Study Of Liver Disease Guidelines Research Articles

Hepatitis B Core-Related Antigen Stratifies the Risk of Liver Cancer in HBeAg-Negative Patients With Indeterminate Phase.

Many patients with chronic hepatitis B (CHB) are classified as indeterminate patients because they fall outside the defined CHB phases. We aimed to explore hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-negative patients with indeterminate phase and investigated whether the risk could be stratified by serum levels of hepatitis B core-related antigen (HBcrAg). Two retrospective cohorts enrolling HBeAg-negative, treatment-naïve CHB patients without cirrhosis were constructed (N = 2,150 in Taiwanese discovery cohort and N = 1,312 in Japanese validation cohort with a mean follow-up period of 15.88 and 12.07 years, respectively). The primary end point was HCC development. According to the American Association for the Study of Liver Disease guidelines, 990 (46%) HBeAg-negative patients had indeterminate CHB phase at baseline in the Taiwanese cohort. Compared with the patients with inactive CHB and those with immune-active CHB, the indeterminate patients exhibited intermediate but diverse risk of HCC. When HCC risk was stratified by a HBcrAg level of 10,000 U/mL, 10-year HCC cumulative incidence was 0.51% and 5.33% for low HBcrAg and high HBcrAg groups, respectively, with a hazard ratio of 4.47 (95% confidence interval: 2.62-7.63). This cutoff was validated to stratify HCC risk not only in different subgroup analyses but also in an independent Japanese cohort. Finally, the overall HBeAg-negative CHB patients could be simply reclassified into high-risk and low-risk groups by combining ALT, hepatitis B virus DNA, and HBcrAg levels in both cohorts. Serum HBcrAg level of 10,000 U/mL stratifies HCC risk in HBeAg-negative patients with indeterminate phase, which is useful for optimizing their clinical management.

Expression and clinical significance of inhibitory receptor Leukocyte-associated immunoglobulin-like receptor-1 on peripheral blood T cells of chronic hepatitis B patients: A cross-sectional study.

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory receptor that is expressed on the surface of multiple immune cells and plays key roles in immune modulation. In patients with chronic hepatitis B (CHB), T cell number and functions are abnormal and the expression of inhibitory receptors is elevated. However, the expression of LAIR-1 on T cells in patients with CHB is still undetermined.We recruited 320 patients with CHB in different disease phases and 17 healthy donors. Serum biochemical and virological examinations were performed for each participant, and their demographic and clinical data were collected. According to the latest American Association for the Study of Liver Disease guidelines, we categorized the patients into 4 groups: immune active, immune tolerant, inactive CHB, and gray zone. Additionally, we tested the expression of LAIR-1 on T cells and T cell subsets using flow cytometry.We observed a significant decrease in LAIR-1 expression on CD3+ T cells and its two subsets (CD4+ and CD8+ T cells) in patients with CHB. LAIR-1 expression on T cells was the lowest in the immune active group. LAIR-1 expression levels on CD4+ and CD8+ T cells showed a significant negative association with hepatitis B virus (HBV) DNA load and were lower in hepatitis B e antigen (HBeAg)-positive patients than in HBeAg-negative patients (P < .05). In addition, LAIR-1 expression levels on CD3+, CD4+, and CD8+ T cells were all negatively associated with liver inflammation and fibrosis parameters, such as alanine aminotransferase and aspartate aminotransferase levels, FibroScan value, and aspartate aminotransferase-to-platelet ratio index score.LAIR-1 expression levels on T cells were associated with HBV DNA load and liver inflammation and fibrosis parameters, indicating that LAIR-1 may play an important regulatory role in HBV-induced T cell immune pathogenesis and may be a therapeutic target for CHB.

