Making an accurate diagnosis of anterior mediastinal lesions: a proposal for a new diagnostic algorithm from the BTOG Thymic Malignancies Special Interest Group.

Due to the rising demand in cross-sectional thoracic imaging, anterior mediastinal lesions are being identified with increasing frequency. Following iterative and multidisciplinary discussions, the BTOG Thymic Malignancies Special Interest Group have developed an algorithm to standardise the diagnostic approach for these relatively uncommon but important conditions which span from benign (thymic remnant, thymic hyperplasia and thymic cysts) to suspected localised thymomas to suspected more aggressive malignancy (thymic carcinoma, lymphoma and germ cell tumours). For each condition, we provide a brief description, an overview of the key radiological findings and a description of the proposed algorithm including the rationale behind the recommendations. We also highlight the role of magnetic resonance (MR) imaging for the characterisation of anterior mediastinal masses in specific indications when the necessary local resources and expertise exist. In addition, we hope this provides the rationale for service development in MR of the anterior mediastinum where current resource and expertise requires development. Through this standardised pathway, we hope to drive improvements in patient care by rationalising surveillance schedules, avoiding unnecessary resections of benign entities with their associated morbidity and optimising the diagnostic work-up prior to the appropriate treatment of anterior mediastinal malignancies.

Life threatening pembrolizumabinduced myositis in a patient treated for advanced adenocarcinoma of the lung.

The advent of immunotherapy in oncology has led to the emergence of a new spectrum of adverse effects. A number of these have the potential to contribute to life-threatening outcomes; and therefore require prompt identification and aggressive treatment to optimise management. In this report, we describe a case of pembrolizumab-induced CTCAE (common toxicity criteria for adverse events) grade 4 myositis in a non-small cell lung cancer patient.

Apolipoprotein E-ε4 deficiency and cognitive function in hepatitis C virus-infected patients.

Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.

Generation of point-mutant FAK knockin mice.

Focal adhesion kinase is a non-receptor protein tyrosine kinase with signaling functions downstream of integrins and growth factor receptors. In addition to its role in adhesion, migration, and proliferation it also has non-kinase scaffolding functions in the nucleus. Focal adhesion kinase (FAK) activation involves the following: (1) ligand bound growth factors or clustered integrins activate FAK kinase domain; (2) FAK autophosphorylates tyrosine (Y) 397; (3) Src binds pY397 and phosphorylates FAK at various other sites including Y861; (4) downstream signaling of activated FAK elicits changes in cellular behavior. Although many studies have demonstrated roles for the kinase domain, Y397 and Y861 sites, in vitro much less is known about their functions in vivo. Here, we report the generation of a series of FAK-mutant knockin mice where mutant FAK, either kinase dead, non-phosphorylatable mutants Y397F and Y861F, or mutant Y397E-containing a phosphomimetic site that results in a constitutive active Y397, can be expressed in a Cre inducible fashion driven by the ROSA26 promoter. In future studies, intercrossing these mice with FAKflox/flox mice and inducible cre-expressing mice will enable the in vivo study of mutant FAK function in the absence of endogenous FAK in a spatially and temporally regulated fashion within the whole organism.

Depressive symptoms in chronic hepatitis C are associated with plasma apolipoprotein E deficiency.

Neuro-psychiatric and cognitive disorders are frequent in patients with chronic hepatitis C (CHC) virus (HCV) infection which adversely impact quality of life, antiviral treatment adherence and outcome. HCV has neurotrophic properties and affects lipid metabolism, essential for cognitive function. We evaluated the relationship of lipid profiles with depression and anxiety symptoms and the effects of 12-weeks of therapy with fluvastatin and omega-3 ethyl esters (n-3 PUFA) in a randomised pilot study of CHC prior non-responders. Participants (n = 60) had fasting lipid profiles and assessment of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) questionnaire at each study visit. At screening 26/60 (43 %) had HADS-A score ≥8 and 13/60 (22 %) had HADS-D scores ≥8. Depressed patients had significantly lower apolipoprotein-E concentrations (30 mg/l vs 39 mg/l, P = 0.029) than those without depression and a tendency toward lower total cholesterol (3.8 vs 4.4 mmol/l, P = 0.053). 3 patients discontinued lipid-modifying treatment because of worsening depression. However, there was a small but significant improvement in anxiety symptoms after 12-weeks of high-dose (2-4 g daily) n-3 PUFA. In conclusion, depression in CHC is associated with plasma apoE deficiency. We postulate that apoE deficiency disrupts blood brain barrier integrity to promote HCV infection of the CNS. High-dose n-PUFAs may alleviate anxiety in some CHC patients but the use of lipid lowering therapy must be balanced against risks of worsening depression.

