Effectiveness of pangenotypic retreatment of chronic hepatitis C after prior failure of pangenotypic therapies.

INTRODUCTION: Despite the overall excellent efficacy of pangenotypic direct­acting antiviral (DAA) options, there is still a small percentage of patients with hepatitis C virus (HCV) infection who do not respond to the therapy. OBJECTIVES: This analysis was designed to evaluate the effectiveness of pangenotypic retreatment in the cases of pangenotypic therapy failure. PATIENTS AND METHODS: The study included patients treated with the pangenotypic regimen, selected from the EpiTer­2 database, a real­world project evaluating DAA­based treatment in Poland. RESULTS: Of a total 15 123 patients, 4345 received 1 course of the pangenotypic treatment (PAN group) and 48 patients were retreated with pangenotypic regimens after a failure of the pangenotypic therapy (PAP group). The patients from the PAP group were more often men (79% vs 53%; P <0.001), had higher median (interquartile range [IQR]) body mass index (27.5 [25.7-30.1] vs 25.7 [22.9-28.7] kg/m2; P <0.001), were more often infected with genotype 3 (58% vs 27%; P <0.001), and more frequently had liver cirrhosis (46% vs 21%; P <0.001) than the patients in the PAN group. Importantly, no significant difference in the treatment effectiveness was found between the PAP and PAN groups with sustained virologic response (SVR) rate of 89.6% vs 93.7% (P = 0.39) in intention­to­treat, and 91.5% vs 97.6% (P = 0.17) in the per-protocol analysis. The selection of a specific retherapy regimen did not affect SVR. CONCLUSIONS: Our study demonstrated the excellent effectiveness of pangenotypic regimens and confirmed that most DAA nonresponders could be successfully retreated with another pangenotypic regimen. The best retreatment strategy is a triple pangenotypic regimen, especially in patients with unfavorable response factors, such as genotype 3 infection, cirrhosis, and male sex.

Hepatitis C Infection as a Risk Factor for Hypertension and Cardiovascular Diseases: An EpiTer Multicenter Study.

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.

HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study.

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.

Five-Year Follow-Up of Cured HCV Patients under Real-World Interferon-Free Therapy.

(1) Background: Treatment of hepatitis C virus (HCV) infections with direct-acting antivirals (DAA) has demonstrated high efficacy and an excellent safety profile. The cured patients showed a sustained virological response and improved liver function, but also a continued risk of hepatocellular carcinoma (HCC) during the 2-3 years of follow-up after treatment; (2) Methods: A total of 192 patients out of 209 of the primary AMBER study were analyzed five years after treatment with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin. Results: We confirmed that HCV clearance after DAA treatment is stable regardless of baseline liver fibrosis. We found that sustained virologic response is associated with a gradual but significant reduction in liver stiffness over 5 years. Liver function improved during the first 2 years of follow-up and remained stable thereafter. The risk of death due to HCC as well as death due to HCV persists through 5 years of follow-up after successful DAA treatment. However, in non-cirrhotic patients, it appears to clear up 3 years after treatment; (3) Conclusions: Monitoring for more than 5 years after curing HCV infection is necessary to assess the long-term risk of possible development of HCC, especially in patients with cirrhosis of the liver.

Cardiovascular risk assessment by electrocardiographic Holter monitoring in patients with chronic hepatitis C.

INTRODUCTION: Cardiovascular diseases are ranked as the third cause of mortality among people infected with hepatitis C virus (HCV), but the relationship of infection with cardiovascular risk remains disputable. We have focused on the comprehensive use of parameters obtainable during long-term electrocardiographic (ECG) Holter monitoring. MATERIAL AND METHODS: Heart rate variability and turbulence (HRV and HRT), deceleration/acceleration capacity (DC/AC), corrected QT interval (QTc) and late potential (LP) were used. 36 persons were included, and 30 healthy subjects formed a control group. All were submitted to 24-hour Holter ECG-monitoring. RESULTS: The studied groups were not statistically significantly different with regards to basic anthropometric parameters. Statistically significantly higher medium and maximum heart rhythm and aminotransferase activities were recorded in patients with hepatitis C. The HRV parameters r-MSSD, p50NN, HF, and absolute DC/AC values were significantly lower in the subjects with hepatitis C than those in the control group. The QTc interval, measured for nocturnal hours, was also significantly longer in that group. There were no differences in the albumin level or basic echocardiographic parameters, including left ventricle ejection fraction. Nor was there any difference in the HRT parameters, or LP. The most interesting observation was the positive correlation among the number of viral RNA copies and DC, and LF. CONCLUSIONS: We confirmed the presence of autonomic disorders with prevalence of sympathetic system activity and prolonged QTc interval in patients with chronic hepatitis C. Those parameters significantly correlated with infection intensity. Our results suggest that HCV infection could be an independent cardiovascular risk factor, not associated with the lipid profile. Further prospective studies are needed.

