Measurement of serum procalcitonin levels for the early diagnosis of spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis.

BACKGROUND: It is difficult to diagnose spontaneous bacterial peritonitis (SBP) early in decompensated liver cirrhotic ascites patients (DCPs). The aim of the study was to measure serum procalcitonin (PCT) levels and peripheral blood leukocyte/platelet (WBC/PLT) ratios to obtain an early diagnostic indication of SBP in DCPs. METHODS: Our cohort of 129 patients included 112 DCPs (94 of whom had infections) and 17 cases with compensated cirrhosis as controls. Bacterial cultures, ascitic fluid (AF) leukocyte and peripheral WBC/PLT counts, and serum PCT measurements at admission were carried out prior to the use of antibiotics. Receiver operating characteristic (ROC) curves were generated to test the accuracies and cut-off values for different inflammatory markers. RESULTS: Among the 94 infected patients, 66 tested positive by bacterial culture, for which the positivity of blood, ascites and other secretions were 25.8%, 30.3% and 43.9%, respectively. Lung infection, SBP and unknown sites of infection accounted for 8.5%, 64.9% and 26.6% of the cases, respectively. Serum PCT levels (3.02 ± 3.30 ng/mL) in DCPs with infections were significantly higher than those in control patients (0.15 ± 0.08 ng/mL); p < 0.05. We used PCT ≥0.5 ng/mL as a cut-off value to diagnose infections, for which the sensitivity and specificity was 92.5% and 77.1%. The area under the curve (AUC) was 0.89 (95% confidence interval: 0.84-0.91). The sensitivity and specificity were 62.8% and 94.2% for the diagnosis of infections, and were 68.8% and 94.2% for the diagnosis of SBP in DCPs when PCT ≥2 ng/mL was used as a cut-off value. For the combined PCT and WBC/PLT measurements, the sensitivity was 76.8% and 83.6% for the diagnosis of infections or SBP in DCPs, respectively. CONCLUSION: Serum PCT levels alone or in combination with WBC/PLT measurements seem to provide a satisfactory early diagnostic biomarker in DCPs with infections, especially for patients with SBP.

Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through ERK signaling pathway.

Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is frequently upregulated in hepatocellular carcinoma (HCC). However, how GPC3 contributes to the progress of HCC is largely unclear. The present study investigated the association between GPC3 expression and HCC clinicopathological characteristics, and particularly focused on the role and underlying mechanisms of GPC3 in HCC epithelial-mesenchymal transition (EMT). Remarkably elevated expression of GPC3 was demonstrated in HCC tumor tissues compared with paired non-tumor tissues in 45 patients with HCC by quantitative real-time PCR, immunohistochemistry, and western blotting, respectively. Furthermore, the tissue expression of GPC3 was increased during HCC progression from Barcelona Clinic Liver Cancer stage A or B to stage C. The enhanced levels of GPC3 in HCC tumor tissues were tightly correlated to the expression of the EMT-associated proteins and tumor vascular invasion. Patients with GPC3-high expression in tumor tissues displayed significantly shorter survival time than those with GPC3-low expression (P=0.001). Consistent with the findings in patients, HepG2 cells, which expressed high levels of GPC3, showed stronger capacity of migration and significant EMT-like changes when compared to those HCC cells with low levels of GPC3, e.g., Hep3B and Huh7 in scratch, Transwell assays and western blotting. Furthermore, administration with exogenous GPC3 in HCC cells activated extracellular signal-regulated kinase (ERK) and significantly enhanced cell migration and invasion. The behavior was significantly inhibited by the ERK inhibitor PD98059. Together, our studies show that GPC3 contributes to HCC progression and metastasis through impacting EMT of cancer cells, and the effects of GPC3 are associated with ERK activation.

Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients.

AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma. METHODS: Thirty-nine patients (mean age 55 years, males: 32) with decompensated liver cirrhosis and refractory ascites were enrolled. All patients received a combination of tolvaptan (15 mg/d for 5-14 d) and diuretics (40-80 mg/d of furosemide and 80-160 mg/d of spironolactone). The etiology of cirrhosis included hepatitis B (69.2%), hepatitis C (7.7%) and alcohol-induced (23.1%). Changes in the urine excretion volume, abdominal circumference and edema were assessed. The serum sodium levels were also measured, and adverse events were recorded. A follow-up assessment was conducted 1 mo after treatment with tolvaptan. RESULTS: Tolvaptan increased the mean urine excretion volume (1969.2 ± 355.55 mL vs 3410.3 ± 974.1 mL, P < 0.001), and 89.7% of patients showed improvements in their ascites, 46.2% of whom showed significant improvements. The overall efficacy of tolvaptan in all patients was 89.7%; the efficacies in patients with hepatocellular carcinoma and hepatorenal syndrome were 84.2% and 77.8%, respectively. The incidence of hyponatremia was 53.8%. In patients with hyponatremia, the serum sodium levels increased after tolvaptan treatment (from 128.1 ± 4.22 mEq/L vs 133.1 ± 3.8 mEq/L, P < 0.001). Only mild drug-related adverse events, including thirst and dry mouth, were observed. CONCLUSION: Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis.

Antiviral drug resistance increases hepatocellular carcinoma: a prospective decompensated cirrhosis cohort study.

AIM: To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients. METHODS: Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort. With two years of follow-up, 198 patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed. RESULTS: Among the antiviral treatment patients, 162 had a complete virological response (CVR), and 36 were drug-resistant (DR). The two-year cumulative incidence of hepatocellular carcinoma (HCC) in the DR patients (30.6%) was significantly higher than that in both the CVR patients (4.3%) and the control group (10.3%) (P < 0.001). Among the DR patients in particular, the incidence of HCC was 55.6% (5/9) in those who failed rescue therapy, which was extremely high. The rtA181T mutation was closely associated with rescue therapy failure (P = 0.006). The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline (8.9 ± 2.3 vs 6.0 ± 1.3, P = 0.043). CONCLUSION: This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients, especially in those who failed rescue therapy.

HBsAg loss is not an ideal indicator for discontinuing treatment of HBeAg-negative chronic hepatitis B: a case report.

We experienced a case of a 36-year-old married man who was found to be hepatitis B virus (HBV) positive at 23 years of age. His liver function was repeatedly abnormal in the past 13 years. In November 2007 he presented with fatigue. Laboratory tests showed serum alanine aminotransferase concentration 255.3 U/l, positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antibody, HBV DNA 3.01 × 10(7) copies/ml; liver biopsy showed necroinflammatory scores 11 and fibrosis scores 4. After 20 weeks of treatment with Peg-IFN α-2b, laboratory tests showed HBV DNA <500 copies/ml and normal liver function. By week 52 of the treatment, HBsAg became negative. By week 92 of continuing treatment, HBsAb became weakly positive and Peg-IFN α-2b treatment was stopped. On follow-up, both HBsAg and HBsAb were negative 28 weeks after discontinuation of Peg-IFN α-2b. We then performed a second liver biopsy and histological examination revealed necroinflammtary scores 2 and fibrosis scores 2. We administered hepatitis B vaccine intramuscularly every 4 weeks combined with IFN α-1b 30 µg intramuscularly every other day. HBsAb was 244.8 IU/l at week 32 of this combined treatment. Follow-up showed that after discontinuation of the combined treatment HBsAb concentration declined rapidly but could be maintained above 100 IU/l by intermittent injections of hepatitis B vaccine. Findings from this case reveal that HBsAg loss may be not sufficient; however, HBsAg seroconversion together with maintenance of certain concentrations of HBsAb may be a better endpoint to HBV treatment.

Probiotic yogurt effects on intestinal flora of patients with chronic liver disease.

