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To extend previous molecular analyses of rejection in liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov #NCT03193151), the present study aimed to define the gene expression selective for parenchymal injury, fibrosis, and steatohepatitis. We analyzed genome-wide microarray measurements from 337 liver transplant biopsies from 13 centers. We examined expression of genes previously annotated as increased in injury and fibrosis using principal component analysis (PCA). PC1 reflected parenchymal injury and related inflammation in the early posttransplant period, slowly regressing over many months. PC2 separated early injury from late fibrosis. Positive PC3 identified a distinct mildly inflamed state correlating with histologic steatohepatitis. Injury PCs correlated with liver function and histologic abnormalities. A classifier trained on histologic steatohepatitis predicted histologic steatohepatitis with cross-validated AUC = 0.83, and was associated with pathways reflecting metabolic abnormalities distinct from fibrosis. PC2 predicted histologic fibrosis (AUC = 0.80), as did a molecular fibrosis classifier (AUC = 0.74). The fibrosis classifier correlated with matrix remodeling pathways with minimal overlap with those selective for steatohepatitis, although some biopsies had both. Genome-wide assessment of liver transplant biopsies can not only detect molecular changes induced by rejection but also those correlating with parenchymal injury, steatohepatitis, and fibrosis, offering potential insights into disease mechanisms for primary diseases.
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Trasplante de Hígado , Hígado , Biopsia , Hígado Graso , Fibrosis , Rechazo de Injerto , Humanos , Hígado/patología , Trasplante de Hígado/efectos adversos , FenotipoRESUMEN
INTRODUCTION AND OBJECTIVES: Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive cholestatic liver disorder caused by mutations in the ABCB4 gene. The aim of this study was to present the phenotypic and genotypic spectrum of 4 Polish PFIC-3 patients diagnosed in a one-referral centre. MATERIALS AND METHODS: The study included 4 patients with cholestasis and pathogenic variants in the ABCB4 gene identified by next-generation sequencing (NGS) of a targeted-gene panel or whole exome sequencing (WES). Clinical, laboratory, histological, and molecular data were collected. RESULTS: Four patients (three males) were identified. The age at first noted clinical signs and symptoms was 6, 2.5, 14, and 2 years respectively; the mean age was 6 years. Those signs and symptoms include pruritus (2 out of 4 patients) and hepatomegaly with splenomegaly (4 out of 4 patients). The age at the time of referral to our centre was 9, 3, 15, and 2.5 years respectively, while the mean age was 7 years. Chronic cholestatic liver disease of unknown aetiology was established in all of them. The NGS analysis was performed in all patients at the last follow-up visit. Three novel variants including c.902T>A, p.Met301Lys, c.3279+1G>A, p.?, and c.3524T>A, p.Leu1175His were identified. The time from the first consultation to the final diagnosis was 14, 9, 3, and 1 year respectively; the mean was 6.8 years. A detailed follow-up was presented. CONCLUSIONS: The clinical phenotype of PFIC-3 could be variable. The clinical and biochemical diagnosis of PFIC-3 is difficult, thus the NGS study is very useful in making a proper diagnosis.
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Subfamilia B de Transportador de Casetes de Unión a ATP/deficiencia , Colestasis Intrahepática/diagnóstico , Colestasis Intrahepática/genética , Mutación/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adolescente , Niño , Preescolar , Colestasis Intrahepática/terapia , Femenino , Estudios de Seguimiento , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , PoloniaRESUMEN
Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. We measured gene expression by microarrays in 235 liver transplant biopsies from 10 centers. Unsupervised archetypal analysis based on expression of previously annotated rejection-related transcripts identified 4 groups: normal "R1normal " (N = 129), T cell-mediated rejection (TCMR) "R2TCMR " (N = 37), early injury "R3injury " (N = 61), and fibrosis "R4late " (N = 8). Groups differed in median time posttransplant, for example, R3injury 99 days vs R4late 3117 days. R2TCMR biopsies expressed typical TCMR-related transcripts, for example, intense IFNG-induced effects. R3injury displayed increased expression of parenchymal injury transcripts (eg, hypoxia-inducible factor EGLN1). R4late biopsies showed immunoglobulin transcripts and injury-related transcripts. R2TCMR correlated with histologic rejection although with many discrepancies, and R4late with fibrosis. R2TCMR , R3injury , and R4late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2TCMR scores. No confirmed cases of clinical antibody-mediated rejection (ABMR) were present in the population, and strategies that previously revealed ABMR in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management.