Low risk of HBV reactivation in a large European cohort of HCV/HBV coinfected patients treated with DAA.

OBJECTIVES: The aim of the study was to analyze the prevalence and clinical characteristics of HCV/HBV coinfection and to evaluate the rate of HBV-reactivation during anti-HCV therapy in a large real-world study. METHODS: Analyzed population consisted of 10,152 chronic hepatitis C patients treated with DAA between 2015 and 2019 in a nationwide study. Prior to the DAA all subjects had HBsAg and 60% anti-HBc testing. RESULTS: 111 of 10,152 patients (1.1%) had detectable HBsAg and 1239 of 6139 (20.2%) anti-HBcAb. The prevalence of occult hepatitis B was 0.48%. HCV/HBV patients were younger with a higher proportion of males, HIV-coinfected, and advanced fibrosis. They were less often diagnosed with diabetes but more often with chronic kidney disease. In HBsAg(+) subjects with baseline HBV-DNA available 6/102 (5.9%) HBV-reactivations during or after DAA therapy were observed, and in two (1.9%) significant hepatic flares were noted. In HBsAg(-)/anti-HBc(+) group 2 (0.16%) reactivations were observed only in patients undergoing immunosuppressive therapy. DISCUSSION: Data from a large European cohort suggest a relatively low risk of HBV-reactivation during DAA-therapy for HCV infection in HBsAg(+) patients. In HBsAg(-)/anti-HBc(+) HBV-reactivation seems to be limited to subjects with immunodeficiency. Importantly, previous exposure to HBV and occult hepatitis B is present in a significant proportion of HCV-infected.

Sofosbuvir/velpatasvir in treatment-experienced HCV-infected patients - short report.

AIM OF THE STUDY: The aim of this overview was to evaluate the efficacy of sofosbuvir/velpatasvir (SOF/VEL) combination in a real-life setting, with particular regard to treatment-experienced individuals. MATERIAL AND METHODS: Seventy-five consecutive patients who were treated with SOF/VEL, completed the 12-week follow-up and had sustained virologic response (SVR) evaluated were included in the analysis. Out of them, 60 (80%) patients were treatment-naïve and 15 (20%) were treatment-experienced. RESULTS: SVR rates reached 89.4% (66/75) in the whole study group and were comparable irrespective of the fibrosis stage or HCV genotype. However, a significant difference in treatment efficacy between treatment-naïve and treatment-experienced individuals was observed, with SVR rates of 98.3% (59/60) and 46.7% (7/15), respectively (p < 0.0001). CONCLUSIONS: Further studies including large real-life cohorts of treatment-experienced patients treated with SOF/VEL are warranted to elucidate the real efficacy of this regimen as a retreatment option.

Comparative effectiveness of 8 versus 12 weeks of Ombitasvir/Paritaprevir/ritonavir and Dasabuvir in treatment-naïve patients infected with HCV genotype 1b with non-advanced hepatic fibrosis.

