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OBJECTIVES To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to

AIM Chronic drug-induced liver injury (DILI) with persistent abnormal liver function tests (LFTs) >6 months after cessation of the insulting drugs could progress to cirrhosis. The aim of the present study was to identify the risk factors of chronic DILI for early recognition and better management. METHODS History of drug intake and results of LFTs were retrospectively retrieved for patients with a discharge diagnosis of DILI for at least 1-year follow up. The risk factors independently associated with chronic DILI were analyzed by multiple logistic regression analyses. RESULTS A total of 33 of the 140 DILI patients had persistent abnormal LFTs >6 months, which were considered as chronic DILI. It was found that the time intervals of alanine aminotransferase and total bilirubin decline from the peak to their half peak (T0.5ALT , T0.5TBIL ) were significantly longer in the chronic DILI group than that in the recovered group (P = 0.001 and P

Wisteria floribunda agglutinin-positive Mac-2-binding protein (M2BP) has been identified as a predictor for the response of interferon α (IFN-α) in patients with viral hepatitis. However, whether serum glycosylation isomer of M2BP (M2BPGi) was associated with the regression of liver fibrosis in patients with chronic hepatitis B (CHB) during IFN-α add-on therapy is still unknown. CHB patients were treated with entecavir for 26 weeks followed by entecavir plus pegylated IFN-α for 52 weeks. Liver biopsies were taken at baseline and treatment week 78. The regression of fibrosis was identified according to Ishak standard or Ishak plus Progressive-Indeterminate-Regressive (P-I-R) standard. Serum M2BPGi and liver function tests were measured at baseline and every 26 weeks of treatment. A total of 72 CHB patients were included in the present study. Serum M2BPGi was correlated with fibrosis and necroinflammation both at baseline and week 78. If Ishak standard was used as the reference, only the percent change of M2BPGi at week 52 from week 26 (Δ%M2BPGi26w-52W ) was independently associated with fibrosis regression at treatment week 78, the area under the ROC curve (AUROC) of Δ%M2BPGi26w-52W for predicting fibrosis regression was 0.705. As for Ishak plus P-I-R standard, the AUROC of the predictive model for fibrosis regression (0.896*M2BPGi52W + 0.363*necroinflammation score0w + 2.051*Ishak score0w - 4.489) was 0.888. These data indicated that dynamic changes of serum M2BPGi were associated with fibrosis regression in CHB patients on IFN-α add-on therapy.

Antiviral treatment with necleos(t)ide analogues contributes to histological improvement and virologic response in chronic hepatitis B (CHB) patients. However, whether adding pegylated interferon alpha2a (Peg-IFN-α-2a) can help additional clinical benefit, particularly on fibrosis regression was still unknown. Chronic hepatitis B patients with pre-treatment biopsy-proven Ishak fibrosis score 2, 3 or 4 were randomly assigned to entecavir (ETV) alone or ETV plus Peg-IFN-α-2a (Peg-IFN-α-2a add-on) group (1:2 ratio). Post-treatment liver biopsy was performed at week 78. Fibrosis regression was defined as decrease in Ishak fibrosis score by ≥ 1 stage or predominantly regressive categorized by P–I–R score. Serum HBV DNA levels were assessed at baseline and every 26 weeks, while HBsAg and HBeAg were evaluated at baseline and every 52 weeks. A total of 218 treatment-naive CHB patients were randomly assigned to ETV alone or Peg-IFN-α-2a add-on group. Totals of 155 patients (ETV alone: Peg-IFN-α-2a add-on, 47:108) were included in statistical analysis. Fibrosis regression rates were 68% (32/47) in the ETV alone and 56% (60/108) in Peg-IFN-α-2a add-on group (p = 0.144). Both groups showed a similar trend of virological suppression during the process of 104-week antiviral therapy (p = 0.132). HBeAg or HBsAg loss or seroconversion rates in the ETV alone group were lower than Peg-IFN-α-2a add-on group though without statistical significance. Peg-IFN-α-2a add-on therapy did not yield additional fibrosis regression and virologic response than ETV alone therapy.

This case highlights a patient with Gilbert syndrome who underwent endoscopic retrograde cholangiopancreatography (ERCP) with removal of bile duct stones, who then experienced an unexplained increase in bilirubin, with total bilirubin (TBIL) levels increasing from 159.5 μmol/L to 396.2 μmol/L and to a maximum of 502.8 μmol/L after 9 d. Following the decrease in the TBIL level, enhanced magnetic resonance cholangiopancreatography (MRCP) was performed to exclude any possible remaining choledocholithiasis. Nevertheless, the serum bilirubin level increased again, with TBIL levels rising from 455.7 μmol/L to 594.8 μmol/L and a maximum level of 660.3 μmol/L with no remaining bile duct stones. A liver biopsy showed severe bile duct cholestasis with no inflammation. Based on the exclusion of other potential causes of hyperbilirubinemia and the fact that both instances of increased bilirubin occurred after ERCP and MRCP, the contrast agents iopromide and gadoterate meglumine were suspected to be the causes of the hyperbilirubinemia. As of the writing of this report, the patient's bilirubin levels have spontaneously returned to baseline levels. In summary, ERCP and MRCP utilizing the contrast agents iopromide and gadoterate meglumine may possibly induce prolonged hyperbilirubinemia.

