Treatment Of Chronic Viral Hepatitis Research Articles

Effectiveness and safety of narlaprevir in real clinical practice of chronic hepatitis C

Objective: to analyze the efficacy and safety of using direct antiviral action drug narlaprevir/ritonavir in combination with the prolonged alpha-interferon and ribavirin drugs in the conditions of day-time hospitals of St. Petersburg and. Novgorod. Materials and methods : The study included. 35 patients with CHC of the 1st genotype. For treating these patients, a three-component regimen was used, which included the use of narlaprevir/ritonavir in combination, with peg-interferon and ribavirin. Results: among all patients included, in the study, a sustained, virological response was noted, in 85,7%. Early virological response was observed, in 91,3% cases. The recurrence rate was observed, in 10% patients. In 3 patients, therapy was interrupted, for the following reasons: due to inefficiency, the development of serious adverse events, and on its own initiative. Conclusion: the data obtained, demonstrate high, virological and. clinical efficacy and. safety of narlaprevir in combination with peg-interferon and ribavirin, in the treatment of chronic viral hepatitis C.

Treatment of chronic viral hepatitis C with direct acting antiviral agent: review

HCV infection treatment regimens are viewed from positions of HCV life cycle and replication, effects of NS3/4A protease inhibitors and NS5A/NS5B inhibitors on HCV strain replication. Evolution of HCV treatment regimens from its discovery to modern DAA agents had led to substantial progress although drug resistance poses a new issue to be addressed.

Endocannabinoid modulation of inflammatory hyperalgesia in the IFN-α mouse model of depression

Depression is a well-recognised effect of long-term treatment with interferon-alpha (IFN-α), a widely used treatment for chronic viral hepatitis and malignancy. In addition to the emotional disturbances, high incidences of painful symptoms such as headache and joint pain have also been reported following IFN-α treatment. The endocannabinoid system plays an important role in emotional and nociceptive processing, however it is unknown whether repeated IFN-α administration induces alterations in this system. The present study investigated nociceptive responding in the IFN-α-induced mouse model of depression and associated changes in the endocannabinoid system. Furthermore, the effects of modulating peripheral endocannabinoid tone on inflammatory pain-related behaviour in the IFN-α model was examined. Repeated IFN-α administration (8000 IU/g/day) to male C57/Bl6 mice increased immobility in the forced swim test and reduced sucrose preference, without altering body weight gain or locomotor activity, confirming development of the depressive-like phenotype. There was no effect of repeated IFN-α administration on latency to respond in the hot plate test on day 4 or 7 of treatment, however, formalin-evoked nociceptive behaviour was significantly increased in IFN-α treated mice following 8 days of IFN-α administration. 2-Arachidonoyl glycerol (2-AG) levels in the periaqueductal grey (PAG) and rostroventromedial medulla (RVM), and anandamide (AEA) levels in the RVM, were significantly increased in IFN-α-, but not saline-, treated mice following formalin administration. There was no change in endocannabinoid levels in the prefrontal cortex, spinal cord or paw tissue between saline- or IFNα-treated mice in the presence or absence of formalin. Furthermore, repeated IFN-α and/or formalin administration did not alter mRNA expression of genes encoding the endocannabinoid catabolic enzymes (fatty acid amide hydrolase or monoacylglycerol lipase) or endocannabinoid receptor targets (CB1, CB2 or PPARs) in the brain, spinal cord or paw tissue. Intra plantar administration of PF3845 (1 μg/10 μl) or MJN110 (1 μg/10 μl), inhibitors of AEA and 2-AG catabolism respectively, attenuated formalin-evoked hyperalgesia in IFN-α, but not saline-, treated mice. In summary, increasing peripheral endocannabinoid tone attenuates inflammatory hyperalgesia induced following repeated IFN-α administration. These data provide support for the endocannabinoid system in mediating and modulating heightened pain responding associated with IFNα-induced depression.

