Safety and efficacy of Thymosin α1 in the treatment of hepatitis B virus-related acute-on-chronic liver failure: a randomized controlled trial.

BACKGROUND/PURPOSE OF THE STUDY: Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is high. Severe infection is the most important complication that affects the outcomes of ACLF patients. Thymosin α1 (Tα1) can improve immune imbalance and this study aimed to investigate the safety and efficacy of Tα1 treatment for HBV-related ACLF. METHODS: From 2017 to 2019, 120 patients with HBV-related ACLF were enrolled in this open-label, randomized, and controlled clinical trial (ClinicalTrial ID: NCT03082885). The control group (N = 58) was treated with standard medical therapy (SMT) only. The experimental group (N = 56) was subcutaneously injected with 1.6 mg of Tα1 once a day for the first week and then twice a week from week 2 to week 12. RESULTS: The 90-day cumulated liver transplantation free survival rate of the Tα1 group was 75.0% (95% confidence interval 63.2-86.8%) versus 53.4% (95% confidence interval 39.7-67.1%) for the SMT group (p = 0.030). No significant difference was found in the survival using competitive risk analysis. The incidences of new infection and hepatic encephalopathy in the Tα1 group were much lower than those in the SMT group (32.1% vs 58.6%, p = 0.005; 8.9% vs 24.1%, p = 0.029, respectively). Mortality from severe infection in the SMT group was higher than in the Tα1 group (24.1% vs 8.9%, p = 0.029). CONCLUSION: Tα1 is safe for patients with HBV-related ACLF and significantly improves the 90-day liver transplantation-free survival rate. There may be a subgroup which may benefit from Tα1 therapy by the mechanism of preventing infection.

Hepatitis A virus-associated fulminant hepatitis with human immunodeficiency virus coinfection.

Hepatitis A virus (HAV) commonly causes acute hepatitis in humans and is transmitted through the fecal-oral route or by ingestion of contaminated food or water. HAV infection generally follows a self-limiting course; it can seldom cause fulminant hepatitis that increases the risk of mortality. To the best of our knowledge, this is the first reported fatal case of fulminant hepatitis caused by HAV in a 40-year-old male with human immunodeficiency virus (HIV) infection. The HAV genotype in this case was IA, which has recently become common globally among people living with HIV (PLWHIV), intravenous drug users, and homeless people especially in developed countries. His HIV infection was stabilized by antiretroviral drugs and his CD4 values were stable. He developed acute hepatic encephalopathy, did not respond to repeated plasma exchange therapy, and died rapidly. It is known that HIV co-infection sometimes leads to fulminant non-HAV hepatitis, although evidence supporting a correlation between fulminant hepatitis A risk and HIV infection is still lacking. This case demonstrated the fatal risk of HAV infection in PLWHIV; it was suggested that education about appropriate preventive measures and vaccination are important for preventing HAV infections among PLWHIV.

Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B.

Hepatitis E virus (HEV) infection is a major cause of morbidity in endemic areas. Its consequences among chronic hepatitis B (CHB) patients have been under-reported. The aim of this study was to assess the impact of superinfective HEV infection (acute and past) on virological and clinical features of patients with CHB infection. Clinical, biochemical, virological and immunological data of 153 CHB patients including 98 with hepatitis B virus (HBV) monoinfection and 55 with HBV-HEV superinfection with both HEV and HBV infection was retrospectively investigated and analyzed in this study conducted in Wuhan, China. An overall anti-HEV IgG seroprevalence was found to be 35.9% in CHB patients. HBV-HEV superinfection patients showed significantly higher rate of complications (ascites, hepato-renal syndrome & encephalopathy) (all with P=0.04), cirrhosis (P<0.001) and acute-on-chronic liver failure (P<0.001) than HBV monoinfection patients. They also displayed elevated ALTs (P<0.001) and total serum bilirubin (P<0.001) with diminished albumin (P<0.001) and HBV viral load (P<0.001). Cytokines assay revealed increased expression of IL-6 (P=0.02), IL-10 (P=0.009) and TNF-α (P=0.003) in HBV-HEV superinfection patients compared to HBV monoinfection patients. Our study demonstrated that HEV superinfection in CHB patients was associated with progressive clinical manifestation, which is likely due to the enhanced expression of cytokines related with hepatocytes necrosis. HEV was also associated with repressed HBV replication, but the underlying mechanism requires further investigation.

Impact of Sustained Viral Response in the Evolution of Minimal Hepatic Encephalopathy: a Prospective Pilot Study.

INTRODUCTION AND AIMS: To determine the prevalence of minimal hepatic encephalopathy (MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE. MATERIAL AND METHODS: We performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment. RESULTS: 64 patients were included. 51.6% were male, the median age was 62years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 KPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p < 0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p = 0.02), higher Child-Pugh scores at 24-weeks post-treatment (p = 0.04), higher baseline INR levels (1.4 vs. 1.1; p < 0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p = 0.02). During follow-up, those patients without MHE at 24weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p = 0.04). CONCLUSION: We found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.

Structural and functional abnormalities of vision-related brain regions in cirrhotic patients: a MRI study.

PURPOSE: Previous studies have focused on global cerebral alterations observed in cirrhosis. However, little was known about the specific abnormalities of vision-related brain regions in cirrhotic patients. In this study, we sought to explore neurological alterations of vision-related regions by measuring brain resting-state network connectivity, based on the structural investigation in cirrhotic patients without clinical sign of hepatic encephalopathy (HE). METHODS: Structural and functional magnetic resonance image (MRI) data were collected from 20 hepatitis B virus (HBV)-related cirrhotic patients without clinical sign of HE and from 20 healthy controls (HC). Voxel-based morphometric (VBM) analysis and brain functional network analysis were performed to detect abnormalities in cerebral structure and function. RESULTS: Cirrhotic patients showed regions with the most significant gray matter reduction primarily in vision-related brain regions, including the bilateral lingual gyri, left putamen, right fusiform gyrus, and right calcarine gyrus, and other significant gray matter reductions were distributed in bilateral hippocampus. Based on structural investigation focused on vision-related regions, brain functional network analysis revealed decreased functional connectivity between brain functional networks within vision-related regions (primary visual network (PVN), higher visual network (HVN), visuospatial network (VSN)) in the patient group compared with HC group. CONCLUSION: These results indicate that structural and functional impairment were evident in the vision-related brain regions in cirrhotic patients without clinical sign of hepatic encephalopathy. The physiopathology and clinical relevance of these changes could not be ascertained from the present study, which provided a basis for further evolution of the disease.

Randomized controlled trial of polyethylene glycol versus lactulose for the treatment of overt hepatic encephalopathy.

BACKGROUND: Overt hepatic encephalopathy (HE) is a frequent complication of cirrhosis and one of the most debilitating manifestations that necessitates hospitalization. Although many treatment modalities are being investigated, none of them are satisfactory. So, newer treatment modalities have to be tried. OBJECTIVE: To evaluate the safety and efficacy of polyethylene glycol (PEG) versus lactulose in the management of HE. PATIENTS AND METHODS: This clinical trial included 100 patients with post-hepatitis C cirrhosis who were admitted with HE. Patients were randomized into two equal groups: group I patients received lactulose and group II patients received PEG. The clinico-epidemiological characteristics of patients, Child-Pugh score, and HE scoring algorithm were registered before and 24 h after administration of the drug. Moreover, any suspected adverse effects were recorded. RESULTS: All 100 patients received treatment. Three patients died within 24 h of admission and did not complete the follow-up period. According to intention-to-treat approach, they were considered as treatment failure. On analysis, 36/50 (72%) patients improved one grade or more in HE scoring algorithm score after 24 h of lactulose therapy versus 47/50 (94%) of those on PEG therapy (P<0.05). The time needed for resolution of HE and length of hospital stay were significantly lower in PEG group versus lactulose group (P<0.001). Both therapies were tolerated, and no significant adverse events were reported. CONCLUSION: Both lactulose and PEG were safe and effective in the treatment of HE. PEG significantly decreased the time needed for resolution of HE and significantly shortened the hospital stay.

HINT: a novel prognostic model for patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: HBV-related acute-on-chronic liver failure (HBV-ACLF) deteriorates rapidly in the short term, which necessitates accurate initial clinical decision making. AIMS: To develop a novel prognostic score for patients with HBV-ACLF and clarify the role of thyroid hormones in HBV-ACLF. METHODS: A retrospective cohort of 635 HBV-ACLF patients was enrolled to develop and validate a novel prognostic score for HBV-ACLF. Additionally, a cross-sectional cohort (n = 199) and a prospective longitudinal HBV-ACLF cohort (n = 56) were recruited to clarify the association between thyroid hormone status and the 30-day mortality of HBV-ACLF. RESULTS: HINT, a novel prognostic score based on hepatic encephalopathy, INR, neutrophil count, and thyroid-stimulating hormone (TSH) using the deriving cohort (n = 426), was significantly higher in non-survivors than survivors (1.17 ± 2.38 vs -1.87 ± 1.26, P < 0.0001). The AUROC of HINT for 30-day mortality was 0.889, which was significantly higher than that of the Child-Pugh, MELD, CLIF-SOFA, CLIF-C ACLF, and COSSH-ACLF scores (all P < 0.05). These results were confirmed in the validation cohort (n = 209), except that the AUROC of HINT was comparable to that of COSSH-ACLF (P = 0.357). Among thyroid hormones, only the TSH level on admission was significantly lower in non-survivors than in survivors (P = 0.01). During the 14-day longitudinal observation, TSH levels increased significantly in the improvement group (P < 0.001) but did not change in the deterioration or fluctuation groups, and gradually increased in survivors (P < 0.001) but not in non-survivors. CONCLUSIONS: HINT, as a prognostic score for HBV-ACLF, is simpler than and superior to the Child-Pugh, MELD, CLIF-SOFA, and CLIF-C ACLF scores and at least comparable with the COSSH-ACLF score. Sequential TSH measurements may facilitate prediction of the clinical course of ACLF.

Role of probiotics in the treatment of minimal hepatic encephalopathy in patients with HBV-induced liver cirrhosis.

Objective This study was performed to investigate the role of probiotics ( Clostridium butyricum combined with Bifidobacterium infantis) in the treatment of minimal hepatic encephalopathy (MHE) in patients with hepatitis B virus (HBV)-induced liver cirrhosis. Methods Sixty-seven consecutive patients with HBV-induced cirrhosis without overt hepatic encephalopathy were screened using the number connection test and digit symbol test. The patients were randomized to receive probiotics (n = 30) or no probiotics (n = 37) for 3 months. At the end of the trial, changes in cognition, intestinal microbiota, venous ammonia, and intestinal mucosal barriers were analyzed using recommended systems biology techniques. Results The patients' cognition was significantly improved after probiotic treatment. The predominant bacteria ( Clostridium cluster I and Bifidobacterium) were significantly enriched in the probiotics-treated group, while Enterococcus and Enterobacteriaceae were significantly decreased. Probiotic treatment was also associated with an obvious reduction in venous ammonia. Additionally, the parameters of the intestinal mucosal barrier were obviously improved after probiotic treatment, which might have contributed to the improved cognition and the decreased ammonia levels. Conclusion Treatment with probiotics containing C. butyricum and B. infantis represents a new adjuvant therapy for the management of MHE in patients with HBV-induced cirrhosis.

Baseline Factors Associated With Improvements in Decompensated Cirrhosis After Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection.

BACKGROUND & AIMS: Treatment with direct-acting antiviral (DAA) agents can reduce Model for End-Stage Liver Disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus. However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy. METHODS: We performed a retrospective analysis of data from 4 trials on the effects of sofosbuvir-based therapy in patients with hepatitis C virus-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C). In these trials, patients were given 12 or 24 weeks of treatment with ledipasvir, sofosbuvir, and ribavirin or velpatasvir, sofosbuvir, and/or ribavirin, or 48 weeks of treatment with sofosbuvir and ribavirin. We collected demographic, clinical, treatment response, and laboratory data from patients and tested their associations with patient outcomes at 36 weeks. The primary outcome was factors associated with reduction of CPT score to class A. RESULTS: The presence of ascites or encephalopathy, serum level of albumin <3.5 g/dL or alanine aminotransferase <60 U/L, and body mass index >25 kg/m2 were associated with an increased risk of not achieving a reduction in CPT to class A, independent of sustained viral response to therapy. Serum level of albumin <2.8 g/dL and abnormal level of bilirubin were associated with an increased risk of liver transplantation or death. We developed a scoring system based on 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated significantly with patient outcomes, which we called the "BE3A score." For patients with scores of 4-5, the hazard ratio for reduction of CPT score to class A was 52.3 (95% confidence interval, 15.2-179.7). CONCLUSIONS: We identified 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated with a reduction of CPT score to class A in patients with hepatitis C virus-associated decompensated cirrhosis receiving DAA therapy. We developed a predictive score using these factors, called the BE3A score, which can be used as a shared decision-making tool, quantifying the potential benefits of DAA therapy for patients with decompensated cirrhosis.

Sofosbuvir plus daclatasvir with or without ribavirin in 551 patients with hepatitis C-related cirrhosis, genotype 4.

BACKGROUND: The Daclatasvir and Sofosbuvir combination therapy (SOF/DCV) has shown efficacy in patients with chronic hepatitis C in clinical trials. AIM: To investigate the efficacy and safety of SOF/DCV for treatment of patients with hepatitis C-related liver cirrhosis genotype 4. METHODS: Multicentre study involving 551 patients with liver cirrhosis genotype 4; 432 naïve patients and 119 treatment-experienced patients. All patients received SOF (400 mg) and DCV (60 mg) daily in addition to weight-based ribavirin (RBV) for 12 weeks and when RBV is contraindicated the treatment duration was extended to 24 weeks. RESULTS: Sustained virological response at 12 weeks after end of treatment (SVR12) rate was 92% in naïve cirrhotic patients and 87% in previous treated patients (by ITT analysis). Virological failure was infrequent, occurring in 42 patients (8%) overall. Thirty-two (6%) were non responders; and 10 (2%) cases were relapsers, 31 patients (7%) were CTP-A and 11 (13.3%) patients were CTP-B (by ITT analysis). The most common adverse events were anaemia, fatigue, headache, pruritus. Serious side effects were recorded mainly in CTP-B cirrhotic patients including HCC and hepatic encephalopathy. CONCLUSIONS: The SOF/DCV combination therapy has proven efficacy and safety in treating patients with hepatitis C-related liver cirrhosis genotype 4 in a large cohort of patients in the real world.

Superinfection of hepatitis E as a factor in the development of acute hepatic encephalopathy on the background of HBV-cirrhosis of the liver.

The article presents an analysis of the clinical case of superinfection of autochthonous acute hepatitis E against the background of HBV-cirrhosis of the liver. HEV infection was diagnosed in a 39 year old man who did not travel outside the region and the country for a long time and used unboiled water. The peculiarity of the disease in the non-endemic region was: a severe course of hepatitis E against the background of HBV etiology, with the development of the clinic for acute hepatic insufficiency and encephalopathy, the presence of severe cytolysis syndrome, cholestasis, hepatic-cell insufficiency and prolonged convalescence. Timely treatment of the patient for medical aid and intensive pathogenetic therapy of hepatit-E superinfection with compensated HBV-cirrhosis allowed to save the patient's life. However, the prognosis for the patient's later life is unfavorable, due to submissive liver necrosis and the risk of rapid decompensation of cirrhosis. When deciphering undifferentiated in Russia acute hepatitis in persons with cirrhosis of another etiology (viral, alcoholic, medicinal), it is necessary to include the definition of HEVRNA and HEV IgM and G. in the survey design.

Acute hepatitis E virus infection causing acute liver failure requiring living-donor liver transplantation in a non-pregnant immunocompetent woman.

We report a rare case of acute liver failure from acute hepatitis E virus (HEV) in a non-pregnant woman without comorbidities who survived after liver transplantation. The source was likely consumption of partially cooked pig liver. HEV genotype 3 is the second most common genotype causing acute hepatitis E in developed countries. Fulminant hepatitis E rarely occurs without a risk factor, as in our patient. Vigilant monitoring for chronic hepatitis E in post-transplant immunocompromised patients is needed.

Aberrant Resting-State Functional Connectivity Density in Patients with Hepatitis B Virus-Related Cirrhosis.

There is increasing evidence that cirrhosis may affect functional connectivity among various brain regions in patients prior to onset of overt hepatic encephalopathy (HE). However, most investigators have focused mainly on alterations in functional connectivity strengths, and the changes in functional connectivity density (FCD) are largely unknown. Here, we investigated alterations in resting-state FCD in patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt HE. Totally, 31 patients with HBV-RC without overt HE and 30 age- and sex-matched healthy controls underwent resting-state functional MRI examinations. FCD mapping was employed to compute local and global FCD maps. Then, short-range and long-range FCD values were calculated and voxel-based comparisons were performed between the two groups. The HBV-RC group showed significant decreases in FCD, including decreased short-range FCDs in the bilateral middle cingulum gyrus/precuneus, the bilateral cuneus, and the left lingual gyrus/inferior occipital gyrus and decreased long-range FCD in the bilateral cuneus/precuneus. In addition, the decreased long-range FCD in the bilateral cuneus/precuneus in the HBV-RC group was related to performance on the psychometric hepatic encephalopathy score (PHES) test. These findings suggest aberrant functional connectivity density in cirrhotic patients prior to overt HE onset, which may provide better insight into understanding the pathophysiological mechanisms underlying the cirrhotic-related cognitive impairment.

Fatal fulminant hepatitis caused by infection with subgenotype A1 hepatitis B virus with C1766T/T1768A core promoter mutations.

Adults initially infected with the hepatitis B virus develop various types of hepatitis ranging from asymptomatic to fulminant, and the clinical course of infection is influenced by a variety of host and viral factors. The viral risk factors associated with fulminant hepatitis reportedly include subgenotype B1, negative HBe antigen, and mutations in the precore and core promoter regions. Here, we present a case of fatal fulminant hepatitis caused by infection with subgenotype A1 hepatitis B virus with C1766T/T1768A double mutations in the core promoter region. A 53-year-old man was hospitalized with acute hepatitis B. Immediately after admission, entecavir was administered. However, his condition deteriorated, developing into fulminant hepatitis 2 days later. Artificial extracorporeal liver support therapy with plasma exchange (PE) and hemodiafiltration (HDF) were started. At one time point, the severity of hepatic encephalopathy decreased from grade II to grade 0, and the prothrombin time also improved, increasing from 11 to 73 %. However, the total bilirubin levels remained at or above 20 mg/dL and blood creatinine levels gradually increased. HDF was restarted, and therapies such as bilirubin adsorption and PE were administered. However, neither hepatic nor renal failure was alleviated, and the patient died 78 days after admission.

Apolipoprotein E-ε4 deficiency and cognitive function in hepatitis C virus-infected patients.

Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.

Nonconvulsive status epilepticus disguising as hepatic encephalopathy.

Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram.

Interferon gamma, interleukin-6, and -17a levels were correlated with minimal hepatic encephalopathy in HBV patients.

BACKGROUND AND OBJECTIVE: Cytokines have been reported to be involved in the cirrhosis and hepatic encephalopathy (HE). Many aspects on the correlation between minimal HE (MHE) and cytokine levels were still unclear. METHODS: Two hundred eighty-nine HBV-infected cirrhotic patients were grouped: non MHE (n = 156), MHE (n = 98) and clinical HE (CHE, n = 213). Another 88 healthy volunteers were included as controls. Clinical and laboratory findings and levels of ten serum cytokines were analyzed. RESULTS: All tested cytokines were significantly elevated in cirrhotic patients and patients with CHE compared with controls. Statistical analysis showed only IL-6, IFNγ and IL-17a were correlated MHE (all three p < 0.001). Multivariate regression analysis indicated that serum IL-6 and IL-17a levels were independent risk factors for MHE. Moreover, all patients with MHE had IL-17a levels higher than 49 pg/mL, whereas those without MHE had IL-17a levels lower than 49 pg/mL. CONCLUSIONS: IL-6, IFNγ, and IL-17a were correlated with MHE in HBV-infected patients. Two independent risk factors (IL-6, IL-17a) for MHE were identified. Our findings pointed out the crucial roles of cytokines in MHE in HBV-infected patients.

Successful Living-Donor Liver Transplant for Fulminant Hepatitis in a Heart Recipient.

Reactivation of hepatitis B virus replication is a known complication of immunosuppressive therapy, which can lead to hepatocellular injury, liver failure, and death. In this report, we describe the case of a 44-year-old man with chronic hepatitis B and a dilated cardiomyopathy status after a heart transplant. Reactivation of the patient 's hepatitis B virus occurred 4 months after the heart transplant. Despite prompt administration of antiviral therapy, he developed fulminant hepatitis with hepatic encephalopathy. A successful living-related liver transplant was performed 7 months after the heart transplant. The patient was followed up for 1 year, and during that time was free of hepatitis B virus. We suggest that routine antiviral therapy should be administered to patients with chronic hepatitis B receiving immunosuppressive therapy.

Hepatitis E infection in patients with severe acute alcoholic hepatitis.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection is a known cause of acute-on-chronic liver failure in developing countries, but its implication in Western countries remains unknown. HEV burden in the setting of severe acute alcoholic hepatitis (AAH) was assessed. METHODS: Patients admitted for severe AAH from 2007 to 2013, with available sera and histologically proven AAH, were included and managed according to current European guidelines. At admission, clinical and biological characteristics were collected; HEV serology and RNA detection were retrospectively performed. RESULTS: Eighty-four patients were included. Mean age was 50.8 ± 9.6 years, 65.5% were male, 91.7% were cirrhotic and 33.3% presented with encephalopathy. Mean MELD and Maddrey scores were respectively 32.4 ± 11.4 and 73.3 ± 37. Liver biopsy showed mild, moderate and severe hepatitis in 25 (29.8%), 23 (27.4%) and 32 (38.1%) patients respectively. Steroids were given to 61 patients (72.6%) of whom 35 (57.4%) presented corticoresistance (mean Lille score: 0.78 ± 0.21). During hospitalization, 24 patients (28.6%) died and 11 (13.1%) were transplanted. Three patients (3.6%) presented markers of acute HEV infection and 21 (25%) markers of past HEV infection. Patient with acute infection were men, cirrhotic, and 2/3 presented with encephalopathy. Steroids were given to two patients without any response. The third patient died. None were transplanted. CONCLUSIONS: A substantial proportion of patients with severe AAH had markers of acute HEV infection, with similar clinical presentation and outcomes. Larger studies are needed to evaluate HEV impact on AAH management, resistance to steroids, and outcome.

Assessment of risk of complications in cirrhosis using portal thallium scans.

AIM: To investigate the usefulness of a novel thallium scan shunt index for assessing portosystemic shunt-related cirrhotic complications. METHODS: We enrolled 209 chronic hepatitis B-related cirrhosis patients. After rectal thallium instillation, radioactive isotope activity in the heart and liver was measured. The ratio of radiation uptake between the heart and the liver was calculated (the shunt index). This value indicates the degree of portosystemic circulation shunting. Blood tests, serum biochemistry tests, abdominal ultrasonography, gastroscopy and examination of clinical features such as the occurrence of varices, bleeding and hepatic encephalopathy were performed. Multivariate analysis was used to identify independent risk factors for complications. We compared the cumulative incidence rates of complications during the follow-up period. RESULTS: The thallium scan shunt index was significantly higher in the decompensated liver cirrhosis group than in the compensated liver cirrhosis group (0.91 ± 0.39 vs 0.39 ± 0.32, P < 0.001). It was also higher in the varices group, the hepatic encephalopathy group, and the variceal bleeding group than in the control group (P < 0.001). Multivariate analysis showed that the index was an independent risk factor for predicting decompensated liver cirrhosis. When the cut-off value was 0.75, the shunt index had a sensitivity of 82.6%, a specificity of 84%, a positive predictive value of 61.5%, and a negative predictive value of 94.4% in diagnosing decompensated cirrhosis. When the shunt index was greater than 0.75, there was a significant increase in the number of decompensated events. CONCLUSION: The thallium shunt index is a good predictor of cirrhosis-related complications.