Course Of Hepatitis Research Articles

Causal mediation analyses for the natural course of hepatitis C: a prospective cohort study.

BackgroundHepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality.MethodsA community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants' serum samples. The cohort data were linked to Taiwan's National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases.ResultsIn 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect.ConclusionBoth intrahepatic and extrahepatic manifestations mediated approximately a half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load.

Insights into the Natural and Treatment Courses of Hepatitis B in Children: A Retrospective Study.

Chronic Hepatitis B virus (HBV) infection in children remains a significant public health challenge. The natural history and treatment outcomes of HBV can vary widely, influencing management strategies. This retrospective study was conducted in Northeast Romania and involved a cohort of 148 pediatric patients diagnosed with chronic viral Hepatitis B. Of these, 59 children underwent antiviral treatment while 89 were not treated. One of the main objectives was the rate of HBeAg (Hepatitis B-e antigen) seroconversion, a marker of disease progression and response to therapy. Among the treated group, 26 children (44%) achieved HBeAg seroconversion following therapy. In contrast, 44 of the untreated children (49%) experienced spontaneous HBeAg seroconversion, indicating a substantial rate of natural resolution within this population subset. The findings highlight a significant proportion of spontaneous seroconversion in untreated pediatric patients, suggesting a potential re-evaluation of treatment criteria and timing for children with chronic HBV infection. The comparable rates of seroconversion between treated and untreated cohorts underscore the need for individualized treatment approaches based on a combination of virological, biochemical, and clinical parameters. Further studies are required to refine management strategies to optimize long-term outcomes in pediatric HBV infections.

OPTIMIZATION OF THE PREGNANCY MANAGEMENT SYSTEM IN HEPATITIS B

Purpose. To determine the effectiveness of optimized pregnancy management tactics for hepatitis B. Materials and methods. To determine the risk of obstetric and perinatal risk, it is necessary to determine medical and social indicators, conduct additional examinations to assess the course of hepatitis B, the state of vascular regulation, quality of life, anxiety and depression levels. At an increased risk of complications, depending on the detected changes, organizational and therapeutic measures are recommended: healthy lifestyle recommendations, psychologist consultation and psychocorrection, arginine glutamate, a combination of magnesium with vitamin B6, oral and vaginal probiotics. Results. The verification of the effectiveness of the use of the recommended treatment and prevention complex demonstrated a positive effect on the general condition and well-being of the woman, improvement of microbiocinosis of the vagina and intestines, the state of the hemostasis system and vascular endothelium, improvement of the quality of life of the patients, reduction of the level of anxiety and depression, which collectively made it possible to achieve the set the goal is to reduce the frequency of obstetric and perinatal complications (placental insufficiency, fetal distress and growth retardation, premature birth, blood loss during childbirth, asphyxia and adaptation disorders in the newborn). Conclusion. The obtained results and the absence of side effects allow recommending the proposed treatment-prophylactic complex for wide use in obstetrics and gynecology practice.

AST to Platelet Ratio Index (APRI), Fib-4 Score, and Pregnancy Outcome of Pregnant Women with Hepatitis B

