Huh7.5.1 cells, a human hepatocyte cell line that supports replication of HCV in vitro, were a gift from Apath (Brooklyn,

NY). Huh7.5.1 cells were grown in RPMI 1640 medium (Invitrogen, Carlsbad, CA) supplemented with 10% fetal bovine serum (FBS), L-glutamine, penicillin, and streptomycin. Cryopreserved primary human hepatocytes (PHHs) from six individual donors were purchased from ZenBio (Research Triangle Park, NC) and used in the current study. Peripheral blood was collected in BD Vacutainer tubes selleck products (containing 143 USP units of sodium

heparin per 10-mL tube, BD, Franklin Lakes, NJ) from patients chronically infected with HCV or from healthy donors. Plasma was separated from blood cells by centrifugation and then stored at −80°C until use. Plasma HCV viral loads were measured using the COBAS TaqMan HCV Test (Roche, Pleasanton, CA) in a certified clinical laboratory. Anti-HCV E2 Abs in these plasma samples were titrated by an enzyme-linked immunosorbent assay (ELISA) assay modified from a previous report19 (and Supporting Material). LY2606368 clinical trial Informed consent was obtained from each participant and all investigational protocols were approved by Institutional Review Boards for Human Research at the Indiana University School of Medicine (Indianapolis, IN). JFH-1, a unique HCV genotype 2a replicon derived from a viral isolate of a patient with

fulminant HCV, was a gift from Apath (Brooklyn, NY). JFH-1 was inoculated into Huh7.5.1 cells at a multiplicity of infection (MOI) of 1. On day 5 of incubation cell-free supernatants were collected by selleck chemicals a centrifugation at 15,000 rpm at 4°C for 10 minutes and then filtered through a 0.2-μm-pore-size filter, followed by virus purification using 20% versus 60% two-layer sucrose gradient ultracentrifugation as described.12 Four fractions collected by aspiration from the top were subjected to: (1) ELISA for measuring HCV core concentration, (2) real-time quantitative reverse-transcription polymerase chain reaction (qPCR) for measuring viral RNA copies, and (3) western blot for measuring CD59. Fraction 3 was also subjected to HCV capture.

99 In clinical studies, unlike controls, migraineurs exhibited a connection between light perception and trigeminal nociception. Boulloche and collaborators100 used PET between attacks to study the way migraineurs’ cortex responds to luminous

stimuli at 3 luminance intensities, each with and without concomitant trigeminal pain stimulation. The stimulation started 30 seconds before PET acquisitions in order to facilitate habituation. In migraine patients (but not in controls), when no concomitant pain stimulation was applied, check details luminous stimuli activated the visual cortex bilaterally (specifically the cuneus, lingual gyrus, and posterior cingulate cortex). Imaging techniques reveal additional functional changes in other brain regions of the migraineur’s brain. Compared with healthy

volunteers, migraine patients had a larger relative activation of the contralateral primary sensorimotor cortex after a simple motor task and a rostral displacement of the supplementary motor area.101 Interestingly, the extent of the supplementary motor area displacement correlated with the degree of subcortical brain damage detected by DTI. Compared with patients afflicted with low-frequency attacks of episodic migraine, responses to pain in www.selleckchem.com/products/ch5424802.html high-frequency migraine sufferers were significantly lower in the caudate, putamen, and pallidum.102 Surprisingly, grey matter volume of the right and left caudate nuclei appeared significantly larger than that of low-frequency patients. These findings indicate that the basal ganglia plays a significant role in the pathophysiology of the episodic migraine. Recently, Maleki and collaborators103 compared selleck kinase inhibitor structural and functional cortical measures in migraineurs who experienced increased frequency of attacks (high frequency [HF]; 8-14 days/month) with those who experienced less frequent migraine attacks (low frequency [LF]; <2 days/month) and with HCs. Patients with HF

attacks showed higher thickness in the area representing the face in the postcentral gyrus, which correlated with the observed stronger functional activation, suggesting adaptation to repeated sensory drive. A reduced cortical volume was observed in the cingulate cortex of this group, in keeping with lower activation. Similarly, significant structural and functional differences (HF > LF) were observed in the insula, potentially reflecting alterations in affective processing. These results point to differential response patterns in the sensory vs affective processing regions in the brain that may indicate an adaptive response to repeated migraine attacks. The brainstem contains descending circuitry that modulates nociceptive processing in the dorsal horn of the spinal cord medulla.