PURPOSE: Since 2017 treatment-naïve patients infected with genotype 1b of hepatitis C virus and minimal or moderate fibrosis can be treated with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir (OPrD) for 8 weeks according to updated Summary of Product Characteristics. The aim of our study was to assess the comparative efficacy of 8 and 12-weeks therapy with OPrD in large cohort of patients eligible for 8 weeks regimen treated in real-world setting. MATERIALS AND METHODS: We analysed data of 3067 HCV genotype 1b infected patients treated with OPrD between 2015 and 2017. Final analysis included patients with none, minimal or moderate fibrosis (F0-F2). RESULTS: A total of 771 patients were enrolled in the study, including 197 (26%) treated for 8-weeks and 574 patients fulfilling criteria for 8-weeks but assigned to 12-weeks regimen. Majority of patients had no or minimal fibrosis (F0-F1). Longer treatment duration was more often administered in patients with moderate fibrosis, comorbidities, concomitant medications. SVR was achieved in 186 (94%) patients treated for 8 weeks and 558 (97%) for 12 weeks (p = 0.07). After exclusion of lost to follow-up patients, sustained virological response (SVR) rate reached 95% and 99%, respectively (p = 0.01). We were not able to identify factors associated with non-response. CONCLUSIONS: This real-word experience study confirmed similar, high effectiveness of 8 and 12-weeks regimens of OPrD in genotype 1b HCV infected patients with non-advanced fibrosis. Despite of reduced SVR rate after 8-weeks regimen, there is no need to extend therapy to 12-weeks in vast majority of such patients and no need to add ribavirin.

Effect of comedication on ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin therapy in chronic hepatitis C - a real-world study.

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.

Is Interferon-Based Treatment of Viral Hepatitis C Genotype 3 Infection Still of Value in the Era of Direct-Acting Antivirals?

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 <80%. The SVR rate in noncirrhotics was higher than in cirrhotics, irrespective of regimen. Adverse events were documented in 52.5%, with the most common being weakness/fatigue and anemia. We confirmed effectiveness and safety of the SOF-based treatment in a real-world cohort of patients with chronic HCV G3 infection. Most notably, we demonstrated good tolerability and high efficacy of the SOF+PegIFNa+RBV regimen.

Effectiveness and safety of ledipasvir/sofosbuvir±ribavirin in the treatment of HCV infection: The real-world HARVEST study.

BACKGROUND: To evaluate the effectiveness and safety of ledipasvir/sofosbuvir (LDV/SOF)±ribavirin (RBV) regimen in a real-world setting. METHODS: Patients received a fixed-dose combination tablet containing LDV and SOF with or without RBV, for 8, 12 or 24 weeks. Patients were assessed at baseline, end of treatment, and 12 weeks after the end of treatment. The primary effectiveness endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: Of the 86 patients, aged 20-80 years, 82.6% were HCV genotype 1b-infected and 50.0% were cirrhotic. More than half (52.3%) had previously followed pegylated interferon-containing (PEG-IFN) treatment regimens, and 38.5% were null-responders. SVR12 was achieved by 94.2% of patients. All non-responders were cirrhotic: two demonstrated virologic breakthrough and the remaining three relapsed. All patients treated with an 8-week regimen achieved SVR12 despite having high viral load at baseline (HCV RNA of >1 million IU/mL in 8/10 patients, including one with a viral load of >6 million IU/mL). Adverse events were generally mild and transient. Most frequently, fatigue (22.1%), headache (15.1%), and arthralgia (7.0%) were observed. Laboratory abnormalities included anemia and hyperbilirubinemia. CONCLUSIONS: Treatment with LDV/SOF±RBV is an effective and safe option for patients with HCV, including those with advanced liver disease or a history of non-response to PEG-IFN-based therapy.

Heart rhythm turbulence and NT-proBNP in decompensated liver cirrhosis--a pilot study.

