Effect of alcohol on clinical complications of hepatitis virus-induced liver cirrhosis: a consecutive ten-year study.

BACKGROUND AND AIMS: Although coexisting alcohol-induced liver disease and hepatitis B or C virus-induced liver cirrhosis (ALD + HBV or ALD + HCV) has been the center of recent hepatology researches, numerous controversies still persist. This study aimed to showcase the influence of alcohol on the laboratory values and on the clinical outcomes of patients with hepatitis B and C virus-induced liver cirrhosis. METHODS: Patients diagnosed with liver cirrhosis (n = 22,287) from January 2010 to December 2019 were enrolled, and divided into five groups according to the etiology: alcohol-induced liver disease (ALD, 1652 cases), hepatitis B virus (HBV, 18,079 cases), hepatitis C virus (HCV, 682 cases), ALD + HBV (1594 cases) and ALD + HCV (280 cases). Laboratory results and proportion of different liver cirrhosis complications were contrasted between groups. RESULTS: The proportions of patients with Child Pugh grade C (28.0% vs 18.8%, P < 0.001) or MELD greater than 18 (24.1% vs 18.5%, P < 0.001) in the ALD + HBV group exceeded significantly those in the HBV group. Multivariate logistic regression revealed that the risk of hepatocellular carcinoma (HCC) and that of esophageal gastric variceal bleeding (EGVB) in the ALD + HBV group was respectively 2.01-fold and 1.74-fold that in the HBV group (HCC: OR = 2.01, 95% CI [1.58-2.55]; EGVB: OR = 1.74, 95% CI [1.30-2.33]) after adjusting for potential confounders. Furthermore, a linear-by-linear analysis test showed a decrease in the risk of HCC and EGVB with the duration of alcohol abstinence. Moreover, patients with both antiviral treatment and alcohol abstinence had the lowest risk of HCC and EGVB (HCC: OR = 0.10, 95% CI [0.05-0.20], P < 0.001; EGVB: OR = 0.17, 95% CI [0.06-0.45], P < 0.001) compared to those without any treatment, those with abstinence alone and those with antiviral therapy alone. Similar pattern was noticed while comparing the ALD + HCV group to the HCV group. CONCLUSION: Heavy alcohol use increased the severity of liver function impairment and the prevalence of HCC and EGVB in hepatitis virus-induced liver cirrhosis patients. Remarkably, long-term alcohol abstinence coupled with antiviral treatment effectively decreased the risk of HCC and EGVB in these populations.

FcGBP and VCAM-1 are ponderable biomarkers for differential diagnosis of alcoholic liver cirrhosis.

BACKGROUND/ AIMS: Early diagnosis of alcoholic liver cirrhosis (ALD) and coexisting ALD and hepatitis B virus-induced cirrhosis (ALD+HBV) is primordial for an optimal management of these conditions. However, the lack of specific noninvasive biomarkers coupled with the inaccuracy of self-reported alcohol consumption make the early diagnosis of these pathologies difficult. This study aimed to identify biomarkers to diagnose ALD and differentiate ALD+HBV from HBV. METHODS: Proteomics mass spectrometry technique was used to identify specific proteins of ALD by contrasting serums of ALD to that of healthy subjects. The accuracy of the selected proteins in diagnosing ALD and discriminating ALD+HBV from HBV was assessed in two independent cohorts using the area under the receiver operator characteristic curve (AUROC). RESULTS: 452 cirrhotic and normal subjects were enrolled in this study. The proteomic results revealed that FcGBP and VCAM-1 were the highest overexpressed proteins while comparing ALD samples to the healthy cohort. The combination of these two biomarkers had an AUROC of 0.986 (P < 0.001, sensitivity: 97.2%, specificity: 100%) in identifying ALD from the healthy cohort, and AUROC of 0.781 (P < 0.001, sensitivity: 81.8%, specificity: 77.0%) in differentiating ALD+HBV from HBV. This combination was more accurate than the combination of AST/ALT, MCV and GGT (ALD vs healthy, AUROC = 0.898; ALD+HBV vs HBV, AUROC = 0.599). The discrimination performance of this combination was further validated in another independent cohort. CONCLUSION: FcGBP and VCAM-1 are two promising biomarkers in the diagnosis of ALD and in the differentiating of ALD+HBV from HBV subjects.

Sodium butyrate protects against lipopolysaccharide-induced liver injury partially via the GPR43/ ß-arrestin-2/NF-κB network.