Opportunistic Screening for Nonalcoholic Fatty Liver Disease (NAFLD) in Ghana: A Prospective Study

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) is a leading cause of cryptogenic cirrhosis and liver transplant in the United States. It is associated with increased length of stay and poor surgical outcomes. NAFLD affects approximately 30% of American adults, and even more Africans. However reported rates of NAFLD in African countries vary widely, where recent studies have shown that up to 50–87% Africans are could be living with NAFLD. The objective of this study was to estimate the prevalence of NAFLD in Ghana and to assess whether NAFLD is associated with increased length of stay and surgical complications. Methods A prospective study on 96 surgical patients aged 18 and older, without a history of alcohol abuse or liver disease, who presented at Eastern Reginal Hospital in Ghana for elective general and gynecological procedures between September and December 2018. A single, expert radiologist screened all patients for NAFLD using an abdominal ultrasound machine. NAFLD was diagnosed in conjunction with the American Association for the study of liver disease guidelines, assessing for increased hepatic echogenicity compared to the spleen and kidneys. Patients were followed up for 30 days and information was collected on length of stay and surgical site occurrences (SSO). Univariate analysis and multivariable logistic regression were performed using SAS 9.4. Results Of 97 patients, mean age 46 ± 14 years, mean BMI 26.9 ± 7.7, and 40 (42%) Male, the mean length of stay was 2.7 days ± 2.7 days. Eighteen (19%) patients had a length of stay ≥ 5 days and 9 (9%) developed a SSO. Ultrasonography revealed that 54 (56%) of patients had NAFLD, of which 15 (28%) patients had moderate disease (25–50% of liver), and 39 (72%) had mild (5–25%) disease. Diabetes, hypertension, obesity, and BMI were not associated with NAFLD. NAFLD and sex were independent predictors of an increased length of stay ≥ 5 days, where patients with NAFLD were 5x as likely to have an extended length of stay, but not SSO compared to those without NAFLD (OR: 4.8 95% CI 1.1–18.5). Conclusions Ghana has almost twice the prevalence of NAFLD compared to the United States, suggesting that NAFLD is very common in Africa. It is associated with delayed surgical recovery leading to more than twice the average length of stay. Funding Sources None.

The role of liver resection in patients with intermediate and advanced stage hepatocellular carcinoma. Retrospective study from two Greek HPB centers

Background: The indications for liver resection in patients with intermediate (BCLC B: single tumor >5 cm or multiple tumors >3 cm each) or advanced stage (BCLC C: presence of macrovascular thrombosis) hepatocellular carcinoma (HCC) are not clear yet. Liver resection is not recommended for this group of patients in the European and the American Association for the Study of Liver Disease guidelines. The aim of this retrospective study was to present the experience of two Greek HPB centers in the surgical management of patients with HCC. Methods: Data from patients with HCC who underwent surgical resection from 01.01.2007 till 30.06.2016 were analyzed. Results: 70 patients were included in the study, with a median age of 69 yrs (range: 21-82). There were 54 male and 16 female patients. The majority of the patients developed HCC on a background of liver cirrhosis (59%) and the most common causes were alcoholic liver disease (ALD) (39%), Hepatitis B (HBV) infection (31%) and hepatic steatosis (23%). The majority of the patients (38/70, 54%) were in intermediate or advanced stage. The 90-day mortality rate was 0. The overall morbidity was 39%. The 1-, 3- and 5yrs overall survival was 89%, 60% and 40 % for all patients and 82%, 50% and 39 % for the patients with BCLC B and BCLC C stage HCC. Conclusion: This study shows that liver resection has a clear role in the management of patients with non-early HCC as is was used widely with acceptable short and long term Results.