Medication Adherence Among Patients With Chronic Hepatitis Receiving Antiviral Treatment.

This study aimed to evaluate medication adherence and associated factors among patients with chronic viral hepatitis. A cross-sectional questionnaire survey was conducted in 171 outpatients receiving antiviral treatment of chronic viral hepatitis at 6 national/regional liver disease treatment centers in Japan. Medication adherence was calculated as the subject-reported number of antiviral tablets taken in the past 2 weeks compared with the prescribed number of tablets. Subjects were divided according to 100% adherence or nonadherence. The impact of items pertaining to everyday experiences and perceptions regarding medication adherence were examined. Factors associated with medication adherence were identified via multiple logistic regression. The mean medication adherence rate was 95.8% ± 9.5% (range = 0%-100%), although a smaller proportion (95 subjects; 55.6%) was 100% adherent. Multiple logistic regression indicated a greater "lack of understanding of need for medication" (1 point: odds ratio (OR) = 1.51, 95% confidence interval (CI) [1.30, 1.76], p ≤ .01) and greater "restriction in life due to medication" (1 point: OR = 1.26, 95% CI [1.03, 1.54], p = 0.03) as associated with nonadherence. In conclusion, to improve medication adherence, healthcare professionals should improve patients' understanding of the need for medication and minimization of life restrictions.

Effectiveness of Treatment of Chronic Viral Hepatitis C by Direct-Acting Antivirals in Togo

Background: Viral hepatitis C is the second leading cause of hepatocellular carcinoma after hepatitis B in Africa and Togo in particular. The advent of direct acting antivirals has revolutionized the care and prognosis of patients infected with hepatitis C virus (HCV). Objective: To evaluate the sustained virological response (SVR) 12 weeks after oral treatment without interferon in HCV infected patients with genotypes 1 and 2. Patients and Method: Descriptive and analytical study based on the retrospective collection of data in the hepatogastroenterology unit of the University Hospital Campus of Lome (Togo) from July 11, 2016 to April 22, 2018. All patients who had a chronic viral hepatitis C with viral replication, naive, regardless of the genotype, regardless of the degree of liver fibrosis, and who had completed their treatment with direct-acting antivirals were included. Results: We recruited 84 patients, 60 of whom were infected with HCV genotype 2 (71.43%) and 24 with HCV genotype 1 (28.57%). There were 58 men and 26 women (sex ratio: 0.45). In HCV genotype 1 patients, the median age was 54.29 years and Sofosbuvir/Ledipasvir was the most used combination (62.50%). In HCV genotype 2 patients, the median age was 54.5 years and Sofosbuvir associated with Ribavirin was the most used treatment (81.66%). The virological response at the end of treatment was 100% (genotype 1) and 93.30% (genotype 2). The SVR 12 was 100% (genotype 1) and 91.70% (genotype 2). Five patients were in treatment failure (genotype 2). Conclusion: Direct-acting antivirals were effective in our patients. The rate of sustained virological response was above 90%.

Лечение хронического вирусного гепатита С комбинацией препаратов "софосбувир-ледипасвир" у пациентки с диализ-зависимой хронической болезнью почек

Лечение хронического вирусного гепатита С комбинацией препаратов "софосбувир-ледипасвир" у пациентки с диализ-зависимой хронической болезнью почек

Management of Chronic Hepatitis C in End-stage Renal Disease.

Treatment for chronic viral hepatitis C has advanced dramatically to current standard of care all-oral direct-acting antiviral regimens with relatively short treatment duration and high efficacy. Patients with comorbid end-stage renal disease have constituted a "special patient population" with data and treatment options lagging behind that of the broader population of patients with chronic hepatitis C until recently. Herein we review the current evidence base for direct-acting antiviral therapy in this population. We provide a suggested algorithm for the evaluation of such patients for therapy. We highlight special considerations in regards to the choice of regimen, duration, and timing in regards to potential kidney transplantation.

