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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

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.

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.

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.

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.

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.

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.

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 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 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 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.

U937 cells have low levels of surface thrombospondin (TSP) under control conditions but express higher levels after treatment for 1 day with 100 nM phorbol myristate acetate (PMA). Increased surface expression is due, in part, to increased biosynthesis. Untreated U937 cells do not adhere to TSP-coated plastic culture dishes but adhere strongly to TSP after stimulation with PMA. Untreated U937 cells also adhere weakly to endothelial cell monolayers while PMA-treated U937 cells attach strongly to monolayers of rat pulmonary artery endothelial cells. Endothelial cell adhesion appears to be mediated, in part, by TSP since antibodies to TSP partially inhibit.