A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid.

AIMS/HYPOTHESIS: We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM. METHODS: We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup (n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM. RESULTS: pGDM was associated with increased IHCL (p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index (p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD-, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD-, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance (p = 0.05), increased rate of VLDL apoB synthesis. CONCLUSIONS/INTERPRETATION: pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.

Coil combination of multichannel MRSI data at 7 T: MUSICAL.

The goal of this study was to evaluate a new method of combining multi-channel (1)H MRSI data by direct use of a matching imaging scan as a reference, rather than computing sensitivity maps. Seven healthy volunteers were measured on a 7-T MR scanner using a head coil with a 32-channel array coil for receive-only and a volume coil for receive/transmit. The accuracy of prediction of the phase of the (1)H MRSI data with a fast imaging pre-scan was investigated with the volume coil. The array coil (1)H MRSI data were combined using matching imaging data as coil combination weights. The signal-to-noise ratio (SNR), spectral quality, metabolic map quality and Cramér-Rao lower bounds were then compared with the data obtained by two standard methods, i.e. using sensitivity maps and the first free induction decay (FID) data point. Additional noise decorrelation was performed to further optimize the SNR gain. The new combination method improved significantly the SNR (+29%), overall spectral quality and visual appearance of metabolic maps, and lowered the Cramér-Rao lower bounds (-34%), compared with the combination method based on the first FID data point. The results were similar to those obtained by the combination method using sensitivity maps, but the new method increased the SNR slightly (+1.7%), decreased the algorithm complexity, required no reference coil and pre-phased all spectra correctly prior to spectral processing. Noise decorrelation further increased the SNR by 13%. The proposed method is a fast, robust and simple way to improve the coil combination in (1)H MRSI of the human brain at 7 T, and could be extended to other (1)H MRSI techniques.

Dynamics of cognitive change in HIV-infected individuals commencing three different initial antiretroviral regimens: a randomized, controlled study.

BACKGROUND: Improvements in neurocognitive (NC) function have been associated with commencing antiretroviral therapy in HIV-infected subjects. However, the dynamics of such improvements are poorly understood. METHODS: We assessed changes in NC function via a validated computerized battery (CogState™, Melbourne, Victoria, Australia) at baseline and after 24 and 48 weeks in a subset of therapy-naïve neuro-asymptomatic HIV-infected subjects, randomized to commence three different antiretroviral regimens. RESULTS: Of 28 subjects enrolled in the study, nine, eight and 11 were randomly allocated to commence tenofovir/emtricitabine with efavirenz (arm 1), atazanavir/ritonavir (arm 2) and zidovudine/abacavir (arm 3), respectively. Overall improvements in NC function were observed at week 24 and function continued to improve at week 48 (changes in z-score for overall cognitive global score of 0.16 and 0.18 at weeks 24 and 48, respectively). Within the NC speed domains, generally greater improvements were observed in arms 2 and 3, compared with arm 1 (changes in z-score for composite speed scores at weeks 24/48 of 0.16/0.16, -0.29/-0.24 and -0.15/-0.31 in arms 1, 2 and 3, respectively; P = 0.04 for change at week 48 in arm 3 versus arm 1). Finally, improvements in executive function occurred later (only observed at week 48) and were driven by improvements in arm 3 (z-score changes of 0.23, 0.06 and -0.78 in arms 1, 2 and 3, respectively; P = 0.02 for change in arm 3 versus arm 1). CONCLUSION: Improvements in NC function continue over the first year after initiating antiretroviral therapy in neuro-asymptomatic HIV-infected subjects.

Neuropsychological tools in hepatology: a survival guide for the clinician.

