Chronic hepatitis E: Advancing research and patient care.

The hepatitis E virus (HEV) was initially thought to exclusively cause acute hepatitis. However, the first diagnosis of chronic hepatitis E in transplant recipients in 2008 profoundly changed our understanding of this pathogen. We have now begun to understand that specific HEV genotypes can cause chronic infection in certain immunocompromised populations. Over the past decade, dedicated clinical and experimental research has substantiated knowledge on the epidemiology, transmission routes, pathophysiological mechanisms, diagnosis, clinical features and treatment of chronic HEV infection. Nevertheless, many gaps and major challenges remain, particularly regarding the translation of knowledge into disease prevention and improvement of clinical outcomes. This article aims to highlight the latest developments in the understanding and management of chronic hepatitis E. More importantly, we attempt to identify major knowledge gaps and discuss strategies for further advancing both research and patient care.

Coping Through Religiosity, Spirituality and Social Support Among Muslim Chronic Hepatitis Patients.

Academics acknowledge religiosity, spirituality and social support as socio-behavioral factors that influence patients' ability to deal with chronic illness. This study has attempted to describe empirical reality of how these factors influence patients. The sample of this study was 500 chronically ill hepatitis patients and was selected through the multistage sampling techniques. Through structured interview schedule, data were collected during the period of September 2016 to March 2017 from five most populated cities of Punjab (Pakistan). Data were analyzed through descriptive (frequency and percentage) and inferential statistics (Cronbach's alpha, Pearson correlation, and structural equation modeling). The study suggests some recommendations and suggestions to policy makers regarding the significance of religiosity, spirituality and social support as coping strategies during chronic illness. The findings illustrate that social support has more association with coping than religiosity and spirituality of the patients.

Defining virus-specific CD8+ TCR repertoires for therapeutic regeneration of T cells against chronic hepatitis E.

BACKGROUND & AIMS: Immunosuppressed patients with chronic hepatitis E virus infection (cHEV), who are ineligible or have failed current treatment with off-label ribavirin, are a potential target population for T cell-based therapy. T cell responses are important for viral control. Herein, we aimed to identify human leukocyte antigen (HLA)-A2 restricted HEV-specific CD8+ T cell epitopes and T cell receptors (TCR) targeting these epitopes, as the basis for a redirected TCR treatment approach for patients with cHEV. METHODS: HEV genotype 3 overlapping peptide pools were used to screen HEV-specific CD8+ T cell immune responses in HLA-A2+ patients with acute HEV infection and healthy donors, by intracellular cytokine staining. CD8+ T cells targeting the identified epitopes were sorted for sequencing of the TCR repertoires by next generation sequencing. Messenger RNA encoding these TCRs were introduced into lymphocytes of healthy donors and patients with cHEV through TCR redirection. TCR-engineered lymphocytes were evaluated for Dextramer®-binding capacity, target sensitivity and cytotoxicity against peptide-loaded T2 cells. RESULTS: HEV-specific responses were observed across open reading frame (ORF)1 and ORF2 of the HEV genome in patients with acute resolving HEV infection. HLA-A2-restricted HEV-specific CD8+ T cell epitopes targeting the HEV RNA helicase and RNA-dependent RNA polymerase were selected for functional studies. Introduction of HEV-specific TCRs into lymphocytes of immunocompetent donors and patients with chronic hepatitis E enabled the lymphocytes to bind HEV Dextramers, secrete multiple cytokines and exert cytotoxicity in a target-specific manner. CONCLUSION: We identified TCRs that target HEV-specific CD8+ T cell epitopes, and characterized their immune properties, which may have clinical potential in future T cell-based therapy. LAY SUMMARY: Patients who are immunosuppressed are vulnerable to developing chronic liver disease following infection with hepatitis E virus (HEV). To-date, there is no approved therapy for chronic hepatitis E. Interferon-α and ribavirin are off-label treatment options, but their applications are limited by side effects. Thus, immunotherapy, more specifically T cell-based therapy, may be an alternative approach. We designed T cell receptor-engineered T cells that effectively conferred immune cells, taken from patients with chronic hepatitis E, with the ability to recognize virus-specific epitopes and mediate killing of target cells in vitro.

Fibrosis in Chronic Liver Disease: An Update on Diagnostic and Treatment Modalities.