Hepatitis B (HBV)-related fibrosis can be reversed after effective antiviral therapy. However, detailed changes of collagen characteristics during fibrosis regression remain unclear. Paired biopsy samples obtained from chronic hepatitis B patients were imaged with second harmonic generation/two photon excitation fluorescence (SHG/TPEF)-based microscopy to identify and quantify collagen features in portal, septal, and fibrillar areas. According to the changes of Ishak stage and qFibrosis score, a total of 117 patients with paired liver biopsy appeared to have four different outcomes after 78-week antiviral therapy: fast reverse (9%), reverse (63%), stable (15%), or progress (13%) on fibrosis. Among 71 collagen features identified by SHG/TPEF analysis, the most prominent fibrosis reversion occurred in the "septal" area, followed by the "fibrillar" area, but not in the "portal" area (P

Summary Background Blepharoptosis is defined as an abnormally low-lying upper eyelid margin in the primary gaze, causing vertical narrowing of the palpebral fissure. It is difficult to achieve consistently satisfactory results in moderate or severe cases despite many surgical methods being available to correct them. Methods Between January 2001 and December 2014, a retrospective cohort study was conducted using medical records and perioperative photographs of 235 patients. All the patients, having presented with moderate or severe bilateral or unilateral blepharoptosis, underwent blepharoptosis correction with the interdigitated orbicularis oculi–frontalis muscle flap suspension technique and contemporaneous double-eyelid surgery. The results, including complications, were followed up and evaluated. Results The mean age of the patients was 17.4 years (range 3–50 years). The follow-up period ranged from 6 months to 8 years, with a mean follow-up of 13 months. Long-term postoperative complications included undercorrection (3.0%), overcorrection (0.7%) and eyelid fold deformity (4.0%). No ectropion, entropion, fornix conjunctival prolapse or exposure keratitis was noted. Conclusions Blepharoptosis correction with interdigitated orbicularis oculi–frontalis muscle flap suspension is an effective technique for the management of moderate or severe blepharoptosis. The results demonstrated very low complication rates and substantial cosmetic and functional improvement using simple manipulation.

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

Background & Aims Progression of liver fibrosis still occurs in some patients with chronic hepatitis B virus (HBV) infection despite antiviral therapy. We aimed to identify risk factors for fibrosis progression in patients who received antiviral therapy. Methods We conducted a longitudinal study of patients with chronic HBV infection and liver biopsies collected before and after 78 weeks of anti-HBV therapy. Fibrosis progression was defined as Ishak stage increase ≥ 1 or as predominantly progressive classified by P-I-R system (Beijing Classification). Levels of HBV DNA and HBV RNA in blood samples were measured by real-time quantitative PCR. HBV RNA in liver tissue was detected by in situ hybridization. Results A total of 239 patients with chronic HBV infection with paired liver biopsies were included. Among the 163 patients with significant fibrosis at baseline (Ishak ≥ stage 3), fibrosis progressed in 22 patients (13%), was indeterminate in 24 patients (15%), and regressed in 117 patients (72%). Univariate and multivariate analyses revealed that independent risk factors for fibrosis progression were higher rate of detected HBV DNA at week 78 (odds ratio, 4.84; 95% CI, 1.30–17.98; P = .019) and alcohol intake (odds ratio, 23.84; 95% CI, 2.68–212.50; P = .004). HBV DNA was detected in blood samples from a significantly higher proportion of patients with fibrosis progression (50%) at week 78 than patients with fibrosis regression (19%) or indeterminate fibrosis (26%) (P = .015), despite low viremia (20–200 IU/mL) in all groups. The decrease of serum HBV RNA from baseline in the fibrosis regression group was larger than that in the fibrosis progression group. Conclusions In a longitudinal study of patients with chronic HBV infection, we associated liver fibrosis progression at week 78 of treatment with higher rates of detected HBV DNA. We propose that a low level of residual HBV may still promote fibrosis progression, and that patients’ levels of HBV DNA should be carefully monitored.

Blepharoptosis is defined as the drooping or lower displacement of the upper eyelids. Various kinds of surgical techniques and modifications have been introduced to improve the surgical outcomes, but the high recurrence rate and unsatisfying cosmetic results remain as a common problem. To solve the problem mentioned above, we came up with our new surgical technique and conducted a retrospective review to verify its effectiveness. A retrospective review was conducted among the patients diagnosed as genuine congenital blepharoptosis and receiving the surgical treatments where our unique technique was used between January 2016 and January 2019. The clinical records and preoperative and postoperative photographs were collected and evaluated. A total of 83 patients were included in our study, 78 (94%) of them acquired good surgical outcomes, while 4 (4.8%) of them got fair results, and 1 (1.2%) of them got a poor result. No long-term lagophthalmos, ectropion, entropion and fornix conjunctival prolapse were noted. Our surgical technique introduced here is effective in the management of genuine congenital blepharoptosis. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

It is unknown whether dynamic changes of liver stiffness measurement (LSM) can predict the reversibility of fibrosis. Therefore, we evaluated the utility of LSM changes in predicting histological changes of fibrosis in patients with chronic hepatitis B (CHB) on antiviral therapy. In a prospective cohort of CHB patients treated with entecavir, virological measurement and biochemical measurement along with LSM were measured at baseline and every 6 months. Liver biopsies were conducted at baseline and month 18 of treatment. Fibrosis regression was defined by the following two criteria: (a) Ishak score decrease ≥1 stage, (b) Ishak score decrease ≥1 stage or predominantly regressive by post-treatment PIR classification. The dynamic changes of LSM and its predictive value for histological reversibility were evaluated with piecewise linear mixed-effects model and ROC analysis. We found that at month 18 of antiviral therapy, liver fibrosis was reserved in 86 of 212 (40.6%) CHB patients by Ishak reversal criterion. Overall, a decline in LSM was associated with attenuation of Ishak score. The rate of LSM decline in the first 6 months was significantly faster in patients with fibrosis reversal (ΔLSM%Ishak = -2.19%/month, P = 0.0025; ΔLSM%Ishak/PIR = -2.56%/month, P = 0.0004). The predictive model based on baseline FIB-4 and Ishak score as well as baseline LSM, PLT, albumin and their changes during the first 6 months could predict histological reversal (AUROCIshak = 0.74, 95% CI: 0.67-0.80; AUROCIshak/PIR = 0.81, 95% CI: 0.74-0.87). We conclude that in CHB patients, changes in LSM during the first 6 months of entecavir therapy can predict histological reversibility of liver fibrosis at month 18 of antiviral therapy.

Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence.A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses.SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN.SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor of vascular origin. Whether HEHE in Chinese patients exhibits similar characteristics compared with Western patients is not well known. The aim of the present study was to summarize the characteristics of HEHE in Chinese patients and identify its prognostic factors. In total, six patients diagnosed with HEHE at the Beijing Friendship Hospital between 2000 and 2012 were combined with 44 previously reported cases in China, retrieved from the literature between 1989 and mid-2012. These 50 cases from China were compared with 402 patients from Western populations. Prognostic factors were identified by the χ2 test and Cox regression analysis. The male to female ratio of the Chinese patients was 1:2.1 with the mean age of 44.2 years (range, 22–86 years). The percentage of asymptomatic Chinese patients was significantly higher than in the Western patients (40.0 vs. 24.8%; P=0.026), and that of extrahepatic metastasis (16.0 vs. 36.6%; P=0.005) was significantly lower in Chinese patients. On imaging study, capsular retraction (59.5%) and calcification (26.0%), as well as positivity of CD34 (93.5%) and CD31 (80.6%), were more frequently found in the Chinese patients. Management for the Chinese patients included liver resection (LRx; 45.7%), liver transplantation (LTx; 5.7%), trans-catheter arterial chemoembolization (14.3%) and palliative treatment (34.3%). Chinese patients with larger-sized tumor nodules [relative risk (RR), 1.58; 95% confidence interval (CI), 1.032–2.422; P=0.035) and diffuse type (RR, 12.17; 95% CI, 1.595–92.979; P=0.016) exhibited unfavorable outcomes. In contrast to Western patients with HEHE, a larger number of Chinese patients were asymptomatic with less extrahepatic metastasis. In China, LRx is widely adopted rather than LTx. Chinese patients with large tumor size or diffuse type may encounter a poorer prognosis.

Purpose: To investigate the long-term histopathologic changes of the frontalis muscle flap after frontalis muscle flap suspension for severe ptosis repair. Methods: Eight 3-month miniature pigs were selected as the experimental animals, and self-comparison was used. The experimental side of the upper eyelid was constructed to have severe ptosis by resection of the levator aponeurosis, while the other side served as the control. Samples of the upper eyelid composite at 6 months and 12 months after ptosis repair were obtained and studied through light microscopy and transmission electron microscopy. Results: The histopathologic study revealed that the frontalis muscle flap kept viable with normal muscular structure and direction 6 months and 12 months after the frontalis suspension procedure. Conclusions: The frontalis muscle flap appears to be a suitable material for frontalis suspension technique because of its feasibility and histopathologic stability.

Background Autologous fat injection into the upper eyelid is a commonly used technique in plastic surgery for volume restoration. However, ptosis, as one of the potential complications of the procedure, has been less well-discussed than other complications. Objective To present five cases of ptosis after autologous fat injection for the correction of sunken eyelid deformity and explore its causes. Methods In this retrospective, non-comparative, and interventional case series, we identified five patients with ptosis. All patients had a history of previous autologous fat injection into the upper eyelid, performed by different plastic surgeons. Preoperative, intraoperative, and postoperative photographs were taken to analyze the causes of ptosis. Results Five patients developed ptosis after autologous fat injection for upper eyelid augmentation and were referred to our group for treatment. Three of the patients had received two injections of autologous fat each. Grafted fat removal with or without levator aponeurosis advancement was required in all five cases. Conclusions Ptosis can develop following autologous fat injection into the upper eyelid. Surgeons should be aware of this complication, which rarely manifests during the procedure itself. Techniques for performing autologous fat injection and knowledge of upper eyelid anatomy should be refined to avoid postprocedural ptosis. Level of Evidence 5![Graphic][1] Risk [1]: /embed/inline-graphic-1.gif

Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

Angiogenesis is considered an important pathophysiological feature of portal hypertension. We investigated the ability of angiogenesis, as CD34-positive microvessel density (MVD), to differentiate portal pressure in a CCl4-induced rat cirrhosis model.Cirrhosis was induced by intraperitoneal injection of carbon tetrachloride in 46 male adult Sprague-Dawley rats. A catheter connected to a highly sensitive pressure transducer was inserted into the portal vein to continuously record portal pressure. Fibrosis area, nodule size and MVD were assessed by image morphometry.Of 42 rats in which portal pressure was measured successfully, 27 (64%) had portal pressure ≥10 mmHg, defined as significant portal hypertension. MVD was 4.5-fold higher and fibrosis area 13.0-fold higher in rats with significant portal hypertension than in rats with portal pressure10 mmHg. Portal pressure was significantly correlated with MVD (r=0.491, p0.001) and fibrosis area (r=0.545, p0.001) in all animals, but only MVD correlated with portal pressure (r=0.731 p0.001) in rats with significant portal hypertension. The area under receiver operating characteristic curve for MVD in all rats was 0.953 (95% CI: 0.875-1.031) and optimum cutoff for MVD was 18/mm², with 96.3% sensitivity and 93.3% specificity.We found that MVD, measured by CD34 immunostaining, was better able than the fibrosis area to discriminate significant portal hypertension in rats, suggesting that MVD could be a surrogate marker for portal hypertension in patients with liver diseases.