BACKGROUND: Heart rhythm turbulence (HRT) is a novel tool for evaluation of cardiovascular mortality. Liver cirrhosis is associated with hemodynamic and myocardial disturbances termed cirrhotic cardiomyopathy. In the stable stage of liver cirrhosis, systolic and myocardial dysfunction is correlated with brain natriuretic peptide (BNP). The aim was to evaluate HRT and its correlation with NT-proBNP, echocardiographic and biochemical parameters in patients with decompensation of liver cirrhosis. MATERIAL/METHODS: The study included 18 patients with decompensated liver cirrhosis and 18 healthy volunteers. Participants underwent echocardiography and 24-hour ECG monitoring. Serum NT-proBNP and other biochemical parameters were measured. Turbulence onset (TO) and turbulence slope (TS) were used to indicate HRT. RESULTS: Mean HR (87/min vs. 75/min), TO (-0.385% vs. -0.92%), NT-proBNP (304.85 pg/ml vs. 83.2 pg/ml), LAd (42.5 mm vs. 34.5 mm), RVdd (29.5 mm vs. 25 mm), SPAP (36.5 mmHg vs. 22.5 mmHg) were significantly (p<0.05) higher in patients with liver cirrhosis. Patients with normal TO and TS had better stage in Child-Pugh classification (P=0.04) than patients with abnormal values. Significant negative correlation was found between creatinine and TO, and between mean HR and TS, and significant positive correlation was found between LAd and TS. LV diastolic dysfunction was noted in a majority of cirrhotic patients (n=16). CONCLUSIONS: Patients with decompensated cirrhosis had elevated levels of NT-proBNP and LV diastolic dysfunction. TO values in cirrhotic patients differed significantly from the control group. These findings can indicate risk of symptomatic heart failure development and may be a marker of cirrhotic cardiomyopathy. HRT parameters seem not to be appropriate death predicators.

Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: a randomized, open-label study.

A randomized, open-label comparative study of entecavir versus adefovir therapy was performed in subjects with chronic hepatitis B who had hepatic decompensation (Child-Turcotte-Pugh score ≥7). Adult subjects were randomized and treated (n = 191) with entecavir 1.0 mg or adefovir 10 mg daily for up to 96 weeks from the date of last subject randomization. Subjects were positive or negative for hepatitis B e antigen and experienced or naive for treatment with nucleos(t)ide analogues. The primary efficacy endpoint was the mean reduction in serum hepatitis B virus (HBV) DNA, as determined by polymerase chain reaction, at week 24, adjusted for baseline HBV DNA and lamivudine resistance status by linear regression analysis. Entecavir demonstrated superiority to adefovir for this endpoint (treatment difference 1.74 log(10) copies/mL [95% confidence interval -2.30, -1.18]; P < 0.0001). The entecavir group showed a greater change from baseline in HBV DNA at all time points through week 48 and a higher proportion of subjects who achieved HBV DNA < 300 copies/mL at weeks 24 (entecavir 49%; adefovir 16%; P < 0.0001) and 48 (entecavir 57%; adefovir 20%; P < 0.0001). Approximately two-thirds of subjects in both groups showed improvement/stabilization in Child-Turcotte-Pugh status. Model for End-Stage Liver Disease score change at week 48 was -2.6 for entecavir and -1.7 for adefovir. Adverse event rates were comparable between groups. Cumulative hepatocellular carcinoma rates were 12% for entecavir and 20% for adefovir. Cumulative death rates were 23% for entecavir and 33% for adefovir. Week 24 mortality rates were 12% for both groups. conclusion: Entecavir demonstrated superior virologic efficacy to adefovir in a population of patients with chronic hepatitis B who had hepatic decompensation. Biochemical and clinical benefits were also demonstrated. Entecavir was well tolerated, and early mortality rates were consistent with rates observed in similar populations treated with lamivudine.

Rosiglitazone treatment in nondiabetic subjects with nonalcoholic fatty liver disease.

INTRODUCTION: Pharmacological treatment options for nonalcoholic fatty liver disease (NAFLD) are limited. It has been suggested that thiazolidinediones may be useful in NAFLD treatment. OBJECTIVES: An open-label prospective study was conducted to assess the efficacy and safety of rosiglitazone treatment in nondiabetic subjects with NAFLD. PATIENTS AND METHODS: A total of 27 subjects (mean age 44 ± 11 years, body mass index 29.2 ± 3.1 kg/m2), with biopsy-confirmed NAFLD and no other complaints, were treated with rosiglitazone 4 mg daily for 6 months. RESULTS: No adverse events were observed during a 6-month treatment with rosiglitazone. Liver enzymes gradually decreased (alanine transaminase from 101 ± 59 to 58 ± 39 IU/l, aspartate transaminase from 52 ± 24 to 37 ± 15 IU/l; P <0.001). Plasma insulin levels decreased significantly by 30% to 50% in each time point of the oral glucose tolerance test. The homeostatic model assessment index decreased from 3.73 ± 1.89 to 2.06 ± 1.68 (P <0.001). No significant changes in plasma glucose were noted. Plasma adiponectin increased from 2198 ± 1853 to 5734 ± 1999 ng/ml (P <0.001). There were no statistically significant changes in body weight, glycated hemoglobin A1c, plasma lipids, or leptin. CONCLUSIONS: Rosiglitazone treatment in patients with NAFLD is safe, well-tolerated and leads to a significant improvement in liver function and insulin sensitivity, without adversely affecting the lipid profile.

