Gene heterogeneity of hepatitis B virus isolates from patients with severe hepatitis B

BACKGROUND: The pathogenesis of severe hepatitis B remains unknown. Reports have indicated that hepatitis B virus (HBV) mutations are important factors in the pathogenesis of this disease. This study was to investigate the genetic heterogeneity of HBV strains from serum samples of patients with fulminant hepatitis B. METHODS: Full-length HBV genomes from 4 patients with severe hepatitis B were cloned and sequenced to observe mutations in every open reading-frame ( ORF). Serum samples of another 25 patients with severe hepatitis B, 30 patients with chronic hepatitis B, and 25 HBV carriers were collected for sequencing and comparison of mutations in preS2, preC and core promoter regions. RESULTS: Of 4 HBV full-length genome sequences, 3 had a G to A mutation at nucleotide A1896 in the preC region and 1 had double mutations of T1762-A1764 in the core promoter region. The 4 sequences showed mutations in the known B or T cell epitopes of the preS2 and C regions. For the other 3 groups, more mutations were seen in the preS2 region in the HBV isolates from the patients with severe hepatitis B than those from the patients with chronic hepatitis B and HBV carriers (P <0.01). There was a significant difference of mutations in the T cell epitope region of preS2 between the patients with severe hepatitis B and those with chronic hepatitis B or HBV carriers (P <0.01). In the preC and core promoter regions, the mutation frequencies of T1653 and C1753 were 48.0% and 24.0% respectively in the patients with severe hepatitis B, but none of these mutations were observed in the patients with chronic hepatitis B group or HBV carriers (P <0.01). The mutation frequency of T1762-A1764 was 76.0% in the patients with severe hepatitis B, 40.0% in the patients with chronic hepatitis B (P <0. 01) , and 16. 0% in the HBV carriers ( P < 0. 01). There was a significant difference in A1896 mutation between the patients with severe hepatitis B and the patients with chronic hepatitis B (P < 0. 05 ) or the HBV carriers (P<0.05). CONCLUSION: Our observations suggest that the accumulation and persistence of high frequency mutations or complex mutations may be associated with the development and deterioration of HBV infection.

Short-term entecavir therapy of chronic severe hepatitis B

BACKGROUND: Chronic severe hepatitis B patients often have limited survival. This investigation aimed to evaluate the short-term effects of nucleoside analog therapy on chronic severe hepatitis B. METHODS: We retrospectively, randomly collected the data of 129 chronic severe hepatitis B patients: 55 were treated with entecavir, and the remaining 74 were not treated with nucleoside analogues. RESULTS: No significant difference in short-term survival rate was found between the group treated with entecavir and that treated without nucleoside analogues. Although entecavir greatly reduced HBV replication in different periods of therapy (P<0.001), the model for end-stage liver disease (MELD) score and liver function (alanine aminotransferase, albumin, bilirubin, prothrombin time) showed no significant change. No significant differences were found in MELD scores and liver function in patients with different HBV DNA levels (<= 10(4) copies/ml, >10(4) to <10(6) copies/ml, >= 10(6) copies/ml). Nor correlation was observed between HBV DNA levels and MELD scores in different periods of therapy (P>0.05). The HBV DNA levels of patients who survived for over 3 months or less than 3 months were not significantly different either. However, the MELD score and parameters of liver function (albumin, bilirubin, prothrombin time) were different between the two groups (P<0.05). CONCLUSION: These results suggest that short-term suppression of HBV replication may not slow down the progression of liver failure in patients with chronic severe hepatitis B.