Hepatitis B virus infection in pregnancy has become a major concern in many developing countries,. The relationship between hepatitis B virus infection and pregnancy is complex and puzzling. This study aimed to investigate the relationship between hepatitis B virus infection and pregnancy outcomes with the insights into the AST to Platelet Ratio Index (APRI) and Fib-4 score. This was a cross-sectional study on pregnant women with hepatitis B virus infections who underwent labor at dr. Zainal Abidin Hospital General Hospital, Aceh, Indonesia. Data were collected from the obstetric ward patient medical records from 2017 to 2019 and 77 pregnant women was identified to be infected with hepatitis B virus, of which 44 had complete medical record data and were included in the analysis. The median APRI in this study was 0.30 (0.1-1.2) while the median FIB-4 score was 0.74 (0.3-1.9). Delivery with live births was identified in 42 (95.5%) women. Term pregnancy and vaginal delivery were observed in 39 (88.6%) and 10 (22.7%) women, respectively, Complicated pregnancy was seen in 14 (31.8%) of pregnancies that included complications such as oligohydramnios, HELLP, severe preeclampsia, placenta previa, and premature rupture of membranes. APRI was higher in the stillbirth group (0.5 [0.2-0.8] p = 0.682) and preterm birth group (0.4 [0.2-0.6], p = 0.502). FIB-4 scores were higher in the stillbirth group (1.2 [0.5-1.8], p = 0.517) and preterm birth group (0.9 [0.4-1.9], p = 0.529). Hence, pregnancy does not always worsen liver function and is not related to the natural course of hepatitis B infection. Pregnancy with hepatitis B without fibrosis is not associated with poor pregnancy outcomes. Routine liver function examination is needed in pregnant mothers with hepatitis B virus infections.

HPgV infection and cryptogenic hepatitis: clinical observation

The causative agent of HPgV infection (HGV, GBV-C) was first described as hepatitis G virus, which was not confirmed during further researches. Human pegivirus-1 cannot be the cause of hepatitis and is not even pathogenic. The article presents an autopsy observation of the fulminant course of hepatitis of unclear etiology with HPgV persistence. Given the difficulties in establishing the etiology of cryptogenic hepatitis, initially, when analyzing this case, it was proposed to link the presence of HPgV with the development of fulminant hepatitis. Despite the detection of the virus in the blood and the hepatitis clinic, there are no causal relationships between these phenomena, as the article provides data from various researches. The wide spread of the virus in the human population and the absence of its etiological role in the development of pathological processes are shown.

Risk Factors for Hepatitis E Virus Infection and Eating Habits in Kidney Transplant Recipients.

There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of patients. We conducted a retrospective single-center study with 59 adult kidney and combined kidney transplant recipients who were diagnosed with HEV infection between 2013 and 2020. The outcomes of HEV infections were analyzed during a median follow-up of 4.3 years. Patients were compared with a control cohort of 251 transplant patients with elevated liver enzymes but without evidence of an HEV infection. Patients' alimentary exposures during the time before disease onset or diagnosis were assessed. Previous intense immunosuppression, especially treatment with high-dose steroids and rituximab, was a significant risk factor to acquire hepatitis E after solid organ transplantation. Only 11 out of 59 (18.6%) patients reached remission without further ribavirin (RBV) treatment. A total of 48 patients were treated with RBV, of which 19 patients (39.6%) had either viral rebounds after the end of treatment or did not reach viral clearance at all. Higher age (>60 years) and a BMI ≤ 20 kg/m2 were risk factors for RBV treatment failure. Deterioration in kidney function with a drop in eGFR (p = 0.046) and a rise in proteinuria was more common in patients with persistent hepatitis E viremia. HEV infection was associated with the consumption of undercooked pork or pork products prior to infection. Patients also reported processing raw meat with bare hands at home more frequently than the controls. Overall, we showed that the intensity of immunosuppression, higher age, a low BMI and the consumption of undercooked pork meat correlated with the development of hepatitis E.

Hepatitis B reactivation: A possible cause of coronavirus disease 2019 vaccine induced hepatitis