To summarize the clinicopathological manifestations of Wilson disease(WD) so as to improve its recognition.A total of 29 WD cases were retrospectively analyzed, including clinical presentations, liver function test, serum ceruloplasmin, 24 hour urinary copper excretion, ATP7B gene analysis and liver histology. All cases were diagnosed from January 2007 to October 2012 at Third Hospital of Hebei Medical University and China-Japan Friendship Hospital.There were 18 males and 11 females with an average age of 25.9 years. The major clinical symptoms included fatigue (n = 18, 62.1%), abdominal distension (n = 4,13.8%) and pruritus (n = 4, 13.8%). The common physical signs were hepatomegaly (n = 11, 37.9%), splenomegaly(n = 15, 51.7%) and ascites (n = 4, 13.8%). The laboratory examinations included abnormal liver function (n = 29, 100%), high level of 24-hour urinary copper excretion (n = 29, 100.0%), low serum ceruloplasmin (n = 24, 82.8%) and Kayser-Fleischer ring (n = 8, 27.6%). ATP7B gene mutations were at exons 5, 8, 11, 12, 16 and 18. The earliest histologic abnormalities of liver included steatosis (both microvesicular and macrovesicular). Timm's stain showed positive or negative staining. There was no or focal hepatocellular necrosis in liver. During chronic hepatitis phase, the major changes included inflammatory cells infiltration in portal area with biliary epithelium degeneration. The periportal area hepatic cells were swollen, cytoplasm slightly stained and accompanied with some copper particles deposition and cholestic changes. There were many spotty or focal lesion of necrosis in liver. During cirrhotic phase, portal area became enlarged by fibrotic tissue, numerous copper particles deposited in wide fibrous septa and small bile ducts were damaged and became proliferative. Hepatocytes around fibrous interval showed cholestatic changes and contained many copper particles. They diagnosed on the basis of clinical presentation(n = 6), clinical presentation and liver histology (n = 4) and clinical presentation, liver histology and gene analysis (n = 19).There is a high misdiagnosis rate of WD based solely on clinical presentation. Cholestic changes around fibrous interval are common histologic features. The most common ATP7B gene mutations are compound heterozygotes in exons 16. Comprehensive evaluations of clinical presentation, liver histology and gene analysis are helpful for early diagnosis and timely treatment so that it helps to reduce the misdiagnosis and missed diagnosis rate of WD.

We aimed to present the use of extended lower trapezius myocutaneous flaps in children with scaring and contractures of the face and neck due to burns.We retrospectively reviewed the use of 12 extended trapezius myocutaneous flaps in 7 males and 4 females ranging in age from 1.5 to 7 years. An expander was embedded under the deep layer of the lower trapezius in order to ensure the integrity of the vascular network between the lower trapezius muscle and the skin. Dissection was performed at the deep layer of the supraspinous muscle where the descending branch of the transverse cervical artery passes between the deep layer of the trapezius muscle and the superficial layer of the supraspinous muscle.All surgeries were performed successfully with no intraoperative complications. The flaps ranged in size from 30 × 18 cm to 38 × 22 cm. There were no postoperative complications, except for mild tip necrosis in one case. There were no donor site complications. All patients had good functional and cosmetic outcomes.The extended lower trapezius myocutaneous flap is valuable in the management of burn reconstruction in the pediatric population.

To evaluate the clinical and histological features of patients with abnormal liver tests of unknown etiology, and then to investigate the diagnosis and differential diagnosis.Patients with abnormal liver function test hospitalized and had liver biopsies during 2008 - 2009 constituted this retrospective study cohort. After excluding those patients diagnosed with hepatotropic viral hepatitis, space occupying lesions of the liver, alcoholic liver disease and obstruction of bile duct caused by stone or malignancy and AMA/AMA-M(2) positive of primary biliary cirrhosis (PBC), the clinical and histological characteristics were evaluated.Out of the 180 patients who underwent liver biopsy, 88 patients were included in the present analysis. The final diagnosis involved 15 categories of diseases, with drug-induced liver injury (DILI) [34.09% (30/88)], autoimmune liver diseases [22.73% (20/88)], and nonalcoholic fatty liver disease (NAFLD) [12.50% (11/88)] being the most common causes, following by genetic and other rare diseases.DILI, autoimmune liver disease and NAFLD were the most common causes of abnormal liver tests in these non-viral liver diseases. Some rare diseases such as hereditary metabolic liver disease also represent a considerable proportion in patients with abnormal liver function test.