Prognostic factors for chronic severe hepatitis and construction of a prognostic model

BACKGROUND: Chronic severe hepatitis is a serious illness with a high mortality rate. Discussion of prognostic judgment criteria for chronic severe hepatitis is of great value in clinical guidance. This study was designed to investigate the clinical and laboratory indices affecting the prognosis of chronic severe hepatitis and construct a prognostic model. METHODS: The clinical and laboratory indices of 213 patients with chronic severe hepatitis within 24 hours after diagnosis were analyzed retrospectively. Death or survival was limited to within 3 months after diagnosis. RESULTS: The mortality of all patients was 47.42%. Compared with the survival group, the age, basis of hepatocirrhosis, infection, degree of hepatic encephalopathy (HE) and the levels of total bilirubin (TBil), total cholesterol (CHO), cholinesterase (CHE), blood urea nitrogen (BUN), blood creatinine (Cr), blood sodium ion (Na), peripheral blood leukocytes (WBC), alpha-fetoprotein (AFP), international normalized ratio (INR) of blood coagulation and prothrombin time (PT) were significantly different in the group who died, but the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and hemoglobin (HGB) were not different between the two groups. At the same time, a regression model, Logit (P)=1.573xAge+1.338xHE-1.608xCHO+0.011xCr-0.109xNa+1.298xINR+11.057, was constructed by logistic regression analysis and the prognostic value of the model was higher than that of the MELD score. CONCLUSIONS: Multivariate analysis excels univariate anlysis in the prognosis of chronic severe hepatitis, and the regression model is of significant value in the prognosis of this disease.

The MELD scoring system for predicting prognosis in patients with severe hepatitis after plasma exchange treatment

BACKGROUND: Hepatic failure caused by severe hepatitis is a clinical syndrome where the major liver functions, particularly detoxification, synthetic functions, and metabolic regulation are impaired to different degrees, and may result in major life-threatening complications such as hepatic encephalopathy, ascites, jaundice, cholestasis, bleeding and hepatorenal syndrome. Plasma exchange (PE) has been found useful in treating patients with fulminant hepatic failure by removing hepatic toxins and replacement of clotting factors, so PE treatment has temporary supportive effects on liver failure caused by severe viral hepatitis. in this study, our aim was to predict the prognosis of patients with severe hepatitis after PE treatment using the end-stage liver disease (MELD) scoring system. METHODS: Two hundred and twenty patients were randomly divided into PE and control groups, and the MELD score was calculated for each patient according to the original formula. The efficacy of PE was assessed by mortality or improvement in biochemical parameters and MELD score. RESULTS: The levels of total bilirubin and international normalised ratio (INR) in patients whose MELD scores were between 30 and 39 were lower than those before PE treatment, as those in patients whose MELD scores were 40 or higher. The mortality of patients in the PE group with MELD scores from 30 to 39 was 50.0%, while it was 83.3% in the control group (P<0.01). The mortality of patients with MELD scores higher than 40 was 90.0% in the PE group and 98.0% in the control group (P>0.05). CONCLUSIONS: PE treatment can decrease the serum total bilirubin level and INR and MELD score of patients with severe hepatitis and improve liver function. Compared with the control group, PE can significantly decrease the mortality of patients with MELD scores from 30 to 39, but has no effect in patients with MELD scores of 40 or higher.

Portalsystemic hemodynamic changes in chronic severe hepatitis B: An ultrasonographic study

AIM： To evaluate portalsystemic hemodynamic changes in chronic severe hepatitis B. METHODS： Hemodynamic parameters included portal vein diameter （PVD）, portal vein peak velocity （PVPV）, portal vein volume （PW）, spleen length （SPL）, spleen vein diameter （SPVD）, spleen vein volume （SPW） and umbilical vein recanalization. They were measured by Color Doppler ultrasonography in 36 patients with chronic severe hepatitis B, compared with 51 normal controls, 61 patients with chronic hepatitis B, 46 patients with compensable cirrhosis, and 36 patients with decompensable cirrhosis. RESULTS： In the group of chronic severe hepatitis B, PVD （12.38 ± 1.23 mm） was significantly different from the normal control, compensable cirrhosis and decompensable cirrhosis groups （P = 0.000-0.026）, but not significantly different from the chronic hepatitis group. PVPV （16.15 ± 3.82 cm/s） dropped more significantly in the chronic severe hepatitis B group than the normal control, chronic hepatitis B and compensable cirrhosis groups （P = 0.000-0.011）. PW （667.53 ± 192.83 mL/min） dropped significantly as compared with the four comparison groups （P = 0.000-0.004）. SPL （120.42 ± 18.36 mm） and SPVD （7.52 ± 1.52 mm） were longer in the normal control and chronic hepatitis B groups （P = 0.000-0.009）, yet they were significantly shorter than those in the decompensable cirrhosis group （P = 0.000）. SPW （242.51 ± 137.70 mL/min） was also lower than the decompensable cirrhosis group （P = 0.000）. The umbilical vein recanalization rate （75%） was higher than the chronic hepatitis B and compensable cirrhosis groups. In the course of progression from chronic hepatitis to decompensable cirrhosis, PVD, SPL and SPVD gradually increased and showed significant differences between every two groups （P = 0.000-0.002）. CONCLUSION： Patients with chronic severe hepatitis B have a tendency to develop acute portal hypertension, resulting in significantly reduced portal vein perfusion, Observation of the portalsystemic hemodynamic changes may be contributed to the disease progression of chronic liver disease.