Coronavirus disease 2019 (COVID-19) vaccines were rapidly implemented globally and vaccine-associated immune-related hepatitis was recently reported. We aim to investigate its impact in regions endemic of chronic hepatitis B (CHB). We retrospectively collected patients who developed hepatitis within 90 days after COVID-19 vaccination in Taiwan. The mechanisms of hepatitis included vaccine induced liver injury (VILI) and immune-related hepatitis, which are direct liver injuries defined as aspartate or alanine aminotransferase (AST or ALT) increased ≥ 5-fold upper limit of normal (ULN) and/or AST or ALT ≥ 3-fold of ULN with concurrent total bilirubin ≥ 2-fold of ULN. Indirect liver injury due to HBV reactivation was defined as HBsAg reverse seroconversion or significant rise in HBV DNA level. The demographics, clinical data, and course of hepatitis were compared statistically. Twenty-five patients were included with a median age of 54. The culprit vaccines were ChAdOx1 nCoV-19 (n=9), mRNA-1273 (n=12), and BNT162b2 (n=4). The characteristics of hepatitis were comparable regardless of vaccine subtypes. The median onset of hepatitis was 25 days post vaccination, with a peak of 10-fold ALT-increase. The etiologies included HBV reactivation (n=10), VILI (n=10), and immune-related hepatitis (n=5). HBV reactivation accounts for 90% of vaccine-induced hepatitis in patients of CHB (n=10), and two patients died. Patients with initial AST levels >500 U/L increased 27-fold risks of liver injury greater than moderate severity compared with those without. COVID-19 vaccine induced hepatitis is a clinical significant complication, and HBV reactivation may account for a possible mechanism.

Hepatitis C Virus and Hepatitis C Virus-Associated Hepatocellular Carcinoma in Egyptian Patients: Driving Disease Progression

Background: Hepatocellular carcinoma is the leading cause of cancer-related death worldwide and it is commonly associated with hepatitis C virus infection. Identifying the key mechanisms and biological markers involved in the hepatitis C virus-associated hepatocellular carcinoma may help in early detection and/or diagnosis of this malignancy. The aim of this study was to evaluate and assess the role of the serum VEGF, NF-kB, and IGF-1 in incidence and development of hepatocellular carcinoma in hepatitis C virus-infected patients. Methods and Results: VEGF, NF-kB, and IGF-1 were measured by ELISA assay in Egyptian patients with hepatitis C virus infection and hepatocellular carcinoma-associated hepatitis C virus infection, healthy individuals. Serum VEGF, NF-kB, and IGF-1 were significantly elevated in HCV and hepatitis C virus-associated hepatocellular carcinoma patients compared to the control group. Additionally patient with hepatitis C virus-associated hepatocellular carcinoma showed significantly higher serum levels of NF-kB, and IGF-1 compared with hepatitis C virus infection patients. Conclusions: Our data supports the role of VEGF, NF-kB, and IGF-1 in development of hepatocellular carcinoma during the course of hepatitis C virus infection and the use of these biomarkers in combination with alpha-fetoprotein (AFP) may offer an improved diagnostic tool for hepatocellular carcinoma early detection.

Viral hepatitis B in patients with hematological malignancies (Overview)

The review presents current data on the role of viral hepatitis B in oncohematological patients. Possible ways of infection, prevention of infection, and activation of hepatitis B in this category of patients are considered. The specific features of the course of hepatitis B in various clinical situations are described: against the background of other viral infections and in the conduct of specific anti-leukemia therapy.

The influence of steroid therapy of complications of infectious mononucleosis on the course of Epstein-Barr virus hepatitis.

The purpose of the study was to characterize the differences in the course of Epstein-Barr virus (EBV) primary infection-induced hepatitis between patients treated with steroids due to complications of infectious mononucleosis (IM) and those not receiving such therapy. We analyzed the changes in the activity of liver enzymes and differences in abdominal ultrasound results. The study was based on reviewing the medical records of children hospitalized for primary EBV infection at the Department of Children's Infectious Diseases, Medical University of Warsaw, Regional Hospital of Infectious Diseases in Warsaw, between August 2017 and March 2023. The study population was divided into two groups: patients treated with steroids (Group 1) and children not receiving steroids (Group 2). Significant differences were obtained for alanine aminotransferase activity only in the first week of IM (205.34 ±115.40 vs. 288.82 ±170.16 IU/l for Group 1 and 2, respectively; p = 0.024), and for aspartate aminotransferase in the first (170.63 ±159.47 vs. 218.85 ±128.22 IU/l for Group 1 and 2, respectively; p = 0.009) and the third week (151.09 ±138.57 vs. 235.50 ±170.27 IU/l for Group 1 and 2, respectively; p = 0.016). The analysis of the results of laboratory tests for the diagnosis of cholestasis (γ-glutamyl transferase and total serum bilirubin concentrations with fractions) did not show significant differences between the groups. Our results indicated that the two cohorts of patients may differ in the course of hepatitis associated with primary EBV infection, especially at the beginning of the disease, when the laboratory features of hepatitis were less pronounced in children treated with steroids.