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Trasplante de Corazón , Trasplante de Riñón , Trasplante de Hígado , Biopsia , Rechazo de Injerto/etiología , Rechazo de Injerto/genética , Trasplante de Hígado/efectos adversosRESUMEN
BACKGROUND: According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs. ledipasvir/sofosbuvir±RBV (LSR) in PI-experienced patients in real-life setting. METHODS: Our analysis included patients registered in the nationwide, investigators initiated, multicentre EpiTer-2 database. Among 4530 patients registered, 335 with genotype 1 (93% 1b) were previously treated with IFN-based regimens with PIs: 127 with boceprevir (BOC), 208 with telaprevir (TVR). Patients with advanced fibrosis (F3/F4) were significantly predominant (BOC 28.4%/61.4%, TVR 18.8%/64.4%, respectively). Subjects were assigned to IFN-free retreatment as follows: BOC - 64 (50.4%) PrODR and 63 (49.6%) LSR; TVR- 103 (49.5%) PrODR and 105 (50.5%) LSR. RESULTS: SVR rates were comparable for particular groups: BOC â PrODR- 100%; BOC â LSR - 98%; TVR â PrODR - 97%; TVR â LSR - 96% (intent-to treat analysis-ITT) and BOC â PrODRâ100%; BOC â LSR - 99%; TVR â PrODR - 99%; TVR â LSR - 98% (modified intent-to treat analysis-mITT). Both treatment regimens had a favourable safety profile. Adverse events (AEs) were generally mild or moderate in severity. Three deaths were reported. The treatment was stopped due to AEs in five patients (three treated with PrODR and two with LSR). CONCLUSION: Efficacy and safety of treatment with PrODR and LSR is comparable in BOC or TVR-experienced patients.
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Anilidas/administración & dosificación , Bencimidazoles/uso terapéutico , Carbamatos/administración & dosificación , Farmacorresistencia Viral Múltiple/efectos de los fármacos , Fluorenos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Macrocíclicos/administración & dosificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Uracilo/análogos & derivados , Uridina Monofosfato/análogos & derivados , 2-Naftilamina , Adulto , Anciano , Anilidas/efectos adversos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Carbamatos/efectos adversos , Estudios de Cohortes , Ciclopropanos , Quimioterapia Combinada , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Humanos , Interferones/administración & dosificación , Interferones/efectos adversos , Lactamas Macrocíclicas , Compuestos Macrocíclicos/efectos adversos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Prolina/análogos & derivados , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/efectos adversos , Ritonavir/efectos adversos , Sofosbuvir , Sulfonamidas/efectos adversos , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/efectos adversos , Uridina Monofosfato/uso terapéutico , Valina , Adulto JovenRESUMEN
UNLABELLED: Available data on prevalence of HCV genotypes in Poland are insufficient. The aim of the study was the analysis of distribution of HCV genotypes in Poland over the period of recent 10 years regarding the age of patients and the regions of the country. MATERIAL AND METHODS: Analysis of HCV genotypes in Poland was carried out between 2003 and 2012, and included 14 651 patients from 22 centers where patients with chronic viral hepatitis C are diagnosed and treated. Genotypes were analyzed in age groups (< 20 years of age, 20-40 years of age, > 40 years of age) as well as in populations of HBV and HIV co-infections. RESULTS: Genotype (G) 1 infection was demonstrated in 79.4%, G2 -0.1%, G3- 13.8%, G4- 4.9%, G6-0.09% and mixed infections in 1.6%. There was no infection with genotype 5. The highest prevalence of G1 was observed in the Lódzkie voivodship (89.2%) and the Slaskie voivodship (86.7%) while the lowest one in the Warminsko-mazurskie (62.0%) and the Podlaskie voivodships (68.2%). Genotype 