Amygdala-prefrontal connectivity during appraisal of symptom-related stimuli in obsessive-compulsive disorder.

BACKGROUND: Cognitive models of obsessive-compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala-prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala-prefrontal connections. However, abnormalities in amygdala-prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly. METHODS: Amygdala-prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples. RESULTS: During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala-ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest. CONCLUSIONS: Our finding of abnormal amygdala-prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala-prefrontal coupling in affective models of OCD.

Neural correlates of emotional reactivity predict response to cognitive-behavioral therapy in obsessive-compulsive disorder.

BACKGROUND: Examining predictive biomarkers to identify individuals who will likely benefit from a specific treatment is important for the development of targeted interventions. The late positive potential (LPP) is a neural marker of attention and elaborated stimulus processing, and increased LPP responses to negative stimuli are characteristic of pathological anxiety. The present study investigated whether LPP reactivity would prospectively predict response to cognitive-behavioral therapy (CBT), the first-line treatment for obsessive-compulsive disorder (OCD). METHODS: To this end, the LPP in response to negative as compared to neutral pictures was examined in 45 patients with OCD, who underwent CBT in a naturalistic outpatient setting. LPP amplitudes were used as predictors of symptom reduction after CBT. RESULTS: We found that higher LPP amplitudes to negative relative to neutral stimuli were predictive of lower self-reported OCD symptoms after completion of CBT, controlling for pre-treatment symptoms. Further, LPP reactivity was negatively correlated with self-reported habitual use of suppression in everyday life. LIMITATIONS: Some participants had already begun treatment at the time of study participation. Overall, results need further replication in larger samples and standardized therapy settings. CONCLUSIONS: The current findings suggest that patients with increased emotional reactivity benefit more from CBT, possibly through less avoidance of anxiety-provoking stimuli during exposure with response prevention, a crucial component in CBT for OCD. Although its clinical utility still needs to be evaluated further, the LPP constitutes a promising candidate as a prognostic marker for CBT response in OCD.

Auditory novelty processing is enhanced in obsessive-compulsive disorder.

BACKGROUND: Cognitive models propose that anxiety disorders are associated with an attentional bias toward potentially threatening stimuli. In this study, it was analyzed whether patients with obsessive-compulsive disorder (OCD) show enhanced responses of their event-related brain potentials to novel stimuli, either in a context of potential threat or in a neutral context. METHODS: In this study, 20 OCD patients and 20 matched healthy control subjects performed a visual recognition task during which irrelevant repeated standard sounds and unitary novel sounds were interspersed. RESULTS: As expected, OCD patients showed an increase in the novelty-P3 amplitude elicited by unitary novel sounds. However, no effect of emotional context conditions was observed. CONCLUSION: It is suggested that the novelty P3 amplitude increase in OCD patients represents a physiological indicator of an enhanced cortical orienting response implicating stronger involuntary shifts of attention. This characteristic is driven by novelty per se and not moderated by potential threat of upcoming events.

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Confirmatory factor analysis and recommendations for improvement of the Autonomy-Preference-Index (API).

OBJECTIVE: Validation of the German version of the Autonomy-Preference-Index (API), a measure of patients' preferences for decision making and information seeking. METHODS: Stepwise confirmatory factor analysis was conducted on a sample of patients (n = 1592) treated in primary care for depression (n = 186), surgical and internal medicine inpatients (n = 811) and patients with minor trauma treated in an emergency department (n = 595). An initial test of the model was done on calculation and validation halves of the sample. Both local and global indexes-of-fit suggested modifications to the scale. The scale was modified and re-tested in the calculation sample and confirmed in the validation sample. Subgroup analyses for age, gender and type of treatment setting were also performed. RESULTS: The confirmatory analysis led to a modified version of the API with better local and global indexes-of-fit for samples of German-speaking patients. Two items of the sub-scale, 'preference for decision-making', and one item of the sub-scale, 'preference for information seeking', showed very low reliability scores and were deleted. Thus, several global indexes-of-fit clearly improved significantly. The modified scale was confirmed on the validation sample with acceptable to good indices of fit. Results of subgroup analyses indicated that no adaptations were necessary. DISCUSSION AND CONCLUSIONS: This first confirmatory analysis for a German-speaking population showed that the API was improved by the removal of several items. There were theoretically plausible explanations for this improvement suggesting that the modifications might also be appropriate in English and other language versions.

Evaluation of the association between plasma concentration of N-terminal proatrial natriuretic peptide and outcome in cats with cardiomyopathy.