Fibrosis is a common outcome of most chronic inflammatory diseases, characterized by the accumulation of excessive extracellular matrix components. Individuals with progressive liver fibrosis develop cirrhosis, are at risk of developing liver cancer, and may succumb to liver failure. Although a number of specific therapies for different diseases have been developed and successfully used, for example, direct antiviral agents in treatment for hepatitis C, effective and specific antifibrotic therapies are still not available. Liver biopsy remains the gold standard of staging liver fibrosis. However, transient elastography is increasingly being used in clinical trials and in hepatology clinics as part of standard-of-care evaluation because it is easy to use. Magnetic resonance (MR)-elastography is most accurate in evaluating fibrosis stage but is costly and time consuming and thus not readily available. Recent advances, however, have been made in areas of diagnostic and therapeutic modalities, with an increasing number of potential drugs currently in phase II and III trials, particularly in the field of non-alcoholic steatohepatitis-related liver fibrosis. These new drugs target multiple pathways involved in the pathogenesis of chronic liver disease, and we anticipate that some of them may soon be approved for use in patients.

[Viral Hepatitis: When to be Considered in Clinical Routine?] / Virushepatitis ­ wann daran denken?

Chronic viral hepatitis can remain unrecognized but may nevertheless lead to liver cirrhosis and hepatocellular carcinoma. Thus, patients with elevated liver enzymes as well as risk groups need to be screened and treated for viral hepatitis. These groups include, in particular, migrants from countries with high HBV or HCV prevalence, persons with previous or current intravenous drug use, and homosexual men. For HBV- or HCV-associated diseases, such as panarteriitis nodosa, cryoglobulinemic vasculitis or B-cell lymphoma, antiviral therapy may lead to remission. Prior to high-dose immunosuppressive therapy, especially with regimes containing rituximab, chronic or resolved HBV infection must be ruled out or antiviral prophylaxis may be required to avoid a potentially fatal HBV reactivation.

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs.

This consensus statement on chronic hepatitis (CH) in dogs is based on the expert opinion of 7 specialists with extensive experience in diagnosing, treating, and conducting clinical research in hepatology in dogs. It was generated from expert opinion and information gathered from searching of PubMed for manuscripts on CH, the Veterinary Information Network for abstracts and conference proceeding from annual meetings of the American College of Veterinary Medicine and the European College of Veterinary Medicine, and selected manuscripts from the human literature on CH. The panel recognizes that the diagnosis and treatment of CH in the dog is a complex process that requires integration of clinical presentation with clinical pathology, diagnostic imaging, and hepatic biopsy. Essential to this process is an index of suspicion for CH, knowledge of how to best collect tissue samples, access to a pathologist with experience in assessing hepatic histopathology, knowledge of reasonable medical interventions, and a strategy for monitoring treatment response and complications.

[The effectiveness of the application of medicinal mineral water from the 'Omonkhona' source in the patients presenting with the diseases of the hepatobiliary system]. / Éffektivnost' primeneniia lechebnoi mineral'noi vody iz istochnika 'Omonkhona' u patsientov s zabolevaniiami gepatobiliarnoi sistemy.

BACKGROUND: Investigations into the medicinal properties of 'Omonkhona' mineral water used for the treatment of hepatobiliary pathology make up the entirely new field of balneological research in Uzbekistan. AIM: The objective of the present study was to identify the hepatoprotective and choleretic components of the 'Omonkhona' mineral water and elucidate their action in the patients presenting with the diseases of the hepatobiliary system. MATERIAL AND METHODS: A total of 77 patients suffering from the diseases of the hepatobiliary system were available for the examination including 38 patients with chronic hepatitis (CH), 17 with chronic cholecystitis (CC), and 22 patients with liver cirrhosis (Cr). All the patient were prescribed drinking the mineral water (from 1.0 to 3.0 liters per day) during consequtive 12-14 days. The clinical, biochemical, and instrumental studies were carried before and after the treatment. RESULTS: The treatment with 'Omonkhona' water resulted either in the complete elimination or the significant alleviation of pain in the right hypochondrium. The patients presenting with CH and CC experienced normalization of ESR even though it remained high in the Cr patients. All the patients exhibited a decrease of specific gravity of the urine, probably due to the diuretic effect of the mineral water. The biochemical studies of blood and bile showed that the initially slightly enhanced bilirubin levels, alanine aminotransferase and alkaline phosphatase activities in the CH and CC patients normalized after a course of the treatment with 'Omonkhona' mineral water (p<0.05). No such changes were documented in the patients with liver cirrhosis. The patients with CH and CC experienced the two-fold reduction in the intensity of inflammation whereas the bilirubin and bile acid levels increased although the relative cholesterol content decreased and the cholate-cholesterol coefficient increased (p<0.05). The Cr patients demonstrated only insignificant changes of these parameters. The ultrasound examination showed that the CC patients treated with 'Omonkhona' mineral water had a decrease in the swelling of the gallbladder walls, the improvement of its motor function and the disappearance of the stagnation phenomenon. In the CH patients, there was a significant decrease in the cranio-caudal size of the right lobe of the liver, the cranio-caudal size of the left lobe, and the anteroposterior size of the left lobe (p<0.05). A decrease in the acoustic conductivity was noted that can probably be attributed to the reduced swelling of the liver parenchyma. The Cr patients had no significant changes of these parameters following the treatment. CONCLUSIONS: The results of this study give evidence that the treatment of the diseases of the hepatobiliary system with 'Omonkhona' mineral water exerts the well apparent positive influence on the patients presenting with CC and CH even though its beneficial effect was less pronounced in the patients with livre cirrhosis.