3 most commonly occurs in the Warminsko-mazurskie (28.1%), and the Podlaskie voivodships (23.0%) and is least common in the Malopolskie (7.9%) and the Lódzkie voivodships (9.0%). Genotype 4 is more common in the Kujawsko-pomorskie (11.7%) and the Podlaskie voivodships (8.6%) and relatively less common in the Lubelskie (1.1%) and the Lódzkie voivodships (1.8%). Prevalence of G1 infection in 2003-2004 was 72% and increased up to 85.6% in 2011-2012, that was accompanied by decrease of G3 prevalence from 17% to 8% in this period. In HBV co-infected (n = 83), G1 infection was demonstrated in 85.5%, G3 - in 7.2%, G4 -4.8%, and mixed genotypes in 6%. Among HIV co-infected (n = 391), a much lower prevalence of G1 (33.0%) and a high of G3 (40.4%) as well as G4 (24.0%) were observed. CONCLUSIONS: There is a geographic variability of HCV genotypes prevalence in Poland. Increase of HCV G1 infections and decrease of G3 and G4 were observed in the last 10 years. Genotypes G3 and G4 occur more often in HCV/HIV co-infected than in HCV mono-infected patients.
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Frecuencia de los Genes , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , ARN Viral/genética , Adolescente , Adulto , Hepacivirus/clasificación , Humanos , Persona de Mediana Edad , Polonia/epidemiología , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de Riesgo , Población Rural/estadística & datos numéricos , Análisis de Secuencia/métodos , Población Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
High alcohol intake leads to an inadequate diet and impaired absorption, transport, and utilization of nutrients in the body, which results in malnutrition. Micronutrient supplementation, such as vitamins A, E, group B vitamins, folic acid zinc, and selenium may have a positive effect on those patients. In this article, the actual supplementation recommendations for vitamins and microelements in ethanol-induced liver disease patients are presented.
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HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.
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Hepatitis C infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, more and more is being heard about extrahepatic manifestations of the hepatitis C infection including its possible influence on the development of hypertension and cardiovascular diseases. In the given work, the frequency analysis of the incidence of hypertension and cardiovascular diseases among 2898 HCV-infected patients treated in Poland and the assessment of their relevance to the HCV genotype and the progression of liver fibrosis can be found. The prevalence of hypertension in the group of analyzed patients was 39% and was significantly associated with old age (OR = 1.08 (1.07-1.08)) and female sex, as well as the progression of liver fibrosis (OR = 1.54 (1.29-1.85)). Hypertension was found in 47.6% of patients with F4 fibrosis, 42.1% of patients with F3 fibrosis, and 25% of patients with F1 fibrosis. The incidence of cardiovascular disease in the studied group of patients was as follows: all incidents, 131 (4.52%); including ischemic heart disease 104, (3.95%); stroke, 2 (0.07%); atherosclerosis, 21 (0.72%); and aneurysms, 4 (0.14%). The obtained results prove that the prevalence of cardiovascular diseases is significantly associated with the advanced age of patients and the progression of liver fibrosis. The relevance of sex and the HCV genotype to the prevalence frequency of cardiovascular diseases in the study group has not been proven. This being the case, no differences in the frequency of their incidence depending on the HCV genotype, including genotype 3, was found. Hepatitis C infection as a non-classical risk factor for cardiovascular disease and hypertension does require further studying.
