Search

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.

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.

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.

Case series Patient: Female, 31-year-old • Female, 40-year-old Final Diagnosis: Alcohol liver disease • COVID-19 Symptoms: Ascites • cough • dyspnea • jaundice Medication: — Clinical Procedure: CT scan Specialty: Anesthesiology • Gastroenterology and Hepatology • Infectious Diseases • General and Internal Medicine Objective: Rare co-existance of disease or pathology 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 Reports: 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.

The aim of the study is to analyze treatments available for patients infected with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the interferon (IFN)-free era and evaluate the efficacy and safety of different therapeutic options administered in a real-world setting. We analyzed data of 198 patients who started antiviral therapy after July 1, 2015, and completed it before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were treatment experienced. Fifty percent of patients were assigned to sofosbuvir (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36% received SOF+RBV, and 5% SOF+daclatasvir (DCV)±RBV. Cirrhotic patients were assigned more frequently to IFN-free regimens. Overall, a sustained virological response was achieved by 84.3% of patients in intent-to-treat (ITT) analysis and 87% in modified ITT analysis. For SOF+PegIFNa+RBV and SOF+DCV±RBV regimens, the sustained virologic response (SVR) rate reached at least 90%, whereas the two other therapeutic options demonstrated efficacy

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.

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.

Background Alcoholic cirrhosis is an indication for 40% of liver transplantations (LT) in Europe. In most centers, 6 months of abstinence is required before listing. However, alcohol recidivism is quite high after LT, and approximately 20–25% of recipients with ALD resume harmful drinking, resulting in liver insufficiency, which casts doubt on the 6-months rule as a reliable marker of abstinence maintenance after LT. Material/Methods We analyzed data on patients who underwent orthotopic LT in Marie Curie Hospital, Szczecin, Poland, from 2000 to 2015 due to alcoholic or cryptogenic cirrhosis. Every ALD patient met the 6-month abstinence requirement. Alcohol recidivism has been studied based on a history of alcohol abuse taken from the patients or from their relatives, and in case of denial, on laboratory tests for alcohol abuse. Five patterns of recidivism were distinguished: death, constant heavy drinking, heavy drinking with abstinence attempts, occasional laps, and a single episode of alcohol intake. The analysis of survival was performed according to the Kaplan-Meier method. Patient survival rates in ALD recipients vs. non-ALD recipients were compared using the log-rank test. Results Alcohol recidivism was finally evaluated in 109 patients: 81 males and 28 females, with a median age of 53.3 years (range 30–66). Harmful drinking was discovered in 16 patients (14.7%), including seven deaths due to alcoholic hepatitis. Sporadic or episodic drinking was found in 29 patients (27%). In heavy drinkers, the abstinence period after transplantation was significantly shorter and patients were younger than the average (median age 43.8 years). Women break abstinence faster than men and are at greater risk of liver insufficiency. Five, 10 and 15-year survival in the ALD group was superior in comparison with non-ALD group, but differences did not reach statistical significance (p=0.066, p=0.063, p=0.075, respectively). Conclusions The prognostic value of a 6-month abstinence period before transplantation is rather low as it does not predict sobriety after transplantation. However, only a minority of such patients drink harmfully. Survival in ALD recipients tends to be better in comparison with survival in the other etiologies. Younger women dependent on alcohol shortly before LT are at greatest risk of recidivism.

BACKGROUND Despite excellent transplantation results, there is a vulnerable period of time in the post-transplant management of pediatric liver recipients, which is the time when a child becomes an adolescent. This period of psychological distress influences compliance and may result in premature transplant failure and graft loss. We performed a retrospective review of pediatric liver transplant recipients, transferred to our service for adults, in order to identify key issues associated with transition into the adult care. MATERIAL AND METHODS We analyzed medical files of 20 liver recipients transferred from pediatric post-transplant outpatient clinic to the post-transplant service for adults, since year 2000 until December 2015. For survival analyses, Kaplan-Meier model with log-rank test and Cox proportional hazards regression model, to calculate hazard ratio (HR), were used. RESULTS Survival rate exceeds 90% in the study population. The major complication was late acute rejection, in most instances due to non-compliance. There were single cases of recurrent liver disease and de novo graft disorders. CONCLUSIONS Dedicated service for young people may be needed to optimize outcomes.