Factors associated with voluntary testing for HBV in the Upper West Region of Ghana.

This study examined the role of health facilities on testing for Hepatitis B virus in a policy context where screening is only available at a cost. We fitted multivariate multinomial logistic regression models to cross-sectional data (n = 1374) collected from Upper West Region of Ghana. The analysis showed that approximately 28% of respondents reported ever testing for HBV. Although source of healthcare influenced HBV testing, traders (RRR = 0.29, p ≤ 0.001) and farmers (RRR = 0.34, p ≤ 0.01) were significantly less likely to test voluntarily. Wealth generally predicted voluntary testing, although less so for mandatory testing. The findings highlight the need for free HBV services targeting the very poor, especially those who use community-level health facilities as their primary source of care.

Improving the hepatitis cascade: assessing hepatitis testing and its management in primary health care in China.

Objective: The study aimed to decentralize hepatitis testing and management services to primary care in China. Methods: A nationwide representative provider survey amongst community health centres (CHCs) using randomized stratified sampling methods was conducted between September and December 2015. One hundred and eighty CHCs and frontline primary care practitioners from 20 cities across three administrative regions of Western, Central and Eastern China were invited to participate. Results: One hundred and forty-nine clinicians-in-charge (79%), 1734 doctors and 1846 nurses participated (86%). Majority of CHCs (80%, 95% CI: 74-87) offered hepatitis B testing, but just over half (55%, 95% CI: 46-65) offered hepatitis C testing. The majority of doctors (87%) and nurses (85%) felt that there were benefits for providing hepatitis testing at CHCs. The major barriers for not offering hepatitis testing were lack of training (54%) and financial support (23%). Multivariate analysis showed that the major determinants for CHCs to offer hepatitis B and C testing were the number of nurses (AOR 1.1) and written policies for hepatitis B diagnosis (AOR 12.7-27.1), and for hepatitis B the availability of reproductive health service. Conclusions: Primary care providers in China could play a pivotal role in screening, diagnosing and treating millions of people with chronic hepatitis B and C in China.

Perfil clínico de pacientes portadores de hepatite B crônica / Clinical profile of patients with chronic hepatitis B

Objetivo: Conhecer as características e o perfil clínico dos indivíduos em tratamento de hepatite B crônica. Métodos: Participaram do estudo 65 pacientes com hepatite B crônica que iniciaram o tratamento entre os anos de 2010 a 2012. Resultados: Todos os pacientes eram da raça branca. Houve predomínio do sexo masculino (60%), e a maioria tinha entre 41 e 50 anos (32,8%). Grande parte dos pacientes (87,9%) não foi imunizada; 10,3% receberam as três doses da vacina e 43,1% possuíam familiar de primeiro grau ou parceiro com hepatite B crônica. A maioria (70,8%) relatou contato com algum fator de risco, sendo que 61,5% referiram ter realizado tratamento dentário. Conclusão: A implantação da vacina para toda população menor de 1 ano de idade, em 1996, pode ser uma explicação para a alta média de idade encontrada e pela inexistência de indivíduos menores de 23 anos no estudo. A vacinação completa, entretanto, ainda apresenta baixa adesão.(AU)

Objective: To get to know the characteristics and clinical profile of subjects being treated for chronic hepatitis B. Methods: Sixty-five patients with chronic hepatitis B who started treatment between the years 2010 to 2012 participated in the study. Results: All patients were white; there was a predominance of males (60%), and most of them were between 41 and 50 years (32.8%). Most patients (87.9%) were not immunized; 10.3% received all the three doses of the vaccine, and 43.1% had a first-degree relative or a partner with chronic hepatitis B. Most of them (70.8%) reported contact with a risk factor, with 61.5% reporting having had dental treatment. Conclusion: The implantation of the vaccine for all the population lower than 1 year of age, in 1996, can be an explanation for the high average age found, and the nonexistence of individuals younger than 23 years in the study. Complete vaccination, however, still presents low adherence.(AU)

Canine Idiopathic Chronic Hepatitis.