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Initiated in April 2008 Polish multicenter study HEP2008 aimed clinical data concerning safety and efficacy of adefovir dipivoxil (ADV, Hepsera, Gilead Sciences) in adult chronically infected HBV with lamivudine (LAM) resistance after earliest treatment. We examined 38 men (70.4%) and 16 women (29.6%) with chronic hepatitis B in age 23-81 (average 53) mostly HBeAg positive (70.4%). Majority of patients received earlier LAM (72%), but others additional entekawir and\ or pegylated interferon. Average time from discovering infection HBV was 95 +/- 77 (10-307) months. Majority of patients received monotherapy ADV, but physicians decided at 12 (22%) persons about continuation of LAM therapy. Median HBV DNA level decreased from a baseline value 6.73 +/- 1.71 (1.8-9.0) to 3.25 log10 copies/mL. At least HBV DNA drop 1 log10 and 2 log10 get 78.8 and 60.6% in 24 week, 84.8 and 69.7% in 48 week. HBV DNA reduction below level 300 and 50 copies/mL it observed in 15.2 and 6.1% in 24 week, 39.4 and 30.3% in 48 week. Patients with undetectable Mean ALT activity dropped significantly and were below limit norm at 24 week in 40%, and at 48 week in 58% of patients. Patients treated ADV and LAM reached great reduction of ALT activity but was no influence on HBV DNA reduction. Results of research have confirmed efficiency and safety 48-week's therapy ADV in patients with LAM resistance.
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Adenina/análogos & derivados , Antivirales/administración & dosificación , Farmacorresistencia Viral , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/administración & dosificación , Organofosfonatos/administración & dosificación , Adenina/administración & dosificación , Adenina/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Polonia , Resultado del Tratamiento , Carga ViralRESUMEN
Ulcerative colitis is a chronic inflammatory bowel disease of the colon. The most frequent symptoms include bloody diarrhoea with rectal urgency and tenesmus. It is often complicated by the presence of primary sclerosing cholangitis, a chronic, cholestatic liver disease, characterised by the inflammation and fibrosis of bile ducts. The presence of primary sclerosing cholangitis seems to alter the course of ulcerative colitis, changing its natural course.
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Liver transplantation (LTx) is an accepted method of hepatocellular carcinoma (HCC) treatment in cirrhotic patients; however, it has many limitations, and there is a substantial risk of recurrence. Most relapses occur within the first 2 posttransplant years. We aimed to present a late extrahepatic recurrence of HCC 10 years after LTx, and we discuss the possible risk factors and ways to improve transplantation results. A 68-year-old patient with liver cirrhosis and HCC on the background of chronic HCV and past HBV infection was transplanted urgently due to the rapid decompensation. Anti-HCV treatment before surgery was unsuccessful. Pretransplant computed tomography showed 1 focal 4.5 cm lesion consistent with HCC. Histopathology of the explanted organ showed 2 nodules outside the Milan criteria. Angioinvasion was not found. The patient achieved a sustained viral response to pegylated interferon and ribavirin 2 years post-LTx. Eight years were uneventful. CT of the abdomen performed occasionally was normal. Ten years after LTx, the patient unexpectedly presented with shortness of breath, fatigue, and weight loss. Two metastatic nodules of HCC in the lungs and pelvis were found. Although late HCC recurrence post-LTx is rare, it should be always considered, especially when risk factors such as viral infections and underestimation of tumor advancement were identified. We advocate that oncological surveillance of HCC relapse has to be continued during the whole posttransplant period. High AFP levels, the unfavorable neutrophil to lymphocyte ratio, and better estimation of primary tumor size seem to be useful in the identification of good candidates for transplantation.