1. Recent Advance in the Treatment of Chronic Viral Hepatitis

1. Recent Advance in the Treatment of Chronic Viral Hepatitis

EInterferon α combined with oxymatrine injection for treatment of chronic viral hepatitis B: Efficacy and effect on hepatic fibrosis and immune function

EInterferon α combined with oxymatrine injection for treatment of chronic viral hepatitis B: Efficacy and effect on hepatic fibrosis and immune function

ANTIVIRAL AND ANTICOAGULANT THERAPY IN A POLYMORBID PATIENT WITH CHRONIC VIRAL HEPATITIS C. TACTICS OF MANAGEMENT, FEATURES OF DRUG-DRUG INTERACTIONS

The article describes current approaches to the treatment of chronic viral hepatitis C genotype 3. The validity of the use of anticoagulants for liver diseases is analyzed. The authors discuss the principles for the use of anticoagulant therapy in patients with prosthetic valves and its issues during the conduct of anti-viral therapy using protease inhibitors, as well as the difficulties in assessment of severity of liver dysfunction and prognosis in chronic liver diseases and cirrhosis in patients receiving treatment with vitamin K antagonists. The discussed issues are illustrated by a clinical case of a patient with a mechanical mitral valve prosthesis and chronic hepatitis C who has received a course of combined antiviral treatment while continuing long-term therapy with vitamin K antagonists.

Interferon-Alpha Reduces Human Hippocampal Neurogenesis and Increases Apoptosis via Activation of Distinct STAT1-Dependent Mechanisms.

BackgroundIn humans, interferon-α treatment for chronic viral hepatitis is a well-recognized clinical model for inflammation-induced depression, but the molecular mechanisms underlying these effects are not clear. Following peripheral administration in rodents, interferon-α induces signal transducer and activator of transcription-1 (STAT1) within the hippocampus and disrupts hippocampal neurogenesis.MethodsWe used the human hippocampal progenitor cell line HPC0A07/03C to evaluate the effects of 2 concentrations of interferon-α, similar to those observed in human serum during its therapeutic use (500 pg/mL and 5000 pg/mL), on neurogenesis and apoptosis.ResultsBoth concentrations of interferon-α decreased hippocampal neurogenesis, with the high concentration also increasing apoptosis. Moreover, interferon-α increased the expression of interferon-stimulated gene 15 (ISG15), ubiquitin-specific peptidase 18 (USP18), and interleukin-6 (IL-6) via activation of STAT1. Like interferon-α, co-treatment with a combination of ISG15, USP18, and IL-6 was able to reduce neurogenesis and enhance apoptosis via further downstream activation of STAT1. Further experiments showed that ISG15 and USP18 mediated the interferon-α-induced reduction in neurogenesis (potentially through upregulation of the ISGylation-related proteins UBA7, UBE2L6, and HERC5), while IL-6 mediated the interferon-α-induced increase in apoptosis (potentially through downregulation of aquaporin 4). Using transcriptomic analyses, we showed that interferon-α regulated pathways involved in oxidative stress and immune response (e.g., Nuclear Factor (erythroid-derived 2)-like 2 [Nrf2] and interferon regulatory factor [IRF] signaling pathway), neuronal formation (e.g., CAMP response element-binding protein [CREB] signaling), and cell death regulation (e.g., tumor protein(p)53 signaling).ConclusionsWe identify novel molecular mechanisms mediating the effects of interferon-α on the human hippocampus potentially involved in inflammation-induced neuropsychiatric symptoms.

Host-directed therapies for bacterial and viral infections.

Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology. Although HDTs encompassing interferons are well established for the treatment of chronic viral hepatitis, novel strategies aimed at the functional cure of persistent viral infections and the development of broad-spectrum antivirals against emerging viruses seem to be crucial. In chronic bacterial infections, such as tuberculosis, HDT strategies aim to enhance the antimicrobial activities of phagocytes and to curtail inflammation through interference with soluble factors (such as eicosanoids and cytokines) or cellular factors (such as co-stimulatory molecules). This Review describes current progress in the development of HDTs for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic.