5). In contrast to db/db mice, in db/m mice only TNF-α increased significantly with MCD feeding. However, TNF-α mRNA levels increased 14-fold in db/db mice fed the MCD diet compared to only a 2-fold increase in db/m mice. Furthermore, ICAM-1 and MCP-1 also increased to a greater extent in db/db mice; 5- and 8.5-fold in db/db mice compared to 2- and 3-fold in db/m mice, respectively (P < 0.05). Although

ICAM protein expression did increase more dramatically after MCD feeding in db/db compared to db/m mice, protein expression in db/db mice did not exceed that of db/m mice on the MCD diet. On densitometric analysis the effect of the MCD diet was only significant in db/db mice (Table 1). Db/m mice fed the MCD diet had a >50% reduction in SAM levels compared to control Natural Product Library cost diet fed animals (P < 0.01). In contrast, the MCD diet had selleck chemicals no significant effect on SAM levels, suggesting that SAM depletion may not play as prominent a role in the development of steatohepatitis or UPR activation of the UPR in db/db mice. There were no significant differences in hepatic SAH levels or SAM/SAH ratio between the groups

(Table S2). Others have demonstrated that JNK1 knockout mice are resistant to MCD-induced steatohepatitis.26 Although complete JNK inhibition in humans may not be advisable, partial inhibition with a pharmacologic inhibitor may be of benefit for the treatment NASH. We performed an experiment to assess the effect of partial JNK inhibition on MCD-induced steatohepatitis. The wildtype strain C57BLKS/J was used instead of the db/db or db/m strain in an attempt to more directly ascertain the effect of JNK inhibition learn more independent of diabetes or defective leptin signaling. Preliminary experiments in wildtype mice documented the presence of steatohepatitis after 2 weeks of MCD feeding. Therefore, MCD and control diet-fed C57BLKS/J mice were treated with SP 600125, a specific pharmacologic JNK inhibitor, for 2 weeks to assess the drug’s ability to attenuate the development of MCD induced liver injury. SP600125 decreased both JNK2/3 and JNK1

protein levels (Fig. 6). As expected, mice fed the MCD diet developed steatohepatitis; however, the severity was not affected by SP600125 did not improve histology in mice fed MCD diet. Serum ALT and hepatic triglyceride content were unchanged in MCD-fed mice treated with SP 600125, compared to MCD-fed mice given vehicle (Table 2A). Although SP 600125 failed to have a biochemical or histological effect, it did significantly reduce downstream inflammatory mediators (MCP-1, TNFα, ICAM, and iNOS). Its effects on UPR activation were less clear, and appeared to be more selective. A significant reduction in mRNA levels was appreciated for CHOP; however, there was no effect on EDEM mRNA levels (Table 2B).

Post EUS/FNA diagnosis showed pseudocyst (46.8%), serous cystadenoma (16.2%), intraductal papillary neoplasm (9%), mucinous cystadenoma (12.6%), neuroendocrine tumour (3.6%), solid pseudopapillary tumour (0.9%) and cystic ductal adenocarcinoma (8.1%). EUS/FNA changed the diagnosis and management in 33.3% (37/111) of the patients. Seventeen patients (45.9%) who were initially diagnosed with benign cyst on imaging had diagnosis changed to malignant/ premalignant

cysts. Only 10 patients underwent surgical resection, 9/10 had malignancy on resection histology. Of the 7 who did not undergo surgery, 4 had metastasis, 2 had premalignant cyst and 1 declined surgery. Twenty (54%) patients who were initially diagnosed with a malignant lesion did not require surgery after EUS/FNA changed the diagnosis. Of these 20, none develop malignant lesion after 6 months of surveillance. The sensitivity and specificity of EUS/FNA and imaging to click here accurately determine the nature of pancreatic cyst are 75% and 81.1% vs. 25% and 68.4% respectively (P value <0.05). Conclusion: EUS/FNA has valuable role in the management of pancreatic cyst. It is more accurate than imaging alone and can correctly stratify which patients should undergo resection. Key Word(s): 1. Pancreatic cyst; 2. EUS; 3. Imaging; Presenting Author: XIAOYONG WANG Additional Authors: LENING XUE Corresponding

Author: XIAOYONG WANG Affiliations: Changzhou No. 2 Hospital, Affiliated with Nanjing Medical University Objective: Recently, several studies have evaluated the association between hepatitis B virus selleck products (HBV) infection and pancreatic cancer risk; however, results have been inconsistent. The goal of this study was to perform a meta-analysis of the published data to evaluate this association. Methods: A search of relevant studies published up to May 2012 was performed. After reviewing each study, extracting data, and evaluating heterogeneity and publication bias, a meta-analysis was performed to evaluate the association of HBV infection and pancreatic cancer risk.