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ABSTRACT: Biliary complications (BC) especially stenosis and strictures are the most common complications after orthotropic liver transplantation (OLT) procedure in adult recipients. The intention of this study was analyzed BC in 273 patients after OLT for the last 4 years in our department.Retrospective study of 273 patients underwent cadaveric donor liver transplantation between January 2014 and December 2017. Most of them (nâ=â268) have anastomosed bile duct in end to end, rest of them (nâ=â5) underwent hepaticojejunostomy. Statistical analysis was performed using Fischer exact test and Student t test. A P value <.05 was considered significant.BC were developed in 48/273 transplants (17.6%). The most frequent was biliary stricture (nâ=â42, 87.5%) followed by bile leak (nâ=â4, 8.3%) and choledocholitiasis (nâ=â2, 4.2%). Treatment was usually using endoscopic retrograde cholangiopancreatography. Recipients with hypotension during and after OLT treated by norepinephrine have a higher index of BC.Self-expanding metal stents implantation seems to be more effective than repeated balloon dilatation of anastomotic strictures with subsequent plastic biliary stent placement and associated with similar complication rate. Good fluid management against inotropic therapy may reduce risk of BC.
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Enfermedades de las Vías Biliares/etiología , Trasplante de Hígado/efectos adversos , Adolescente , Adulto , Anciano , Enfermedades de las Vías Biliares/patología , Enfermedades de las Vías Biliares/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Stents Metálicos Autoexpandibles , Adulto JovenRESUMEN
BACKGROUND: This study analysed the NS3 and NS5A mutation frequencies, persistence and drug susceptibility in a cohort of real-life patients, with failed hepatitis C virus (HCV) therapy following directly acting antiviral (DAA) treatment. METHODS: NS3/NS5A Sanger sequences from 105 patients infected with HCV genotype (G) 1a (6,5.7%), G1b (94,89.5%), G3a (4,3.8%), and G4 (1,1.0%) post DAA treatment failure were analysed. NS3 and NS5A resistance-associated substitutions (RASs) were identified using the geno2pheno algorithm and associated with clinical variables. Time trends were examined using logistic regression. RESULTS: NS5A RAS were found in 87.9% of sequences derived from patients exposed to this class of agents, whereas NS3 RAS was found in 59.1% of HCV protease-exposed subjects. The frequency of the NS3 RAS increased with fibrosis stage, from 40.0% among F0/F1 individuals to 81.8% among patients with liver cirrhosis (F4, p = 0.094). NS5A mutation frequencies were 7.6% for 28A/V/M, 10.6% for 30 K/Q/R, 42.4% for 31I/F/M/V, and 75.8% for 93H. For NS3, the most common RASs were 56F-23.7%, 168A/E/I/Y/T/V-14.0%, and 117H-5.4%. Susceptibility to glecaprevir/pibrentasvir, velpatasvir/voxlaprevir, and elbasvir/grazoprevir was retained in 92.9%, 43.4%, and, 25.3% of patients, respectively. The frequency of NS3 RAS decreased with time elapsed from failure to sampling (p = 0.034 for trend). NS5A RAS frequency remained stable over the 24-months. CONCLUSIONS: Following DAA treatment failure, NS5A and NS3 RASs were common with increasing frequency among patients with advanced liver disease. In most cases, despite the presence of RASs, susceptibility to DAA combinations with higher genetic barrier was retained.
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Sustitución de Aminoácidos , Antivirales/farmacología , Farmacorresistencia Viral/genética , Hepacivirus/genética , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , PoloniaRESUMEN
Liver injury-expressed as elevated liver enzymes-is common in patients with COVID-19. Little is known about the potential mechanisms of liver damage by SARS-CoV-2. A direct cytopathic effect on hepatocytes as well as injury related to hypoxia or hepatotoxicity are being considered. The aim of the study was to compare the clinical characteristic of COVID-19 disease in patients with normal and abnormal liver enzymes activity. A group of 150 patients with COVID-19, hospitalized in our center, was analyzed. Patients with the known liver comorbidities were excluded (n = 15). Clinical features and laboratory parameters were compared between patients with normal and abnormal aminotransferase values. Liver injury expressed as any alanine aminotransferase (ALT) elevation was noted in 45.6% of patients hospitalized due to COVID-19. The frequencies of aspartate aminotransferase (AST) elevation were lower. It was noted that elevated ALT/AST unfavorably affected other parameters related to liver function such as albumin level; gamma-glutamyl transpeptidase (GGTP); and partly, ALP activity and influenced inflammation-related parameters. The most probable cause of mild hepatitis during COVID-19 was anoxia and immune-mediated damage due to the inflammatory response following SARS-CoV-2 infection. A direct cytopathic effect of SARS-CoV-2 on hepatocytes, albeit less probable, can be considered as well. The use of potentially hepatotoxic drugs may contribute to liver damage.