The current study shows that a clonal derivative of the Jurkat cell line up-regulates both the avidity and density of the alpha 6/beta 1 receptor in response to phorbol 12-myristate 13-acetate (PMA). This derivative attaches to fibronectin and, to a lesser degree, laminin constitutively. Adhesion and spreading are dramatically up-regulated following treatment with PMA. The response on fibronectin peaks within 4 hours, is insensitive to cyclohexamide, can be blocked by monoclonal antibodies (Mabs) to the beta 1 and alpha 5 subunits of the beta 1 family of integrins, and is not associated with increased expression of the alpha 5 or beta 1 epitopes at the cell surface. In contrast, the response on laminin is biphasic. The early phase parallels the response on fibronectin. The second phase peaks after 48-72 hours of treatment with PMA, is sensitive to cycloheximide, can be blocked by Mabs to the beta 1 and alpha 6 subunits, and is associated with increased expression of the alpha 6 epitope. Both the density independent and dependent responses to PMA in Jurkat cells are blocked by the protein kinase inhibitor staurosporine. The HSB-2, CEM, Molt-4, and HPB-ALL T-lymphoblastic cell lines also up-regulate attachment to fibronectin and laminin following treatment with PMA. All four lines constitutively attach to fibronectin and show rapid up-regulation of attachment following treatment with PMA. None of the lines attach to laminin prior to PMA treatment; however, specific adhesion developed after 4-120 hours of treatment. The most mature lines (Jurkat and HPB-ALL) up-regulated adhesion on laminin more rapidly than the less phenotypically mature lines (CEM, Molt-4, and HSB-2). In summary, clonal derivatives of the Jurkat cell line up-regulated attachment to laminin through protein kinase dependent increases in alpha 6/beta 1 receptor avidity and density. In addition, the expression of functional receptors for laminin is linked to developmental maturity in a series of T-lymphoblastic cell lines.

In China, liver failure is also termed as severe hepatitis in whom chronic severe hepatitis B (CSHB) is most common. The aim of this study was to assess whether CSHB based on different liver injury extent can meet the international definition of acute-on-chronic liver failure(ACLF)criteria, according by their clinical and pathological feature.A total of 91 patients with CSHB were involved in the study. The clinical findings, laboratory data and liver pathology features were retrospectively analyzed and grouped by hepatitis virus B carrier state (HBC), chronic hepatitis B (CHB) or liver cirrhosis (LC) before they started liver failure.74 out of the 91 patients were male and 17 were female, the mean age was 40.6+/-11.2 years. 9.9%, 7.7% and 82.4% of the patients were based on HBC, CHB and LC respectively. The ages of HBC group were youngest. The mean age of HBC group (years) (25.8+/-6.6) was significantly lower than that of CHB group (36.9+/-9.0) and LC group (42.0+/-10.5)with P values of 0.032 and 0.001 respectively. Most cases presented with sub-acute liver failure characterized by high icterus and ascites. Predisposing factors included exertion, superinfection, virus variation, drugs or alcoholic injury. No difference found between PTA (F = 0.906, P = 0.408) and TBil (F = 0.839, P = 0.436) among the above three groups. The Alb and CHE levels in LC group were (30.3+/-5.1) g/L and (2926.8+/-1471.1) U/L respectively, which were lower than both HBC group [Alb (35.6+/-5.1) g/L, CHE (4363.5+/-2063.2) U/L] and CHB group [Alb (37.4+/-5.0) g/L, CHE (5167.1+/-1522.1) U/L] (F = 9.450; F = 9.297; P value less than 0.01).The level of CHO (1.8+/-1.0) mmol/L in LC group was lower than that of HBC group (2.9+/-1.0mmol/L, P = 0.034), while serum HBV DNA level of HBC group [(6.8+/-1.7) log10copies/ml] was higher than that of LC group [(4.2+/-2.6) log10copies/ml]. The liver tissue in HBC and CHB group showed massive or submassive necrosis which distribute evenly in different parts of liver and similarly in slides, most like acute/subacute severe hepatitis. The chronic lesion was easily covered by extensive necrosis in CSHB based on CHB, with portal fibrosis can be seen by masson stain. Characteristic picture of LC group were massive or submassive necrosis with some nodules were intact or only patchy necrosis of the parenchyma, disparity of extent and stage of necrosis existed in slides, which were the major difference in histopathological change in HBC and CHB group.Most of CSHB cases were based on liver cirrhosis, which match with the international definition of ACLF, while small part of CSHB cases based on HBC and CHB are identical to acute/subacute liver failure.

To elucidate clinical and pathological features of primary sclerosing cholangitis (PSC) in order to improve clinician's awareness of this rare disease.We retrospectively analyzed clinical data and follow-up information of 27 PSC patients who were admitted to Beijing Friendship Hospital from January 1990 to November 2009. The patients were classified into classic PSC and small-duct PSC according to biochemistry and imaging results. After 3 to 6 months of therapy, those patients with serum ALTor = 1.5, TBilor = 2 and ALPor = 2.5 ULN were determined as good responders. The treatment results between the two groups were compared.9 out of 27 cases of PSC were small duct PSC and 18 cases were large bile duct or classic PSC. Male patients (7) were less than females (20) and the average age was 47.6 years. Main clinical symptoms included jaundice (85.2%), pruritis (48.1%),fatigue (68.4 %), abdominal pain (40.7%) and fever (14.8%), main physical sign included hepatomegaly (44.4%), splenomegaly (48.1 %) and ascites (14.8%). Laboratory features included elevated IgG (81.8%), positive ANA (69.6%) and pANCA (52.9%). 22% of these PSC patients had ulcerative colitis or Sjogren's syndrome. A small percentage of patients were responsive to standard therapy, of which small duct PSC had a better response than classic PSC (66.7 % vs 33.3%, P = 0.041).Ulcerative colitis (22.2%) is not as common as reported by western countries. Small duct PSC has a better treatment response. Searching of effective treatment regimen for large bile duct PSC is warranted in future studies.