The role of liver resection in patients with intermediate and advanced stage hepatocellular carcinoma. Retrospective study from two Greek HPB centers

Background: The indications for liver resection in patients with intermediate (BCLC B: single tumor >5 cm or multiple tumors >3 cm each) or advanced stage (BCLC C: presence of macrovascular thrombosis) hepatocellular carcinoma (HCC) are not clear yet. Liver resection is not recommended for this group of patients in the European and the American Association for the Study of Liver Disease guidelines. The aim of this retrospective study was to present the experience of two Greek HPB centers in the surgical management of patients with HCC. Methods: Data from patients with HCC who underwent surgical resection from 01.01.2007 till 30.06.2016 were analyzed. Results: 70 patients were included in the study, with a median age of 69 yrs (range: 21-82). There were 54 male and 16 female patients. The majority of the patients developed HCC on a background of liver cirrhosis (59%) and the most common causes were alcoholic liver disease (ALD) (39%), Hepatitis B (HBV) infection (31%) and hepatic steatosis (23%). The majority of the patients (38/70, 54%) were in intermediate or advanced stage. The 90-day mortality rate was 0. The overall morbidity was 39%. The 1-, 3- and 5yrs overall survival was 89%, 60% and 40 % for all patients and 82%, 50% and 39 % for the patients with BCLC B and BCLC C stage HCC. Conclusion: This study shows that liver resection has a clear role in the management of patients with non-early HCC as is was used widely with acceptable short and long term results.

Pre-treatment alphafeto protein in hepatocellular carcinoma with non-viral aetiology \u2013 a prospective study

BackgroundAlpha-fetoprotein (AFP) is a biomarker for hepatocellular carcinoma (HCC). The significance of pre-treatment AFP (pt-AFP) in non-viral HCC (nvHCC) is not clear.MethodsPatients with nvHCC, referred to a Hepatobiliary Clinic from September 2011–2015 were screened. HCC was diagnosed using American Association for the Study of Liver Disease guidelines, and TNM staged. nvHCC was diagnosed when HBsAg and anti-HCVAb was negative. Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores were calculated. AFP level was evaluated against patient characteristics, tumour characteristics and survival.ResultsThree hundred eighty-nine patients with nvHCC [age 64(12–88) years; 344(88.4%) males] were screened. Median AFP was 25.46 ng/ml (1.16–100,000). 41.2% (n = 160) Of patients had normal AFP level. 22.9% (n = 89) had AFP over 400 ng/ml. Female gender (P < 0.05), vascular invasion (P < 0.001), tumours over 5 cm (P < 0.05), late TNM stage (P < 0.001) and non-surgical candidates had higher AFP levels. Diffuse type (P < 0.001), macro vascular invasion (P < 0.001) and late stage tumours (P < 0.001) had AFP over 400 ng/ml. Having AFP below 400 ng/ml was associated with longer survival (16 vs. 7 months, P < 0.001).ConclusionPre treatment AFP has a limited value In diagnosing nvHCC, Having a AFP value over 400 ng/ml was associated with aggressive tumour behaviour and poor prognosis.

Veritable antiviral capacity of natural killer cells in chronic HBV infection: an argument for an earlier anti-virus treatment

BackgroundThere is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity.MethodsA total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ) were classified according to the latest American Association for the Study of Liver Disease guidelines. Peripheral blood mononuclear cells from patients and healthy controls were tested for NK cell frequency, phenotype and function using flow cytometry.ResultsA significant decrease in activating receptor NKp44 and NKp46 expression and significant increase of exhaustion molecule Tim-3 expression were observed in NK cells from CHB patients. Reduced cytokine secretion and preserved or elevated cytotoxic function were also observed. Patients in the IT group exhibited comparable cytokine secretion and cytolytic capacity as age-matched IA patients. NK cell anti-viral functions were preserved in GZ patients. Some of the NK cell function in patients who were excluded from treatment by the current treatment guidelines was less compromised than patients who qualified for treatment.ConclusionOur findings provide evidence of veritable NK cell immunity during different natural history phases in treatment-naïve patients with chronic HBV Infection. Chronic HBV infection hindered NK cell function in CHB patients. However, the presumed IT and GZ statuses of CHB patients based on the clinical parameters may not accurately reflect the inner immune status of these patients and should be reconsidered. Some patients excluded from treatment by the current treatment guidelines may be able to be selected as candidates for treatment.