HEPATITIS A. THE FEATURES OF DISEASE COURSE IN ADULTS.

The aim: To analyze the incidence of Hepatitis A in Ukraine and Poltava region and to study the clinical and epidemiological features of the course of Hepatitis A in adult patients. Materials and methods: The course of HA in 96 hospitalized patients was analyzed. The diagnosis of HA was established on the basis of clinical and epide¬miological data and confirmed by the results of laboratory studies (serological and molecular biological). Results: In 2019, in the Poltava region, there was an increase in the incidence of Hepatitis A with a predominance among sick people of working age, among the urban population. This part of people aged from 60 to 75 years old constitutes 9.4%. This study showed that the waterway was the dominant way of HA transmission. The course of the disease in most hospitalized patients was typical and cyclic, with a predominance of a mixed variant of the pre-jaundice period and jaundice. One third of patients survey that they had fever, which persisted with jaundice. Conclusions: The findings of this study indicates that the patients older than 40 years were more likely to have concomitant chronic pathology than younger patients, and Hepatitis A was more severe with the development of prolonged cholestasis, wave-like course and recurrence. In most patients under the age of 40, the course of Hepatitis A was mild, but splenomegaly and severe cytolytic syndrome were more common.

From the Editor’s Desk…

From the Editor’s Desk…

Favourable outcome of acute hepatitis E infection in patients with ANCA-associated vasculitis

BackgroundHepatitis E virus (HEV) infection is a frequent cause of acute viral hepatitis. Immunocompromised patients are at increased risk for viral infection and chronic courses of hepatitis. Whether patients with autoimmune diseases are at risk of developing clinically relevant hepatitis or even chronic liver disease after HEV infection is discussed controversially. ANCA-associated vasculitis is a rare autoimmune disease with potentially life-threatening organ involvement, thus requiring intensive immunosuppression with glucocorticoids, cyclophosphamide, or rituximab. As there are no reports available on the infection with HEV in patients with ANCA-associated vasculitis, clinical decision making in such cases is based on experiences from other disease entities. Therefore, in this study we analyzed the course of liver disease and the therapeutic management of autoimmune vasculitis in a retrospective cohort of five patients with ANCA-associated vasculitis and acute hepatitis E.ResultsFour patients were on immunosuppressive maintenance therapy and one patient was on remission induction therapy with cyclophosphamide and high dose glucocorticoids. All patients had at least one potentially hepatotoxic co-medication at the time of hepatitis. Hepatitis-associated clinical symptoms were recorded in four of five patients. The course of hepatitis was characterized by strongly elevated transaminases, a temporary liver failure was observed in one case. The management of hepatitis E included cessation of the immunosuppressants in all patients, whereas oral glucocorticoids were not discontinued. Under this regime, all patients cleared the virus without additional anti-viral treatment. Liver enzymes normalized one month after they peaked. In the follow-up period of at least 1.5 years (range 1.5–12 years), no chronic liver disease was observed, although one patient died of cholangiocarcinoma with liver metastases some years after HEV infection. Vasculitis was not active in our patient cohort at the time of HEV infection. However, inflammatory flares occured in three of five patients after discontinuation of the immunosuppressive therapy. Immunosuppressants were paused for a median time of 4 weeks and after their resumption vasculitic disease activity was controlled in all patients.ConclusionsAcute HEV infection in patients with ANCA-associated vasculitis shows a favorable outcome of liver disease but bears the risk of inflammatory flares due to cessation of immunosuppression.