РОЛЬ ПЕРВИННОЇ МЕДИЧНОЇ ДОПОМОГИ ХВОРИМ НА ГЕМОКОНТАКТНІ ІНФЕКЦІЇ (ВІЛ-ІНФЕКЦІЯ ТА ГЕПАТИТИ В і С)

Проаналізовано існуючі проблеми надання медичної допомоги хворим на ВІЛ-інфекцію та гемоконтактні вірусні гепатити в Україні. Показані роль первинної медичної допомоги у веденні пацієнтів даної категорії, основні завдання, які стоять перед сімейними лікарями. Також відзначені досягнуті успіхи в реалізації державної програми лікування хронічних вірусних гепатитів, розширенні доступу пацієнтів до отримання специфічної противірусної терапії.

ETIOTROPIC THERAPY OF VIRAL HEPATITIS

Treatment of chronic viral hepatitis is not a fully resolved problem, especially in children. There are no convincing criteria for recovery. The paper presents various schemes used for etiotropic therapy of viral hepatitis at the present stage — interferons and antiviral drugs. For the treatment of hepatitis B, synthetic nucleoside and nucleotide analogues are used as an antiviral therapy, in the case of hepatitis C — ribavirin and protease and polymerase inhibitors. In children, interferon therapy remains important with the use of domestic drugs, including rectal forms of interferon administration (VIFERON®). At the same time, active research is underway to study non-interferon regimens for the treatment of chronic viral hepatitis in pediatric practice, but so far the choice of drugs for non-interferon therapy is limited to individual drugs. With hepatitis B, it is a lamivudine, prescribed from 3 years (the reception of which is accompanied by frequent development of resistance) and — tenofovir (appointed from 12 years). With hepatitis C, ribavirin can be administered from 3 years.

Use of telehealth to treat and manage chronic viral hepatitis in regional Queensland

For regional and rural Queenslanders, chronic viral hepatitis treatment is a major unmet health need, with restricted access to specialists outside of tertiary, largely metropolitan hospitals. To increase treatment of chronic viral hepatitis in regional Queensland, a team-based telehealth model was expanded. This expansion embedded an initial nursing consultation prior to specialist telehealth consultation. We conducted a retrospective audit of the introduction and expansion of hepatology telehealth services. Activity from July 2014–June 2015 (pre-expansion) was compared with July 2015– June 2016 (post-expansion). Interviews were conducted with key staff to determine factors contributing to success of the service and identify ongoing challenges to the service model. A greater than four-fold increase in clinical consultation was observed (131 telehealth consultations pre-expansion vs 572 post-expansion; p < 0.001). The failure to attend rate decreased (13.0% vs 6.5%, pre vs post-expansion respectively; p = 0.030), suggesting engagement with the service increased. Staff cited nurse-conducted primary assessment prior to specialist consultation and personalised patient treatment packs as key contributors to increased patient flow and engagement. This expanded team approach appears effective in delivering specialised treatment to an underserved area in regional Central Queensland. It may serve as a model to further expand telehealth management of chronic disease for regional Queenslanders.

Oxymatrine Induces Liver Injury through JNK Signalling Pathway Mediated by TNF-α In Vivo.

Oxymatrine (OMT) is a traditional Chinese medicine monomer and has been used for the treatment of chronic viral hepatitis and many other diseases. We aimed to investigate whether OMT could induce hepatotoxicity in mice and explored the preliminary mechanisms of toxic effects. Twenty-four Institute for Cancer Research male mice were randomly divided into four groups: control group, 40, 160 and 320 mg/kg OMT-treated group. OMT was orally administered once daily for 7 days. The OMT-treated group exhibited an improved liver index and increase in serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase,augmented liver histological injury, elevated levels of malondialdehyde and tumour necrosis factor alpha (TNF-α) accompanied by the activation of caspase-9/-8/-3, up-regulated expressions of tumour necrosis factor receptor l (TNFR1), TNF receptor-associated structure domain (TRADD) and phosphorylation of stress-activated protein kinase/c-jun N-terminal protein kinases (p-SAPK/JNK). Altogether, these results suggest that OMT at a dose of 320 mg/kg leads to liver damage and is related to the activation of JNK signalling pathway mediated by TNF-α in the liver of mice.

