Hepatic pathological characteristics and factors influencing alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B / 中华肝脏病杂志

Objective: To analyze the hepatic pathological characteristics and factors influencing an alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B (CHB) and further explore the optimal ALT threshold strategy for initiating antiviral therapy. Methods: Clinical data of treatment-naïve CHB patients who underwent liver biopsies from January 2010 to December 2019 were retrospectively collected. Multiple regression models were used to explore the ALT levels and significant risk of hepatic histological changes (≥G2/S2). Receiver operating characteristic curve was used to evaluate the value of different models in diagnosing liver tissue inflammation≥G2 or fibrosis ≥ S2. Results: A total of 447 eligible CHB patients, with a median age of 38.0 years and 72.9% males, were included. During ALT normalization, there was significant liver inflammation (≥G2) and fibrosis (≥S2) in 66.9% and 53.0% of patients, respectively. With an ALT rise of 1-2×ULN, the proportions of liver inflammation≥G2 and fibrosis≥S2 were 81.2% and 60.0%, respectively. After adjusting for confounding factors, higher ALT levels (> 29 U/L) were found to be associated with significant liver inflammation (OR: 2.30, 95% CI: 1.11 ~ 4.77) and fibrosis (OR: 1.84, 95% CI: 1.10 ~ 3.09). After the measurement of glutamyltransferase-platelet ratio (GPR), the proportion of CHB patients with≥G2/S2 was significantly reduced under different treatment thresholds of ALT standards, and in particular, the erroneous evaluation of liver fibrosis≥S2 was significantly improved (33.5% to 57.5%). Conclusion: More than half of CHB patients have a normal ALT or one within 2 × ULN, regardless of whether or not there is apparent inflammation and fibrosis. GPR can significantly improve the precise assessment of different conditions of treatment thresholds for the ALT value in CHB patients.

Regulation and influence of mitochondria on macrophages during hepatitis B virus infection / 中华肝脏病杂志

Hepatitis B virus (HBV) infection is an important public health concern, as approximately 3.5% of the world's population is currently chronically infected. Chronic HBV infection is the primary cause of cirrhosis, hepatocellular carcinoma, and deaths related to liver disease globally. Studies have found that in HBV infection, viruses can directly or indirectly regulate mitochondrial energy metabolism, oxidative stress, respiratory chain metabolites, and autophagy, thereby altering macrophage activation status, differentiation types, and related cytokine secretion type and quantity regulations. Therefore, mitochondria have become an important signal source for macrophages to participate in the body's immune system during HBV infection, providing a basis for mitochondria to be considered as a potential therapeutic target for chronic hepatitis B.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B / 中南大学学报(医学版)

OBJECTIVES@#Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).@*METHODS@#This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.@*RESULTS@#Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).@*CONCLUSIONS@#The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

Demographic characteristics and associated influencing factors in treated patients with chronic hepatitis B with hypoviremia : a single-center retrospective cross-sectional study / 中华肝脏病杂志

Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.

Caracterización de la evolución clínica del trasplante renal en pacientes con virus de la hepatitis C positivo / Characterization of the clinical course of kidney transplantation in patients with positive hepatitis C virus

Introducción: La infección por el virus de la hepatitis C es un evento común en los receptores de trasplante renal que la arrastran desde su estancia en los tratamientos de hemodiálisis previos al implante. La positividad al virus C se ha asociado a una evolución desfavorable después del trasplante, dado por una mayor frecuencia de complicaciones clínicas, metabólicas e inmunológicas que repercuten de forma negativa tanto en la supervivencia del injerto como del paciente. Objetivos: Caracterizar la evolución clínica de los pacientes trasplantados de riñón con virus de la hepatitis C positivo y determinar la evolución de este grupo de enfermo de acuerdo a variables demográficas, clínicas y de supervivencia. Método: Estudio analítico, transversal, retrospectivo en pacientes trasplantados renales del Hospital Clínico Quirúrgico Hermanos Ameijeiras, desde el año 2005 al 2017. Se excluyeron los menores de 15 años, los retrasplantes, los trasplantes dobles y los combinados o cuando no se pudo obtener la información. Se comparan las variables escogidas entre enfermos que llegan al trasplante con serología positiva al virus C, (HVC positivos), con los HVC negativos. Resultados: Del total de 156 enfermos, 65 por ciento (102) fueron HVC positivos, no se encontraron diferencias entre grupo en cuanto a edad y sexo de receptores y donantes, así como tampoco en el tratamiento inmunosupresor utilizado. El donante vivo se empleó menos en los HVC positivos donde se encontraron más enfermos con poliquistosis renal. La necrosis tubular aguda (NTA) y el rechazo fueron más frecuentes en los HVC positivos, siendo la primera estadísticamente significativa, p=0,0421, también resultaron significativamente más frecuente en el grupo HVC positivo, la proteinuria, p=0,041, la elevación de enzimas hepáticas, p=0,047 y la diabetes postrasplante, p=0,047. La supervivencia del injerto y los pacientes fue menor en los HVC positivos. Conclusiones: En este estudio la hepatitis por virus C impacta negativamente en la evolución del injerto y propicia la aparición de algunas complicaciones clínicas, lo que sin dudas pudiera influir en una menor expectativa de vida tanto para el injerto como para el enfermo(AU)