Hepatitis B virus pathogenesis relevant immunosignals uncovering amino acids utilization related risk factors guide artificial intelligence-based precision medicine.

Background: Although immune microenvironment-related chemokines, extracellular matrix (ECM), and intrahepatic immune cells are reported to be highly involved in hepatitis B virus (HBV)-related diseases, their roles in diagnosis, prognosis, and drug sensitivity evaluation remain unclear. Here, we aimed to study their clinical use to provide a basis for precision medicine in hepatocellular carcinoma (HCC) via the amalgamation of artificial intelligence. Methods: High-throughput liver transcriptomes from Gene Expression Omnibus (GEO), NODE (https://www.bio.sino.org/node), the Cancer Genome Atlas (TCGA), and our in-house hepatocellular carcinoma patients were collected in this study. Core immunosignals that participated in the entire diseases course of hepatitis B were explored using the "Gene set variation analysis" R package. Using ROC curve analysis, the impact of core immunosignals and amino acid utilization related gene on hepatocellular carcinoma patient's clinical outcome were calculated. The utility of core immunosignals as a classifier for hepatocellular carcinoma tumor tissue was evaluated using explainable machine-learning methods. A novel deep residual neural network model based on immunosignals was constructed for the long-term overall survival (LS) analysis. In vivo drug sensitivity was calculated by the "oncoPredict" R package. Results: We identified nine genes comprising chemokines and ECM related to hepatitis B virus-induced inflammation and fibrosis as CLST signals. Moreover, CLST was co-enriched with activated CD4+ T cells bearing harmful factors (aCD4) during all stages of hepatitis B virus pathogenesis, which was also verified by our hepatocellular carcinoma data. Unexpectedly, we found that hepatitis B virus-hepatocellular carcinoma patients in the CLSThighaCD4high subgroup had the shortest overall survival (OS) and were characterized by a risk gene signature associated with amino acids utilization. Importantly, characteristic genes specific to CLST/aCD4 showed promising clinical relevance in identifying patients with early-stage hepatocellular carcinoma via explainable machine learning. In addition, the 5-year long-term overall survival of hepatocellular carcinoma patients can be effectively classified by CLST/aCD4 based GeneSet-ResNet model. Subgroups defined by CLST and aCD4 were significantly involved in the sensitivity of hepatitis B virus-hepatocellular carcinoma patients to chemotherapy treatments. Conclusion: CLST and aCD4 are hepatitis B virus pathogenesis-relevant immunosignals that are highly involved in hepatitis B virus-induced inflammation, fibrosis, and hepatocellular carcinoma. Gene set variation analysis derived immunogenomic signatures enabled efficient diagnostic and prognostic model construction. The clinical application of CLST and aCD4 as indicators would be beneficial for the precision management of hepatocellular carcinoma.

Clinical significance of novel biomarkers to predict the natural course of hepatitis B infection.

Chronic hepatitis B (CHB) can be divided into immune tolerance (IT), immune clearance (IC), hepatitis B e antigen (HBeAg)-negative inactive/quiescent carrier (ENQ), and HBeAg-negative hepatitis (ENH) phases. The conventional biomarkers used to distinguish these phases have limitations. We examined the clinical significance of hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) as novel biomarkers. One hundred eighty-nine patients without treatment currently were categorized by CHB phase (IT = 46, IC = 45, ENQ = 49, ENH = 49). The associations of HBV RNA and HBcrAg with HBV DNA and alanine transaminase (ALT) were analyzed. The decision tree model was used to distinguish the four phases in the natural course of CHB. The concentrations of HBV RNA and HBcrAg were highest in the IT and IC phases (P < 0.01). Serum HBV RNA was similar to HBcrAg in treatment-naïve patients. HBV RNA and HBcrAg correlated with HBV DNA in the HBeAg+ and HBeAg- status (HBV RNA: e+ r = 0.51, e- r = 0.62; HBcrAg: e+ r = 0.51, e- r = 0.71), but their association with HBV DNA differed among phases. The accuracy, sensitivity, and specificity of HBcrAg with ALT in distinguishing the CHB phases were 95.65%, 95.83%, and 95.55%, respectively. Serum HBV RNA and HBcrAg may be useful to monitor CHB progression.