BACKGROUND: Butyrate acts as a regulator in multiple inflammatory organ injuries. However, the role of butyrate in acute liver injury has not yet been fully explored. In the present study, we aimed to investigate the association between butyrate and lipopolysaccharide (LPS)-induced acute liver injury and the signaling pathways involved. METHODS: LPS-induced acute liver injury was induced by intraperitoneal injection of LPS (5 mg/kg) in G-protein-coupled receptor 43 (GPR43)-knockout (KO) and wild-type female C57BL/6 mice. Sodium butyrate (500mg/kg) was administered intraperitoneally 30 min prior to LPS exposure. Liver injury was detected by serum markers, tissue morphology, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Pro-inflammatory-factor levels were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (RT-PCR). Cell models were first treated with sodium butyrate (4 µmol/mL), followed by LPS (1 µg/mL) half an hour later in GPR43 small interfering RNA (siRNA)-transfected or control RAW264.7 cells. Cell-inflammation status was evaluated through detecting pro-inflammatory-factor expression by RT-PCR and also through checking toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB)-element levels including TLR4, TRAF6, IKKß, IкBα, phospho-IкBα, p65, and phospho-p65 by Western blot. The interaction between GPR43 and ß-arrestin-2 was tested by co-immunoprecipitation. RESULTS: Sodium butyrate reversed the LPS-induced tissue-morphology changes and high levels of serum alanine aminotransferase, aspartate transaminase, myeloperoxidase, TUNEL, and pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The ameliorating effect of sodium butyrate was weakened in GPR43-KO mice and GPR43 siRNA RAW264.7 cells, compared with those of GPR43-positive controls. Sodium butyrate downregulated some elements of the TLR4/NF-κB pathway, including phospho-IκBα and phospho-p65, in RAW264.7 cells. Increased interactions between GPR43 and ß-arrestin-2, and between ß-arrestin-2 and IкBα were observed. CONCLUSION: Sodium butyrate significantly attenuated LPS-induced liver injury by reducing the inflammatory response partially via the GPR43/ß-arrestin-2/NF-κB signaling pathway.

Diagnosis of eosinophilic gastroenteritis is easily missed.

AIM: To analyze the clinical characteristics of eosinophilic gastroenteritis (EGE) and to investigate the situations of missed diagnosis of EGE. METHODS: First, the clinical characteristics of 20 EGE patients who were treated at our hospital were retrospectively summarized. Second, 159 patients who underwent gastroscopy and 211 patients who underwent colonoscopy were enrolled. The pathological diagnosis showed only chronic inflammation in their medical records. The biopsy slides of these patients were reevaluated to determine the number of infiltrating eosinophils in order to assess the probability of a missed diagnosis of EGE. Finally, 122 patients who experienced refractory upper gastrointestinal symptoms for at least one month were recruited. At least 6 biopsy specimens were obtained by gastroscopy, and the number of eosinophils that had infiltrated was evaluated. Those who met the pathological diagnostic criteria of EGE underwent further examination to confirm the diagnosis of EGE. The probability of a missed diagnosis of EGE was prospectively investigated. RESULTS: Among the 20 patients with EGE, mucosal EGE was found in 15 patients, muscular EGE was found in 3 patients and serosal EGE was found in 2 patients. Abdominal pain was the most common symptom. The number of peripheral blood eosinophils was elevated in all 20 patients, all of whom were sensitive to corticosteroids. Second, among the 159 patients who underwent gastroscopy, 7 (4.40%) patients met the criteria for pathological EGE (eosinophil count ≥ 25/HPF). Among the 211 patients who underwent colonoscopy, 9 (4.27%) patients met the criteria for pathological EGE (eosinophil count ≥ 30/HPF). No patients with eosinophil infiltration were diagnosed with EGE in clinical practice before or after endoscopy. Although these patients did not undergo further examination to exclude other diseases that can also lead to gastrointestinal eosinophil infiltration, these might be the cases where the diagnosis of EGE was missed. Finally, among the 122 patients with refractory upper gastrointestinal symptoms, eosinophil infiltration was seen in 7 patients (5.74%). The diagnosis of EGE was confirmed in all 7 patients after the exclusion of other diseases that can also lead to gastrointestinal eosinophil infiltration. A positive correlation was observed between the duration of the symptoms and the risk of EGE (r = 0.18, P < 0.01). The patients whose symptoms persisted longer than 6 mo more readily developed EGE. None of the patients were considered to have EGE by their physicians before endoscopy. CONCLUSION: Although EGE is a rare inflammatory disorder, it is easily misdiagnosed. When a long history of abdominal symptoms fails to improve after conventional therapy, EGE should be considered.

Successful treatment of ileal ulcers caused by immunosuppressants in two organ transplant recipients.

Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-year-old man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at post-operative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus was found in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant might be effective to treat these ulcers.

Acute diarrhea and metabolic acidosis caused by tuberculous vesico-rectal fistula.

Acquired vesico-rectal fistula is an uncommon complication of pelvic malignant tumors, surgical injury, inflammatory disorders such as tuberculosis infection, radiotherapy and less commonly diverticulum of the urinary tract. The fistula is often identified by urinary tract abnormalities such as dysuria, recurrent urinary tract infection, pneumaturia, and fecaluria. Here, we report an unusual case of a patient with a vesico-rectal fistula of tuberculous origin, presenting with severe acute diarrhea, metabolic acidosis, hyperchloremia and hypokalemia while with only mild urinary tract symptoms. The patient was cured by tuberculostatic therapy.

Intestinal obstruction caused by extramedullary hematopoiesis and ascites in primary myelofibrosis.

Primary myelofibrosis (PMF) is a clonal hematopoietic stem cell disorder. It is characterized by bone marrow fibrosis, extramedullary hematopoiesis with hepatosplenomegaly and leukoerythroblastosis in the peripheral blood. The main clinical manifestations of PMF are anemia, bleeding, hepatosplenomegaly, fatigue, and fever. Here we report a rare case of PMF with anemia, small bowel obstruction and ascites due to extramedullary hematopoiesis and portal hypertension. The diagnosis was difficult to establish before surgery and the differential diagnosis is discussed.