To investigate characteristics and outcomes of drug induced chronic liver injury after removing causative drugs.Between Apr 2001 and Mar 2010, patients diagnosed as drug induced liver injury and with chronic courses, were observed. Chronic liver injury was defined as persistent biochemical abnormality for more than 6 months after drugs withdrawal.Forty patients were observed with mean age 41 years and female 28 (70%). Of the 40 patients, 32 (80%) cases showed hepatocellular injury at the onset of liver damage, 4 (10%) cases showed cholestatic injury, and 4 (10%) cases showed mixed injury. Of 32 patients with hepatocellular injury, 24 (75%) cases resemble acute icteric hepatitis at the onset of liver damage. Of 27 patients with hepatocellular injury who underwent liver biopsy, 14 (51.9%) cases showed chronic hepatitis with a mean follow up of 17 months. Of total 40 patients, 15 (37.5%) patients resolved; 18 (45%) cases remained persistent liver injury, 4 (10%) cases developed cirrhosis, 3 (7.5%) cases died. Herbs (45.5%) are the commonest drugs implicated in chronic liver injury.Most cases with drug induced chronic liver injury after removing causative drugs resemble acute icteric hepatitis at the onset of liver damage. Some patients can resolve, some may progress to cirrhosis. Herbs are important drugs for drug induced chronic liver injury.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. Because small HCCs possess most of the characteristics of early HCC, we investigated small HCCs to screen potential biomarkers for early diagnosis.Proteins were extracted from 10 sets of paired tissue samples from HBV-infected small-HCC patients. The extracted proteins were well resolved by two-dimensional electrophoresis. These HCC-associated proteins were then identified by MALDI-TOF/TOF MS following image analysis. Western blotting and immunohistochemistry were used to assess glutamine synthetase (GS) and phenazine biosynthesis-like domain-containing protein (PBLD) expression in liver tissue. Enzyme-linked immunosorbent assays in 152 serum samples (from 49 healthy donors, 24 patients with liver cirrhosis, and 79 with HCC) were used to further assess the significance of GS clinically.Fifteen up-regulated and three down-regulated proteins were identified. Western blotting confirmed GS overexpression and decreased PBLD expression in liver tissue. Immunohistochemistry showed that GS was expressed in 70.0% (84/120) of HCCs and 35.8% (43/120) of nontumor tissues; PBLD was expressed in 74.2% (89/120) of nontumor tissues and 40.8% (49/120) of HCCs. The Chi-square test showed significant expression differences between HCCs and adjacent tissues. Consistent with this, serum GS levels in HCC patients were significantly higher than those in liver cirrhosis patients and healthy donors, while the latter two groups were also significantly different. In addition, a diagnostic cutoff value of 2.6 mg/ml was used for GS; it was elevated in 19 (76.0%) of 25 HCC patients with AFPor=20 ng/ml and 47 (88.7%) of 53 HCC patients with AFPor=200 ng/ml.GS and PBLD are abnormally expressed in most HCCs. GS may be a novel serum marker for early HCC, especially for those patients with low AFP levels (or=200 ng/ml).

Bulbous nasal tips and lower dorsa are common facial features in Chinese people, and surgery to reshape these is frequently requested. The use of silicone implants in rhinoplasty has been widely used in China for many years, but is not suitable for patients seeking Caucasian tip shapes. The creation of an excessively high tip supported only by a silicone implant inevitably leads to implant extrusion. Although many rhinoplasty techniques have been used in Caucasian patients, there is currently no suitable method for Chinese patients, whose anatomy differs from that of Caucasians. The present study was aimed to investigate the clinical outcome of a novel method of rhinoplasty in Chinese people.Eighty patients underwent rhinoplasty using our method between 2002 and 2006. We classified the patients into three types, according to the distance between tip defining points, and used different techniques accordingly. Furthermore, an innovative cartilage carving method and a tip fibro-fatty tissue flap were designed and combined with traditional techniques, such as insertion of silicone implant, cartilage grafts, suture techniques and cephalic trimming to reshape the nasal contours. The followup period was 10 - 60 months (average, 21 months).Remarkable modifications in nasal contours were achieved. No complications developed in any of the 80 patients. Seventy-eight patients were satisfied with the results. The outcomes remained unchanged over time.Our method is effective and suitable for the treatment of Chinese patients with lower dorsa and bulbous nasal tips.

To summarize the clinical and pathological features of Gilbert syndrome.The clinical features and liver histological findings of 16 cases of Gilbert syndrome were reviewed.Of the 16 cases (13 males and 3 females, with an age range from 14 to 40 years), all had recurrent jaundice, unconjugated hyperbilirubinemia and lipofuscin granules in the hepatocytes around the hepatic perivenular areas. The genetic analysis of the two patients showed that the site of genetic mutations were located at exon 1 (Gly71Arg).The diagnosis of Gilbert disease can be improved by combining the data of clinical features, the genetic analysis findings and the histological changes of the livers of the patients.

Hepatic injury is rarely associated with undifferentiated connective tissue diseases (UCTD). We report, here, a case of a middle-aged woman with UCTD-related hepatic injury, including its case history, clinical manifestations, laboratory findings, treatment and its short-term effect. The patient was admitted to the hospital with symptoms of fatigue, anorexia, low-grade fever and skin rashes. She had a past history of left knee joint replacement. Laboratory tests showed elevated levels of serum transaminase, IgG and globulin, accelerated erythrocyte sedimentation rate, eosinophilia and a high titer of antinuclear antibodies (1:320). Imaging studies showed interstitial pneumonitis and hydropericardium. Liver biopsy showed the features which were consistent with those of connective tissue diseases-related polyangitis. After treatment with a low-dose of oral prednisone, both symptoms and laboratory findings were significantly improved. UCTD-related hepatic injury should be considered in the differential diagnosis of connective tissue diseases with abnormal liver function tests. Low-dose prednisone may effectively improve both symptoms and laboratory tests.

To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment.Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure.We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.