Introduction: Hepatitis C virus infection is a common event in kidney transplant recipients that has dragged it along since their stay in hemodialysis treatments prior to implantation. Positivity to virus C has been associated with an unfavorable evolution after transplantation, due to higher frequency of clinical, metabolic and immunological complications that negatively affect both graft and patient survival. Objectives: To describe the clinical evolution of kidney transplant patients with positive hepatitis C virus and to determine the evolution of this group of patients according to demographic, clinical and survival variables. Method: An analytical, cross-sectional, retrospective study in kidney transplant patients at Hermanos Ameijeiras Hospital was carried out from 2005 to 2017. This study excluded children under 15 years of age, re-transplants, double and combined transplants or when it was not possible to gather the information. The variables chosen among patients who arrive at transplantation with positive serology for virus C (positive HCV) were compared with negative HCV. Results: One hundred and fifty six patients were the total, 65 percent (102) were HVC positive, no differences were found between groups in terms of age and sex of recipients and donors, nor in the immunosuppressive treatment used. The living donor was less used in positive HVC where more patients with polycystic kidney disease were found. Acute tubular necrosis (ATN) and rejection were more frequent in positive HVC, the former being statistically significant, p = 0.0421, proteinuria, p = 0.041, elevation was also significantly more frequent in the positive HVC group of liver enzymes, p = 0.047 and post-transplant diabetes, p = 0.047. Graft and patient survival was lower in positive HCV. Conclusions: In this study, hepatitis C virus has negative impact on the evolution of the graft and favors the appearance of some clinical complications, which undoubtedly could influence a shorter life expectancy for both the graft and the patient(AU)

Dermatomiositis asociada con carcinoma hepatocelular relacionado con el virus de la hepatitis B: un reporte de caso en Perú / Dermatomyositis associated with hepatitis B virus-related hepatocellular carcinoma: a case report in Peru

La dermatomiositis (DM) es una miopatía inflamatoria de causa desconocida caracterizada por inflamación muscular, debilidad músculo-esquelética proximal y manifestaciones cutáneas típicas. Se ha asociado a malignidades como un síndrome paraneoplásico. Reportamos el caso de un paciente varón de 33 años, diagnosticado de hepatitis B, VHB crónico inactivo, que presentó lesiones papulares, pruriginosas y descamativas en cara, manos, zona inguinal y pies. Al examen físico se evidenció pápulas de Gottron, signo del heliotropo, debilidad muscular simétrica proximal. Se realizó una biopsia de piel donde se encontraron hallazgos compatibles con DM. Tras una ecografía abdominal se encontró una tumoración hepática, cuyo resultado en biopsia fue de carcinoma hepatocelular moderadamente diferenciado. Posteriormente se le realiza segmentectomía con lo cual síntomas de DM disminuyen. Es un caso infrecuente, y de sumo interés por lo que se decide reportar.

Dermatomyositis is an idiopathic inflammatory myopathie characterized by proximal skeletal muscle weakness, typical skin manifestations and muscle inflammation. This disease has been associated with malignancies as a paraneoplastic syndrome. We present a patient of thirty-three years diagnosed with hepatitis B, chronic inactive HBV who presents papular, pruritic and desquamative lesions on the face, hands, inguinal area and feet. At the physical examination is evidentiated Gottron's papules, heliotrope sign and proximal symmetric muscular weakness. Findings compatible with DM were found in a skin biopsy. An abdominal ultrasound revealed a liver tumor whereby a biopsy was performed and the result was a moderately differentiated hepatocellular carcinoma. Subsequently, a segmentectomy has been made and consequently the DM symptoms decreased. This case is of great interest and rare reason why we decided to reported it.