Neuropsychological assessment has three main applications in clinical hepatology: (i) to detect, grade and monitor liver failure-related cognitive alterations in end-stage liver disease (hepatic encephalopathy), (ii) to substantiate complaints of attention or concentration difficulties in patients with non-cirrhotic chronic hepatitis C viral infection, and (iii) to screen patients who are being considered for liver transplantation for early signs of dementia. However, there is limited agreement on how cognitive assessment should be conducted in these patients, and how results should be interpreted and used to implement clinical decisions. In this review, we summarize the available literature on neuropsychological dysfunction in patients with cirrhosis and with chronic hepatitis C viral infection and provide some guidance on how to utilize neuropsychological assessment in practice.

Cerebral microglial activation in patients with hepatitis C: in vivo evidence of neuroinflammation.

Patients with chronic hepatitis C infection may exhibit neuropsychological symptoms and cognitive impairment. Post-mortem studies of hepatitis C virus HCV quasispecies and replicative intermediates indicate that the brain might act as a separate compartment for viral replication and microglia may be the locus for infection and subsequent neuroinflammatory activity. We sought to use two independent in vivo imaging techniques to determine evidence of neuroinflammation in patients with histologically mild chronic hepatitis C. Using positron emission tomography (PET) with a ligand for microglial/brain macrophage activation, (11)C-(R)-PK11195 (PK11195) and cerebral proton magnetic resonance spectroscopy, we determined whether there was evidence of neuroinflammation in a pilot study of 11 patients with biopsy-proven mild chronic hepatitis C, compared to healthy volunteers. Patients were characterized by cognitive testing and the fatigue impact scale to assess for CNS impairment. PK11195 binding potential was significantly increased in the caudate nucleus of patients, compared to normal controls (P = 0.03). The caudate and thalamic binding potential were more significantly increased in six patients with genotype 1 infection (P = 0.007) and positively correlated with viraemia (r = 0.77, P = 0.005). Basal ganglia myo-inositol/creatine and choline/creatine ratios were also significantly elevated in patients with chronic hepatitis C compared to normal controls (P = 0.0004 and P = 0.01, respectively). Using PET, we demonstrated evidence of microglial activation, which positively correlated with HCV viraemia and altered cerebral metabolism in the brains of patients with mild hepatitis C. This provides further in vivo evidence for a neurotropic role for HCV.

Increased prevalence of non-alcoholic fatty liver disease in European women with a history of gestational diabetes.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) is common in type 2 diabetes but it is unknown whether NAFLD is prevalent in European women at risk of type 2 diabetes. We studied the prevalence of, and risk factors for, NAFLD in European women with previous gestational diabetes (GDM) at high risk of type 2 diabetes. METHODS: A total of 110 women with previous GDM and 113 without previous GDM, with non-diabetic glucose tolerance were recruited retrospectively from antenatal databases. Participants underwent liver ultrasound scan examination, anthropometry and blood sampling for liver function tests and to determine levels of fasting lipids, NEFA and insulin and glucose concentrations in order to derive insulin sensitivity and insulin secretion indices (HOMA%S and HOMA%B, respectively). RESULTS: There was no significant difference in BMI in women with previous GDM compared with those without previous GDM (28.9 ± 0.6 vs. 27.9 ± 0.6 kg/m(2), respectively; p = 0.12). Women with previous GDM had higher fasting and 2 h glucose concentrations following a 75 g OGTT ([mean ± SEM] fasting glucose 5.3 ± 0.1 vs. 5.1 ± 0.1 mmol/l, p = 0.02; 2 h glucose 6.8 ± 0.2 vs. 5.8 ± 0.3 mmol/l, p = 0.02), dyslipidaemia (LDL-cholesterol 3.3 ± 0.1 vs. 2.8 ± 0.1 mmol/l; HDL-cholesterol [median {interquartile range}] 1.3 [1.2-1.6] vs. 1.8 [1.5-1.9] mmol/l; triacylglycerol 1.3 [0.9-1.6] vs. 1.0 [0.7-1.7] mmol/l, all p ≤ 0.03), higher insulin secretion and lower insulin sensitivity. NAFLD prevalence was greater in women with previous GDM compared with those without previous GDM: 38% (95% CI 28-47%) vs. 17% (95% CI 10-24%), p = 0.001. In multiple logistic regression analysis, lower insulin sensitivity and raised serum alanine transaminase concentrations were associated with NAFLD. CONCLUSIONS/INTERPRETATION: NAFLD is prevalent in European women with previous GDM. Impaired insulin sensitivity and increased liver transaminase activity are closely associated with NAFLD in these women.