To analyze the histopathological and clinical features of viral chronic hepatitis patients with negative serological viral markers.62 hepatitis patients with negative serological markers were assayed with serological viral hepatitis markers, liver function test and liver biopsies were enrolled in the study. Serum HBV DNA of HBV cases was analyzed by PCR. Liver specimens were examined by immunohistochemistry for HBsAg and HBcAg.The fit rate of histopathological diagnosis with clinical diagnosis is 53.2%, the fit rate is 69.1% in moderate chronic hepatitis group. The immunohistochemistry showed that HBsAg and/or HBeAg positive rate was 45.2%, 53.6% had moderate chronic hepatitis and 25% had mild hepatitis. 13 (46.4%) had G1 hepatitis, 10 (35.7%) had G2 hepatitis, 3 (10.8%) had G3 hepatitis and 2 (7.1%) had G4 hepatitis, and serum HBV DNA positive rate was 35.7%. There were no differences in HBV DNA levels between different hepatitis group and fibrosis stage group (P0.05). There were no differences in all indexes between HBV DNA negative group and HBV DNA positive group (P0.05). There were no differences in all indexes between HBV patients and other patients (P0.05).Occult HBV infection may account for a high proportion of the cases with chronic hepatitis of unknown etiology. Most patients are chronic mild hepatitis, but they still have HBV replication and can progress to liver cirrhosis. Serum PCR test, liver biopsy and immunohistochemistry are helpful for the diagnosis.

To analyze the frequency and the clinical and virological features of HBeAg-negative and HBeAg-positive chronic hepatitis B.Four hundred and seventeen chronic hepatitis B patients, 286 males and 131 females seen in our center were studied. Liver biopsies were taken from 83 patients.The cases with HBeAg-negative chronic hepatitis B were 241 (57.8%), with an average age of 43.7+/-10.8 and a history of 16.8+/-8.5 years. HBeAg-positive chronic hepatitis B cases were 176 (42.2%), with an average age of 36.95+/-11 and a history of 12.3+/-8.0 years. HBeAg-negative patients were significantly older (P0.01) in age and had a longer disease history. ALT levels and the percentage of HBV DNA were higher than 10(5) copies/ml in HBeAg-negative patients and were significantly lower than those in the HBeAg-positive patients [(37.66+/-32.93) U/L vs. (82.09+/-107.57) U/L, 38.2% vs. 94.3%, P0.01]. Liver biopsies from 47 HBeAg-negative patients showed that the number of cases with inflammation scores of G1, G2, G3 and G4 were 5, 27, 14, 1 and the number of cases with fibrosis scores of S1, S2, S3 and S4 were 10, 12, 5, 20, respectively. In the 36 HBeAg-negative patients the respective number of cases with inflammation scores of G1, G2, G3 and G4 were 5, 14, 15, 2, and with fibrosis scores of S1, S2, S3, S4 were 8, 12, 6, 10. Although histopathological inflammation and fibrosis scores had no statistical difference between HBeAg-negative and positive patients (P0.05), 53.2% patients of HBeAg-negative group and 44.5% patients of HBeAg-positive group had a fibrosis score ofor= S3.Despite lower serum ALT and HBV DNA, HBeAg-negative chronic hepatitis B still has a significant disease progression. This observation may help to develop better clinical management in HBeAg-negative chronic hepatitis B patients.

To study the histopathological changes of livers in idiopathic portal hypertension (IPH).Liver specimens from 29 cases with idiopathic portal hypertension were studied. Histological preparations of the livers were stained with haematoxylin eosin and Masson's trichrome; reticular fibers in the liver tissues were demonstrated. The slides were also stained using some immunohistochemistry methods, and the pathological changes of the livers were analyzed.The characteristic changes found in these IPH livers were dense portal fibrosis; obliteration, with or without phlebitis, of the branches of the portal vein; dilatation of the sinusoids; atrophy and nodular hyperplasia of liver cells.Histopathological changes of the livers in IPH are dense portal fibrosis, portal vein branch obliteration and nodular hyperplasia of liver cells. These are the main features for a histopathological diagnosis of IPH.

To investigate the histopathological features in livers of chronic severe hepatitis B (CSHB) patients.Histology of 42 livers was studied. HE, Masson, Sweet and D-PAS staining and cytokeratin 7, CD68 and proliferating cell nuclear antigen immuno-histochemical staining were used in the study.In CSHB, the livers showed massive or submassive necrosis in a background of other histological changes of chronic hepatitis B. The characteristic pictures of these livers were necrosis of all the hepatocytes in some nodules, while in other nodules there were only patchy necroses of the parenchyma. In some other nodules the necrotic hepatocytes were all removed and only the scaffolding stroma remained. Meanwhile, regeneration of hepatocytes and bile ductules were also seen.The liver histopathological changes in CSHB are identical, but not of the same degree as those of acute severe and subacute severe hepatitis B. In making differential diagnoses for liver aspiration biopsies of these patients, this fact should be kept in mind.

To discuss the diagnostic value of an ultrasonic assessing system for detecting the severity of hepatic fibrosis in patients with chronic hepatitis B (CHB).Ultrasonographic variables were analyzed in 110 CHB patients. An ultrasonic semi-quantitative scoring system using seven ultrasonic morphologic parameters, a Fisher discriminating function and three quantitative ultrasonic parameters was developed. The performance of these methods was also studied and compared.The areas under the curve of the scoring system for different liver fibrosis stages wereor= S2: 0.946,or= S3: 0.914, and S4: 0.915. The total score was well correlated with the histological stage of fibrosis (r=0.824, P0.001). There was a significant difference between the stages of fibrosis. The accuracy of the Fisher discriminating function for identifying three study endpoints was 76.5%, 78.2% and 67.3%. Combining the ultrasonic scoring system and the discriminating function, the specificity was 85%-90% and the accuracy was 77%-84%.Our ultrasonic semi-quantitative scoring system is a noninvasive method for quantitating liver fibrosis. If it is used together with a discriminating function, the accuracy of diagnosing liver fibrosis can be significantly increased.