Operative timing of liver transplantation for patients with severe hepatitis

BACKGROUND: Fulminant hepatic failure manifests a rapid onset, serious complications, and a high mortality, but still there is a possibility of recovery. Once the patient is able to pass a crisis, the liver is able to regenerate completely and regain its normal function. Therefore it is of vital importance to determine the eligible timing for transplantation. Premature surgery might result in a loss of the chance of internal medical treatment and misuse of liver resources, whereas delayed surgery might increase the difficulty of treatment in the preoperative period and the possibility of complications and medical expense, which eventually result in decreased rate of success and survival. This problem remains worldwide how to choose the optional timing of operation. METHODS: Thirty-six patients with severe hepatitis were treated by orthotopic liver transplantation. The distribution of MELD scores in these patients was: 10-19 in 8 patients, 20-29 in 10, 30-39 in 11, and 40 in 7. They were divided into two groups: MELD score <30 and MELD score >= 30. Parameters (1-year survival rate, complications, preoperative use of artificial liver, operative time, volume of bleeding and blood transfusion, and average hospital costs) were examined as prognostic factors after liver transplantation. RESULTS: The I-year survival rate of the MELD score <30 group was higher than that of the >= 30 group (77.8% and 33.3%, P=0.007), and the rate of complications in the <30 group was lower (P=0.012). There were no differences in the timing of artificial liver treatment, operative time, operative hemorrhage, and transfusion between the two groups (P=0.742). But the average daily hospital cost in the MELD score >= 30 group was higher (P=0.008). CONCLUSION: This study shows that when the MELD score is <30 it may be the optimal time to perform liver transplantation for patients with severe hepatitis.

Study on the relationship between interleukin-10 promoter polymorphism and the chronic severe hepatitis

The aim of this study is to investigate whether three mononucleotide polymorphisms at the locus -1082,-819 and -592 in the promoter region of the IL-10 gene are associated with chronic severe hepatitis. The IL-10-592 and IL-10-1082 polymorphisms were genotyped by polymerase chain reactionrestriction fragment length polymorphism analysis （PCR-RFLP） while polymerase chain reaction-sequence specific primer （PCR-SSP） assay was used to test the IL-10-819 polymorphism. The polymorphisms of IL-10-1082, -819 and -592 genes were detected in 98 patients with chronic severe hepatitis （CSH）, 478 patients with chronic hepatitis B （CHB）, 223 asymptomatic （chronic） HBV carriers （ASC） and 267 patients with self-restricted HBV. There was significant difference of the polymorphisms of IL-10-1082, IL-10-819 and IL-10-592 genes between CSH group and other groups. The frequency of AA genotype at IL-10 gene promoter -1082 locus in chronic severe hepatitis patients was higher than that in asymptomatic HBV carriers （2 = 13. 314, P = 0.001）, and self-restricted HBV patients （χ^2 = 13.545, P = 0.000）; the frequency of CC and AC genotype at IL-10 gene promoter -592 locus in chronic severe hepatitis patients was higher than that in chronic hepatitis patients（χ^2 = 15.970, P=0.000） （χ^2 =20.414, P=0.000）, asymptomatic HBV carriers （χ^2 =21.283, P= 0.000） （χ^2 = 28.309, P = 0.000） and self-restricted HBV patients（χ^2 = 17.047, P = 0.000） （χ^2 = 16.528, P = 0.000） ; the frequency of TC genotype at IL-10 gene promoter -819 locus in chronic severe hepatitis patients was higher than that in chronic hepatitis patients（χ^2 = 58.961, P = 0.000）, asymptomatic HBV carriers （ χ^2 = 53. 255, P = 0. 001 ） and self-restricted HBV patients （χ^2 = 39.616, P = 0.001）. So interleukine-10 gene polymorphism was associated with the chronic severe hepatitis.