The World Small Animal Veterinary Association's Liver Standardization Group produced standardized criteria for the histologic diagnosis of canine chronic hepatitis (CH). They define CH by the presence of hepatocellular apoptosis or necrosis, a variable mononuclear or mixed inflammatory cell infiltrate, regeneration, and fibrosis. There are variations in histologic appearance between breeds. Hepatic copper accumulation is an important cause of canine CH. However, where copper accumulation has been ruled out, dogs are said to have idiopathic CH. This article reviews theories regarding the etiopathogenesis of canine CH other than copper accumulation, and its clinical features, diagnostic findings, and management.

Oral branched-chain amino acid granules improve structure and function of human serum albumin in cirrhotic patients.

BACKGROUND AND AIMS: The aim of this study was to evaluate structural and functional alterations of human serum albumin (HSA), with a special focus on the oxidized and reduced forms, in patients with chronic liver disease. We also investigated whether oral branched-chain amino acid (BCAA) supplementation could induce structural changes and improve the functions of HSA. METHODS: The proportion of reduced and oxidized HSA was determined in 16 healthy controls and in 20 chronic hepatitis and 100 cirrhotic patients with stable conditions. To evaluate the functional properties of HSA, this study focused on the antioxidant and binding functions. The radical scavenging activity and binding ability of purified HSA were measured in 68 participants. After BCAA administration for 6 months, 29 patients were evaluated for HSA structural changes, with 19 out of the 29 patients also analyzed for HSA functional changes. RESULTS: There was a significant decrease in the amounts of reduced HSA in conjunction with liver disease progression. Receiver operating characteristic curve analysis demonstrated that the levels of reduced HSA had high accuracy in determining disease progression. Functional alterations were strongly correlated to the levels of reduced HSA. BCAA supplementation led to substantial increases in the amount of reduced HSA. The altered HSA was able to scavenge significantly more radicals and restore the binding ability. CONCLUSION: This study describes structural alterations and functional disturbances of HSA in patients with chronic liver disease, and indicates that the levels of reduced HSA might reflect disease progression and the functional properties of HSA. Moreover, oral BCAA supplementation increases the amount of reduced HSA, thereby leading to the restoration of HSA function in cirrhotic patients.

Efficiency of Cell Therapy in Liver Cirrhosis.

We studied safety and clinical efficacy of transplantation of autologous bone marrow cell in complex therapy of 158 patients with chronic hepatitis and cirrhosis of the liver. The efficiency of cell therapy was assessed in 12 months after single injection of the cells. The positive response (alleviation of liver cirrhosis or stabilization of the pathological process) was observed in 70% cases. The efficacy of therapy correlated with the severity and etiology of the disease and was maximum in patients with Child-Pugh class A (in 82.5% cases) and class B liver cirrhosis (in 79% cases); in patients with class C liver cirrhosis, the positive response was achieved in 42.5% cases. In 39 patients, ultrasonic examination performed in 3 years after transplantation revealed no focal lesions or ectopic ossification foci.

Diagnosis and treatment challenges in a patient with splenic tumor and chronic viral hepatitis.

UNLABELLED: Non-Hodgkin lymphoma is a cancer of the lymphatic tissue located in various parts of the body: lymph nodes, spleen, thymus, adenoids, tonsils, and bone marrow. The disease occurs mainly in adults, with a higher incidence within the age range of 45 to 60 years. We present a clinical case of non-Hodgkin lymphoma diagnosed in a patient with chronic viral hepatitis B and D. The particularity of this case consists in the diagnosis of primitive spleen lymphoma, described in less than 1% of the cases, and also the difficult antiviral therapy recommendation for the liver disease, given the associated co-morbidity. ABBREVIATIONS: NHL = Non-Hodgkin lymphoma, HDV = Hepatitis delta virus, HCV = Hepatitis C virus, HBV = Hepatitis B virus, CT = Computerized tomography, CEUS = Contrast enhanced ultrasonography, CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone, R-CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab.