To investigate the antifibrotic effects of silymarin on hepatic fibrosis.Sixty-one male Wistar rats were randomly divided into three groups: control group (15 rats); DMN model group (23 rats), injected intraperitoneally with dimethylnitrosamine (DMN) 10 mg/kg twice per week for 8 weeks to induce hepatic fibrosis; and silymarin group (23 rats), injected intraperitoneally with DMN and given silymarin 50 mg/kg by gastric gavage daily for 8 weeks. Eight weeks late all rats were sacrificed. Blood samples were collected to measure the alanine transaminase (ALT), aspirate aminotransferase (AST), albumin, and total bilirubin (TBIL). The hydroxyproline (Hyp) content in the liver tissue was measured. The histopathological changes as well as the fibrosis stages and score were examined by microscopy.The levels of ALT, AST, and TBIL of the silymarin groups were 59 U/L +/- 19 U/L, 159 U/L +/- 39 U/L, and mean rank 24 respectively, all significantly lower than those of the DMN model group (128 U/L +/- 25 U/L, 246 U/L +/- 61 U/L, and mean rank 37 respectively, P0.01, P = 0.001, and P = 0.003). Compared with DMN rats, the level of Hyp of the silymarin was lower by 42.6%, the hepatic score of the silymarin was 6.2 +/- 2.4, significantly than that of the DMN model group (12.8 +/- 4.4, P = 0.001), and more cases in the silymarin group were at the lower stages.Silymarin markedly inhibits and reverse the progression of hepatic fibrosis induced by dimethylnitrosamine.

To investigate the malignant tendency of liver basophilic cells in rats by examining the liver dynamic pathological changes during the hepatocarcinogenesis induced by diethylnitrosamine (DEN).One hundred forty male Sprague-Dawley rats, about 200 g each, were randomly divided into a normal group and a model group. The model group rats were administered 1% DEN intragastrically once a week for 14 weeks. The normal control group rats were given saline instead of DEN. Seven to ten rats of the model group were sacrificed at 2, 3, 5, 8, 10, 12, 14, 18 weeks. The remaining rats were followed to the end of the experiment at 26 weeks. Histopathological changes of the livers were analyzed, and the localization of GST-P and PCNA in the livers were detected in situ by immunohistochemistry.According to the characteristics of the lesions in the model group, histological liver change patterns were categorized into three phases: (1) liver injury phase (2 to 5 weeks) with centrilobular necrosis, a small amount of collagen deposition in the necrotic regions with fibrous septa development and cell proliferation; (2) the cirrhosis phase (8 to 12 weeks) with significant hepatocellular regeneration and collagen deposition. As the regenerative nodules and fibrous septa formed, cirrhosis with uniform sized nodules developed in all the rats at 12 weeks. In the regenerative nodules, significant hepatocellular metamorphosis was seen; (3) In the carcinomatous transformation and nodular remodeling phase (after 14 weeks), two types of cancer, namely hepatocellular carcinoma and cholangiocarcinoma were found. Incidence of the cancer was 62.5% at 18 weeks. Basophilic cell lesions appeared beginning at 10 weeks. Pale bodies were seen in some basophilic cells. Small cell changes appeared starting at 12 weeks. Some of these cells containing droplets like lipid vacuoles, invaded into the surrounding liver tissues. Both basophilic cell lesions and small cell changes were all positive for proliferating cell nuclear antigen (PCNA).Development of foci of basophilic small cells, with cells containing lipid vacuoles and pale bodies, and invading into the surrounding liver tissues are the changes highly suggestive of an early hepatocellular carcinoma transformation.

Adhesive or too highly located folds upper eyelid and even blepharoptosis are common complications of double eyelid operation. To correct such deformities.We shifted down the double eyelid line, removed adhesion thoroughly, relieved orbital fat and restarted the volume with infraorbicularis oculi fat flap.We had treated 32 case in past two years. The results were satisfying.The method are acted easy and gained fine result, so behaving to extend application.

To compare the capability in predicting the prognosis of chronic severe hepatitis among 3 prediction systems: Model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP) system, and King's College Hospital (KCP) system, and to explore the capability of MELD in predicting the curative effect of artificial liver.Scoring was made among 66 patients of chronic severe liver diseases with the underlying disease of hepatitis B, 11 in early stage, 14 in middle stage, 15 in late stage, and 26 unclassified, by MELD, CTP, and KCP systems. The accuracy of each system was evaluated by ROC curve, the differences between the systems was analyzed by Kaplan-Meier survival curve.The MELD score of the patients at admission predicted the mortality within 3 months with the c-statistic of 0.894, higher than those of the CTP and KCP systems (0.703 and 0.89 respectively). The MELD scores of the patients in the early stage was 24 +/- 4, significantly lower than those in the middle and late stages (31.11 +/- 2.90 and 41.38 +/- 9.98 respectively, all P0.01). The MELD score was positively correlated with the stage of disease (r = 0.737, P0.01). The mortally was 10.7% for the patients with an admission MELD scoreor = 30, was 47% for the patients with an admission MELD score of 31 approximately 39, and was 60% the patients with an admission MELD score ofor = 40.The predictive capability of MELD system is better than the KCP and CTP systems. Artificial liver support treatment is the best choice e for the patients with an admission MELD score of 31-39. An admission MELD score40 is the indication for liver transplantation.