A comparison of 31P magnetic resonance spectroscopy and microbubble-enhanced ultrasound for characterizing hepatitis c-related liver disease.

We compared in vivo hepatic (31) P magnetic resonance spectroscopy ((31) P MRS) and hepatic vein transit times (HVTT) using contrast-enhanced ultrasound with a microbubble agent to assess the severity of hepatitis C virus (HCV)-related liver disease. Forty-six patients with biopsy-proven HCV-related liver disease and nine healthy volunteers had (31) P MRS and HVTT performed on the same day. (31) P MR spectra were obtained at 1.5 T. Peak areas were calculated for metabolites, including phosphomonoesters (PME) and phosphodiesters (PDE). Patients also had the microbubble ultrasound contrast agent, Levovist (2 g), injected into an antecubital vein, and time-intensity Doppler ultrasound signals of the right and middle hepatic veins were measured. The HVTT was calculated as the time from injection to a sustained rise in Doppler signal 10% greater than baseline. The shortest times were used for analysis. Based on Ishak histological scoring, there were 15 patients with mild hepatitis, 20 with moderate/severe hepatitis and 11 with cirrhosis. With increasing severity of disease, the PME/PDE ratio was steadily elevated, while the HVTT showed a monotonic decrease. Both imaging modalities could separate patients with cirrhosis from the mild and moderate/severe hepatitis groups. No statistical difference was observed in the accuracy of each test to denote mild, moderate/severe hepatitis and cirrhosis (Fisher's exact test P =1.00). (31) P MRS and HVTT show much promise as noninvasive imaging tests for assessing the severity of chronic liver disease. Both are equally effective and highly sensitive in detecting cirrhosis.

Personal perspectives: having a series of cardiac events.

It has never been clear to me whether being a medically qualified patient has positive or negative associations. In 2019, after a prostatectomy, where I had extended bleeding per urethra, I suffered two myocardial infarctions, underwent three coronary angiograms and eventually coronary stenting. Junior doctors never examined me at any point, while senior ones worried over the risk of stent placement in an actively bleeding patient. I report my views on how this seemed as a largely passive, but still actively thinking patient.

Why is there a paucity of clinical trials in Africa?

Disproportionately few clinical trials are undertaken on the African continent, in part due to lingering neocolonial attitudes in the Global North which keep research activity primarily in developing countries, while being skeptical of the abilities of those in the Global South to undertake organized clinical studies. In the era of the COVID-19 pandemic, applicable research and clinical trials should be undertaken in relevant populations in order to extrapolate to a population level. This is all the more important in Africa, which has a rich genetic diversity. We suggest that a lack of organized research ethics committees across the continent and a deficiency of appropriate training are responsible in part for the reluctance of clinical trial organizers in the developed countries of the Global North to engage with medical leadership in Africa. We consider ways of alleviating this problem, including suggesting a pan-continental surveillance of ethics committee agendas and of training, either through the auspices of the African Union or the World Health Organization. In addition, medical leadership in African nations must be encouraged to take ownership of their medical ethics agendas to facilitate decent international clinical trial participation for the good of the continent as a whole.

The COVID-19 era: the view from Nigeria.

