New mutation of the ceruloplasmin gene in the case of a neurologically asymptomatic patient with microcytic anaemia, obesity and supposed Wilson's disease.

BACKGROUND: Aceruloplasminaemia is a very rare autosomal recessive disorder caused by a mutation in the ceruloplasmin gene, which is clinically manifested by damage to the nervous system and retinal degeneration. This classical clinical picture can be preceded by diabetes mellitus and microcytic anaemia, which are considered to be early manifestations of aceruloplasminaemia. CASE PRESENTATION: In our report, we describe the case of a patient with aceruloplasminaemia detected in an early stage (without clinical symptoms of damage to the nervous system) during the search for the cause of hepatopathy with very low values of serum ceruloplasmin. Molecular genetic examination of the CP gene for ceruloplasmin identified a new variant c.1664G > A (p.Gly555Glu) in the homozygous state, which has not been published in the literature or population frequency databases to date. Throughout the 21-month duration of chelatase treatment, the patient, who is 43 years old, continues to be without neurological and psychiatric symptomatology. We observed a decrease in the serum concentration of ferritin without a reduction in iron deposits in the brain on magnetic resonance imaging. CONCLUSION: Currently, there is no unequivocal recommendation of an effective treatment for aceruloplasminaemia. Early diagnosis is important in the neurologically asymptomatic stage.

Tacrolimus-induced parkinsonism in a patient after liver transplantation - case report.

BACKGROUND: Hepatic encephalopathy may manifest by a wide spectrum of neuropsychiatric symptoms, including cognitive impairment, seizures or extrapyramidal symptoms. The liver transplant can lead to improvement of the signs of encephalopathy but subsequent immunosuppressive treatment might possess pronounced neurotoxicity. CASE PRESENTATION: We present a case report of a patient with chronic liver disease who developed signs of Parkinsonism after an orthotopic liver transplant, with consecutive immunosuppressant treatment with tacrolimus. Despite the improvement of liver functions due to the cytostatic treatment, a progressive worsening of neuropsychiatric symptoms associated with the presence of tremor was observed. Metabolic as well as endocrine dysfunctions were excluded as the primary causes of this condition. A brain CT did not reveal structural pathology. Signs of severe, symmetric Parkinsonism - with resting tremor, bradykinesia, rigidity and severe postural instability were observed. A brain MRI was performed with the presence of T2- hyperintensities in basal ganglia bilaterally. Tacrolimus blood concentration was elevated; hence the dose was reduced and later switched to less toxic sirolimus. Subsequently, clinical signs markedly improved after treatment modification. Improvement of clinical symptomatology after tacrolimus discontinuation supports the drug-induced etiology of this neurological condition. CONCLUSIONS: Cytostatic treatment after solid organ transplantation often leads to signs of encephalopathy. If necessary, the dose of cytostatics needs to be reduced, or a less toxic agent must be chosen for the therapy. This modification is usually efficient with no further need for neurological intervention.

Thallium intoxication. Case Report.

We report a rare case of serious voluntary intoxication by laboratory thallium monobromate combined with alcohol intake by a 24-years old man. The diagnosis of thallium intoxication was based on history, nonspecific but typical clinical symptoms including gastrointestinal complaints, painful polyneuropathy, alopecia, and confirmed by the finding of increased thallium concentration in the urine. The treatment, performed at the due time, consisted of decontamination of the stomach by irrigation, administration of active charcoal and Prussian blue, correction of water and mineral dysbalance, symptomatic treatment, and led to complete recovery.

Alcoholic Liver Disease-Related Hepatocellular Carcinoma: Characteristics and Comparison to General Slovak Hepatocellular Cancer Population.

Hepatocellular carcinoma (HCC) has multiple molecular classes that are associated with distinct etiologies and, besides particular molecular characteristics, that also differ in clinical aspects. We aim to characterize the clinical aspects of alcoholic liver disease-related HCC by a retrospective observational study that included all consequent patients diagnosed with MRI or histologically verified HCC in participating centers from 2010 to 2016. A total of 429 patients were included in the analysis, of which 412 patients (96%) had cirrhosis at the time of diagnosis. The most common etiologies were alcoholic liver disease (ALD) (48.3%), chronic hepatitis C (14.9%), NAFLD (12.6%), and chronic hepatitis B (10%). Patients with ALD-related HCC were more commonly males, more commonly had cirrhosis that was in more advanced stages, and had poorer performance status. Despite these results, no differences were observed in the overall (median 8.1 vs. 8.5 months) and progression-free survival (median 4.9 vs. 5.7 months). ALD-HCC patients within BCLC stage 0-A less frequently received potentially curative treatment as compared to the control HCC patients (62.2% vs. 87.5%, p = 0.017); and in patients with ALD-HCC liver function (MELD score) seemed to have a stronger influence on the prognosis compared to the control group HCC. Systemic inflammatory indexes were strongly associated with survival in the whole cohort. In conclusion, alcoholic liver disease is the most common cause of hepatocellular carcinoma in Slovakia, accounting for almost 50% of cases; and patients with ALD-related HCC more commonly had cirrhosis that was in more advanced stages and had poorer performance status, although no difference in survival between ALD-related and other etiology-related HCC was observed.