Role of the GALAD and BALAD-2 Serologic Models in Diagnosis of Hepatocellular Carcinoma and Prediction of Survival in Patients.

GALAD and BALAD-2 are statistical models for estimating the likelihood of the presence of hepatocellular carcinoma (HCC) in individual patients with chronic liver disease and the survival of patients with HCC, respectively. Both models use objective measures, particularly the serum markers α-fetoprotein (AFP), AFP-L3, and des-γ-carboxyprothrombin. We aimed to validate these models in an international cohort of patients with HCC and assess their clinical performance. We collected data on cancer diagnosis and outcomes of 6834 patients (2430 with HCC and 4404 with chronic liver disease) recruited from Germany, Japan, and Hong Kong. We also collected data from 229 patients with other hepatobiliary tract cancers (cholangiocarcinoma or pancreatic adenocarcinoma) and 92 healthy individuals (controls). For reference, the original UK cohort (on which the GALAD model initially was built and BALAD-2 was validated) was included in the analysis. We assessed the effects of tumor size and etiology on GALAD model performance, and its ability to correctly discriminate HCC from other hepatobiliary cancers. We assessed the performance of BALAD-2 in patients with different stages of HCC. In all cohorts, the area under the receiver operating characteristic curve (AUROC), quantifying the ability of GALAD to discriminate patients with HCC from patients with chronic liver disease, was greater than 0.90-similar to the series on which the model originally was built (AUROC, 0.97). GALAD discriminated patients with HCC from those with other hepatobiliary cancers with an AUROC value of 0.95; values were slightly lower for patients with small unifocal HCCs, ranging from 0.85 to 0.95. Etiology and treatment of chronic viral hepatitis had no effect on the performance of this model. BALAD-2 analysis assigned patients with HCC to 4 distinct prognostic groups-overall and when patients were stratified according to disease stage. We validated the performance of the GALAD and BALAD-2 models for the diagnosis of HCC and predicting patient survival, respectively (based on levels of the serum markers AFP, AFP-L3, and des-γ-carboxyprothrombin), in an international cohort of almost 7000 patients. These systems might be used in HCC surveillance and determination of patient prognosis.

Treatment of Chronic Viral Hepatitis with Pegylated Interferon in Ivory Coast

Background: In the Ivory Coast, chronic infection by hepatitis B and C virus is the leading cause of cirrhosis and hepatocellular carcinoma. The absence of universal health coverage makes the treatment inaccessible to all. Objectives: To assess the efficacy of Pegylated Interferon in clinical practice in patients with chronic viral hepatitis B and C and determine the hematologic side effects. Patients and Methods: A descriptive retrospective study from January 2012 to November 2013 on a cohort of patients chronic carriers of hepatitis B virus (n = 11) treated with Pegylated Interferon to 180 mcg per week and hepatitis C virus (n = 30) treated with a combination therapy associating pegylated Interferon to 180 mcg per week and Ribavirin assayed according to the genotype. Results: Out of 1860 patients seen in hepatogastroenterology consultation 422 had viral hepatitis B or C that is a prevalence of 22.7% and 41 patients were treated (9.7%) by Pegylated Interferon. Among these 41 patients mentioned earlier, 30 had HCV (73.17%) with a case of HIV + HVC co-infection, 11 patients had HBV (26.83%) including 3 cases of HBV + HDV co-infection. Patients’ age ranged from 24 - 69 years with an average of 49.2 ± 12.2 years including 46.5 years for HBV and 51.9 years for HCV. The sex ratio was 1.56. The original transaminases were on average 93.37 IU/l for AST and 110.47 for ALT. The average RNA HCV was 1,685,331 IU/ml and the DNA HBV 33,312,767 IU/ml. Patients with HCV were of genotype 1 in 56.66%, genotype 2 in 40% and one case of genotype 4 (3.34%) from Central Africa. Fibrosis score at institution of treatment was significant (≥A2 and/or ≥F2) in 86.9% of cases of Fibrotest®, 100% of cases of Fibrometer®. We observed 48.8% of neutropenia < 750/mm3, 33.3% of anemia and 29.3% of thrombocytopenia < 100,000/mm3. There was no dose reduction of Pegylated Interferon and Ribavirin. For HBV there were 3 partial responses, 3 responders including 1 HBV + HDV co-infected non responder to HDV, 2 non responders including 1 HBV + HDV co-infected to Week 48. For HCV, there was 52.94% of cases of sustained viral response (SVR) including 44.44% of genotype 1, 83.33% of genotype 2 and 100% of genotype 4. Conclusion: The free antiviral treatment program helped treat 10% of chronic viral hepatitis B and C. Our results are not different from those of the literature. Difficulties remain in the performance of non supported diagnostic tests.