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BACKGROUND COVID-19 is an infectious disease caused by SARS-CoV-2. It has spread rapidly through the world, endangering human life. The main target of COVID-19 is the lungs; however, it can involve other organs, including the liver. Patients with severe COVID-19 have an increased incidence of abnormal liver function, and patients with liver disorders are considered to be at a higher risk of severe COVID-19 infection. The mechanism of liver injury reported in 14% to 53% of COVID-19 patients is poorly recognized and several possibilities need to be considered (cytokine storm, direct viral action, hypoxia). The incidence of underlying liver comorbidities in patients with a COVID-19 infection ranges from 1% to 11%. CASE REPORT This is a report of 2 nosocomial COVID-19 infections and severe COVID-19 pneumonia in 2 patients who were hospitalized during treatment for alcoholic liver disease (ALD). Case 1 and case 2 were a 31-year-old woman and a 40-year-old woman, respectively, with decompensated ALD and symptoms of the COVID-19 infection. Both patients were transferred from another hospital to our hospital after confirmation of COVID-19 during their hospitalization. The course of the infection progressed rapidly in both patients with the development of multiple-organ failure and death over a short period. CONCLUSIONS There are no clear recommendations on the management of ALD in the COVID-19 pandemic. Alcoholic hepatitis may be a risk factor for severe COVID-19 and a poor outcome. A high percentage of nosocomial COVID-19 infections are observed; therefore, special precautions should be taken to minimize the risk of COVID-19 exposure.
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Infecciones por Coronavirus/diagnóstico , Infección Hospitalaria/diagnóstico , Hepatopatías Alcohólicas/terapia , Neumonía Viral/diagnóstico , Síndrome Respiratorio Agudo Grave/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , COVID-19 , Terapia Combinada , Infecciones por Coronavirus/complicaciones , Infección Hospitalaria/terapia , Progresión de la Enfermedad , Resultado Fatal , Femenino , Hospitalización , Humanos , Hepatopatías Alcohólicas/diagnóstico , Insuficiencia Multiorgánica , Pandemias , Neumonía Viral/complicaciones , Radiografía Torácica/métodos , Respiración Artificial , Medición de RiesgoRESUMEN
Hepatitis delta (HDV) virus still poses a serious health problem worldwide. Being a satellite particle, it may complete its life cycle only in the presence of HBs antigen produced by hepatitis B virus (HBV). According to epidemiological data, about 5% of HBs antigen carriers are infected with this virus, which equates to approximately 15-20 million individuals worldwide. Although the infection with both HBV and HDV viruses is considered to be the worst form of viral hepatitis, the only approved treatment, with pegylated interferon α, is not satisfactory. Thus effective and safe therapy is still lacking, which stands in contrast to the latest development in therapeutic areas of HBV and hepatitis C virus (HCV) infections. As the exact data on prevalence of this infection in some countries as well as natural history of this disease are still incomplete, further studies are warranted. Polish investigations on this field are very scarce and at most dating from the 1990s. This publication makes another attempt to broaden our knowledge of this temporarily forgotten but still ongoing and complex problem.