A Study of the Association between Diabetes Mellitus and Chronic Hepatitis B Virus Infection / Un Estudio de la Asociación entre la Diabetes Mellitus y la Infección Crónica por el Virus de la Hepatitis B

ABSTRACT Background: Hepatitis B virus (HBV) infection and diabetes mellitus are major health problems associated with significant morbidity and mortality. The published literature suggests an association of diabetes mellitus with liver disease. However, the role of HBV infection in diabetes aetiology is still controversial. The present study was conducted to explore the veracity of this enigmatic association among Pakistani subjects. Methodology: The blood samples and clinical information were collected from chronic HBV-positive patients Group 1 (n = 120), and their age and gender were matched with those of the healthy control subjects Group 2 (n = 120). Hepatitis B virus-positive patients were also subdivided into two groups; (Group 1a and Group 1b) with and without liver cirrhosis for evaluation of the prevalence of diabetes. Results: The study revealed that there were statistically significant differences in the biochemical parameters in the HBV-positive and control groups. There was no correlation between diabetes and HBV with the prevalence of diabetes mellitus being similar in subjects with and without HBsAg (11.7% in the positive group and 10% in the controls). Since there were a relatively large number (32.5%) of HBV-positive patients with liver cirrhosis, a comparison of biochemical parameters was also carried out to evaluate the extent of the liver damage and its association with diabetes. During the comparison of HBV patients with and without cirrhosis for the prevalence of diabetes, no aetiologic association was found with diabetes. Conclusion: Study revealed that there was no correlation between HBV infection and diaabetes despite the significantly different biochemical parameters in the HBV-infected group and control subjects.

RESUMEN Antecedentes: La infección por el virus de la hepatitis B (VHB) y la diabetes mellitus son problemas de salud importantes asociados con morbilidad y mortalidad significativas. La literatura publicada sugiere una asociación de la diabetes mellitus con las enfermedades hepáticas. Sin embargo, el papel de la infección por VHB en la etiología de diabetes sigue siendo contro-versial. El presente estudio fue conducido con el propósito de explorar la veracidad de esta enigmática asociación entre sujetos paquistaníes. Metodología: Se recogieron muestras de sangre e información clínica de pacientes crónicos VHB positivos Grupo 1 (n = 120), y su edad y género fueron comparados con los de los sujetos sanos del control Grupo 2 (n = 120). Los pacientes positivos al virus de la hepatitis B también se subdividieron en dos grupos, a saber, (Grupo 1a y Grupo 1b) con y sin cirrosis hepática en relación con la prevalencia de la diabetes. Resultados: El estudio reveló que hubo diferencias significativas en estos dos grupos en los parámetros bioquímicos entre el grupo de control y el grupo VHB positivo. En estos dos grupos no hubo correlación entre la diabetes y el VHB. Puesto que hubo un número relativamente grande (32.5%) de pacientes VHB positivos con cirrosis hepática, se realizó también una comparación de los parámetros bioquímicos a fin de comprender el grado del daño hepático y su asociación con la diabetes. Durante la comparación de los pacientes con VHB con y sin cirrosis en relación con la prevalencia de diabetes, no se halló asociación etiológica con la diabetes. Conclusión: Este estudio reveló que no hubo correlación entre la infección por VHB y la diabetes, a pesar de los parámetros bioquímicos significativamente diferentes entre el grupo infectado por el VHB y los sujetos del control.

Transplante hepático na hepatite delta: experiência da América do Sul / Liver transplantation in hepatitis delta: south america experience