Predicting the risk of mortality in children with dengue-induced hepatitis admitted to the paediatric intensive care unit

BACKGROUND Dengue-associated acute liver failure(PALF)accounts for a high mortality rate in children admitted to the pediatric intensive care unit(PICU).To date,there is a lack of data on clinical algorithms for estimating the risk of mortality in pediatric patients with dengue-induced severe hepatitis(DISH).AIM To determine the prevalence of PALF and identify the predictors of mortality among patients with DISH.METHODS This single-institution retrospective study was performed at a tertiary pediatric hospital in Vietnam between 2013 and 2022.The primary outcome was in-hospital mortality in pediatric patients with DISH,which was defined as either aspartate aminotransferase>350 IU/L or alanine aminotransferase>400 IU/L.Prognostic models for estimating the risk of death among patients with DISH were developed using a predefined set of clinical covariables and hepatic biomarkers on PICU admission and during the first 72 hours of admission.Area under the curve,multivariable logistic regression,and multiple imputation using the chained equation for missing values were performed.Backward stepwise model selection based on the Akaike information criterion was employed.Bootstrapping,calibration slope,and Brier score were used to assess the final models.RESULTS A total of 459 children with DISH were included in the analysis.The median patient age was 7.7 years(interquartile range:4.3-10.1 years).The prevalence of dengue-associated PALF in children with DISH was 18.3%.Thirty-nine DISH patients developing PALF(8.5%)died.Hepatic biomarkers,including the international normalized ratio(INR)≥2.11 and total serum bilirubin(≥1.7 mg/dL),showed high predictive values for mortality(all P values<0.001).Multivariable models showed the significant clinical predictors of death from dengue-induced PALF in patients with DISH,including reduced level of consciousness(pain and unresponsive levels on the Alert,Verbal,Pain,Unresponsive scale),high vasoactive-inotropic score(>30),and elevated levels of blood lactate,INR,and serum bilirubin.The final prognostic model demonstrated high discrimination,Brier score,and an acceptable calibration slope.CONCLUSION The prevalence of PALF in children with DISH is 18.3%.We developed robust prognostic models to estimate the risk of death in hospitalized children with severe dengue-induced hepatitis.

Changes in intestinal microflora in patients with chronic severe hepatitis

Objective To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease.Methods We classified nineteen patients with chronic severe hepatitis as the CSH group, thirty patients with chronic hepatitis (CH) as the CH group and thirty-one healthy volunteer as the control group. Fecal flora from all subjects were analyzed. Concentrations of plasma endotoxin, serum cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and liver function were assessed.Results The number of fecal bifidobacterium (P<0.001, P<0.05 respectively), as well as bacteroidaceae (P<0.001, P<0.01 respectively) were significantly deceased in patients with chronic severe hepatitis compared with the CH and control groups, while the number of enterobacteriaceae (P<0.001, P<0.05 respectively) and yeasts (P<0.01, P<0.05 respectively) were significantly increased. Levels of plasma endotoxin, serum TNF-α, IL-1β and total bilirubin (TBiL) were significantly increased in the CSH group. The concentration of endotoxin positively correlated with levels of both TNF-α, IL-1β and TBiL (P<0.001, respectively). Levels of plasma endotoxin were positively correlated with the number of fecal enterobacteriaceae and negatively correlated with bifidobacterium (P<0.05, P<0.001, respectively).Conclusion Intestinal flora in patients with chronic severe hepatitis were severely disturbed and gut mircobiological colonization resistance was impaired. Changes in intestinal flora may have a pivotal role in both the elevation of plasma endotoxin and further hepatic lesions resulting in liver failure.