Subgroup analyses were carried out according to the original studies’ designs and separate meta-analyses were performed. Pooled odds ratios (ORs) with 95% confidence intervals selleck kinase inhibitor (CIs) were calculated using the fixed- or random-effect models. Results: Nine studies, encompassing seven case-control and two cohort studies, were analyzed. Overall, there was an association between hepatitis B surface antigen (HBsAg) -positive carrier state and a higher risk of pancreatic cancer (OR = 1.24, 95% CI: 1.08 to 1.43). Among the case-control studies, the HBsAg carrier state (HBsAg-positive: OR = 1.24, 95% CI: 1.06 to 1.46) and past exposure to HBV without evidence of HBV recovery (HBsAg-negative/anti-HBc-positive/anti-HBs-negative: OR = 1.76, 95% CI: 1.29 to 2.39) were significantly associated with pancreatic cancer risk.

Even a single 24-h FVIII level provided adequate

data for initial dose tailoring and gave predictions of FVIII levels 5–17 months later that were not appreciably worse than predictions based on the full PK analysis. By contrast, dose tailoring buy Ibrutinib based on body weight failed completely. In conclusion, PK-based dose tailoring of FVIII can be performed using limited blood sampling during prophylactic treatment. “
“Summary.  On-demand therapy with recombinant activated factor VII (rFVIIa) can provide effective haemostasis for spontaneous bleeds in haemophilia patients with inhibitors. However, treatment approaches vary amongst physicians, positively or negatively affecting outcomes. A panel of physicians proposed recommendations for securing and maintaining predictable efficacy with rFVIIa, comparing Nutlin-3a mouse these with ‘real-life’ patient management, using a questionnaire circulated to other expert physicians from haemophilia care centres in Europe and the United States. For rFVIIa treatment of spontaneous bleeds in inhibitor patients, early intervention with the highest appropriate dose is recommended. Home-based therapy can facilitate early intervention. If additional rFVIIa therapy is required after the initial dose, rFVIIa 90 μg kg−1 may be administered

at 2–3 h intervals. Treatment should be tailored to bleed site/severity, recognizing the advantages of appropriate adjunct therapy. Questionnaire selleck compound results suggested that many respondents adopted strategies in line with the recommendations. Most (36/46) recommended initial therapy within 1 h of bleed onset. rFVIIa 270 μg kg−1 was the most frequently prescribed/recommended initial dose for paediatric (aged ≤15 years; 22/44 respondents) and adult (aged >15 years; 23/44 respondents) patients. However, there may be opportunity for improved bleed management on occasion, with regard, for instance, to dosing and dose interval. To secure and maintain predictable efficacy with rFVIIa, judicious dose selection

and treatment timing are important, together with adjunct therapy where necessary. As inhibitor patients present with different bleeding scenarios, a tailored treatment approach should be adopted. “
“Summary.  Long used in established industrialized nations to treat patients with haemophilia and inhibitors, factor eight inhibitor bypassing activity (FEIBA) has, in recent years, been introduced into more geographically diverse settings. Data are needed on how successfully FEIBA therapy has been implemented in new regions. To determine the efficacy and safety of FEIBA for the treatment of acute bleeding and surgical haemostasis in a newly industrialized country. A multicentre registry of haemophilia A patients with inhibitors receiving FEIBA treatment was established in Turkey.

e., two to three cases per year).33, 34, 36, 183, 184 These single-center reports all derive from transplant affiliated programs, so one must assume a bias toward more severe cases. This is especially relevant when considering issues related to prognosis. Development of an evidence based approach to the diagnosis and management of PSC in children is especially problematic given this relatively limited published data and an absence of controlled therapeutic trials.