ABSTRACT BACKGROUND: The Amazon region is one of the main endemic areas of hepatitis delta in the world and the only one related to the presence of genotype 3 of the delta virus. OBJECTIVE: To analyze the profile, mortality and survival of cirrhotic patients submitted to liver transplantation for chronic hepatitis delta virus and compare with those transplanted by hepatitis B virus monoinfection. METHODS: Retrospective, observational and descriptive study. From May 2002 to December 2011, 629 liver transplants were performed at the Walter Cantídio University Hospital, of which 29 patients were transplanted due to cirrhosis caused by chronic delta virus infection and 40 by hepatitis B chronic monoinfection. The variables analyzed were: age, sex, MELD score, Child-Pugh score, upper gastrointestinal bleeding and hepatocellular carcinoma occurrence before the transplantation, perioperative platelet count, mortality and survival. RESULTS: The Delta Group was younger and all came from the Brazilian Amazon Region. Group B presented a higher proportion of male patients (92.5%) compared to Group D (58.6%). The occurrence of upper gastrointestinal bleeding before transplantation, MELD score, and Child-Pugh score did not show statistical differences between groups. The occurrence of hepatocellular carcinoma and mortality were higher in the hepatitis B Group. The survival in 4 years was 95% in the Delta Group and 75% in the B Group, with a statistically significant difference (P=0.034). Patients with hepatitis delta presented more evident thrombocytopenia in the pre-transplantation and in the immediate postoperative period. CONCLUSION: The hepatitis by delta virus patients who underwent liver transplantation were predominantly male, coming from the Brazilian Amazon region and with similar liver function to the hepatitis B virus patients. They had a lower incidence of hepatocellular carcinoma, more marked perioperative thrombocytopenia levels and frequent episodes of upper gastrointestinal bleeding. Patients with hepatitis by delta virus had lower mortality and higher survival than patients with hepatitis B virus.

RESUMO CONTEXTO: A região Amazônica é uma das principais áreas endêmicas da hepatite delta no mundo e a única relacionada com a presença do genótipo 3 do vírus delta. OBJETIVO: Analisar o perfil, mortalidade e sobrevida dos pacientes cirróticos submetidos a transplante hepático por hepatite crônica pelo vírus delta e comparar com os transplantados pela monoinfecção do vírus da hepatite B. MÉTODOS: Estudo retrospectivo, observacional e descritivo. Entre maio de 2002 a dezembro de 2011, foram realizados 629 transplantes de fígado no Hospital Universitário Walter Cantídio, dos quais 29 pacientes foram transplantados por cirrose causada pela infecção crônica do vírus delta e 40 pela monoinfecção crônica da hepatite B. As variáveis analisadas foram: origem, idade, sexo, escore de MELD, classificação de Child-Pugh, ocorrência de hemorragia digestiva alta e carcinoma hepatocelular antes do transplante, número de plaquetas perioperatória, mortalidade e sobrevida. RESULTADOS: O Grupo Delta foi mais jovem e todos oriundos da região Amazônica Brasileira. O Grupo B apresentou maior proporção de pacientes do sexo masculino (92,5%) em relação ao Grupo D (58,6%). A ocorrência de hemorragia digestiva alta antes do transplante, escore de MELD e classificação de Child-Pugh não obtiveram diferenças estatísticas entre os grupos. A ocorrência de carcinoma hepatocelular e a mortalidade foram maiores no grupo com hepatite B. A sobrevida em 4 anos foi de 95% no Grupo delta e 75% no Grupo B com diferença estatisticamente significante (P=0,034). Pacientes com hepatite delta, apresentaram mais acentuada plaquetopenia no pré-transplante e no pós-operatório imediato. CONCLUSÃO: Os pacientes com hepatite por vírus delta submetidos ao transplante hepático eram predominantemente homens, vindos da região da Amazônia brasileira e com função hepática semelhante a dos pacientes com vírus da hepatite B. Apresentavam menor incidência de carcinoma hepatocelular, níveis de trombocitopenia perioperatória mais acentuados e episódios frequentes de hemorragia digestiva alta. Os pacientes com hepatite por vírus delta apresentaram menor mortalidade e maior sobrevida que os pacientes com vírus da hepatite B.

Risk factors analysis and a new risk scoring system predicting hepatocarcinogenesis for chronic genotype C HBV infected patients / 中华流行病学杂志

Objective: To investigate the effects of hepatitis B virus (HBV) genotype and mutations on the development of hepatocellular carcinoma (HCC) and to establish a new qualified HCC risk scores. Methods: A cohort study enrolling patients with chronic HBV infection was conducted. HBV genotypes were identified by nested multiplex PCR. HBV mutations in the basic core promoter region and PreS region were sequenced after PCR amplification. Scores on risk factors were set based on nomogram. Results: Totally, 1 525 patients were followed-up in this research. A total of 1 110 patients infected with genotype C were followed-up for 8.52 (Q(R): 5.36-11.68) years on average, of whom the incidence of HCC was 11.93/1 000 person-years. In genotype C HBV infected patients, male gender, aged 40 years and over, and four DNA mutations (T1674CG, A1762T/G1764A, A3120T, and A2962G) can increase the risk of HCC (P<0.05); interferon therapy can reduce the risk of HCC (P<0.05). A new HCC predicting model was established according to the results. After validation, the predicted disease-free survival rate was consistent with the real one. Conclusions: Hepatitis B virus genotypes and mutations were closely associated with HCC. The new risk scoring system can well predict HCC occurrence in genotype C HBV infected patients.