Model for end-stage liver disease-sodium predicts prognosis in patients with chronic severe hepatitis B

Background Serum sodium predicts prognosis in chronic severe hepatitis B and may improve the prognostic accuracy of the model for end-stage liver disease （MELD） score, but the available information is limited. The present study was undertaken to study the clinical use of the serum sodium incorporated MELD （MELD-Na） and assess its validity by the concordance （c）-statistics in predicting the prognosis of the patient with chronic severe hepatitis B.Methods A total of 426 adult patients with a diagnosis of chronic severe hepatitis B between January 1, 2007, and December 31, 2007 at a single center were studied. The scores of serum sodium, MELD, MELD-Na, and ΔMELD-Na （ΔMELD-Na=MELD-Na at 14 days after medical treatment -MELD-Na score on admission） of the patients with chronic severe hepatitis B were calculated. The 3-month mortality in the patients was measured, and the validity of the models was determined by means of the concordance （c） statistics.Results The average MELD, MELD-Na scores of survival group were 25.70±5.08 and 26.60±6.90, and those of dead group were 35.60±6.78 and 42.80±9.57 on admission. There was a significant difference in MELD and MELD-Na between the survival and dead groups （P 〈0.01）. The average △MELD-Na score of the survival group was -0.97±3.51, and that of the dead group was 3.45±2.38 at 2 weeks after the treatment. There was a significant difference in △MELD-Na between the survival and dead groups （P 〈0.01）. The areas under the receiver-operating characteristic curves of Na, MELD and MELD-Na for the occurrence of death in 3 months were 0.742, 0.875 and 0.922. The 3-month mortality of the MELD-Na scores group 〈25, 25-30, 31-34, 35-40 and 〉40 were 2.0%, 5.4%, 35.4%, 53.8 % and 86.9%, respectively. There was a significant difference in the 3-month mortality between the five groups （P 〈0.05）. The 3-month mortality of the △MELD-Na〉0 group was 65.9%, and that of the △MELD-Na ≤0 group was 15.8%; there was a significant difference in the 3-month mortality between the two groups （P 〈0.05）.Conclusions MELD-Na score is a valid model to predict the 3-month mortality in patients with chronic severe hepatitis B. △MELD-Na is a clinically useful parameter for predicting the therapeutic effect of chronic severe hepatitis B.

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B

AIM: To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS: Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n = 28)and control group (n = 20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk,and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA.RESULTS: Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs40%, P＜0.05). After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1±4.1 vs 30.2±5.3,31.9±5.1 g/L), prealbumin (79.6±28.0 vs 106.6±54.4,108.4±55.0 g/L), cholesterol (76.3±16.7 vs 85.6±32.3,96.1±38.7 mg/dL), and IGFBP1 (56.8±47.2 vs 89.7±50.3ng/mL after 2 wk) were significantly increased compared to control group (P＜0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed.CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.

Clinical Observation on the Treatment of Chronic Severe Hepatitis B by Retention Enema with Huchang Jiedu Decoction(护肠解毒汤)

Objective： To observe the efficacy of retention enema with Huchang Jiedu Decoction （护肠解毒汤, HJD） in treating chronic severe hepatitis B （CSHB）. Methods： Sixty patients of CSHB were equally randomized into the treated group and the control group. Both groups were treated with conventional integrative medicine, but to patients in the treated group, retention enema with HJD was given in addition, once every day for 3 weeks. The dominant symptoms, physical signs, and related biochemical indices, as well as the incidence of complications in patients before and after treatment, were observed. Results： Good therapeutic effects were shown in the treated group, with a total effective rate better than that in the control group （83.3% versus 60.0%, P〈0.05）, superior in terms of lowering alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, total bilirubin （TBil）, globulin （GIb）, and endotoxin （ET） levels and increasing prothrombin activity （PTA）, total cholesterol （TC）, and calcium （Ca） levels, as well as eliminating ascites and preventing hepatic encephalopathy （P〈0.05）; especially in treating middle/early stage patients with Chinese medicine syndrome differentiated as water-toxin accumulation pattern. Conclusion： Retention enema with HJD is surely effective in treating CSHB, and its primary mechanism may be related to the mitigation of enterogenous endotoxemia.

