Related Cirrhosis Research Articles

Risk assessment of hepatocellular carcinoma development for indeterminate hepatic nodules in patients with chronic hepatitis B.

Background/AimsA risk prediction model for the development of hepatocellular carcinoma (HCC) from indeterminate nodules detected on computed tomography (CT) (RadCT score) in patients with chronic hepatitis B (CHB)-related cirrhosis was proposed. We validated this model for indeterminate nodules on magnetic resonance imaging (MRI).MethodsBetween 2013 and 2016, Liver Imaging Reporting and Data System (LI-RADS) 2/3 nodules on MRI were detected in 99 patients with CHB. The RadCT score was calculated.ResultsThe median age of the 72 male and 27 female subjects was 58 years. HCC history and liver cirrhosis were found in 47 (47.5%) and 44 (44.4%) patients, respectively. The median RadCT score was 112. The patients with HCC (n=41, 41.4%) showed significantly higher RadCT scores than those without (median, 119 vs. 107; P=0.013); the Chinese university-HCC and risk estimation for HCC in CHB (REACH-B) scores were similar (both P>0.05). Arterial enhancement, T2 hyperintensity, and diffusion restriction on MRI were not significantly different in the univariate analysis (all P>0.05); only the RadCT score significantly predicted HCC (hazard ratio [HR]=1.018; P=0.007). Multivariate analysis showed HCC history was the only independent HCC predictor (HR=2.374; P=0.012). When the subjects were stratified into three risk groups based on the RadCT score (<60, 60–105, and >105), the cumulative HCC incidence was not significantly different among them (all P>0.05, log-rank test).ConclusionsHCC history, but not RadCT score, predicted CHB-related HCC development from LI-RADS 2/3 nodules. New risk models optimized for MRI-defined indeterminate nodules are required.

Slowing of Alpha Waves on EEG, an Early Marker of Minimal Hepatic Encephalopathy

Introduction: Minimal Hepatic Encephalopathy (MHE) is the mildest form of spectrum of Hepatic Encephalopathy (HE) which remains undiagnosed due to lack of awareness. MHE has a negative effect on patient's daily functioning due to cognitive impairment. Electro-Encephalo-Gram (EEG) and Mini Mental State Examination (MMSE) are useful in early diagnosis and follow up of MHE. Aim: To study evidence of MHE in patients with liver cirrhosis by psychometric tests and also its correlation with EEG changes. Materials and Methods: The study was carried out as a prospective case control study of 70 patients diagnosed with Cirrhosis of liver, over a period of two years in accordance with European Association for the Study of the Liver (EASL) and Asociacion Latinoamericana parael Estudio del Higado (ALEH) criteria with MMSE score &gt;24 and were diagnosed as Minimal Hepatic Encephalopathy if 2 out of 3 psychometric tests were abnormal EEG was performed in them and was compared with 70 healthy controls. Results: Study showed male predominance (90%) with mean age of 45.49 ± 11.76. Alcohol related cirrhosis (70%) was found to be more common than HBV (8.57%) and HCV (2.86%) infection related cirrhosis. Pedal edema, icterus, pallor and ascites were the most common presenting manifestations. Most cirrhotic cases (80%) were under Child Pugh Class-A. On USG of abdomen all cases had Coarse echotexture and nodular surface of liver among them 11 cases had Hepatomegaly, 10 cases had splenomegaly, 42 cases had ascites and 24 cases had increased portal venous diameter of mean size 14.02 ± 0.48 mm. MMSE score of all selected cirrhotic cases was &gt;24. Psychometric Tests i.e. Number Connection Test-A, Number Connection Test-B and Line tracing test were performed in all selected cirrhotic cases and they were not able to perform it within designated time. All cases were subjected to EEG and compared with equal number of comparable healthy controls, which shows change in frequency and amplitude of Alpha wave which was highly significant whereas no significant changes of frequency and amplitude of Beta, Theta and Delta waves between cases and controls. Conclusion: There is significant changes in alpha wave frequency and amplitude in patients with minimal hepatic encephalopathy.

Effect of sofosbuvir on QT interval and other electrocardiography (ECG) findings in patients with HCV related decompase cirrhosis

Effect of sofosbuvir on QT interval and other electrocardiography (ECG) findings in patients with HCV related decompase cirrhosis

Is HBV viral load at admission associated with development of acute-on-chronic liver failure in patients with acute decompensation of chronic hepatitis B related cirrhosis?

BackgroundHepatitis B virus (HBV) reactivation is one of the most common precipitating events associated with acute decompensation (AD) or acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB)-related cirrhotic patients. However, whether their serum HBV deoxyribonucleic acid (DNA) levels are associated with ACLF incidence and short-term mortality rate is still ambiguous.MethodsThe ACLF incidences, 28-day and 90-day liver transplantation (LT)-free mortality rates, previous nucleoside/nucleotide analogues (NUCs) treatments and serum HBV DNA levels at admission (ad-levels) of 111 hospitalized patients with AD of CHB-related cirrhosis were analyzed.Results43 (38.7%) patients developed ACLF. The 28-day and 90-day LT-free mortality rates of the ACLF cases were 15.4 and 40.9%, respectively. Though NUCs inhibited HBV replication effectively, there were no differences in the ACLF incidence between antiviral treatment-naïve patients and NUCs treatment-experienced patients with or without interruptions (37.5, 41.7 and 45.5%, respectively, P>0.05). The serum HBV DNA ad-level was similar between the patients with and without ACLF development (logarithms: 4.50 ± 1.96 vs 4.32 ± 1.99; ≥2000 IU/ml: 67.4% vs 67.6%; both P>0.05), so was between the ACLF patients died or survived in 28 or 90 days (logarithms: 4.31 ± 1.91 vs 5.54 ± 2.53, 4.81 ± 1.76 vs 4.84 ± 2.40, respectively, both P>0.05).ConclusionSerum HBV DNA ad-level and previous NUCs treatment are not associated with incidence of ACLF and short-term mortality rate in the hospitalized patients with AD of CHB-related cirrhosis.

Surveillance for Hepatocellular Carcinoma: Current Best Practice and Future Direction.

Hepatocellular cancer (HCC) is the fourth leading cause of cancer-related deaths worldwide and the fastest growing cause of cancer deaths in the United States. The overall prognosis of HCC remains dismal, except for the subset of patients who are diagnosed at early stage and receive potentially curative therapies, such as surgical resection and liver transplantation. Given this, expert society guidelines recommend HCC surveillance every 6 months in at-risk individuals. Despite these recommendations, the effectiveness of HCC surveillance remains a subject of debate. We discuss current best practices for HCC surveillance and the evidence that support these recommendations. We also describe several initiatives that are underway to improve HCC surveillance and outline areas that may serve as high-yield targets for future research. Overall, we believe these efforts will help the field move toward precision surveillance, where surveillance tests and intervals are tailored to individual HCC risk. Doing so can maximize surveillance benefits, minimize surveillance harms, and optimize overall value for all patients.

NUDT15 Polymorphism Confer Increased Susceptibility to Thiopurine-Induced Leukopenia in Patients With Autoimmune Hepatitis and Related Cirrhosis.

The aim of this study was to investigate the influence of NUDT15 R139C and thiopurine S-methyltransferase (TPMT) on azathioprine (AZA) induced leukopenia in patients with autoimmune hepatitis (AIH) and related cirrhosis. A total of 149 Chinese AIH patients with a history of AZA treatment were retrospectively evaluated. The clinical and epidemiological characteristics of the patients were obtained from an electronic database and reviewed. NUDT15 (rs116855232) and TPMT∗3C (rs1142345) SNPs were genotyped using a PCR method. Twelve patients developed leukopenia, and this adverse drug reaction was significantly associated with the T risk allele in NUDT15 [P < 0.00001, odds ratio = 20.41; 95% confidence interval (CI) (7.84, 53.13)], with the sensitivity and specificity of 91.67 and 89.05%, respectively. The median maintenance dosages for patients with the rs116855232 CC and CT genotypes were 1.23 (0.95, 1.53) mg ⋅ kg−1 ⋅ d−1 and 0.96 (0.83, 1.19) mg ⋅ kg−1 ⋅ d−1, respectively (P = 0.028). In contrast, no significant association was observed for TPMT∗3C genotypes. Notably, subgroup analysis of the 13 patients with leukopenia before therapy, these white blood cell (WBC) counts did not show further reduction after AZA treatment and maintenance dosage was 1.13 (0.94, 1.60) mg ⋅ kg−1 ⋅ d−1. Therefore, NUDT15 polymorphism is significantly associated with thiopurine-induced leukopenia in Chinese patients with AIH and related cirrhosis. Adjusting the AZA dosage should be considered in patients according to the NUDT15 R139C genotypes.

Genetic variants of XRCC1 and risk of hepatocellular carcinoma in chronic hepatitis C patients

ABSTRACTBackground: Hepatitis C virus (HCV) related liver cirrhosis occurs in about 20% of chronically infected patients over a duration of 10–20 years, and within 5 years approximately 10–20% of these cirrhotic patients will develop hepatocellular carcinoma (HCC). Previous studies report that the X-ray repair cross-complementing group1 gene (XRCC1) is important in the risk of HCC development; however, results obtained from these studies are conflicting rather than conclusive. We hypothesised an association between single nucleotide polymorphisms (SNPs) in XRCC1 with the HCC risk on a background of chronic hepatitis C.Materials and methods: We recruited 210 subjects, 70 with HCC, 70 with cirrhosis and 70 healthy controls. Two SNPs [c.1254C>T(rs2293035) and c.1517G>C(rs139599857)] in XRCC1 were genotyped using created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods.Results: The TT genotype, CT genotype and T-allele in c.1254C>T (rs2293035) were linked to risk of HCC compared to the CC genotype: OR 3.58 [confidence interval (CI) 95%: 1.19–10.7] p = 0.019; OR 2.16 (CI 95%: 1.04–4.47) p = 0.037 and OR 2.10 (CI 95%: 1.2–3.3) p = 0.006, respectively. Regarding c.1517G>C (rs139599857), the CC genotype, GC genotype and C-allele were linked with higher risk of developing HCC compared to GG genotype: OR 4.77 (CI 95%: 1.3–16.9), p = 0.016; OR 3.02 (CI 95%: 1.46–6.2), p = 0.002 and OR 2.4 (CI 95%: 1.4–4.0), p = 0.001, respectively.Conclusion: We conclude that the T-allele of c.1254C>T (rs2293035) and the C allele of c.1517G>C (rs139599857) genetic variants may be associated with increased HCC risk among chronic hepatitis C patients.

Hepatocellular carcinoma in patients with autoimmune hepatitis - a systematic review of the literature published between 1989-2016.

Background and aimsLiver cancer is one of the most common cause of deaths from cancer. Hepatocellular carcinoma (HCC) was reported at a frequency of 7% of patients with autoimmune hepatitis (AIH) - related cirrhosis in 1988. We aimed to provide a systematic literature review on the frequency of HCC in patients with AIH, after the discovery of hepatitis C virus (HCV), in order to avoid any possible confounding etiology.MethodsA literature search of the PubMed database between 1989–2016 was performed, using the relevant keywords “hepatocellular carcinoma” and “autoimmune hepatitis”. We followed the PRISMA statement guidelines during the preparation of this review.ResultsEleven studies (n=8,460 patients with AIH) were retained for the final analysis. HCC was diagnosed in 0–12.3% of the AIH patients included in these studies. The overall occurrence of HCC in patients with AIH was estimated in two studies, at 5.1% and 6.2%, respectively. In patients with AIH and cirrhosis, the percentage of HCC varied between 0.2%–12.3%. The proportion of HCC in patients with AIH without cirrhosis was estimated at 1.03%. The percentage of cirrhosis in AIH patients varied from 18.7% to 83.3% in Japan, and from 12% to 50.2% in the other areas. The mean follow-up of the patients with AIH was of 10 years.ConclusionsThe development of HCC in patients with AIH appeared to be similar before and after the discovery of HCV, and it was mainly associated to cirrhosis. The number of patients developing cirrhosis in relation with AIH was impressive. The long evolution of AIH to cirrhosis and, eventually, to HCC, has been be suggested.

Effect of Fufang Biejia Ruangan Tablet on lowering biochemical and virological parameters of hepatic fibrosis in patients with chronic hepatitis B: Protocol for a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Background:Liver cirrhosis is one of the end-stage chronic liver diseases. Individuals with chronic hepatitis B (CHB) are at an increased risk of developing liver cirrhosis. Practice guidelines underline that Nucleos(t)ide analogs (NAs) should be the first-line treatment for hepatitis B virus (HBV)-related cirrhosis. However, prolonged use of NAs may lead to drug resistance and kidney impair and does not reverse the fibrosis of liver. Fufang Biejia Ruangan Tablet (RGT), as a traditional Chinese medicine (TCM), has been proved to be effective in the treatment of liver fibrosis. Hence, we will perform meta-analysis in order to evaluate the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB.Methods:To search for relative literatures up to February 2019 by computer from the following databases: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodicals Database, Chinese BioMedical Database and Wanfang Data. Included criteria are randomized controlled trials and cohort studies of hepatic fibrosis in patients with CHB treated by RGT. The primary outcome measures include biochemical and virological parameters. We will use Stata 13.0 software for data synthesis, sensitivity analysis, meta regression, subgroup analysis, and risk of bias assessment. The reporting bias will be assessed by a funnel plot and the funnel plot symmetries will be evaluated by Begg and Egger tests. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence.Results:This systematic review will provide a synthesis of RGT for hepatic fibrosis in patients with CHB from various evaluation aspects including biochemical and virological parameters, HBV DNA levels HBeAg status and seroconversion, adverse events incidence.Conclusion:The systematic review will provide evidence to assess the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB.PROSPERO registration number:ROSPERO CRD 42018095122.

FRI-129-A defect in the Nrf2/HO-1 pathway and Nox2 activation results in regulatory T cell mitochondrial dysfunction in alcohol related cirrhosis

FRI-129-A defect in the Nrf2/HO-1 pathway and Nox2 activation results in regulatory T cell mitochondrial dysfunction in alcohol related cirrhosis

LIVER STIFFNESS MEASURMENT BY FIBROSCAN FOR PREDICTING THE GRADES OF OESOPHAGEAL VARICES IN HCV CIRRHOTIC PATIENTS

Introduction: oesophageal varices is one of the most common and life threatening complications of liver cirrhosis. the need for use of non invasive modalities for its prediction rather than endoscopy is important to decrease burdens and increase patient compliance . Aim: to predict oesophageal varices presence by fibroscan and possible grading by degree of liver stiffness in Hepatitis C Virus related cirrhotic patients. Methods: the study was carried out on 150 patients with HCV related liver cirrhosis attending Ministry of Health outpatient clinics and hospitals after being writtenly consented that they agreed to participate in this study All patients were subjected to full history taking & thorough clinical examination, full laboratory investigations include complete blood picture, liver profile tests , kidney function tests, abdominal ultrasound , liver stiffness measurement by fibroscan and upper GIT endoscopy. The patients were divided according to upper GIT endoscopy results into three groups. Group 1: included 50 patients with liver cirrhosis and without oesophageal varices. Group 2: included 50 patients with liver cirrhosis and small oesophageal varices (Grade II Fibroscan; Grading; Non-invasive methods

Serum Clusterin as a Diagnostic Tool for HCV Related Hepatocellular Carcinoma

AbstractBackground: Hepatocellular carcinoma (HCC) is consid-ered one of the major malignant tumors in the world. The number of cases increases every years and HCC almost always has a fulminant course with grave prognosis.Aim of Study: Was to evaluate the clinical use of serum clusterin levels as a diagnostic tool for HCC with hepatitis C virus related cirrhosis.Subjects and Methods: A total of 100 subjects, 80 patients and 20 healthy controls were enrolled in this study. Patients were divided into 2 groups; group I: (30 patients) with HCV related liver cirrhosis, group II: (50 patients) with hepatocel-lular carcinoma. Serum levels of alpha fetoprotein (AFP) and clusterin (CLU) were measured. Alpha fetoprotein based on Chemiluminescent microparticle immunoassay (CMIA). Serum CLU concentration was performed using enzyme linked immunosorbent assay technique (ELISA).Results: The mean values of serum clusterin increase significantly among HCC patients than controls and cirrhotic patients. The cirrhotic patients show significant decrease than controls group. The sensitivity and specificity for clusterin was 72.5% and 92% and for AFP was 77.3% and 100%, respectively. The AUC for clusterin was 0.8 (p<0.001) com-pared with 0.9 (p<0.001) for AFP. The combined parallel approach improved the diagnostic sensitivity to 96.5%. We found positive correlation between AFP and sCLU (r=0.31 and p=0.003).Conclusion: Serum CLU levels should be a useful potential biomarker for HCC diagnosis.

Cardiac health in patients with hepatitis B virus-related cirrhosis.

Not only alcoholic cirrhosis related to cardiac dysfunction, cirrhosis caused by nonalcoholic etiology including hepatitis B virus (HBV) infection also related to impaired cardiac health. The aims of present study were to perform a noninvasive evaluation of cardiac function and to evaluate exercise performance in HBV related cirrhotic patients without typical symptoms of cardiac disease.Seventy-nine HBV related cirrhotic patients and 103 matched subjects without a previous history of cardiac involvement were recruited. Clinical examination and cardiac health evaluation were performed. The incidence, risk factors of cardiac dysfunction and exercise tolerance were investigated.A correlation between QTc interval and model for end-stage liver disease score (R = 0.239, P = .018) was detected, however, the connection between QTc prolongation and the severity of liver disease was uncertain. Patients with HBV related cirrhosis had a tendency toward left ventricular wall thickening (P = .007). Forty-one patients (51.90%) were in accordance with the definition of cirrhotic cardiomyopathy, and a significant increase in the incidence of cardiac diastolic dysfunction (CDD) could be found with increasing Child-Pugh grade (P = .004). HBV related cirrhotic patients with CDD had a higher level of pro-brain natriuretic peptide (P = .025), international normalized ratio (P = .010) Child-Pugh score (P = .020), and a higher proportion of ascites (P < .001). The higher Child-Pugh score (odds ratio = 1.662, P = .010) was an independent diagnostic predictor of CDD. The cardiac depression and exercise tolerance also got worse with increasing Child-Pugh score (P < .001).Impaired cardiac health was common in HBV related cirrhotic patients. Cardiogenic factors must be carefully considered in the integral therapy of cirrhosis. Hepatology physicians should lay emphasis on exercise training in daily life.

Portal vein thrombosis in patients with liver cirrhosis and its impact on early and long-term outcomes after liver transplantation.

Portal vein thrombosis (PVT) is a common complication amongst patients with liver cirrhosis. The PVT risk factors and its impact on post liver transplant outcome has not been well defined, yet. This study aimed to investigate PVT prevalence, its risk factors and influence on early and long-term outcomes after liver transplantation. Adult (>18years) patients with liver cirrhosis undergoing liver transplantation between March 2013 to March 2015 were included. Presence or absence of PVT was recorded at transplant. PVT risk factors in patients with liver cirrhosis and its impact on early and long-term outcomes were analysed. Portal vein thrombosis was diagnosed in 174 patients (17.3%). Large oesophageal varices (grade II and III vs grade I) (OR: 2.5; 95% CI: 1.46-4.26; P=0.001), diabetes mellitus before transplantation (OR: 2.03; 95% CI: 1.13-3.64; P=0.017) and cryptogenic-NASH (OR: 1.36; 95% CI: 1.08-1.72; P=0.008) as a cause of underlying liver disease were the independent risk factors for PVT. PVT (OR: 2.05; 95% CI: 1.10-3.81; P=0.023) was an independent predictor of early (within 90days) posttransplant mortality, but did not influence long-term survival. Portal vein thrombosis prevalence is high in pretransplant period. NASH related cirrhosis and diabetes mellitus might be risk factors for PVT. More intense screening of these patients for PVT is warranted.

Associated vitamin D deficiency is a risk factor for the complication of HCV-related liver cirrhosis including hepatic encephalopathy and spontaneous bacterial peritonitis.

The influence of vitamin D, 25-hydroxyvitamin D (25(OH)D), deficiency on hepatitis C virus (HCV)-related cirrhosis had been poorly elucidated especially in patients with hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). We aimed to investigate the association between vitamin D deficiency and the risk of SBP or HE, including the mortality rate. Serum 25(OH)D levels were prospectively determined in 135 patients. Of them, 45 patients had complications with HE and 45 patients had complications with SBP; 45 cirrhotic patients without complication served as the control group. Vitamin D deficiency was defined as 25(OH)D levels < 20ng/ml. Receiver operating characteristic (ROC) and Kaplan-Meier method with log-rank test were used in our statistical analysis. Predictors of survival were determined using Cox regression analysis. Serum 25(OH)D levels were significantly (P < 0.05) lower in the HE and SBP groups than in the control group (6.81 ± 2.75, 7.15 ± 2.10, 16.28 ± 6.60, respectively). Moreover, serum 25(OH)D levels were significantly lower in the high HE grade than in the low grade (P < 0.001). Regarding the SBP group, classic SBP was associated with lower 25(OH)D levels compared to other types (P < 0.001). ROC curve revealed that lower 25(OH)D levels less than 7.1ng/ml and 6.6ng/ml could predict the mortality in SBP and HE patients, respectively, with high sensitivity and specificity. Serum 25(OH)D levels < 5ng/ml were associated with significant higher mortality rate (HR = 2.76, P = 0.001). Lower 25(OH)D levels were associated with HE and SBP in cirrhotic patients. In addition, it may be considered a prognostic parameter for the severity of liver cirrhosis.

Restless leg syndrome a common undiagnosed comorbidity of clinical significance in cirrhosis.

Our aim was to study the prevalence and association of restless leg syndrome (RLS) in liver cirrhosis subjects. Sleep disturbances are common in cirrhosis. RLS is a chronic sensorimotor sleep disorder with an irresistible urge to move limbs. Two hundred consecutive cirrhosis patients, presenting at Mahatma Gandhi Medical College & Hospital, Jaipur were evaluated. 157 subjects meeting the inclusion criteria were selected for further evaluation. Revised International Restless Legs Syndrome Study Group (IRLSSG) criteria 2012, was used for diagnosed of RLS. Severity of RLS was evaluated by a validated Hindi translation of International RLS severity (IRLS) scoring system. Of studied 157 cirrhotic, the mean age was 46.4 ± 10 years, 109 (69.43%) males and 48 (30.57%) females. 41 (26.11%) cirrhotic subjects had RLS. Child Turcotte Pugh (CTP) Class (A 9/55, B 15/68, C 17/34; p 0.043) and alcohol as etiology for liver dysfunction (p 0.03) were significantly associated with RLS. RLS is common comorbidity in cirrhosis, especially in alcohol related cirrhosis. RLS has a clinical correlation with prognosis & severity of cirrhosis.

Spleen-Associated Effects on Immunity in Hepatitis B Virus-Related Cirrhosis with Portal Hypertension.

Our study aimed to investigate the histologic and immunological changes of portal hypertension (PH) pre- and postsplenectomy in hepatitis B virus (HBV)-related cirrhosis. Peripheral blood samples were obtained from 30 patients with HBV-related cirrhosis and PH at pre- and postsplenectomy time points and from 15 healthy subjects. Spleen tissue specimens were collected from 15 of the patients with HBV-related cirrhosis and from 8 control patients who had undergone splenectomy due to trauma. Immunohistochemical staining was performed to evaluate the immune effector cells and the expression of negative immune regulators. Flow cytometry was used to investigate the immunophenotypes and percentages. The spleen of cirrhotic patients with PH showed extensive depletion of splenic CD4, CD8, and human leukocyte antigen DR cells along with overexpression of the inhibitory receptors programmed death-1 (PD-1) and T cell immunoglobulin domain and mucin domain-3 and their ligands (PD-L2 and galectin-9). Peripheral blood of patients with PH showed remarkable decrease in proportions of CD8 T cell and natural killer (NK) cells and increase in regulatory T (Treg) cells, as well as high expression of PD-1 in CD4/8 T cells. Compared with presplenectomy patients, cirrhotic patients with PH showed increased proportions of CD8 and NK cells, decreased proportion of Treg cells, and decreased expression of PD-1 in peripheral blood CD4/8 T cells after splenectomy. PH-spleen could lead to peripheral tolerance and immunosuppression in HBV cirrhotic patients, and splenectomy may cause beneficial immunological changes.

International Liver Transplantation Consensus Statement on End-stage Liver Disease Due to Nonalcoholic Steatohepatitis and Liver Transplantation.

Nonalcoholic steatohepatitis (NASH)-related cirrhosis has become one of the most common indications for liver transplantation (LT), particularly in candidates older than 65 years. Typically, NASH candidates have concurrent obesity, metabolic, and cardiovascular risks, which directly impact patient evaluation and selection, waitlist morbidity and mortality, and eventually posttransplant outcomes. The purpose of these guidelines is to highlight specific features commonly observed in NASH candidates and strategies to optimize pretransplant evaluation and waitlist survival. More specifically, the working group addressed the following clinically relevant questions providing recommendations based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system supported by rigorous systematic reviews and consensus: (1) Is the outcome after LT similar to that of other etiologies of liver disease? (2) Is the natural history of NASH-related cirrhosis different from other etiologies of end-stage liver disease? (3) How should cardiovascular risk be assessed in the candidate for LT? Should the assessment differ from that done in other etiologies? (4) How should comorbidities (hypertension, diabetes, dyslipidemia, obesity, renal dysfunction, etc.) be treated in the candidate for LT? Should treatment and monitoring of these comorbidities differ from that applied in other etiologies? (5) What are the therapeutic strategies recommended to improve the cardiovascular and nutritional status of a NASH patient in the waiting list for LT? (6) Is there any circumstance where obesity should contraindicate LT? (7) What is the optimal time for bariatric surgery: before, during, or after LT? (8) How relevant is donor steatosis for LT in NASH patients?

A study on the relationship between tissue factor expression and liver damage in diabetic patients with hepatitis C virus-related cirrhosis

Objective The aim of this study was to identify a possible role for tissue factor (TF) in the pathogenesis of hepatic damage in patients with hepatitis C virus (HCV)-related cirrhosis with type 2 diabetes mellitus (T2DM). Background HCV infection and T2DM are both prevalent diseases worldwide. The exact mechanism by which type 2 diabetes worsens liver function is needed to be clarified. TF is a key link that connects hemostatic, immune, and inflammatory processes. Materials and methods The study included 80 participants divided into three groups: 30 patients with HCV-related cirrhosis and T2DM, 30 cirrhotic patients, and 20 healthy controls. Flow cytometry analysis was used for measuring TF (CD142) and the costimulatory molecule (CD86) on lipopolysaccharide-activated monocytes (CD14 positive cells) in peripheral blood in different studied groups. Results Our results have shown higher TF and CD86 expression in cirrhotic patients with T2DM compared with those with cirrhosis and healthy controls (34.06 ± 5.99, 24.65 ± 6.76 and 11.90 ± 3.04 for TF and 72.09 ± 12.57, 49.38 ± 15.07 and 9.35 ± 3.07 for CD86, respectively; P Conclusion On the basis of our data, we suggest a possible role for TF in the pathogenesis of liver damage through exaggerating the inflammatory process. This can, at least partially, explain the worsened liver function in HCV-related cirrhosis in patients with T2DM.

Treatment of steroid-resistant acute rejection after living donor liver transplantation

Introduction: Liver transplantation (LT) is the definitive treatment for the end-stage liver disease. Acute rejection used to be a common complication up to 70% of recipients within the first year. Steroid pulse therapy is useful treatment for this complication but is not a preferred treatment for steroid-resistant acute rejection (SRAR). We report the successful treatment of patient diagnosed with steroid-resistant acute rejection. Method: The patient, a 42-year-old male, who diagnosed chronic hepatitis b related liver cirrhosis, underwent living donor liver transplantation in 28th December 2015. This patient was given 20mg basiliximab as induction therapy on days 0 and 4 post-transplantation. The maintenance immunosuppressive regimens for this patient included a double regimen (tacrolimus and steroid). At 20 months after transplantation, he was admitted to our hospital presenting with the elevated serum levels of the liver enzymes and total bilirubin. We performed liver biopsy, after vascular or biliary complications were excluded by computed tomography. A liver biopsy showed acute cellular rejection. Steroid pulse therapy was not effective. Result: We was suspicious of steroid-resistant acute rejection, so liver biopsy was repeated to obtain exact diagnosis. Second liver biopsy also confirmed acute cellular rejection. He received 1.5mg/kg/day antithymocyte globulin for 5 days. He received antihistamine and antipyretic before antithymocyte globulin infusion to reduce or prevent adverse effects of antithymocyste globulin. Patient was stopped tacrolimus and 5mg/kg/day ganciclovir, ceftazidime prophylaxis was given during antithymocyte globulin therapy. After antithymocyte globulin treatment, His liver enzymes and total bilirubin were decreased. He was discharge 34 days later, and almost normalized his liver enzymes and total bilirubin. Conclusion: We have shown that antithymocyte globulin is safe and effective for treatment of steroid-resistant acute rejection, preventing from graft loss of chronic rejection.