Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests

AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow(BF) was analyzed by arterial spin labeling(ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy(MHE). Images were collected using a 3 Tesla MR scanner(Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score(PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins(IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated.RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere(P = 0.03) and vermis(P = 0.012) and reduced in occipital lobe(P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE(P = 0.02). Bimanual coordination was impaired in patients without MHE(P = 0.05) and much more in patients with MHE(P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE(P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE(P< 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A(NCT-A), B(NCT-B)and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with CFF. BF in cerebellar hemisphere correlates with plasma cGMP and nitric oxide(NO) metabolites. BF in vermis cerebellar also correlates with NO metabolites and with 3-nitrotyrosine. IL-18 in plasma correlates with BF in thalamus and occipital lobe.CONCLUSION: Non invasive BF determination in cerebellum using ASL may detect MHE earlier than the PHES. Altered NO-cGMP pathway seems to be associated to altered BF in cerebellum.

Miliary tuberculosis infection during hepatitis C treatment with sofosbuvir and ledipasvir plus ribavirin

Chronic hepatitis C virus(HCV) infection is one of the main causes of chronic liver disease worldwide. In the last 5 years, treatment for HCV infection has experienced a marked development. In 2014, the use of ledipasvir/sofosbuvir with or without concomitant weight-based ribavirin was approved with a very significant increase in the sustained virological response. However, new side effects have been associated. We report the first case of an HCV infected patient treated for 12 wk with the combination of sofosbuvir/ledipasvir plus ribavirin who developed a miliary tuberculosis(TB) infection while on therapy. The patient was a 65-year-old woman, who referred malaise, asthenia, hyporexia, 7 kg weight loss, productive cough, evening fever and night sweats, right after finishing the treatment. The chest computed tomography-scan revealed a superior mediastinal widening secondary to numerous lymphadenopathies with extensive necrosis and bilateral diffuse lung miliary pattern with little subsequent bilateral pleural effusion, highly suggestive of lymph node tuberculosis with lung miliary spread. A bronchoscopy was performed and bronchial suction showed more than 50 acid-alcohol resistant bacillus per line. A Mycobacterium tuberculosis DNA was detected in blood by polymerase chain reaction, which confirmed the diagnosis of miliary tuberculosis. Some cases of TB infection have been identified with α-interferon-based therapy and with the triple therapy of pegylated interferon, ribavirin and boceprevir or telaprevir. However, significant infection has not been reported with sofosbuvir/ledipasvir plus ribavirin.We believe that the case is relevant to increase awareness of opportunistic infections and particularly TB infection. Although the international guidelines offer no recommendation regarding TB screening, we wonder whether it would be advisable to screen for opportunistic infections prior to the introduction of HCV therapy.