Retrospective analysis of hepatitis B virus chronic infection in 247 patients: clinical stages, response to treatment and poor prognostic factors

Abstract Background: Chronic hepatitis B is a major cause of cirrhosis, and the natural history of the disease has several clinical stages that should be thoroughly understood for the implementation of proper treatment. Nonetheless, curing the disease with antiviral treatment remains a challenge. Aims: To describe the clinical course, response to treatment, and poor prognostic factors in 247 hepatitis B virus chronic infection patients treated in a tertiary hospital in Brazil. Methods: This was a retrospective and observational study, by analyzing the medical records of HBV infected patients between January 2000 and January 2015. Results: Most patients were male (67.2%) and 74.1% were HBeAg negative. Approximately 41% had cirrhosis and 8.5% were hepatitis C virus coinfected. The viral load was negative after two years on lamivudine, entecavir and tenofovir in 86%, 90.6%, and 92.9% of the patients, respectively. The five-year resistance rates for lamivudine, adefovir, entecavir, and tenofovir were 57.5%, 51.8%, 1.9%, and 0%, respectively. The overall seroconversion rates were 31.2% for HBeAg and 9.4% for HBsAg. Hepatocellular carcinoma was diagnosed in 9.7% of patients, liver transplantation was performed in 9.7%, and overall mortality was 10.5%. Elevations of serum alanine aminotransferase (p = 0.0059) and viral load (p < 0.0001) were associated with progression to liver cirrhosis. High viral load was associated with progression to hepatocellular carcinoma (p < 0.0001). Significant risk factors associated with death were elevated alanine aminotransferase (p = 0.0039), liver cirrhosis (p < 0.0001), high viral load (p = 0.007), and hepatocellular carcinoma (p = 0.0008). HBeAg positive status was not associated with worse outcomes, and treatment may have been largely responsible. Conclusions: Elevations of viral load and serum alanine aminotransferase may select patients with worse prognosis, especially progression to cirrhosis and hepatocellular carcinoma, which were strongly association with death.

Metastatic Lymphoepithelioma-like Hepatocellular Carcinoma: a Potential Diagnostic Pitfall and Demonstration of Pd-l1 Expression

Abstract: Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare primary hepatic neoplasm with female predominance and relatively good prognosis. We report a 73-year-old female with chronic hepatitis B who developed metastatic lesions 5 years after underwent resection for LEL-HCC. The metastatic lesions showed a spectrum of morphologic findings, which could be mistaken for other entities such as lymphoma, particularly in lesions with single-cell infiltrative pattern and abundant tumor-infiltrating lymphocytes. Immunohistochemical study to confirm the origin of the neoplastic cells is important to make the diagnosis. We also highlighted the clinicopathologic correlation and potential therapeutic implication of programmed death ligand-1 expression in LEL-HCC.

Evolution of hepatitis B serological markers in HIV coinfected patients: a case study

ABSTRACT OBJECTIVE To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers. METHODS The study population consisted of patients met in an AIDS Outpatient Clinic in São Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir. RESULTS Among 2,242 HIV positive patients, we identified 105 (4.7%) patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B “e” antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105) of patients with chronic hepatitis B, and 50% (8/16) of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B “e” antigen positive patients, 57% (35/61) presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35) of those who initially cleared hepatitis B “e” antigen presented seroreversion or reactivation of this marker. CONCLUSIONS Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.

Prevalence of malnutrition in children with chronic hepatitis b infection

ABSTRACT Background - There have been limited studies investigating the impact of chronic hepatitis B virus infection on the growth of children. Objective - Our objective was to investigate the prevalence of malnutrition in children with chronic hepatitis B infection. Methods - The nutritional status of patients was retrospectively evaluated in the outpatient Clinic of Pediatric Gastroenterology between February and November 2014. During the study, biochemical laboratory parameters, duration of disease, liver biopsy scores, and medication were evaluated. Additionally body mass index and body mass index centiles were calculated. Results - Of the 96 patients in this study, 68 were male and 28 were female, and the mean age was 144.7±43.9 months and 146.1±47.3 months, respectively. According to body mass index centiles five (5.2%) patients were underweight, seven (7.3%) patients were overweight, and seven (7.3%) patients were obese. Conclusions - Moderate rates of malnutrition (including obesity) were found in chronic hepatitis B infection. Additional nutritional status information of healthy and sick children should be assessed in the infection's early period, and timely interventions should be initiated.