Distribution of disease phase, treatment prescription and severe liver disease among 1598 patients with chronic hepatitis B in the Chronic Hepatitis Cohort Study, 2006-2013.

Limited information exists regarding the distribution of disease phases, treatment prescription and severe liver disease among patients with chronic hepatitis B (CHB) in US general healthcare settings. To determine the distribution of disease phases, treatment prescription and severe liver disease among patients with CHB in general US healthcare settings. We analysed demographic and clinical data collected during 2006-2013 from patients with confirmed CHB in the Chronic Hepatitis Cohort Study, an observational cohort study involving patients from healthcare organisations in Michigan, Pennsylvania, Oregon and Hawaii. CHB phases were classified according to American Association for the Study of Liver Disease guidelines. Of 1598 CHB patients with ≥12 months of follow-up (median 6.3 years), 457 (29%) were immune active during follow-up [11% hepatitis B e antigen (HBeAg)-positive, 16% HBeAg-negative, and 2% HBeAg status unknown], 10 (0.6%) were immune tolerant, 112 (7%) were inactive through the duration of follow-up and 886 (55%) were phase indeterminate. Patients with cirrhosis were identified within each group (among 21% of immune active, 3% of inactive and 9% of indeterminate phase patients) except among those with immune-tolerant CHB. Prescription of treatment was 59% among immune active patients and 84% among patients with cirrhosis and hepatitis B virus (HBV) DNA >2000 IU/mL. Approximately, one-third of the cohort had active disease during follow-up; 60% of eligible patients were prescribed treatment. Our findings underscore the importance of ascertainment of fibrosis status in addition to regular assessment of ALT and HBV DNA levels.

Early TIPS versus endoscopic therapy for secondary prophylaxis after management of acute esophageal variceal bleeding in cirrhotic patients: a meta-analysis of randomized controlled trials.

American College of Gastroenterology and American Association for the Study of Liver Disease guidelines recommend endoscopic and pharmacologic treatment for esophageal variceal bleed. Transjugular intrahepatic portosystemic shunt (TIPS) placement is reserved for cases of therapeutic failure. Several studies have suggested improved prevention of rebleeding and improved survival without excess hepatic encephalopathy in patients who receive TIPS within the first 5 days after bleeding (early TIPS). In this meta-analysis, we evaluated the safety and efficacy of early TIPS versus endoscopic therapy for secondary prophylaxis after acute esophageal variceal bleeding in cirrhotic patients. Pubmed, Medline, Embase, ClinicalTrials.gov, and ISI Web of Science were searched for randomized controlled trials that compared early TIPS to endoscopic therapy. The primary outcome was mortality at 1 year; secondary outcomes were rebleeding and hepatic encephalopathy at 1 year. Nine randomized controlled trials involving 608 cirrhotic patients were identified. Early TIPS was associated with a significant risk reduction in 1-year mortality (RR, 0.68; 95% CI, 0.49-0.96; P = 0.03) and 1-year incidence of variceal rebleeding (RR, 0.28; 95% CI, 0.20-0.40; P < 0.001) without significant heterogeneity among studies (I(2) = 30% and 47%, respectively). No significant difference in the incidence of hepatic encephalopathy at 1 year was observed (RR, 1.36; 95% CI, 0.72-2.56; P = 0.34); however, there was significant heterogeneity among studies (I(2) = 68%). TIPS placed within 5 days after a major esophageal variceal hemorrhage is superior to endoscopic treatment in reducing subsequent bleeding. Early TIPS placement is also associated with superior 1-year survival without significantly increasing the incidence of hepatic encephalopathy.