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A case is presented of mucormycosis in a patient with acute myeloblastic leukemia following liver transplantation for Wilson's disease. A 58-year-old female was admitted to the Department of Haematology with deterioration of her general condition, loss of appetite, tiredness and difficulty with mental contact for a few days. Blood and urine cultures for bacteria and fungus, galactomannan antigen were negative. Whole body computed tomography demonstrated bilateral hilar lymphadenopathy with necrotic lesions: splenomegaly with a hypodensive lesion 13 × 20 × 19 mm and lower pulmonary infiltrates suggested fungal etiology. Magnetic resonance imaging of the brain showed thickened meninges. Finally, mucormycosis was diagnosed. Treatment with amphotericin B lipid complex was started, resulting in an partial improvement of the general condition and decreased level of inflammatory markers. However, the patient's condition continued to deteriorate, with sepsis etiology Escherichia coli, and despite the intensive managements she eventually died.
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Degeneración Hepatolenticular/cirugía , Leucemia Mieloide Aguda/complicaciones , Trasplante de Hígado/efectos adversos , Mucormicosis/etiología , Complicaciones Posoperatorias/etiología , Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Resultado Fatal , Femenino , Degeneración Hepatolenticular/complicaciones , Humanos , Persona de Mediana Edad , Mucormicosis/diagnóstico , Mucormicosis/diagnóstico por imagen , Mucormicosis/tratamiento farmacológico , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/tratamiento farmacológicoRESUMEN
BACKGROUND There is a worldwide increase in use of liver transplantation (LT) for treatment of hepatocellular carcinoma (HCC). We analyzed our experience with LT for HCC to determine long-term and recurrence-free survival, accuracy of imaging diagnosis of HCC compared to the explant pathology, recurrence rate of HCC, and predictors of recurrence. MATERIAL AND METHODS The whole explant was examined by the same pathologist and compared with the baseline diagnosis established according to clinical, laboratory, and radiological data. A group of patients with pathologically confirmed HCC was characterized, with special attention to etiology, survival, recurrence, and diagnostic accuracy of imaging techniques. RESULTS Among 718 patients transplanted from 2000 to 2018 in our center, HCC was found in 166 explanted livers. In 42 cases the clinical diagnosis of HCC was not accurate, being either false positive or negative; however, the specificity and sensitivity of CT/MRI in HCC recognition was 97.87% and 88.24%, respectively. Five- and 10-year survival was 81.27% and 66.57%, respectively, and it was inferior to the overall survival. The recurrence rate was 9.6% with a median time to recurrence of 14 months and a median survival time of 9 months. Poor differentiation of HCC and HCV etiology of the baseline disease, but not previous DAA treatment, were the risk factors of HCC recurrence. CONCLUSIONS Adherence to strictly defined selection criteria for LT in HCC patients guarantees the success of LT in HCC treatment.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Trasplante de Hígado , Recurrencia Local de Neoplasia/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
AIM OF THE STUDY: This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy. MATERIAL AND METHODS: Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used. RESULTS: Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic. CONCLUSIONS: Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions.
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BACKGROUND/AIMS: Comparison of the iron status in patients who responded and did not respond to combination treatment with interferon alpha and ribavirin in chronic hepatitis C. METHODOLOGY: The study group comprised of 61 patients with chronic hepatitis C (genotype 1) treated with alpha 2b interferon and ribavirin. The iron metabolism was evaluated based on serum iron level, total iron binding capacity, transferrin saturation, serum ferritin concentration and hepatic iron concentration. In the evaluation of antiviral treatment efficacy biochemical and virological responses were taken into account. RESULTS: End of treatment response was observed in 38 patients (62%). Significant differences in iron parameters were not observed between responders and non-responders. Also, sustained viral response, 6 months after treatment completion, was reached in 32 patients (52.5%). Iron metabolism parameters did not differ significantly in the group of sustained responders versus non- responders. Finally, ALT normalization was observed in 42 patients (68.9%). Again, no significant differences in iron status were observed between patients with and without biochemical response excluding significantly higher serum ferritin concentration in non-responders. CONCLUSIONS: Results of this study show that iron status does not significantly influence the efficacy of treatment with interferon and ribavirin in patients with chronic hepatitis C.