BACKGROUND: Patients with chronic liver disease generally have intestinal flora imbalance that is related to the development and worsening of the disease. OBJECTIVE: The purpose of this study was to evaluate the effects of probiotic yogurt on intestinal flora of patients with chronic liver disease. METHODS: A randomized controlled trial, pretest-posttest control group design, was used. Patients were randomized to an experimental group (41 patients) or a control group (40 patients). Patients in the experimental group were given probiotic yogurt (one cup each time, three times per day for 14 days) containing Bacillus bifidus, Lactobacillus acidophilus, Lactobacillus bulgaricus, and Streptococcus thermophilus within 2 hours after meals. Levels of fecal flora, symptoms and signs, and laboratory examination indexes were collected. RESULTS: After intervention, the experimental group had a lower Escherichia coli count and reduced intestinal flora imbalance (p < .05). Comparison of the experimental and control groups after the intervention showed that the former had improved symptoms and signs, including significant improvement in debilitation, food intake, appetite, abdominal distension, and ascitic fluid (p < .05). CONCLUSION: Probiotic yogurt reduces the levels of intestinal flora imbalance and has an additional therapeutic effect on patients with chronic liver disease.

[Ischemic hepatitis in hepatitis B related liver cirrhotic patients with upper gastrointestinal hemorrhage: clinical features and prognostic implications].

OBJECTIVE: To investigate the incidence, clinical features and prognostic implications of ischemic hepatitis in hepatitis B related liver cirrhotic patients with upper gastrointestinal hemorrhage. METHODS: By retrospective review of the medical records of all 264 inpatients with upper gastrointestinal hemorrhage of hepatitis B related liver cirrhosis from January 1st 2007 to November 30th 2008, 11 patients with ischemic hepatitis (IH) were identified. The clinical features and prognostic implications were compared between the IH patients and 30 patients without ischemic hepatitis (control group). RESULTS: The incidence of ischemic hepatitis was 4.17% in hepatitis B related liver cirrhotic patients with upper gastrointestinal hemorrhage. The patients in IH group were younger than those in control group, the average age was (43.1+/-5.7) in IH group and (52.3+/-11.1) in control group (P=0.013). The serum alanine aminotransferase and aspartate aminotransferase were increased more than 20-fold above the upper limit of normal values, and returned to normal values within 10 days. Compared to the control group, total bilirubin, lactate dehydrogenase, alkaline phosphates, gamma-glutamyltransferase, blood urea nitrogen, creatinine, and white blood cells were increased, while serum cholinesterase was decreased in IH group (P<0.05). The fatality rate of ischemic hepatitis was much higher than that of control group (54.5% vs 16.7%, P=0.041). The main causes of death in IH group were infection, hepatorenal syndrome and hepatic encephalopathy. The patients in IH group lost 200 to 3600 milliliter blood, and hemorrhagic shock occurred in 63.6% (7/11) of IH patients. Therefore the bleeding volume was not correlated with the occurrence rate of ischemic hepatitis. CONCLUSION: Ischemic hepatitis may occur secondary to upper gastrointestinal hemorrhage in hepatitis B related liver cirrhosis. The risk factors of ischemic hepatitis in cirrhositic patients with upper gastrointestinal hemorrhage are young and with hemorrhagic shock, and poor liver function. It is important to use antibiotics in time to improve the prognosis of these patients.

[Efficacy and durability of generic adefovir dipivoxil in patients with HBeAg positive chronic hepatitis].

OBJECTIVE: To study the efficacy and durability of generic adefovir dipivoxil (ADV) in patients with HBeAg positive chronic hepatitis. METHODS: 54 nucleosides-naïve patients with HBeAg positive chronic hepatitis were enrolled in this randomized, double-blinded, placebo-controlled, prospective study. 38 patients received ADV (10 mg once daily) and the others received placebo. Then all the patients were treated with ADV for 96 weeks and were followed up for 12 weeks. RESULTS: (1) At week 12, the level of ALT declined significantly in ADV group(135.84 +/- 10.63 U/L to 58.92 +/- 4.95 U/L, P < 0.001) compared with placebo group (145.56 +/- 17.19 U/L to 159.50 +/- 37.05 U/L) (P < 0.001). The HBV-DNA level also declined significantly in adefovir group compared with placebo group (2.51 vs. 1.04 log10 copies/ml, P < 0.001). (2) The rates of normal ALT, normal of AST and undetectable HBV-DNA at 48 and 96 weeks of therapy with ADV were 63.30%, 70.50%, 87.80%, 88.60%, 53.06%, 54.55%, respectively. (3) There were 17 patients discontinuated ADV after 96 weeks. The follow-up results showed that HBV-DNA became positive again in all these 17 patients and abnormal liver function developed in 88.24% (15/17) patients. CONCLUSIONS: Treatment of chronic hepatitis B with generic ADV was effective and well tolerated, but relapse may develop when treatment was discontinued.