SummaryBackground Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. Aim To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. Methods Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. Results A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child–Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. Conclusions The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.

Attempt to create simple practical algorithm for prospective assessment of PEG interferon/ribavirin related treatment response in individuals with chronic hepatitis C (CHC) basing on the risk factors defined prior to the treatment initiation.Retrospective assessment of 45 female and 39 male previously untreated CHC patients aged 20 to 73 years, with genotype 1, undergoing standard treatment with PEG-IFNa2b+RBV was performed. For the final analysis 78 patients were included (38 effectively treated and 40 treatment failures). Thirty-six sustained virological response (SVR) related factors, which were routinely measured before treatment initiation were compared (including physical, biochemical, serologic and histopathologic). From this group the risk factors of the highest predictive value for treatment failure were selected. Cut-off values for statistical significance were defined for each parameter, with risk score (RS) calculated and compared in the group with and without SVR.Seven factors related to treatment failure were identified: HCV600000 IU/L, blood platelet count150000/ul, GGTP45 IU/ml, total serum protein7.8 g/dl, glycaemia105 mg/dl, detectable HBc IgG antibodies and cirrhosis. In the group with RS 1 the likelihood of SVR was 70% (p0.028), while in patients with RS 3 the response was reduced to 23.8% (p0.016), with no SVR achieved among patients with RS3.Low risk score (0-2) is associated with high probability of treatment success with scores3 predictive for treatment failure. The presented model is a simple tool for prediction of treatment success for clinical use before PegIFN/RBV treatment initiation among genotype 1 CHC patients.

Background/Aims: Though there is a consensus that the HLA DQB1*0301 allele is important in untreated HCV clearance, this association is not universal and a number of genes outside the major histocompatibility complex may also play a role in host responses to HCV infection. Prime candidates, at present, are the genes encoding pro-inflammatory and immuno-regulatory cytokines. The aim of this study was to investigate the relationship between a number of these candidate genes and both spontaneous and treatment related clearance of hepatitis C virus infection. Methods: Three members of the interleukin-1 gene family: IL-1A, IL-1B and IL-1RN, three polymorphic sites in the interleukin-10 gene promoter (− 1082, − 819, − 592) and two in the tumour necrosis factor-alpha promoter (− 308, − 238) were studied in two independent DNA banks, each with appropriate controls. Standard PCR-based genotyping techniques were used. Results: No significant difference in the distribution of any of the polymorphisms was found in either study set. Conclusions: These findings in two large groups suggest that future investigations should focus on other candidate genes and may support the view that MHC-encoded susceptibility to chronic HCV infection may be determined by MHC class II rather than MHC class III genes.

AIMS/BACKGROUND Recent evidence suggests that spontaneous clearance of hepatitis C virus (HCV) may be associated with the HLA DQB1*0301 allele but there is still some debate over the role of other alleles and HLA haplotypes in HCV infection. As this may best be resolved by studying genetically different populations, we have investigated HLA class II-encoded susceptibility and resistance to HCV infection in a relatively sedentary population of patients from northwestern Poland. METHODS The distributions of HLA class II DRB1, DQA1, DQB1 and DPB1 alleles were determined by standard PCR-protocol in 129 unrelated patients with chronic hepatitis C (anti-HCV and HCV-RNA positive) and 103 healthy unrelated racially-matched control subjects. Fifty-five patients were treated with alpha-interferon (5 MIU thrice weekly for 6 months) out of whom 29 showed a complete response and 26 were non-responders. RESULTS A significantly reduced frequency of the DQB1*0301 allele in the patients was observed (24.0% vs. 38.8%; p=0.015). Additionally, two different DR-DQ haplotypes were found to be associated with chronic HCV infection: DRB1*1501-DQA1*01-DQB1*0602 (24.0% vs. 12.6%; p= 0.027) and DRB1*0701-DQA1*0201-DQB1*02 (31.8 vs. 12.6%; p=0.0006), the latter difference being most pronounced in those patients who responded to alpha-interferon treatment (41.4% vs. 12.6%; p=0.00048). CONCLUSIONS The results confirm the negative association between chronic HCV and DQB1*0301 and identify two novel genetic associations. In particular, the DRB1*0701-DQA1*0201-DQB1*02 haplotype is associated with both chronic infection and response to alpha-interferon. Interestingly, the same haplotype is reportedly associated with non-response to hepatitis B vaccination.