OBJECTIVE: To determine whether plasma N-terminal proatrial natriuretic peptide (NT-proANP) concentration could predict the outcome (survival duration) of cats with cardiomyopathy (CM). DESIGN: Case-control study. ANIMALS: 51 cats with CM (25 with and 26 without congestive heart failure [CHF]) and 17 healthy cats. PROCEDURES: Cats were thoroughly examined and assigned to 1 of 3 groups (control, CM with CHF, and CM alone). Plasma NT-proANP concentrations were measured by use of a human proANP(1-98) ELISA. Survival durations were compared between CM groups. RESULTS: Plasma NT-proANP concentrations differed significantly among the 3 groups, and survival durations differed significantly between the 2 CM groups. Median (range) NT-proANP concentration was 413 fmol/mL (52 to 940 fmol/mL) in the control group, 1,254 fmol/mL (167 to 2,818 fmol/mL) in the CM alone group, and 3,208 fmol/mL (1,189 to 15,462 fmol/mL) in the CM with CHF group. At a cutoff of 517 fmol/mL, NT-proANP concentration had a sensitivity of 90% and specificity of 82% for detecting CM. Multivariate analysis revealed that only the variable left atrium-to-aortic diameter ratio was a significant predictor of survival duration. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma NT-proANP concentration may have potential as a testing marker for distinguishing healthy cats from cats with CM. It may also be useful for distinguishing CM cats with CHF from those without CHF The value of NT-proANP concentration as a predictor of survival duration was not supported in this study and requires further evaluation.

Heightened degree connectivity of the striatum in obsessive-compulsive disorder induced by symptom provocation.

BACKGROUND: Neurosurgical intervention studies have provided direct evidence that the ventral striatum/nucleus accumbens (NAc) mediates symptoms of obsessive-compulsive disorder (OCD), yet meta-analysis of functional neuroimaging studies using symptom provocation revealed no striatal activation differences, and the existing studies reporting hyperactivity found abnormalities in dorsal but not ventral striatal subdivisions. Resting-state neuroimaging evidence holds that corticostriatal areas are more connected both locally and to distant regions, but the functional inferences to be drawn from these altered network characteristics regarding the present experience of OCD symptoms remain limited. METHODS: The present study tested whether symptom provocation induces abnormally high striatal network connectivity using two independent datasets of unmedicated patients with OCD. One study (14 patients, 14 matched controls) required passive viewing of OC-related, emotionally aversive and neutral pictures, the other (21 patients, 21 controls) involved self-referential evaluation of the same picture types, as well as distraction from these stimuli (engagement in a simple task). RESULTS: Heightened local connectivity of the dorsal striatum occurred during passive viewing of briefly presented OC-related pictures in patients, however group differences were also observed in a neutral control condition. In contrast, distracted symptom provocation selectively yielded local connectivity differences of the ventral striatum, as heightened NAc connectivity to its immediate neighborhood was exclusively observed when OC-related pictures were accompanied by concurrent task demands. LIMITATIONS: Small samples sizes. CONCLUSIONS: In moderately affected patients with OCD, symptom provocation induces a discrete, condition-specific network abnormality anchored in NAc, the location targeted by deep brain stimulation for refractory patients with OCD.

Evidence of interactions between white sharks and large squids in Guadalupe Island, Mexico.

Shark-cephalopod interactions have been documented in trophic ecology studies around the world. However, there is little information about the encounters between white sharks Carcharodon carcharias and squids in the eastern North Pacific Ocean. Here we provide evidence of interactions between white sharks and large squids in the waters of Guadalupe Island, Mexico. Through the use of non-invasive techniques, we found the presence of evident scars made by large squids on the body of the white sharks, mainly on the head and trunk, of at least 14 sharks recorded during August-December in the years 2008, 2012, 2013, 2017 and 2019. The mean length of the white sharks was 3.7 m (SD ± 0.6; total length), although the majority of the sharks with scars were adult and subadult males (n = 9; 64%). One of these males was photographically recaptured during the same season in which the individual showed new scars, confirming that the squid-white shark interaction likely occurs near Guadalupe Island. Our results highlight the importance of the twilight zone for white sharks and the use of shared habitat and trophic interactions between squid and white sharks, in which future ecosystem studies should consider both species for management and conservation purposes.

Measurement of N-terminal proatrial natriuretic peptide in plasma of cats with and without cardiomyopathy.