Lower Viral Response to Pegylated Interferon Alpha 2a Treatment of Chronic Hepatitis B in Roma People in Eastern Slovakia.

Aim. To evaluate the compliance and virological response to pegylated interferon alpha 2a treatment of chronic hepatitis B in Roma population compared to majority Caucasian population in Slovakia. Methods. Retrospective evaluation of a cohort of all Roma patients treated with pegylated interferon alpha 2a from 2007 to 2013 in 3 centers for treatment of chronic viral hepatitis B. The Study included 43 Roma patients with chronic viral hepatitis B and randomly selected control group. Treatment duration was 48 weeks. Viral response was evaluated after 24 weeks, at the end of treatment, and 24 weeks after the end of treatment. Results. Complete treatment course was finished by 79.1% of Roma patients compared to all patients from the control group (p = 0.0009). There was a tendency toward lower viral response rate in Roma at all time points; however significant difference was only at end of treatment viral response (51.2% Roma versus 81.4% majority, p = 0.003). We also did not find significant difference at the rate of HBsAg loss. Conclusion. Roma patients with chronic hepatitis B have significantly worse compliance to treatment with pegylated interferon and they have significantly lower rate of end of treatment viral response.

Safety of the Association of Pegylated Interferon and Ribavirin in the Treatment of Chronic Viral Hepatitis C in the Blacks: A Ten Year Observation

Background: Sub Saharan population are the most affected by chronic hepatitis C. The interferon- based regimen has been the only available treatment in the last decade. The announced direct acting antivirals will still be associated to the actual regimen. Reports on the safety of these protocols are so far Caucasians-based, and data from sub Saharan populations are lacking. Aim: To describe the secondary effects of the combination of Pegylated interferon and ribavirin I the treatment of chronic hepatitis C in black Africans. Methods: it was a multicenter study in which we included chronic hepatitis C patients, over ten years, treated by the association of Pegylated interferon-Inf and ribavirin, from all the centers of treatment in the country. Patients should be naive to this treatment, fulfill the condition of treatment according to manufacturer, namely Hoffmann La Roche. Side effects were recorded during follow up. The base line follow up biological tests included: Liver function tests; full blood count; TSH; kidney function test. Results: All the patients reported at least one adverse event, related to treatment. The clinical adverse events were dominated by asthenia; flu-like syndrome; head ache and myalgia; we registered 6 cases of depression. The most biological adverse events were of hematologic origin. Conclusion: The adverse effects related to combination therapy using Pegylated interferon alfa-2a and ribavirin in the treatment of chronic HCV in the blacks, are similar to those indicated by the manufacturer. These adverse effects tend to be in relation the duration of treatment. Some of them can become intractable, alternative treatment or psychological support from patients association can be helpful.