Resting energy expenditure and glucose, protein and fat oxidation in severe chronic virus hepatitis B patients.

AIM: To study and determine the resting energy expenditure (REE) and oxidation rates of glucose, fat and protein in severe chronic hepatitis B patients. METHODS: A total of 100 patients with liver diseases were categorized into three groups: 16 in the acute hepatitis group, 56 in the severe chronic hepatitis group, and 28 in the cirrhosis group. The REE and the oxidation rates of glucose, fat and protein were assessed by indirect heat measurement using the CCM-D nutritive metabolic investigation system. RESULTS: The REE of the severe chronic hepatitis group (20.7 +/- 6.1 kcal/d per kg) was significantly lower than that of the acute hepatitis group (P = 0.014). The respiratory quotient (RQ) of the severe chronic hepatitis group (0.84 +/- 0.06) was significantly lower than that of the acute hepatitis and cirrhosis groups (P = 0.001). The glucose oxidation rate of the severe hepatitis group (39.2%) was significantly lower than that of the acute hepatitis group and the cirrhosis group (P < 0.05), while the fat oxidation rate (39.8%) in the severe hepatitis group was markedly higher than that of the other two groups (P < 0.05). With improvement of liver function, the glucose oxidation rate increased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION: The glucose oxidation rate is significantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These results warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.

Comparison scoring model of severe viral hepatitis and model of end stage liver disease for the prognosis of patients with liver failure in China.

AIM: To estimate the prognosis of patients with liver failure using a scoring model of severe viral hepatitis (SMSVH) and a model of end stage liver disease (MELD) to provide a scientific basis for clinical decision of treatment. METHODS: One hundred and twenty patients with liver failure due to severe viral hepatitis were investigated with SMSVH established. Patients with acute, subacute, and chronic liver failure were 40, 46 and 34, respectively. The follow-up time was 6 mo. The survival rates of patients with liver failure in 2 wk, 4 wk, 3 mo and 6 mo were estimated with Kaplan-Meier method. Comparison between SMSVH and MELD was made using ROC statistic analysis. RESULTS: The survival curves of group A (at low risk, SMSVH score or= 5) were significantly different (The 4-wk, 3-mo, 6-mo survival rates were 94.59%, 54.05%, 43.24% in group A, and 51.81%, 20.48%, 12.05% in group B, respectively, P < 0.001). The survival curves of group C (SMSVH scores unchanged or increased), group D (SMSVH scores decreased by 1) and group E (SMSVH scores decreased by 2 or more) were significantly different .The survival rates of groups C, D and E were 66.15%, 100%, 100% in 2-wk; 40.0%, 91.18%, 100% in 4-wk; 0%, 58.82%, 80.95% in 3-mo and 0%, 38.24%, 61.90% in 6-mo, respectively, P < 0.001). The area under the ROC curve (AUC) of SMSVH scores at baseline and after 2 wk of therapy was significantly higher than that under the ROC curve of MELD scores (0.804 and 0.934 vs 0.689, P < 0.001). CONCLUSION: SMSVH is superior to MELD in the estimation of the prognosis of patients with severe viral hepatitis within 6 mo. SMSVH may be regarded as a criterion for estimation of the efficacy of medical treatment and the decision of clinical treatment.

[Model for predicting survival of patients with severe virus hepatitis and its clinical application].