OBJECTIVE: To determine whether plasma N-terminal proatrial natriuretic peptide (Nt-proANP) concentrations in cats with cardiomyopathy (CM) differ from values in healthy cats and evaluate whether plasma Nt-proANP concentrations can be used to discriminate cats with CM and congestive heart failure (CHF) from CM-affected cats without CHF. ANIMALS: 16 cats that had CM without CHF, 16 cats that had CM with CHF, and 11 healthy control cats. PROCEDURES: All cats underwent a physical examination, assessment of clinicopathologic variables (including plasma thyroxine concentration), thoracic radiography, and echocardiography. On the basis of findings, cats were assigned to 1 of 3 groups (control cats, cats with CM and CHF, and cats with CM without CHF). Venous blood samples were obtained from all 43 cats, and plasma Nt-proANP concentrations were measured by use of a human proANP(1-98) ELISA. RESULTS: Plasma Nt-proANP concentrations differed significantly among the 3 groups. Median Nt-proANP concentration was 381 fmol/mL (range, 52 to 450 fmol/mL), 763 fmol/mL (range, 167 to 2,386 fmol/mL), and 2,443 fmol/mL (range, 1,189 to 15,462 fmol/mL) in the control group, in cats with CM without CHF, and in cats with CM and CHF, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of plasma Nt-proANP concentration could be of benefit in the assessment of cats with naturally occurring CM and might have potential as a screening marker for the disease. Furthermore, measurement of plasma NtproANP concentration may be useful for distinguishing cats with CM and CHF from those with CM and no CHF.

Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma.

OBJECTIVE: To compare response rates and remission and survival times in dogs with lymphoma treated with a continuous, multiagent, doxorubicin-based chemotherapeutic protocol or with a short-term single-agent protocol incorporating doxorubicin. DESIGN: Nonrandomized controlled clinical trial. ANIMALS: 114 dogs with lymphoma. PROCEDURES: Dogs were treated with a chemotherapeutic protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n=87) or doxorubicin alone (27). RESULTS: 63 of 86 (73%) dogs treated with the multiagent protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs treated with the single-agent protocol had a complete remission. Dogs with lymphoma classified as substage

HMGA2 expression in a canine model of prostate cancer.

Prostate cancer is the most prevalent cancer in western countries, being the third leading cause of male cancer death. To check its possible significance as a prognostic marker, allowing a better prognosis of the tumor, we analyzed the high-mobility group protein-A2 gene (HMGA2) expression level because HMGA2 overexpression has been shown to correlate with the malignant potential of various neoplasias. Aside from man, the dog is the only mammalian species that shows spontaneously occurring prostate carcinoma with striking similarities to prostate cancer growth and progression in man, making it an adequate animal model for this neoplasia. We used real-time quantitative reverse-transcription polymerase chain reaction for HMGA2 expression analyses in a subset of canine prostate tissue samples. Our investigations reveal that HMGA2 expression levels in all carcinomas were higher than those of any of the nonmalignant tissues. Thus, canine prostate cancer represents a spontaneously occurring model to test therapeutic effects resulting from reduced expression of HMGA2.

The impact of patient participation on adherence and clinical outcome in primary care of depression.

OBJECTIVE: Patient participation in shared treatment decision-making is hypothesized to improve depression treatment adherence and clinical outcomes in depressed patients. The study aim was to evaluate the impact of patient participation on these factors and to determine the variance of clinical outcome as the primary outcome variable. METHODS: A survey was administered to 30 general practitioners and 207 depressed patients, at initial consultation and 6-8 weeks later. General practitioners documented their clinical practice and patients completed questionnaires including Brief-PHQ for depression and clinical outcome, patient participation scale, and visual analogue scales for treatment adherence. Assessment of correlations was followed by the development of a structural equation model (as a latent variable analysis) to define a model to explain the entire set of the variables' relationships. RESULTS: Sixty percent of the variance in clinical outcome was attributable to patient adherence (beta=0.41) and baseline depression severity (beta=0.65). Depression severity predicted clinical outcome but not patient participation. Participation predicted adherence (beta=0.39) but did not directly affect clinical outcome. Adherence was explainable by physician- (beta=0.57) and patient-reported treatment adherence (beta=0.66). CONCLUSION: In a specific pathway via adherence, patient participation in decision-making influences clinical outcome in primary care of depression. PRACTICE IMPLICATIONS: The research findings reveal the significance of patient participation as a key factor to address for improving treatment adherence and clinical outcome. Quality improvement strategies for depression treatment should emphasize patient participation.

The effects of a shared decision-making intervention in primary care of depression: a cluster-randomized controlled trial.

OBJECTIVE: Patient-centred depression care approaches should better address barriers of insufficient patient information and involvement in the treatment decision process. Additional research is needed to test the effect of increased patient participation on outcomes. The aim of this study was to assess, if patient participation in decision-making via a shared decision-making intervention leads to improved treatment adherence, satisfaction, and clinical outcome without increasing consultation time. METHODS: Cluster-randomized controlled intervention study based on physician training and patient-centered decision aid compared to usual care in primary care settings in Südbaden region of Germany. Twenty-three primary care physicians treating 405 patients with newly diagnosed depression were enrolled. Patient involvement was measured with the patient perceived involvement in care scale (PICS) and a patient participation scale (MSH-scale). Patient satisfaction was measured by the CSQ-8 questionnaire. Treatment adherence was evaluated by patient and provider self-report. Depression severity and remission outcomes were assessed with the Brief PHQ-D. RESULTS: Physician facilitation of patient participation improved significantly and to a greater extent in the intervention compared to the control group. There was no intervention effect for depression severity reduction. Doctor facilitation of patient participation, patient-rated involvement, and physician assessment of adherence improved only in the intervention group. Patient satisfaction at post-intervention was higher in the intervention group compared to the control group. The consultation time did not differ between groups. CONCLUSION: A shared decision-making intervention was better than usual care for improving patient participation in treatment decision-making, and patient satisfaction without increasing consultation time. Additional research is needed to model causal linkages in the decision-making process in regard to outcomes. PRACTICE IMPLICATIONS: The study results encourage the implementation of patient participation in primary care of depression.

Measuring (shared) decision-making--a review of psychometric instruments.

In recent years shared decision-making (SDM) has gained importance as an appropriate approach to patient-physician communication and decision-making. However, there is a conceptual variety that implies problems of inconsistent measurement, of defining relationships of SDM and outcome measures, and of comparisons across different studies. This article presents the results of a literature search of psychometric instruments measuring aspects of decision-making. Altogether 18 scales were found. The majority covers the patients' perspective and relates to preferences for information and participation, decisional conflict, self-efficacy as well as to the evaluation of decision-making process and outcomes. The scales differ widely in their extent of validation. Although this review is not exhaustive, it presents a variety of available decision-making instruments. Yet, many of them still need to show their psychometric quality for other settings in further studies.

Patient and citizen participation in German health care--current state and future perspectives.

Patient participation within the German healthcare system is described at three different levels: the macro level as active patient influence on the regulation of medical care, the meso level in terms of institutions enhancing patient information and counselling, and the micro level focusing on the actual treatment decision-making process in the medical encounter. The main focus of the present publication is on the health care system-specific influences on patient participation in medical decision-making and on the current state of research and implementation of shared decision-making in Germany. We describe institutions promoting patient involvement, their aims and initiatives as well as recent changes in German legislation. Against the background of German health politics' endorsement of patient participation the German Ministry of Health funded a research consortium with shared decision-making intervention projects in various disease areas. The present state of the intervention projects' results is outlined as well as subsequently funded transfer projects and future perspectives of research grants. Supported by health politics and the utilisation of scientific evidence shared decision-making's transfer into practice is considered to be relevant to the German health care system.

The assessment of depressive patients' involvement in decision making in audio-taped primary care consultations.

OBJECTIVE: In primary care of depression treatment options such as antidepressants, counseling and psychotherapy are reasonable. Patient involvement could foster adherence and clinical outcome. However, there is a lack of empirical information about the extent to which general practitioners involve patients in decision making processes in this condition, and about the consultation time spent for distinct decision making tasks. METHODS: Twenty general practice consultations with depressive patients prior to a treatment decision were audio-taped and transcribed. Patient involvement in decision making was assessed with the OPTION-scale and durations of decision making stages were measured. RESULTS: Mean duration of consultations was 16 min, 6s. The mean of the OPTION-items were between 0.0 and 26.9, in a scale range from 0 to 100. Overall, 78.6% of the consultation time was spent for the step "problem definition" (12 min, 42 s). CONCLUSION: Very low levels of patient involvement in medical decisions were observed in consultations about depression. Physicians used the majority of their time for the definition of the patient's medical problem. PRACTICE IMPLICATIONS: To improve treatment decision making in this condition, general practitioners should enhance their decision making competences and be more aware of the time spent in each decision making stage.

Postoperative adjuvant treatment of invasive malignant mammary gland tumors in dogs with doxorubicin and docetaxel.