Thus pediatric hepatologists are reliant on data derived from experiences with adult patients, although caution must be exercised in application of these approaches. An urgent need exists for prospective multi-centered studies of PSC in children. A number of lines of evidence suggest that PSC in children is different and not just an earlier stage in the disease process. Firstly, selleckchem some inherited diseases and immunologic defects may produce a clinical picture like PSC. These entities usually present clinically during childhood and may have an expanded spectrum of disease, which includes milder variants that when unrecognized are labeled as PSC. For example, mild to moderate defects in the ABCB4 (MDR3) gene are a likely cause of a number of cases of small duct PSC in children.185, 186 selleck screening library Secondly, overlap syndrome of autoimmune hepatitis and PSC appears to

be significantly more common in children. In some centers evaluation of the biliary system is a standard part of the evaluation of all children with autoimmune hepatitis and those with biliary disease are diagnosed as having autoimmune sclerosing cholangitis (ASC). In these centers ASC is felt to be part of a broad spectrum of autoimmune liver disease in children.36 The exact criteria for diagnosis of autoimmune overlap in PSC are not well defined nor prospectively correlated with clinical course and/or therapeutic response. Next many reports show that children with PSC have higher serum ALT/AST and gamma glutamyltranspeptidase (γGTP) levels than their adult counterparts. This has been interpreted to be evidence of a distinct disease learn more process. Finally, many of the important and potentially life-threatening

sequelae of PSC, such as cholangiocarcinoma, are rarely observed in childhood.187 Thus many of the clinical approaches taken in adults related to these issues are of less importance in children. Measurement of γGTP is important in identifying potential biliary disease in children, in light of elevated levels of alkaline phosphatase associated with bone growth.188 Serum aminotransferase elevations may be more significantly elevated in children.189 MRC is an appropriate first biliary imaging approach in children and often circumvents the need for ERC.190 Liver biopsy may be of greater relevance in children, especially as it pertains to diagnosis of small duct PSC and in the identification of histologic features of autoimmune or immune-mediated disease.

e., two to three cases per year).33, 34, 36, 183, 184 These single-center reports all derive from transplant affiliated programs, so one must assume a bias toward more severe cases. This is especially relevant when considering issues related to prognosis. Development of an evidence based approach to the diagnosis and management of PSC in children is especially problematic given this relatively limited published data and an absence of controlled therapeutic trials.

Thus pediatric hepatologists are reliant on data derived from experiences with adult patients, although caution must be exercised in application of these approaches. An urgent need exists for prospective multi-centered studies of PSC in children. A number of lines of evidence suggest that PSC in children is different and not just an earlier stage in the disease process. Firstly, http://www.selleckchem.com/products/abt-199.html some inherited diseases and immunologic defects may produce a clinical picture like PSC. These entities usually present clinically during childhood and may have an expanded spectrum of disease, which includes milder variants that when unrecognized are labeled as PSC. For example, mild to moderate defects in the ABCB4 (MDR3) gene are a likely cause of a number of cases of small duct PSC in children.185, 186 learn more Secondly, overlap syndrome of autoimmune hepatitis and PSC appears to

be significantly more common in children. In some centers evaluation of the biliary system is a standard part of the evaluation of all children with autoimmune hepatitis and those with biliary disease are diagnosed as having autoimmune sclerosing cholangitis (ASC). In these centers ASC is felt to be part of a broad spectrum of autoimmune liver disease in children.36 The exact criteria for diagnosis of autoimmune overlap in PSC are not well defined nor prospectively correlated with clinical course and/or therapeutic response. Next many reports show that children with PSC have higher serum ALT/AST and gamma glutamyltranspeptidase (γGTP) levels than their adult counterparts. This has been interpreted to be evidence of a distinct disease see more process. Finally, many of the important and potentially life-threatening

sequelae of PSC, such as cholangiocarcinoma, are rarely observed in childhood.187 Thus many of the clinical approaches taken in adults related to these issues are of less importance in children. Measurement of γGTP is important in identifying potential biliary disease in children, in light of elevated levels of alkaline phosphatase associated with bone growth.188 Serum aminotransferase elevations may be more significantly elevated in children.189 MRC is an appropriate first biliary imaging approach in children and often circumvents the need for ERC.190 Liver biopsy may be of greater relevance in children, especially as it pertains to diagnosis of small duct PSC and in the identification of histologic features of autoimmune or immune-mediated disease.