Hepatitis and the polyglandular autoimmune syndrome, type 1.

Autoimmune polyglandular syndrome, type 1 (APS-1) is a rare syndrome. Here we present a case report of a 24-year-old female patient who complained of progressive weakness. While autoimmune hepatitis was diagnosed, no improvement of biochemical parameters was obtained after immunosuppressive treatment. Hypoparathyroidism and adrenocortical failure were identified. Her health status clearly improved once proper control of the calcium-phosphate metabolism was obtained and after the administration of substitution hydrocortisone doses, leading to full normalization of biochemical liver tests. The reported case illustrates a rare form of APS-1 failure, in which the diagnosed autoimmune hepatitis was only the first symptom.

[Is healthcare personnel the only professional group exposed tothe risk of occupational HBV, HCV or HIV infections?]. / Czy ryzyko narazenia zawodowego na zakazenie wirusami HBV, HCV, HIV dotyczy tylko pracowników ochrony zdrowia.

BACKGROUND: Our paper presents the problem of exposure to potentially infectious material among health care workers, and also in police officers, prison guards, cleaning service personnel and ordinary citizens. MATERIALS AND METHOD: In the study period, 200 patients were admitted to the Infectious Diseases Clinic after exposure to potentially infectious materials in order to evaluate the risk of HBV, HCV and HIV infections and initiate post exposure prophylaxis. HBsAg, a-HCV and a-HIV were carried out on the day of admission, a-HBs was measured in patients who had been vaccinated against hepatitis B virus. Clinical evaluation of HBV, HCV, HIV infections was performed in the source patients' plasma. RESULTS: The study population consisted of 93 health-care workers (63 nurses, 25 physicians, and 5 medical students), 30 policemen, 23 prison guards, 42 cleaning service workers employed in health-care centers. The remaining 12 patients were inhabitants of the Lodz region who had not been occupationally exposed to potentially infectious material. CONCLUSIONS: Although "safe needles" are in use, exposure among health care personnel still occurs. The problem of occupational exposure among police officers and prison guards is highly underestimated. The lack of control over the vaccination against hepatitis B virus in groups not related with health care creates the risk of new infections.

[Attention abnormalities in patients with chronic hepatitis C after pegylated interferon alpha and ribavirin treatment]. / Zaburzenia uwagi utrzymujace sie u chorych na przewlekle zapalenie watroby typu C po zakonczeniu leczenia pegylowanym interferonem alfa i rybawiryna.

THE AIM OF THE STUDY: To (a) describe the influence of peg-IFNalpha 2a and 2b on attention processes and (b) to assess whether attention abnormalities induced by peg-IFNalpha/RBW resolve 8 weeks after treatment discontinuation in chronic hepatitis C patients. MATERIAL AND METHODS: 26 chronic hepatitis C patients treated with peg-IFNalpha2a (n=18) or 2b (n=8) and RBV were enrolled in the study. Attention processes were tested three times: before the beginning (t=0), after 12 weeks of medication (t=1) and 8 weeks after treatment discontinuation (t=2). Attention was assessed with Brickenkamp d2 test and the results were compared in groups of patients treated with different kinds of peg-IFNalpha. RESULTS: The two kinds of peg-IFNalpha did not differ significantly regarding the influence on attention processes. 8 weeks after treatment discontinuation (t=2) there was observed a significant decrease all aspects of attention measured by d2 test, i.e. work accuracy, speed of processing and ability to focus attention comparing with t=0 and t=1. CONCLUSIONS: Peg-IFNalpha/RBW therapy is connected with a decrease in attention processes performance and the two kinds of peg-interferon alpha (2a and 2b) may exert a similar influence. Attention dysfunction did not resolve 8 weeks after treatment discontinuation and may be the irreversible effect of the dorso-lateral prefrontal cortex or anterior cingulate cortex damage.