Inflammatory Indexes as Prognostic Factors of Survival in Geriatric Patients with Hepatocellular Carcinoma: A Case Control Study of Eight Slovak Centers.

Background and Aims: Hepatocellular cancer (HCC) often occurs in geriatric patients. The aim of our study was to compare overall survival and progression-free survival between geriatric patients (>75 years) and patients younger than 75 years and to identify predictive factors of survival in geriatric patients with HCC. Material and Methods: We performed a retrospective analysis of patients with HCC diagnosed in Slovakia between 2010−2016. Cases (HCC patients ≥75 years) were matched to controls (HCC patients <74 years) based on the propensity score (gender, BCLC stage and the first-line treatment). Results: We included 148 patients (84 men, 57%) with HCC. There were no differences between cases and controls in the baseline characteristics. The overall survival in geriatric patients with HCC was comparable to younger controls (p = 0.42). The one-, two-, and three-year overall survival was 42% and 31%, 19% and 12%, and 12% and 9% in geriatric patients and controls, respectively (p = 0.2, 0.4, 0.8). Similarly, there was no difference in the one- and two-year progression-free survival: 28% and 18% vs. 10% and 7% in geriatric HCC patients and controls, respectively (p = 0.2, 1, -). There was no case−control difference between geriatric HCC patients and younger HCC controls in the overall survival in the subpopulation of patients with no known comorbidities (p = 0.5), one and two comorbidities (p = 0.49), and three or more comorbidities (p = 0.39). Log (CRP), log (NLR), log (PLR), and log (SII) were all associated with the three-year survival in geriatric HCC patients in simple logistic regression analyses. However, this time, only log (NLR) remained associated even after controlling for the age and BCLC confounding (OR 5.32, 95% CI 1.43−28.85). Conclusions. We found no differences in overall survival and progression-free survival between older and younger HCC patients. Parameters of subclinical inflammation predict prognosis in geriatric patients with HCC. A limitation of the study is small number of the treated patients; therefore, further investigation is warranted.

Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Clinical Patterns, Outcomes, and Prognostic Factors for Overall Survival-A Retrospective Analysis of a Slovak Cohort.

OBJECTIVE: To compare NAFLD-related HCC and other etiology-related HCC and to describe predictive factors for survival in patients with NAFLD-related HCC independent of the BCLC staging system. METHODS: We performed a multicenter longitudinal retrospective observational study of patients diagnosed with HCC during the period from 2010 through 2016. RESULTS: 12.59% of patients had NAFLD-related HCC, and 21.91% had either NAFLD or cryptogenic etiology. NAFLD-related HCC patients were younger (p = 0.0007), with a higher proportion of women (p < 0.001) compared to other etiology-related HCC patients. The NAFLD group had a significantly lower proportion of patients with liver cirrhosis at the time of HCC diagnosis (p < 0.0001), and they were more frequently diagnosed with both diabetes and metabolic syndrome when compared to other etiology-related HCC (p < 0.0001). We did not find any difference in the overall survival or in the progression-free survival between NAFLD-related and other etiology-related HCC patients staged as BCLC B and BCLC C. NAFLD-related HCC patients with three or more liver lesions had a shorter overall survival when compared to patients with one or two liver lesions (p = 0.0097), while patients with baseline CRP values of ≥5 mg/L or with PLR ≥ 150 had worse overall survival (p = 0.012 and p = 0.0028, respectively). ALBI Grade 3 predicted worse overall survival compared to ALBI Grade 1 or 2 (p = 0.00021). In NAFLD-related HCC patients, PLR and ALBI remained significant predictors of overall survival even after adjusting for BCLC. CONCLUSION: NAFLD-related HCC patients have a similar prognosis when compared to other etiology-related HCC. In NAFLD-related HCC patients, ALBI and PLR are significant predictors of the overall survival independent of the BCLC staging system.

Wernicke encephalopathy-a rare complication of hyperemesis gravidarum.

We report a rare case of Wernicke encephalopathy (WE) in a 35-year-old woman with hyperemesis gravidarum (HG). Initially, the disease manifested as passivity, a loss of interest, sleeping too much, apathy and disorientation. The correct diagnosis was established after the detection of typical pathological findings of WE in the thalamus by magnetic resonance imaging (MRI), which was indicated for the appearance of eye symptomatology in the form of nystagmus. Subsequent treatment with thiamine led to rapid improvement in the patient's clinical status and a favorable course of pregnancy.

Late-Onset Wilson's Disease.

Wilson's disease is a rare autosomal recessive disease, caused by impaired secretion of copper into bile due to a defective function of the ATPase 7B enzyme. Clinical manifestation is predominantly hepatic and neurological. Wilson's disease is traditionally considered a disease of children and young adults. It rarely manifests after 40 years of age. In our case report, we present a 67-year-old female in whom Wilson's disease manifested as tremors of the upper extremities and chin that were originally assessed as part of cerebral atherosclerosis and Parkinson's disease. Only the histological finding of liver steatofibrosis, performed due to suspected metastatic changes of the liver, led in the context of neurological symptoms to correct diagnosis and successful treatment.