If we were told that one day the entire world would take its guidance for managing a health crisis from empirical thought, nobody would have believed it. However, with the December 2019 arrival of COVID-19 in China, the world subsequently went into a frenzied state that resulted in the widespread adoption of untested strategies or potential cures; circumstantial evidence provided without randomized control trials (RCTs) was published rapidly and widely considered the gold standard in medical research and therapeutics. Nigeria and much of the rest of the world blindly adopted treatments like chloroquine or hydroxychloroquine and various prevention strategies, often without monitoring the efficacy of these treatment and social control strategies. COVID-19 provided Nigeria a critical opportunity to create or strengthen its national laboratory system by building up its Level 3 laboratories in all parts of the country with the capability to perform PCR tests and viral isolation. There was also an opportunity to establish hospitals in every region of a sufficient standard to reduce the numbers of Nigerians travelling abroad to seek medical treatment; to invest in building capacity to develop antiviral medications and vaccines in Nigeria, and to ensure better international health policies. Rather, Nigerian leaders, government and health managers decided (like most other nations of the world) to shut down the society using isolationist policies that were not necessarily tailored to local needs. Despite adopting these methods, COVID-19 cases continued to skyrocket in Nigeria. In the future, before adopting such broad sweeping policies, there should be local tailoring to assess their effectiveness in different communities. Given that the country has much experience in controlling Lassa and Marburg Fever outbreaks, Nigeria should lead by developing new strategies, new protocols and new local guidelines, based on validated and reproducible studies to ensure that the public health authorities are not caught unaware by any new outbreaks of emerging or remerging diseases.

Convergent evolution of pain-inducing defensive venom components in spitting cobras.

Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.

Hepatic vein transit times of a microbubble agent in assessing response to antiviral treatment in patients with chronic hepatitis C.

Microbubble measurement of hepatic vein transit times (HVTT) may have the potential to assess severity of hepatitis C virus (HCV)-related liver disease, where there is a shorter HVTT with more severe disease. We investigated the utility of this test as a marker of response to antiviral treatment. Thirty-seven patients with biopsy-proven HCV-related disease undergoing antiviral treatment were studied. All had baseline scans and then repeat scans 6 months after the end of treatment. HVTT using Levovist were obtained from the right and middle hepatic veins, and the shorter time was used for analysis. The aspartate aminotransferase to platelet ratio index (APRI) scores were calculated retrospectively. There were seven patients with mild hepatitis, 23 with moderate/severe hepatitis and seven with cirrhosis. The mean baseline HVTT in responders ± SE increased from 27.3 ± 2.29 s to 33.5 ± 2.8 s posttreatment (P = 0.01). In the 10 nonresponders, the HVTT remained the same; 43.3 ± 9 s baseline compared to 44 ± 7.8 s posttreatment (P = 0.84). This trend was also seen with the APRI score where in responders, the mean score decreased from 1.1 ± 0.2 to 0.74 ± 1 (P = 0.03) and in nonresponders, the score remained unchanged; 0.88 ± 0.2 compared to 0.84 ± 0.2 (P = 0.31). HVTT measurement lengthened, while APRI scores decreased in patients who responded to antiviral treatment while both remained the same, shortened (HVTT) or increased (APRI), respectively, in patients who were nonresponders. These results are encouraging and indicate that these tests could be potentially used as markers of response to treatment and could obviate the need for serial biopsies in antiviral future treatment studies.

Optimal combinations of ultrasound-based and serum markers of disease severity in patients with chronic hepatitis C.

Combinations of noninvasive markers may improve discrimination of chronic liver disease severity. The aims of this study were to compare four validated serum and ultrasound-based markers of hepatic disease severity head-to-head with liver biopsy and to assess optimal combinations with consideration of cost. A total of 67 patients with biopsy-proven chronic hepatitis C underwent all four techniques on the same visit [aspartate aminotransferase (AST) to platelet ratio index (APRI); Enhanced Liver Fibrosis (ELF) panel; transient elastography (TE) and ultrasound microbubble hepatic transit times (HTT)]. Markers were combined according to increasing financial cost and ordinal regression used to determine contributions. APRI, ELF, TE and HTT predicted cirrhosis with diagnostic accuracy of 86%, 91%, 90% and 83% respectively. ELF and TE were the most reliable tests with an intra-class correlation of 0.94 each. Either ELF or TE significantly enhanced the prediction of fibrosis stage when combined with APRI, but when combined together, did not improve the model further. Addition of third or fourth markers did not significantly improve prediction of fibrosis. Combination of APRI with either ELF or TE effectively predicts fibrosis stage, but combinations of three or more tests lead to redundancy of information and increased cost.

Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals?

Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV.