Efficacy of short‐term dexamethasone therapy in acute‐on‐chronic pre‐liver failure

Aim: Acute‐on‐chronic pre‐liver failure (pre‐ACLF) is defined as a severe acute episode of chronic hepatitis B characterized by serum bilirubin of 171 µmol/L or more, alanine aminotransferase of five times or more the upper limit of normal and prothrombin activity of more than 40%, having a potential for progression to acute‐on‐chronic liver failure (ACLF). This study is to evaluate the efficacy of short‐term dexamethasone in pre‐ACLF. Methods: One hundred and seventy patients were assigned to dexamethasone therapy and control group at a ratio of 1:2. For the two groups, we compared biochemical indicators, the incidence of ACLF and mortality. The influential factors on the mortality of patients with pre‐ACLF were studied by Cox proportional hazards models. Results: The significantly lower incidence of ACLF and higher survival rate were observed in patients on dexamethasone therapy (8.9%, 96.4%, respectively) than in control patients (70.2%, 52.6%, respectively; P < 0.001). Dexamethasone treatment was an independent factor influencing the survival rate (P < 0.001, odds ratio = 0.055, 95% confidence interval = 0.013–0.225). During 4 weeks of treatment, serum bilirubin levels of survival patients were significantly lower in the dexamethasone group than control group. Conclusion: Five‐day dexamethasone therapy is effective in improving the liver function and survival rate of patients with pre‐ACLF.     

Clinical,virological and histopathological features: long‐term follow‐up in patients with chronic hepatitis C co‐infected with S. mansoni

Abstract: Background/Aims: Infection with Schistosoma mansoni is endemic in Egypt leading to hepatic schistosomiasis and eventually portal hypertension. The prevalence of antibodies against hepatitis virus C among Egyptians is 14–51%. The aim of the present study was to investigate the influence of schistosomiasis on chronic hepatitis C with respect to the natural course of the disease, immunology, virology and histology. Patients and Methods: One hundred and twenty‐six Egyptian patients classified into three groups: group A: chronic hepatitis C (n=33); group B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic schistosomiasis (n=63) were enrolled and prospectively followed for 62.7±22 months. Patients infected with other hepatic viruses and/or parasites were excluded. Detailed history, clinical examination, CD4⁺ and CD8⁺ lymphocyte counts in blood, hematological and blood chemical values, abdominal ultrasonography, upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity index in the liver biopsy were determined. Results: Thirty patients (48%) with HCV and schistosomiasis had liver cirrhosis and Child‐Pugh class C vs. five (15%) in HCV patients and none in the schistosomal group. HCV RNA levels ranged between 0.07 and 13×10⁵ copies/ml in group A, and between 1 and 25×10⁵ copies/ml in group C. HCV genotype 4 was detected in 58 patients with co‐infection (92%) and 21 patients with HCV alone (64%). Patients with coinfection showed higher grading and staging scores in their liver biopsies. Hepatocellular carcinoma was detected only in patients with coinfection. During follow‐up, the mortality rate was 12%, 3% and 48% in group A, B and C, respectively. Conclusions: Patients with concomitant HCV and schistosomiasis infection were characterized by more advanced liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma as well as a much higher mortality rate.     

Exogenous melatonin protects small‐for‐size liver grafts by promoting monocyte infiltration and releases interleukin‐6

Defective regeneration of small‐for‐size (SFS ) liver remnants and partial grafts remains a key limiting factor in the application of liver surgery and transplantation. Exogenous melatonin (MLT ) has protective effects on hepatic ischemia‐reperfusion injury (IRI ), but its influence on graft regeneration is unknown. The aim of the study is to investigate the role of MLT in IRI and graft regeneration in settings of partial liver transplantation. We established three mouse models to study hepatic IRI and regeneration associated with partial liver transplantation: (I) IR +PH group: 60 minutes liver ischemia (IR ) plus 2/3 hepatectomy (PH ); (II ) IR +exPH group: 60 minutes liver IR plus extended hepatectomy (exPH ) associated with the SFS syndrome; (III ) SFS ‐LT group: Arterialized 30% SFS liver transplant. Each group was divided into MLT or vehicle‐treated subgroups. Hepatic injury, inflammatory signatures, liver regeneration, and animal survival rates were assessed. MLT reduced liver injury, enhanced liver regeneration, and promoted interleukin (IL ) 6, IL 10, and tumor necrosis factor‐α release by infiltrating, inflammatory Ly6C+ F4/80+ monocytes in the IR +PH group. MLT ‐induced IL 6 significantly improved hepatic microcirculation and survival in the IR +exPH model. In the SFS ‐LT group, MLT promoted graft regeneration and increased recipient survival along with increased IL 6/GP 130‐STAT 3 signaling. In IL 6 ^?/? mice, MLT failed to promote liver recovery, which could be restored through recombinant IL 6. In the IR +exPH and SFS ‐LT groups, inhibition of the IL 6 co‐receptor GP 130 through SC 144 abolished the beneficial effects of MLT . MLT ameliorates SFS liver graft IRI and restores regeneration through monocyte‐released IL 6 and downstream IL 6/GP 130‐STAT 3 signaling.     

In vivo1H magnetic resonance spectroscopy‐derived metabolite variations between acute‐on‐chronic liver failure and acute liver failure

Background and Aims: Acute‐on‐chronic liver failure (ACLF), acute liver failure (ALF) and chronic liver disease (CLD) are common forms of liver failure and present with similar clinical profiles. The aim of this study was to compare brain metabolite alterations in all the three groups of patients with controls, using in vivo proton magnetic resonance spectroscopy (MRS), and to look for any significant differences in metabolites that may help in differentiating between these three conditions. Methods: Nine patients with ACLF, 10 with ALF, 10 patients with CLD and 10 age‐matched controls were studied. The relative concentrations of N‐acetylaspartate (NAA), choline (Cho), glutamine/glutamate (Glx) and myoinositol (mI) with respect to creatine (Cr) were measured. Results: ACLF (3.07±0.72), ALF (4.39±1.25) and CLD (3.15±0.69) patients exhibited significantly increased Glx/Cr ratios compared with controls (2.14±0.42). The NAA/Cr ratio was significantly decreased in both ACLF (mean=0.84±0.28) and CLD (mean=0.97±0.21) patients as compared with that in controls (mean=1.24±0.20). No significant difference among ALF, ACLF and CLD patients was noted in the Cho/Cr ratios. ACLF patients showed significantly lower mI/Cr and Glx/Cr ratios compared with the ALF group. Conclusion: In vivo proton MRS‐derived cerebral metabolite alterations in hepatic encephalopathy owing to ALF are significantly different from the one owing to ACLF and CLD; these may be due to the differences in the pathogenesis of these two overlapping clinical conditions.     

Clinicopathological analysis of non‐alcoholic steatohepatitis

OBJECTIVE : Based on liver biopsy samples collected during the past 10 years, the present study aimed to investigate the incidence of fatty liver, the relationship between fatty liver and other underlying liver diseases, and the clinical and pathological characteristics, and the risk factors of fatty liver. METHODS : From a total of 658 liver biopsy specimens collected from 1988 to 1997, there were 71 cases of fatty liver and 68 cases of non‐alcoholic fatty liver. Matched by sex and age, 155 specimens of non‐fatty liver were used as controls. All patients from which the biopsies were taken were tested for liver function, blood lipid profile, blood glucose and hepatitis virus markers. The liver biopsy samples were all investigated by the same pathologist. RESULTS : The prevalence of fatty liver among all the liver biopsies was 10.8%. The alanine aminotransferase, aspartate aminotransferase, total bilirubin and con‐jugated bilirubin levels in the fatty liver group were significantly lower than those in the non‐fatty liver group, whereas the triglyceride levels were higher. Pathologically, steatosis in patients with fatty liver was mainly located around the hepatic lobules, and macrovesicular steatosis was common. Of the 68 cases of non‐alcoholic fatty liver, hepatic cell necrosis was found in 35 cases (51.5%), inflammatory cell infiltration in 46 cases (67.6%) and fibrosis to various degrees in 19 cases (27.9%). CONCLUSION : Non‐alcoholic fatty liver is closely related to hyperlipidemia. In asymptomatic subjects with abnormal liver function, a liver biopsy is the only way to establish the type and severity of liver lesions.     

Fibrosis evolution in chronic hepatitis B e antigen‐negative patients across a 10‐year interval

The degree of liver fibrosis in chronic hepatitis B (CHB) infection influences outcome and management. Existing data describing the long‐term dynamic changes of liver fibrosis are limited. This study aimed to evaluate the evolution of liver fibrosis in CHB across a 10‐year period. CHB patients with liver stiffness measurement (LSM) by transient elastography 10 years ago were recruited for follow‐up LSM. Fibrosis stages were classified according to EASL‐ALEH guidelines. Fibrosis progression/regression was arbitrarily defined as ≥1 fibrosis stage change from baseline. A total of 459 hepatitis B e antigen (HBeAg)‐negative patients (224 untreated, 235 treated with nucleos(t)ide analogues [NAs]) were recruited. The mean age at baseline LSM was 41.7 ± 9.0 years (56.2% male). Over 10 years, the proportion of patients with advanced fibrosis/cirrhosis significantly reduced from 16.3% to 5.7% (P < 0.001). Fibrosis progression and regression were observed in 8.7% and 37.5%, respectively. No treatment with NAs (OR 2.259, 95% confidence interval [CI]: 1.032‐4.945), metabolic syndrome (OR 4.379, 95% CI: 1.128‐16.999) and hepatic steatosis (OR 7.799, 95% CI: 2.271‐26.776) was associated with fibrosis progression. Liver stiffness decline demonstrated positive correlation with the time after HBsAg seroclearance (r = ?0.50, P < 0.001). Median liver stiffness was higher both at baseline (14.0 vs 6 kPa, P < 0.001) and 10 years (9.1 vs 4.9 kPa, P < 0.001) in patients with cirrhosis‐related complications/hepatocellular carcinoma compared with those without. In conclusion, CHB‐related liver fibrosis changed dynamically across 10 years. Metabolic syndrome and hepatic steatosis were associated with fibrosis progression, while antiviral therapy was associated with fibrosis regression. Patients with HBsAg seroclearance demonstrated time‐dependent decline in liver stiffness.