3C). The importance of these genes to liver fibrosis and inflammation is not yet fully understood. However, recent studies have demonstrated that Igfbp7, which is highly expressed in Mdr2:CCR1 DKO mice, functions as a potential tumor suppressor

for HCC.[26] This may explain why, in the presence of inflammation and fibrosis, growth of tumors in Mdr2:CCR1 DKO mice is attenuated. Here, we showed that liver fibrosis in Mdr2-KO mice is dependent on CCR5 expression. In humans, fibrosis is believed to be a prerequisite for HCC. To test the effect of CCR5 and CCR1 depletion selleck kinase inhibitor on tumor development, we performed monthly MRI scans of Mdr2-KO, Mdr2:CCR1 DKO, and Mdr2:CCR5 DKO mice starting from the age of 9 months. At the age of 9 months, all strains exhibited hepatomegaly, compared to age-matched WT controls. At the age of 16 months, MRI scanning revealed that 75% of Mdr2 KO mice had detectible tumors in the liver, as opposed to only 33% of Mdr2:CCR5 DKO mice (Fig. 4A). Interestingly, tumors in Mdr2:CCR1

DKO mice were already detectible at 13 months of age, and by the age of 16 months 88% had detectable tumors, suggesting that tumorigenesis in these mice is not affected. At the age of 16 months, Mdr2-KO and Mdr2:CCR1 DKO mice revealed sever inflammation associate with fibrosis and increased body/liver index (Fig. 4B). In accord with MRI scanning, macroscopical analysis of harvested livers from 16-month-old mice revealed that 90% of Mdr2-KO and 95% of Mdr2:CCR1 DKO mice had notable scattered tumors. Knocking out CCR5 resulted in a 60% reduction in tumor development Ganetespib mouse (Fig. 4C). Furthermore, Mdr2:CCR5 DKO mice that did develop tumors had significantly fewer and smaller tumors, compared to Mdr2 KO mice, resulting in a 20-fold decrease in tumor volume (Fig.

4C). Furthermore, hematoxylin and eosin (H&E) staining of livers from 16-month-old mice revealed that in Mdr2:CCR5 DKO mice that had no macroscopically detected tumors; there was only a mild inflammatory process with a tumor-clear profile and no dysplastic nodules (Fig. 4D). Remarkably, however, Mdr2:CCR1 DKO mice, which began developing tumors earlier than Mdr2-KO mice, find more had smaller tumors, with a 5-fold decrease in tumor volume, compared to Mdr2-KO mice (Fig. 4E). This may indicate that whereas CCR1 is not crucial in the initiation of inflammatory damage, it may be critical in tumor progression, possibly by controlling the recruitment of the immune cells that support tumor growth. Here we show that the chemokine receptor, CCR5, is at the heart of the inflammatory response that induces tumorigenesis. Macrophages that seem to be the main provokers of the ongoing inflammation in Mdr2-KO mice are completely dependent on CCR5 for their recruitment into the liver. The involvement of macrophages in tumor development and progression is undisputed.

3C). The importance of these genes to liver fibrosis and inflammation is not yet fully understood. However, recent studies have demonstrated that Igfbp7, which is highly expressed in Mdr2:CCR1 DKO mice, functions as a potential tumor suppressor

for HCC.[26] This may explain why, in the presence of inflammation and fibrosis, growth of tumors in Mdr2:CCR1 DKO mice is attenuated. Here, we showed that liver fibrosis in Mdr2-KO mice is dependent on CCR5 expression. In humans, fibrosis is believed to be a prerequisite for HCC. To test the effect of CCR5 and CCR1 depletion Protease Inhibitor Library on tumor development, we performed monthly MRI scans of Mdr2-KO, Mdr2:CCR1 DKO, and Mdr2:CCR5 DKO mice starting from the age of 9 months. At the age of 9 months, all strains exhibited hepatomegaly, compared to age-matched WT controls. At the age of 16 months, MRI scanning revealed that 75% of Mdr2 KO mice had detectible tumors in the liver, as opposed to only 33% of Mdr2:CCR5 DKO mice (Fig. 4A). Interestingly, tumors in Mdr2:CCR1

DKO mice were already detectible at 13 months of age, and by the age of 16 months 88% had detectable tumors, suggesting that tumorigenesis in these mice is not affected. At the age of 16 months, Mdr2-KO and Mdr2:CCR1 DKO mice revealed sever inflammation associate with fibrosis and increased body/liver index (Fig. 4B). In accord with MRI scanning, macroscopical analysis of harvested livers from 16-month-old mice revealed that 90% of Mdr2-KO and 95% of Mdr2:CCR1 DKO mice had notable scattered tumors. Knocking out CCR5 resulted in a 60% reduction in tumor development Ku-0059436 in vitro (Fig. 4C). Furthermore, Mdr2:CCR5 DKO mice that did develop tumors had significantly fewer and smaller tumors, compared to Mdr2 KO mice, resulting in a 20-fold decrease in tumor volume (Fig.