Different forms of interferon alpha (IFN-α) have been used for several years in the treatment of chronic viral hepatitis type C (CVHC). Currently, pegylated forms of interferon alpha (PegIFN-α) in combination with ribavirin is the standard treatment. During therapy with IFN-α, side-effects occur, including thyroid diseases. The aim of this study was an evaluation of administered interferon's impact on the frequency of autoimmune thyroiditis (ATI) occurrence among patients with CVH type C treated with INF-α and an assessment as to whether the type of interferon used is significant in ATI development.149 patients aged 18-70 (mean 43.9 ± 2.3 years) with CVH type C participated in the study. The serum concentrations of thyrotrophin (TSH), free tyrosine (FT4), triiodothyronine (FT3), thyreoglobulin (Tg), antithyroid antibodies: antiperoxidase (TPOAb) and antithyreoglobulin (TgAb) were evaluated before, and after six and 12 months of treatment. Additionally, the thyroid echostructure was evaluated with ultrasonography. Sixty out of 149 patients received Peg-INF-α, and 89 patients were treated with recombinant IFN-α.ATI was confirmed in nine patients (6.04%) with CVH type C before the introduction of interferon. Seven of them underwent an exacerbation of hypothyroidsm during therapy with interferon. In 24 patients (17.14%), who did not have the signs of ATI at baseline, an elevated concentration of antithyroid antibodies was detected during therapy with interferon. The mean concentrations of TPOAb before, and after six and 12 months of treatment were, respectively: 12.4; 310.4 and 141.3 IU/ml, and the mean concentrations of TgAb were, respectively: 17.40; 108.0; and 125.6 IU/ml. After six months of treatment in this group of patients, 11 had hypothyroidsm and six had hyperthyroidsm. After 12 months of therapy, four patients had hypertthyroidsm and four showed signs and symptoms of hypothyroidsm; the remaining patients were in a euthyroid state. In ultrasound examination, reduction of echogenicity among patients with ATI before treatment was revealed in 75% of cases at baseline, in 83.3% after six months and in 100% after 12 months of treatment. In the group of patients presenting with ATI during IFN-α therapy, in which no disorders were found in initial examination, after six months of treatment a reduction of echogenicity was found in 69.2%, and after 12 months in 75%, of patients.Among patients treated with interferon due to CVH type C, there is a risk of the development of ATI or the exacerbation of an existing one. There is no significant difference in ATI presentation in relation to the type of IFN-α used for treatment.

Though there is a consensus that the HLA DQB1*0301 allele is important in untreated HCV clearance, this association is not universal and a number of genes outside the major histocompatibility complex may also play a role in host responses to HCV infection. Prime candidates, at present, are the genes encoding pro-inflammatory and immuno-regulatory cytokines. The aim of this study was to investigate the relationship between a number of these candidate genes and both spontaneous and treatment related clearance of hepatitis C virus infection.Three members of the interleukin-1 gene family: IL-1A, IL-1B and IL-1RN, three polymorphic sites in the interleukin-10 gene promoter (- 1082, - 819, - 592) and two in the tumour necrosis factor-alpha promoter (- 308, - 238) were studied in two independent DNA banks, each with appropriate controls. Standard PCR-based genotyping techniques were used.No significant difference in the distribution of any of the polymorphisms was found in either study set.These findings in two large groups suggest that future investigations should focus on other candidate genes and may support the view that MHC-encoded susceptibility to chronic HCV infection may be determined by MHC class II rather than MHC class III genes.