Effect of variants in LGP2 on MDA5-mediated activation of interferon response and suppression of hepatitis D virus replication

Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I, melanoma differentiation-associated protein 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2), sense viral RNA to induce the antiviral interferon (IFN) response. LGP2, unable to activate the IFN response itself, modulates RIG-I and MDA5 signalling. HDV, a small RNA virus causing the most severe form of viral hepatitis, is sensed by MDA5. The mechanism underlying IFN induction and its effect on HDV replication is unclear. Here, we aimed to unveil the role of LGP2 and clinically relevant variants thereof in these processes. RLRs were depleted in HDV susceptible HepaRGNTCP cells and primary human hepatocytes. Cells were reconstituted to express different LGP2 versions. HDV and IFN markers were quantified in a time-resolved manner. Interaction studies among LGP2, MDA5, and RNA were performed by pull-down assays. LGP2 is essential for the MDA5-mediated IFN response induced upon HDV infection. This induction requires both RNA binding and ATPase activities of LGP2. The IFN response only moderately reduced HDV replication in resting cells but profoundly suppressed cell division-mediated HDV spread. An LGP2 variant (Q425R), predominating in Africans who develop less severe chronic hepatitis D, mediated detectably higher basal and faster HDV-induced IFN response as well as stronger HDV suppression. Mechanistically, LGP2 RNA binding was a prerequisite for the formation of stable MDA5-RNA complexes. MDA5 binding to RNA was enhanced by the Q425R LGP2 variant. LGP2 is essential to mount an antiviral IFN response induced by HDV and stabilises MDA5-RNA interaction required for downstream signalling. The natural Q425R LGP2 is a gain-of-function variant and might contribute to an attenuated course of hepatitis D. HDV is the causative pathogen of chronic hepatitis D, a severe form of viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Upon infection, the human immune system senses HDV and mounts an antiviral interferon (IFN) response. Here, we demonstrate that the immune sensor LGP2 cooperates with MDA5 to mount an IFN response that represses HDV replication. We mapped LGP2 determinants required for IFN system activation and characterised several natural genetic variants of LGP2. One of them reported to predominate in sub-Saharan Africans can accelerate HDV-induced IFN responses, arguing that genetic determinants, possibly including LGP2, might contribute to slower disease progression in this population. Our results will hopefully prompt further studies on genetic variations in LGP2 and other components of the innate immune sensing system, including assessments of their possible impact on the course of viral infection.

Antibody response to an accelerated course of Hepatitis B vaccination.

There are several courses with different dosing intervals for Hepatitis B vaccination. This independent study is looking at the antibody response after three doses of the accelerated course. The primary aim of the study was to examine data available at an Occupational Health Service for the antibody response to one or if nonresponsive, two accelerated Hepatitis B courses. A secondary aim is to determine if there is a difference in response for different sex and age groups. This is a retrospective anonymous and blinded study looking at the antibody response in 1032 healthcare personnel given the accelerated course of the Hepatitis B vaccine over a period of over 6 years. An anti-Hbs response 4 months after the start of the vaccination of >10 IU/ml was taken as indicative of a response. After one course, 93% of the healthcare personnel developed antibody levels thought to confer immunity. After two courses, nearly 99% of the healthcare personnel had developed an adequate immune response. The response was better in females and <40 years old, a difference that was statistically significant for those aged <40. The accelerated course confers high levels of immunity after 4 months and this supports the current practice of offering the accelerated dose to UK healthcare personnel who can be at immediate and higher risk of infection. Though some groups are less responsive, all groups mount a good response so all those at risk should be encouraged to have this vaccination.