Effect of medical ozone therapy on renal blood flow and renal function of patients with chronic severe hepatitis

Background Medical ozone therapy system was reported to have certain effects on the treatment of severe hepatitis, but its mechanism is not very clear. One of the causes of death of severe hepatitis is complication of renal damage or hepatorenal syndrome. The present study aimed to observe effects of medical ozone therapy system on plasma renin activity （PRA）, angiotensin II （All）, aldosterone （ALD）, renal blood flow and renal function of patients with chronic severe hepatitis and explore mechanisms of medical ozone therapy in the treatment of severe hepatitis. Methods Eighty-five cases with chronic severe hepatitis were randomly divided into ozone therapy group （43 cases） and control group （42 cases）. The patients in the ozone therapy group were treated with basic treatments plus ozone therapy system. Basic autohemotherapy was used. One hundred milliliter venous blood was drawn from each patient, and was mixed with 100 ml （35 pg/ml） medical ozone and then was returned the blood to the patient intravenously, once every other day for 20 days. Only the basic treatments were given to the control group. PRA, All, ALD, renal blood flow and damage to renal function of the two groups before treatment and 20 days after treatment were compared. Survival rates were also compared. Results Twenty days after the treatment, in ozone therapy group, PRA was （1.31±0.12） ng.m^-1.h^1, All （111.25±17.35） pg/ml, ALD （251.31±22.60） pg/ml, which decreased significantly compared with those before treatment （PRA （2.23±0.13） ng.ml^-1.h^-1, All （155.18±19.13） pg/ml, ALD （405.31±29.88） pg/ml, t=4.67-14.23, P 〈0.01 ）, also lower than those of control group 20 days after the treatment （PRA （2.02±0.11） ng.ml^-1.h^-1, All （162.21±15.32） pg/ml, ALD （401.20±35.02） pg/ml, t=4.97-15.61, P 〈0.01）; renal blood flow was （175.15±28.20） ml/min, which increased compared with that before the treatment （（125.68±21.25） ml/min） and was higher than that of control group 20 days after the treatment （（128.59±23.15） ml/min, t=4.78, 4.61, P 〈0.01）. Renal damage occurred in 2 cases （5%） in ozone therapy group, less than that in control group （9 cases, 21%） （X^2=5.295, P 〈0.05）. Thirty-three cases （77%） in ozone therapy group vs. 16 cases （38%） in control group survived （X^2=12.993, P 〈0.01 ）. Conclusions Basic treatment plus medical ozone therapy for patients with chronic severe hepatitis could decrease PRA, All and ALD levels significantly increase renal blood flow, prevent renal damage to certain extent and improve survival rate of the patients.

Assessment of prognosis and curative effect in patients with chronic severe hepatitis using the model for end-stage liver disease scores

Severe hepatitis is the most severe liver disease, with poor prognosis and high mortality. We explored the practical use of the model for end-stage liver disease （MELD） on clinical and the molecular adsorbents recirculating system （MARS） on chronic severe hepatitis to predict the short-term prognosis of patients with chronic severe hepatitis using the MELD score and the curative effect of MARS treatment.

Diagnosis and Clinical Management of Acute Severe Hepatitis of Unknown Origin: Operational Recommendation of Peking Union Medical College Hospital

Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022,which has exceeded the past annual incidences of related regions,and has aroused wide concern.Affected patients were predominantly children under 16years of age,presented with symptoms of acute hepatitis with markedly elevated liver enzymes,and had been ruled out of common viral infections such as hepatitis A,B,C,D,and E.Similar cases have not been reported in China yet.However,considering that the severe acute hepatitis has involved worldwide areas,still with unknown origin,and incidences of severity is relatively high,we formulated this recommendation to standardize diagnosis and treatment of acute severe hepatitis of unknown origin in Peking Union Medical College Hospital,to get fully prepared to the possible public health events.

DETECTION OF PLASMA SOLUBLE INTERLEUKIN－2 RECEPTOR IN PATIENTS WITH SEVERE AND CHRONIC ACTIVE HEPATITIS B

Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.