BACKGROUND: Treatment outcome after surgery alone is unsatisfactory in dogs with invasive malignant mammary gland tumors. HYPOTHESIS: Adjuvant doxorubicin or docetaxel will improve the treatment outcome in dogs with high-risk malignant mammary gland tumors, and the use of docetaxel will be feasible in affected dogs. ANIMALS: Thirty-one dogs with malignant mammary gland tumors of histologic stages II and III (vascular or lymphatic invasion, regional lymph node metastasis, or distant metastasis) were used. METHODS: A prospective clinical trial in which dogs were treated with surgery alone (n = 19) or also received adjuvant chemotherapy (n = 12) with doxorubicin or docetaxel was conducted. Docetaxel was given as an IV infusion at a dose of 30 mg/m2 preceded by dexamethasone and diphenhydramine administration. RESULTS: The recurrence-free interval ranged from 13 to 2,585 days (median not reached); the median metastasis-free interval and overall survival were 294 days and 370 days, respectively. Dogs treated with chemotherapy had a tendency toward higher long-term local control and survival rates, but there was no significant difference in the recurrence-free interval (P = .17), time to metastasis (P = .71), and overall survival (P = .12). Factors found to influence the time to metastasis and overall survival included lymph node metastasis (P = .009) and tumor fixation to underlying structures (P = .043, time to metastasis), as well as age (P = .018) and histologic stage (P < .001, survival). Mild allergic skin reactions were the most frequently observed complications of docetaxel treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemotherapy did not lead to an improved outcome in this population. Docetaxel treatment was well tolerated. Additional investigations of adjuvant chemotherapy in dogs with high-risk mammary cancer are warranted.

Adapting another person's affective state modulates brain potentials to unpleasant pictures.

Emotional processing is influenced by top-down processes such as reappraisal of emotion-inducing events. Besides one's own stimulus appraisal, information from the social environment can be used to modify the stimulus' meaning. This study investigated whether perspective taking changes participants' brain potentials to unpleasant pictures. Event-related potentials (ERPs) were measured while twenty-nine participants evaluated arousal of neutral or negative pictures. Subsequently, they received bogus feedback about another person's picture evaluation. Then, the same picture was presented again and participants were instructed to view the picture from the other person's perspective. Higher bogus- versus self-ratings of picture arousal increased P300 and late positive potential (LPP) amplitudes to unpleasant stimuli, whereas lower bogus- versus self-ratings did not influence ERPs. Thus, perspective taking only modulated ERPs when bogus ratings signaled potential underestimation of arousal. Resulting increases in responsiveness might constitute an adaptive mechanism preparing the organism against harm.

Increased chromosomal alterations and micronuclei formation in human hepatoma HepG2 cells transfected with the hepatitis B virus HBX gene.

The protein encoded by the hepatitis B virus (HBV)-X gene, HBX, has been implicated to be involved in the development of HBV-associated liver cancer. HBX is a multifunctional regulatory protein that has been identified as a potential oncogene but its exact function remains unclear. HBX was documented to interact with several factors involved in cellular DNA repair as well as compromise the cell's ability to repair damaged DNA. We previously documented an accumulation of genetic alterations in two HepG2 cell lines independently transfected with HBV. In this report, we investigate the effect of the HBV-X gene (HBX) on the stability of the host genome using HepG2 stable transfectants (HepG2-HBX) and vector controls (HepG2-neo). We document that all HepG2-HBX clones analyzed contain HBX gene integrated and HBX transcript. Our data demonstrate that HepG2-HBX cells have an increased number of chromosome alterations and micronuclei formation compared to vector controls. A total of 10 de novo chromosomal rearrangements involving nine different chromosomes were detected in the HepG2-HBX clones, while no new rearrangements were found in vector controls. Each HepG2-HBX clone contained independently occurring de novo alterations not found in other HBX or vector clones. A three-fold increase of micronuclei formation was detected in HepG2-HBX cells compared to vector controls. Micronuclei originated from all chromosomes, however, preliminary data indicated that micronuclei originating from chromosomes 2, 3, 7, 18 and 20 were found in a greater amount in cells expressing the HBX gene. Interestingly, chromosomes 2, 18 and 20 were three of the chromosomes found rearranged in HepG2-HBX clones. These data provide evidence that genomic integrity was affected in cells expressing the HBX gene. De novo cytogenetic alterations identified in HepG2-HBX clones implicate the involvement of HBX in the process and support the hypothesis that HBX may interfere with normal cellular processes responsible for genomic integrity, increasing the risk for acquiring genetic mutations in infected hepatocytes.