deterioration in nutritional status. (Arch Dis Child 1999;81:129-132)

Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureus. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5 untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. P atients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. Dwight et al 1 reported that 28% of patients with chronic hepatitis C had current depressive disorders. They concluded that disability and fatigue were related more closely to severity of depression than to progression of liver disease. More recently, Forton et al 2 addressed the hypothesis that hepatitis C virus (HCV) itself may affect cerebral function and provide the substrate for the chronic fatigue syndrome frequently associated with HCV infection. The investigators used proton magnetic resonance spectroscopy and showed elevations in choline-creatine ratios in the basal ganglia and white matter of patients with histologically mild hepatitis C that were not present in healthy volunteers and patients with hepatitis B. This elevated ratio was unrelated to hepatic encephalopathy or a history of intravenous drug abuse. The investigators suggested that a biological process underlies extrahepatic symptoms in chronic HCV infection, although they did not speculate on its nature. Furthermore, because HCV has been found to replicate in lymphoid cells and monocyte/ macrophages 3-5 and these cells can enter the central nervous system (CNS), 6 a possibility remains that psychosomatic syndromes observed in patients with HCV infection are related to viral replication in the CNS.We studied two patients with recurrent hepatitis C after cadaveric liver transplantation for end-stage liver disease caused by HCV infection who presented a clinical picture of profound depression. These patients subsequently died,...

HCV complexity and diversity in the E2 region correlated with the severity of recurrence of HCV infection after OLT. Increased diversity of quasi species at transmission correlated with a higher FS at 1 year. However, increased diversity of quasi species in the post-OLT period correlated with a lower FS at 1 year. The dynamics of HCV quasi species in patients who undergo transplantation are predictive of outcome.