Peripheral Blood Mononuclear Cell Gene Expression Remains Broadly Altered Years after Successful Interferon-Based Hepatitis C Virus Treatment.

BACKGROUND: Inflammatory gene expression in peripheral blood mononuclear cells (PBMCs) is altered in chronic Hepatitis C Virus (HCV) infection. Duration of changes after pegylated interferon- (peg-IFN-) based HCV treatment is unclear. METHODS: PBMC mRNA expression of 184 inflammatory response genes was analyzed (nCounter GX Human Inflammation Kit, Nanostring) from peg-IFN treatment nonresponders (NR, n = 18), sustained virologic responders (SVR, n = 22), and spontaneous clearers (SC, n = 15). Logistic regression was used for comparison. RESULTS: Median time from last treatment was 2 and 2.7 years in SVR and NR, respectively (p = NS). Mean mRNA counts were significantly different for 42 and 29 genes comparing SVR to SC patients and NR to SC, respectively, and no genes comparing SVR to NR. Differential expression of 24 genes was significantly different in both SVR and NR groups compared to SC. Among these 24 acute and chronic inflammatory cascade genes, significant upregulation was noted for proinflammatory transcription regulators Fos, CEBPB, and MyD88 in SVR and NR compared to SC. HDAC4 was significantly downregulated in SVR and NR compared to the SC group. CONCLUSIONS: PBMC inflammatory gene expression patterns in SVR resemble NR more than SC patients. A generalized inflammatory response persists in PBMCs long after successful peg-IFN treatment for HCV infection.

[Hepatitis E--overview of the latest knowledge]. / Hepatitida E--prehled soucasných poznatku.

Hepatitis E (HE) is a ubiquitous infection, occurring both in developing and in developed countries. It is caused by the hepatitis E virus (HEV), a small, non-enveloped RNA virus. The reported incidence in the Czech Republic in 2013 was 2 cases per 100,000 inhabitants and the number of HE cases has been growing over the past years. Besides the long known fecal-oral transmission, zoonotic and blood product transmission of HEV has recently been observed in industrialized countries. Most infections are asymptomatic. Symptomatic infection may present as acute hepatitis with nonspecific flu-like symptoms and liver enzymes elevation. In immunocompromised patients, HEV can lead to chronic hepatitis E and can even cause acute liver failure in pregnant women. Several extrahepatic manifestations have also been reported. Antiviral therapy has been successfully used in chronic hepatitis E. The first vaccine available for clinical use is licensed in China so far.

Tratamiento de la infección por virus de la hepatitis C en los pacientes candidatos a trasplante hepático / No disponible

No disponible

Phosphate-dependent glutaminase response to liver injury and hyperbaric oxygenation.

Activity of phosphate-dependent glutaminase was determined in hepatocytes of white female rats, both in healthy animals and in rats with chronic CCl4-hepatitis on day 3 after liver resection and hyperbaric oxygenation. In healthy animals, activity of phosphate-dependent glutaminase was not altered after hepatic resection, but it was elevated in animals with chronic CCl4-hepatitis. Hyperbaric oxygenation inhibited activity of hepatocytic phosphate-dependent glutaminase in non-operated healthy rats but stimulated it after hepatic resection. In animals with chronic CCl4-hepatitis; hyperbaric oxygenation restricted the stimulating effect of hepatic resection on phosphate-dependent glutaminase activity.

Hepatitis E virus: new faces of an old infection.

Hepatitis E virus is one of the most common causes of acute hepatitis worldwide, with the majority of cases occurring in Asia. In recent years, however, an increasing number of acute and chronic hepatitis E virus infections have been reported in industrialized countries. The importance of this infection resides in the associated morbidity and mortality. In acute cases, a high mortality rate has been reported in patients with previously undiagnosed alcoholic liver disease. Hepatitis E infection can become chronic in immunocompromised patients, such as solid organ transplant recipients, patients receiving chemotherapy, and HIV-infected patients, and lead to the development of hepatic fibrosis and cirrhosis. Hence, treatment strategies involving reductions in immunosuppressive regimens and therapy with ribavirin or peg-interferon have been evaluated. In terms of prevention, a promising new vaccine was recently licensed in China, although its efficacy is uncertain and potential adverse effects in risk groups such as chronic liver disease patients and pregnant women require investigation. In conclusion, physicians should be aware of hepatitis E as a cause of both acute and chronic hepatitis in immunocompromised patients. The best treatment option for HEV infection remains to be defined, but both ribavirin and peg-interferon may have a role in therapy for this condition.