[Depressive disorders and symptoms accompanying pegylated interferon alpha and ribavirin treatment of chronic hepatitis C patients]. / Zaburzenia i objawy depresyjne towarzyszace leczeniu chorych na przewlekle zapalenie watroby typu C pegylowanym interferonem alpha i rybawiryna.

UNLABELLED: The aim of the study was to describe describe the frequency of depressive symptoms and episodes accompanying peg-interferon alpha and ribavirin (peg-IFN-alpha/RBV) treatment of chronic hepatitis C patients (CHC). MATERIAL METHODS: 47 CHC patients were enrolled in the study. They were divided into two groups: experimental and control consisting of 26 and 21 participants, respectively. Experimental group patients were given peg-IFN-alpha/RBV2a (n = 18) or 2b (n = 9) and ribavirin treatment in doses recommended by manufacturers. Control group patients did not receive the above treatment. Both groups underwent psychiatric examination using semi-structured clinical interview (MINI) at the beginning (t0) and after 12 weeks of treatment or observation (t12). Depressive episodes were diagnosed according to ICD-10 criteria. Hamilton Rating Scale for Depression (HRSD) was used to assess depressive symptoms intensity at the same time points. RESULTS: Three and two participants in the control and experimental group were diagnosed with depression in t0. Six new patients developed depression in t12 twelve weeks after peg-IFN-alpha/RBV treatment. No new cases were seen in the control group. There was also observed a significant increase in depressive symptoms intensity during peg-IFN-alpha/RBV treatment. No significant changes in the frequency of depressive episodes and their intensity were seen in the control group over the period of observation. CONCLUSIONS: The findings suggest a connection between peg-IFN-alpha/RBV therapy and the development of depressive symptoms and episodes. The above changes may be the effect of IFN-alpha-induced neurotransmission abnormalities in limbic system and basal ganglia. The above findings necessitate a routine psychiatrist involvement in the management of CHC.

[Cognitive disturbances observed in chronic hepatitis C patients during pegylated interferon alpha and ribavirin therapy]. / Zaburzenia procesów poznawczych obserwowane u pacjentów z przewleklym zapaleniem watroby typu C w trakcie terapii pegylowanym interferonem alfa i rybawirynq.

UNLABELLED: Chronic hepatitis C (CHC) patients treated with peg-interferon alpha and ribavirin (peg-IFNalpha/RBV) complain of irritability, attention and memory disturbances which may indicate cognitive impairment associated with treatment. AIM: Assessment of the probable connection between peg-IFNalpha/RBV treatment and the development of cognitive disturbances in CHC patients. METHOD: 47 CHC patients were divided into two groups: experimental (n=26) and control (n=21). The experimental group patients were given peg-IFNalpha2a (n=18) or peg-IFNalpha2b (n=8) plus RBV in standard doses as recommended by the manufacturers. Control group patients did not receive the above treatment. Both groups underwent a neuropsychological examination consisting of R. Brickenkamp d2 test, Auditory Verbal Learning Test and Hooper Visual Organization Test at the beginning (t=0) and after 12 weeks of treatment or observation (t=1). RESULTS: The experimental group patients showed significant deterioration in all the measured cognitive functions in t=1 comparing to t=0. Cognitive decline was not seen in the control group. The observed cognitive performance changes could not be correlated sufficiently enough with the presence of organic affective disorders diagnosed according to ICD-10 criteria. CONCLUSIONS: The findings suggest that peg-IFNalpha/RBV therapy of CHC patients is connected with the deterioration in cognitive functioning including attention, auditory verbal memory and visuo-spatial skills. These changes may be the effect of peg-IFNalpha-induced neurotransmission abnormalities in the dorso-lateral prefrontal cortex, anterior cingulate cortex, hippocampus and parieto-orbital cortical regions and can impair patients' ability to drive a motor vehicle, operate machinery, or their engagement in hazardous activities requiring attention and coordination. Medical professionals should thoroughly inform patients about the possibility of cognitive decline associated with peg-IFNalpha/RBV therapy.