PTH-094 An Analysis of The Relationship Between Ethnicity and Hepatitis B (HBV) Phenotypes Over An 8 Year Period: Abstract PTH-094 Table 1

Introduction Ethnicity is associated with certain HBV phenotypes which in turn affect prognosis. Methods We performed a search for patients with HBV DNA measured at GSTT(March 2007 to March 2015). sAg+ve patients were analysed for:Ethnic group,HIV,Hep C and D co-infection,eAg status, ALT and viral load. Phenotypes were assigned to patients at diagnosis and at last f/up.ALT cut offs were >30 U/L for men and >20 U/L for females.The American Association for the Study of Liver Disease guidelines divide HBV phenotype into 4 groups although a recent study defined an “Indeterminant” group for patients who do not fit into any phenotype Results 1799 patients were sAg+ve,mean f/up duration was 39.2 months(SD 41.2).45% of the cohort were lost to f/up.47% were male, mean age at diagnosis was 36(No difference between ethnicities).82% were eAg-ve,1.5% Hepatitis D+ve,10% HIV+ve,2% hepatitis C+ve. 49% of the cohort were African/Afro-Caribbean,14% Caucasian,10% Chinese,1.5% South Asian, 2.6% South East Asian(other than Chinese),0.3% Arab,3.4% Mixed,2.3% unknown,6.6% “other”. The table shows HBV phenotype at diagnosis compared to last f/up in all patients and then according to the 3 main ethnic groups.Rates of seroconversion and treatment are also shown. 90.5% of African/Afro-Caribbeans were eAg-ve compared to 71% of Caucasians and 63.9% of Chinese(P Comparing the 3 largest ethnic groups only,in 2007,70% were African/Afro-Caribbean,19% Caucasian,11% Chinese compared to 51%,36% and 13% respectively in 2014. Conclusion Ethnicity is significantly associated with HBV phenotypes with a higher percentage of immunotolerants being Chinese and a higher percentage of African/Afro-Caribbeans being inactive. Compared to 2007,a higher percentage of HBV patients in 2014 were Caucasian reflecting changes in immigration.This may affect HBV outcomes and demand on Hepatology services. Disclosure of Interest None Declared

Role of liver resection in the management of multinodular hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer related deaths worldwide. Various treatment modalities have been applied to HCC depending on the tumor load, functional capacity of the liver and the general condition of the patient. According to Barcelona Clinic Liver Cancer staging strategy and The American Association for the Study of Liver Disease guidelines, surgical resection is not advocated in the tretment of multinodular HCC. Despite this, many recent clinical studies show that, resection can achieve good results in patients with multinodular HCC and 5-year survival rate around 40% can be reached. If resection or transplantation is not performed, these patients are usually managed with palliative procedures such as transarterial chemoembolization, radioembolization and cytotoxic chemotherapy and 5-year survival of this group of patients will be extremely low. Although survival rates are lower and complications may be increased in this group of patients, liver resection can safely be performed in selected patients in experienced centers for the management of multinodular HCC.

Position paper of the Italian Association for the Study of the Liver (AISF): The multidisciplinary clinical approach to hepatocellular carcinoma

Patients with hepatocellular carcinoma should be managed with a multidisciplinary approach framed in a network where all the diagnostic techniques and therapeutic resources are available in order to provide the optimal level of care. Given this assumption, the Coordinating Committee of the Italian Association for the Study of the Liver nominated a panel of experts to elaborate practical recommendations for the multidisciplinary management of hepatocellular carcinoma aiming to provide: (1) homogeneous and efficacious diagnostic and staging work-up, and (2) the best treatment choice tailored to patient status and tumour stage at diagnosis. The 2010 updated American Association for the Study of Liver Disease Guidelines for hepatocellular carcinoma were selected as the reference document. For each management issue, the American Association for the Study of Liver Disease recommendations were briefly summarised and discussed, according to both the scientific evidence published after their release and the clinical expertise of the Italian centres taking care of these patients. The Italian Association for the Study of the Liver expert panel recommendations are finally reported.