4C). Furthermore, hematoxylin and eosin (H&E) staining of livers from 16-month-old mice revealed that in Mdr2:CCR5 DKO mice that had no macroscopically detected tumors; there was only a mild inflammatory process with a tumor-clear profile and no dysplastic nodules (Fig. 4D). Remarkably, however, Mdr2:CCR1 DKO mice, which began developing tumors earlier than Mdr2-KO mice, click here had smaller tumors, with a 5-fold decrease in tumor volume, compared to Mdr2-KO mice (Fig. 4E). This may indicate that whereas CCR1 is not crucial in the initiation of inflammatory damage, it may be critical in tumor progression, possibly by controlling the recruitment of the immune cells that support tumor growth. Here we show that the chemokine receptor, CCR5, is at the heart of the inflammatory response that induces tumorigenesis. Macrophages that seem to be the main provokers of the ongoing inflammation in Mdr2-KO mice are completely dependent on CCR5 for their recruitment into the liver. The involvement of macrophages in tumor development and progression is undisputed.

Currently, many naturally occurring and synthetic deacetylase agonists (e.g., resveratrol and SRT-501) are in clinical trials for treatment of a host of human diseases.33 Furthermore, resveratrol has been shown to attenuate fatty liver and oxidative stress in alcohol-exposed mice.34 An exciting possibility is that specific deacetylase activators or acetyltransferase inhibitors will be useful in treating alcoholic liver disease. The authors thank Dr. Scot Kuo, Mike Delannoy, and Barbara Smith (Johns Hopkins School of Medicine Microscope Facility) for assistance with TEM and instrument training. The authors also thank Dr. Ann Hubbard (Johns Hopkins School of Medicine) for providing lab space for some of

PD98059 in vivo the studies and for providing the many antibodies and viruses used in these studies. Additional Supporting Information may be found in the online version of this article. “
“Advanced

liver fibrosis in nonalcoholic steatohepatitis (NASH) is often accompanied by a reduction in hepatic fat to the point of complete fat loss (burnt-out NASH), but the mechanisms behind this phenomenon have not been elucidated. Adiponectin is raised in cirrhosis of selleck any cause and has potent antisteatotic activity. In this study we examined 65 patients with advanced biopsy-proven NASH (fibrosis stage 3-4) and 54 with mild disease (fibrosis stage 0-1) to determine if disappearance of steatosis correlated with changes in serum adiponectin. All patents had fasting blood tests and anthropometric measures at the time of liver biopsy. Liver fat was accurately quantitated by morphometry. Serum adiponectin was measured by immunoassay. When compared to those with early disease, patients with advanced NASH were more insulin-resistant, viscerally obese, and older, but there was no difference in liver fat content or adiponectin levels. Adiponectin had a significant negative correlation with liver fat percentage in the whole cohort (r = −0.28, P < 0.01), driven by patients

with learn more advanced NASH (r = −0.40, P < 0.01). In advanced NASH, for each 4 μg/L increase in adiponectin there was an odds ratio OR of 2.0 (95% confidence interval [CI]: 1.3-3.0, P < 0.01) for a 5% reduction in hepatic fat. Adiponectin was highly and significantly associated with almost complete hepatic fat loss or burnt-out NASH (12.1 versus 7.4 μg/L, P = 0.001) on multivariate analysis. A relationship between adiponectin, bile acids, and adipocyte fexaramine activation was demonstrated in vivo and in vitro, suggestive of hepatocyte-adipocyte crosstalk. Conclusion: Serum adiponectin levels in advanced NASH are independently associated with hepatic fat loss. Adiponectin may in part be responsible for the paradox of burnt-out NASH. (HEPATOLOGY 2012) Nonalcoholic steatohepatitis (NASH) is characterized histologically by hepatic steatosis, inflammation, ballooning of hepatocytes, and liver fibrosis.