OBJECTIVE: To study prospectively the short-time survival of patients with severe virus hepatitis using model of severe liver diseases (MSLD) established by our previous study. METHODS: One hundred and three patients with severe hepatitis were included by cohort study. Of them, there were 85 patients with severe chronic hepatitis patients, 10 acute and 8 subacute severe hepatitis patients, respectively. The follow-up endpoint was 6 months. The cutoff score of the MSLD was determined by receiver operating characteristic cure (ROC) statistic analysis, and the survival of severe hepatitis patients in 2 weeks, 4 weeks, 3 months and 6 months were estimated by Kaplan-Meier statistic analysis. RESULTS: The cutoff MSLD score for predicting survival was 5. The survival curves of group A (total MSLD score< or =4) was significantly better than group B (total MSLD score> or =5, P<0.000). After treatment for 2 weeks, the survival rate in 2 weeks and 4 weeks was 37.9% and 3.5%, respectively, if MSLD score had no change or increased. The survival rate in 2 weeks, 4 weeks and 3 months was respectively 61.5%, 15.4%, 5.8% if the MSLD score decreased 1. Then, the survival in 2 weeks, 4 weeks, 3 months and 6 months was respectively 95.0%, 90.0%, 63.9% and 52.4% if MSLD score decreased 2 or more. CONCLUSION: It is suggested that MSLD may be valuable in predicting 6-month survival of severe virus hepatitis patients. It may be used to determine the efficacy of medical treatment and to guide clinical decision.

[Use of glucocorticoid in treatment of severe acute respiratory syndrome cases].

OBJECTIVE: To explore the effect of glucocorticoid in the treatment for severe acute respiratory syndrome (SARS). METHODS: Clinical data of 70 patients with SARS admitted to Youan Hospital in Beijing during March to May, 2003 were analyzed. RESULTS: (1) Sixty-three of 70 cases of SARS recovered and seven cases died, with a case-fatality ratio of 10%. (2) Average length of hospital stay was 16.9 days for the all 70 cases, and 16.8 days for the 11 cases without glucocorticoid treatment, without statistical significance (F = 1.018, P = 0.39). (3) The other 59 cases were administered with 40 mg to 640 mg of methylprednisolone daily. (4) Average hospital stay was 15 days for the 23 cases with lower dose of 40 mg to 80 mg methylprednisolone daily, 18.5 days for the 27 cases with medium dose of 120 mg to 240 mg daily, and 17.9 days for the nine cases with higher dose of 320 mg to 640 mg daily (F = 1.018, P = 0.39). CONCLUSIONS: Earlier use of glucocorticoid therapy with suitable doses could alleviate their clinical symptoms, improve their clinical courses, and promote the absorbance of infiltration in their lungs on chest-X-ray films for the cases with SARS. However, current clinical data showed that glucocorticoid therapy could not shorten the length of hospitalization for the cases with SARS.

[Clinical features of severe acute respiratory syndrome in forty-one confirmed health care workers].

OBJECTIVE: To investigate the clinical features of severe acute respiratory syndrome (SARS). METHODS: Forty-one medical care workers (aged 23 - 55 years, with a average of 32 years; men/women = 8/32) who were admitted to our hospital and diagnosed with SARS during March and April, 2003 were retrospectively analyzed. RESULTS: Thirteen of all the patients were physicians and the rest were nurses. The disease was mainly transmitted through air droplet in a short distance, and overwork induced tiredness was involved in disease stimulation. Seventy-three percent of the patients presented fever as their first symptom. Ten patients complained inertia and myalgia. One patient showed no clinical symptoms, and bilateral infiltrates was found in his chest X-ray. Among the 41 cases, 6 (15%) were diagnosed as severe type. At the first week, the counts of white blood cells (WBCs), lymphocyte and platelets were (4.4 +/- 1.5) x 10(9)/L, 0.22 +/- 0.12 and (143 +/- 37) x 10(9)/L, which were significantly lower when compared with those at the 2nd to 4th week. Abnormal liver function was found in 27 cases (mostly with elevated serum ALT), with 70% occurred at the 3rd or 4th week. In terms of CT, 30 patients (73%) showed pathological changes in lungs, and bilateral lung involvement was found in 35.59%. Of 36 cases treated with steroids, 86% received middle or low dosage (80 - 240 mg/d). Artificial ventilation was used for twenty-seven patients, and air pipe mechanical ventilation was used for 1 case. Mortality in this study was 5%. CONCLUSIONS: Inertia and myalgia may be the earlier symptoms of health care workers with SARS include, which are parallel to CT manifestations. There is no objective index for the assessment of the severity of the disease at early stage. The medicine associated toxicities may be the main reason of liver lesions. damages. Middle or low dosage of steroid was reasonable to be used as early as possible.