Real-Life Data on Sofosbuvir/Ledipasvir in Patients with Chronic Viral Hepatitis C Genotype 1b: A Single-Center Experience.

The course of hepatitis C disease has changed with the use of direct-acting antiviral drugs in the treatment of the disease. The aim of this study was to evaluate the real-life efficacy and safety of the sofosbuvir/ledipasvir drug regimen in the treatment of patients with genotype 1b. Treatment-naive or -experienced 49 genotypes 1b patients treated with sofosbuvir/ledipasvir participated in the study. Laboratory and hepatitis C virus RNA values were evaluated at baseline, week 12, and week 24 of treatment (36th week for those who received 24 weeks of treatment). The sustained virologic response rate was 100% in patients who completed treatment. At the end of the study, there was a significant decrease in alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and alpha-fetoprotein levels (P = .000014, P = .000581, P = .000012, and P = .000821), respectively. Renal function tests (creatinine, estimated glomerular filtration rate) worsened (P = .003 and P = .007, respectively). Hepatocellular carcinoma (HCC) was developed in 2 patients during post-treatment follow-up. In Kaplan-Meier analysis, the probability of not developing HCC was 86.5% at 26 months. The sofosbuvir/ledipasvir combination is effective in treating genotype 1b chronic hepatitis C with high sustained virologic response rates. Because there are few drug interactions, it may be a suitable option for patients taking multiple medications or who are transplant recipients. Renal function should be monitored closely during and after treatment, as there is a risk of worsening renal function after treatment.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication

Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

HTLV-1 and Co-infections.

Human T lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes lifelong T-cell infection in humans, impacting the host immune response. This virus causes a range of clinical manifestations, from inflammatory conditions, including neuronal damage (HTLV-1 associated myelopathy, HAM) to life-threatening leukemia (adult T-cell leukemia, ATL). Human T lymphotropic virus type 1 is also associated with increased risk of all-cause mortality, but the mechanisms remain unclear. As a blood-borne and sexually transmitted infection (STI), HTLV-1 shares transmission routes to many other pathogens and although it has worldwide distribution, it affects mainly those in low- and middle-income tropical areas, where the prevalence of other infectious agents is high. These factors contribute to a high incidence of co-infections in people living with HTLV-1 (PLHTLV). This comprehensive review addresses the impact of HTLV-1 on several co-infections and vice-versa. There is evidence of higher rates of HTLV-1 infection in association with other blood borne (HCV, HBV) and sexually transmitted (Syphilis, Chlamydia, HPV, HSV) infections but whether this represents increased susceptibility or opportunity is unclear. Higher frequency of Mycobacterium tuberculosis (MTb) and Mycobacterium leprae (M. leprae) is observed in PLHTLV. Reports of opportunistic infections and high frequency of crusted scabies in patients with HTLV-1 points to immune impairment in those individuals. Human T lymphotropic virus type 1 may influence the persistence of pathogens, exemplified by the higher rates of Schistosoma mansoni and Strongyloides stercoralis (St. stercoralis) treatment failure observed in PLHTLV. This retrovirus is also associated with increased tuberculosis (TB) severity with some evidence pointing to a deleterious impact on leprosy outcome as well. These findings are supported by immune alterations observed in those co-infected individuals. Although the role of HTLV-1 in HCV outcome is debatable, most data indicate that HTLV may negatively impact the clinical course of hepatitis C. Co-infections may also influence the risk of developing HTLV-1 associated disease, but data are still limited. The impact of HTLV-1 on the response to more common infections, might contribute to the increased mortality rate of HTLV-1. Large scale prospective controlled studies on the prevalence and impact of HTLV-1 in co-infections and vice-versa are needed. Human T lymphotropic virus type 1 impact in public health is broad. Measures to increase awareness and to prevent new infections are needed.