Lymphocyte-to-white blood cell ratio is associated with outcome in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF)remains unclear.AIM To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients.METHODS This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital.Patients were divided into survivor and non-survivor groups according to their 28-d prognosis.The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses.Patients were divided into low-and high-LWR groups according to the cutoff values.Kaplan-Meier analysis was performed according to the level of LWR.RESULTS During the 28-d follow-up time,135 patients died,and the mortality rate was 40.90%.The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients.A lower LWR level was an independent risk factor for poor 28-d outcomes(hazard ratio=0.052,95%confidence interval:0.005-0.535).The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh,model for end-stage liver disease,and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores.In addition,the 28-d mortality was higher for patients with LWR<0.11 than for those with LWR≥0.11.CONCLUSION LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBVACLF patients.

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

AIM: To study and determine the resting energy ex- penditure (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 as- sessed 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 improve- ment of liver function, the glucose oxidation rate in- creased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION: The glucose oxidation rate is signifi-cantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These re- sults warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.

Analysis of prognosis on patients with severe viral hepatitis using the model for end-stage liver disease

AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis.METHODS: One hundred and twenty-one patients were divided into plasma exchange group and non-plasma exchange group, and were graded with MELD formula.The death rate was observed within 3 mo.RESULTS: Eighty-one patients died within 3 mo (35 cases in PE group, 46 cases in non-PE group). The mortality of patients in PE group whose MELD score between 20-30and 30-40 were 31.6% and 57.7%, respectively, but in non-PE cases they were 67.6%, 81.3% respectively.There was significant difference between PE group and non-PE group (P＜0.05). However, the mortality of patients whose MELD score higher than 40 were 93.3% in PE group and 100% in non-PE group and there was no significant difference between the two groups (P= 0.65＞0.05). The optimal cut-off values of MELD to predict the prognosis of patients were 30 in PE group whose sensitivity, specificity and C-statistic were 80.0%, 52.0% and 0.777, but in non-PE group they were 25, 82.6%, 86.7% and 0.869, respectively.CONCLUSION: The MELD score can act as a disease severity index for patients with severe viral hepatitis, and the mortality of the patient increases with the increase of the MELD score. The MELD can accurately predict the short-term prognosis of patients with severe viral hepatitis.

Clinical features and risk factors of acute hepatitis E with severe jaundice

AIM:To compares the clinical features of patients infected with hepatitis E virus(HEV) with or without severe jaundice.In addition,the risk factors for HEV infection with severe jaundice were investigated.METHODS:We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group.Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum.We used χ2 analysis,Fisher's exact test,and Student's t test where appropriate in this study.Significant predictors in the univariate analysis were then included in a forward,stepwise multiple logistic regression model.RESULTS:No significant differences in symptoms,alanine aminotransferase,aspartate aminotransferase,al-kaline phosphatase,or hepatitis B virus surface antigen between the two groups were observed.HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase(GGT)(median:170.31 U/L vs 237.96 U/L,P = 0.007),significantly lower ALB levels(33.84 g/L vs 36.89 g/L,P = 0.000),significantly lower acetylcholine esterase(CHE) levels(4500.93 U/L vs 5815.28 U/L,P = 0.000) and significantly higher total bile acid(TBA) levels(275.56 μmol/L vs 147.03 μmol/L,P = 0.000) than those without severe jaundice.The median of the lowest point time tended to be lower in patients with severe jaundice(81.64% vs 96.12%,P = 0.000).HEV infected patients with severe jaundice had a significantly higher viral load(median:134 vs 112,P = 0.025) than those without severe jaundice.HEV infected patients with severe jaundice showed a trend toward longer median hospital stay(38.17 d vs 18.36 d,P = 0.073).Multivariate logistic regression indicated that there were significant differences in age,sex,viral load,GGT,albumin,TBA,CHE,prothrombin index,alcohol overconsumption,and duration of admission between patients infected with acute hepatitis E with and without severe jaundice.CONCLUSION:Acute hepatitis E patients may naturally present with severe jaundice.