Surgical resection improves the survival of selected hepatocellular carcinoma patients in Barcelona clinic liver cancer stage C

Sorafenib is the only approved agent recommended by the American Association Study of Liver Disease guidelines for hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C. To calculate and compare overall survival rates in hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C treated with various therapies or supportive care alone. This was a retrospective study, in which medical data from 411 newly diagnosed hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C and Child-Pugh class A were analyzed and compared. Eighty-eight patients were treated with supportive care and 323 were treated with surgical resection (68/323, 21.1%), local ablation therapy (8/323, 2.5%), transarterial embolization (140/323, 43.3%), systemic chemotherapy or radiotherapy (96/323, 29.7%), and sorafenib (11/323, 3.4%). Median survival was 11 months (95% confidence interval, 9.0-13.1) in treated patients compared with 3.9 months in the supportive care group (hazard ratio, 0.45; 95% confidence interval, 0.35-0.59; p<0.001). Patients who underwent surgical resection had the longest survival compared to patients undergoing other treatments (33.4 months versus 8.1 months, p<0.001). Surgical resection resulted in excellent outcomes. Although sorafenib is currently recommended, oncologists should endeavour to select optimal candidates for surgical resection to gain more survival benefit.

Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma

I read with great interest the study by Forner et al.,1 which validates the American Association for the Study of Liver Disease guidelines. The methods and interpretation of the results, however, raise several concerns. It is well known that the biopsy of small nodular lesions in cirrhosis is not entirely reliable. In fact, needle placement may be difficult and a sampling error may occur. Moreover, it is very difficult to distinguish well-differentiated hepatocellular carcinoma (HCC) from dysplasia nodules on small biopsy specimens, because there is not a clear-cut dividing line between a dysplasia nodule and a well-differentiated tumor.2, 3 In the study by Forner et al.,1 however, a biopsy result was considered the gold standard, and the pathologic results of surgical samples in 60 HCC nodules were not well described. Were the abovementioned factors taken into account in the results of the study by Forner et al.?1 It is well known that cirrhosis is characterized by fibrous septa and many regenerative nodules. These features produce a coarse pattern on ultrasound, which may impair identification of small tumors.3 In the discussion of the study by Forner et al.,1 however, the authors stated that if they recruited patients with multiple nodules, the prevalence of HCC might have been higher. In fact, the patients with multiple nodules had commonly more regenerative nodules than HCC nodules. That is to say, if the authors recruited patients with multiple nodules, the prevalence of HCC might have been lower and the study would have validated the American Association for the Study of Liver Disease guidelines more effectively. Therefore, could the diagnosis of HCC nodules 20 mm or smaller be established without a positive biopsy if both contrast-enhanced ultrasound and magnetic resonance imaging are conclusive in patients with multiple nodules or a sole nodule? Ze-Zhou Song M.S.*, * Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Hepatitis C virus infection in HIV-infected patients

Because of shared routes of transmission, hepatitis C and HIV coinfection is common in the United States, affecting 15% to 30% of HIV-infected individuals. In the era of highly effective antiretroviral therapy, hepatitis C virus (HCV)-related liver disease has emerged as a significant cause of morbidity and mortality. Accordingly, the Infectious Diseases Society of America and the American Association for the Study of Liver Disease guidelines for the management of HCV recommend that patients with HIV/HCV undergo medical evaluation for HCV-related liver disease and consideration for HCV treatment and, if indicated, orthotopic liver transplantation. However, the treatment of patients with HIV/HCV is complicated by the relatively high prevalence of medical and psychiatric comorbidities and the challenges of anti-HCV therapy in the setting of HIV disease and antiretroviral therapy. Nonetheless, recently completed randomized controlled trials provide evidence of the safety, tolerability, and efficacy of HCV treatment with pegylated interferon-alpha plus ribavirin in HIV-infected individuals. This review focuses on the epidemiology, natural history, and management of HCV in the HIV-infected patient.