RESUMO Contexto - Há limitados estudos investigando o impacto da infecção crônica pelo vírus da hepatite B no crescimento das crianças. Objetivo - O objetivo deste estudo foi investigar a prevalência de desnutrição em crianças com infecção crônica da hepatite B. Métodos - O estado nutricional dos pacientes foi avaliado retrospectivamente em ambulatório de gastroenterologia clínica pediátrica, entre fevereiro e novembro de 2014. Durante o estudo, parâmetros bioquímicos do laboratório, duração da doença, classificação de biópsias hepáticas e medicação foram avaliadas. Além disso, o índice de massa corporal e suas porcentagens foram calculados. Resultados - Dos 96 pacientes, 68 eram do sexo masculino e 28 eram do sexo feminino e idade média era 144.7±43.9 e de 146.1±47.3 meses, respectivamente. De acordo com as porcentagens de índice de massa corporal, cinco (5,2%) pacientes estavam abaixo do peso, sete (7,3%) pacientes estavam com sobrepeso, e sete (7.3%) estavam obesos. Conclusão - Taxas moderadas de desnutrição (incluindo obesidade) foram encontradas em infecção crônica da hepatite B. Informação sobre o estado nutricional das crianças infectadas deve ser colhida inicialmente para que intervenções oportunas sejam tomadas.

Factors Influencing the Diagnostic Accuracy of Acoustic Radiation Force Impulse Elastography in Patients with Chronic Hepatitis B

BACKGROUND/AIMS: To determine factors predictive of discordance in staging liver fibrosis using liver biopsy (LB) and acoustic radiation force impulse (ARFI) elastography in patients with chronic hepatitis B (CHB). METHODS: Consecutive patients with CHB who underwent LB and ARFI elastography on the same day from November 2010 to March 2013 were prospectively recruited from three tertiary hospitals. RESULTS: We analyzed 105 patients (median age of 47 years). The F0-1, F2, F3, and F4 fibrosis stages were identified in 27 (25.7%), 27 (25.7%), 21 (20.0%), and 30 (28.6%) patients, respectively. The areas under the receiver operating characteristics curves for ARFI elastography in assessing ≥F2, ≥F3, and F4 was 0.814, 0.848, and 0.752, respectively. The discordance of at least one stage between LB and ARFI was observed in 68 patients (64.8%) and of at least two stages in 16 patients (15.2%). In a multivariate analysis, advanced fibrosis stage (F3-4) was the only factor that was negatively correlated with one-stage discordance (p=0.042). Moreover, advanced fibrosis stage was negatively (p=0.016) correlated and body mass index (BMI) was positively (p=0.006) correlated with two-stage discordance. CONCLUSIONS: Advanced fibrosis stage (F3-4) was a predictor of nondiscordance between LB and ARFI elastography; BMI also influenced the accuracy of ARFI elastography.

Noninvasive Diagnosis of Hepatocellular Carcinoma: Elaboration on Korean Liver Cancer Study Group-National Cancer Center Korea Practice Guidelines Compared with Other Guidelines and Remaining Issues

Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed "washout" in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule > or = 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis.

New perspectives of biomarkers for the management of chronic hepatitis B

With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.

Obesity and hepatocellular carcinoma in patients receiving entecavir for chronic hepatitis B

BACKGROUND/AIMS: This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. METHODS: This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). RESULTS: The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm² (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m² (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm² (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). CONCLUSION: HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.

Regression of esophageal varices during entecavir treatment in patients with hepatitis-B-virus-related liver cirrhosis

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.

Observational descriptive study of cutaneous manifestations in patients from Mato Grosso with viral chronic hepatitis

Abstract: BACKGROUND: Extrahepatic manifestations are seen in association with chronic infection by hepatitis B or C virus including cutaneous disorders. The frequency of these findings seems to vary among different places and reports. There is a lack of information about this issue in Brazil. OBJECTIVES: To estimate the prevalence of cutaneous findings affecting HBV or HCV carriers from a reference outpatient unit in Mato Grosso. METHODS: A cross-sectional observational study. RESULTS: 108 patients were studied. 88.9% presented some cutaneous findings but must of them were nonrelated to chronic viral infection. Four patients had cutaneous or autoimmune syndromes that may be HBV or HCV related. CONCLUSION: In our study we found no statistical association between viral hepatitis and skin diseases.