Besides, the relative utility and synergistic effects of these two cell types on the injured liver EPZ-6438 research buy remain unclear. Methods: MSCs, HSCs and the combination of both cells were obtained from the bone marrow of male mice expressing enhanced green fluorescent protein(EGFP)and injected into the female mice with or without liver fibrosis. The distribution of the stem cells, survival rates, liver function, fibrotic areas, hepatocyte regeneration, growth factors and cytokines of the recipient mice were analyzed.

Results: We found that the liver content of the EGFP-donor cells was significantly higher in the MSCs group than in the HSCs or MSCs + HSCs group. The survival rate for the MSCs group was significantly higher than that of the HSCs or MSCs + HSCs group; all surpassed the control group. After MSC-transplantation, the injured livers were maximally restored, with smaller fibrotic areas and less collagen than the controls. The fibrotic areas had decreased to a lesser extent in the mice transplanted with HSCs or MSCs + HSCs. Compared with mice in the HSCs group, the mice that received MSCs had better improved liver function. MSCs exhibited more remarkable paracrine effects and immunomodulatory properties on hepatic stellate BGB324 nmr cells and

native hepatocytes in the treatment of the liver pathology. Synergistic actions of MSCs and HSCs were most likely not observed because the stem cells in liver were detected mostly as single cells, and single MSCs are insufficient to provide a beneficial niche for HSCs. Conclusion: MSCs exhibited a greater homing capability for the injured liver and modulated fibrosis and inflammation more effectively than did HSCs. Synergistic effects of MSCs and HSCs were not observed MCE in liver injury. Key Word(s): 1. MSC; 2. HSC; 3. Liver injury; Presenting Author: QINGHUA HU Additional Authors: HAITAO ZHU, ZHONGWEI LIU, KUNLUN CHEN, KAIFA TANG, CHUAN QIU Corresponding

Author: QINGHUA HU Affiliations: Department of Medicine, 323 Hospital of PLA; School of Medicine, Xi’an Jiaotong University; Affiliated Hospital of Guiyang Medical College; School of Public Health & Tropical Medicine, Tulane University Objective: Liver tissue engineering and regenerative medicine have emerged as potential alternative therapies for liver failure. Ideal scaffolds are considered as important components for successful tissue engineering. This work aims to assess the structural and biochemical properties of rat liver decellularized bioscaffold (LDB) with different protocols and provide a relatively optimized method. Methods: Livers were immediately harvested after SD rats were sarcrificed. The catheter in the portal veins of liver were attached to a flow pump and then perfused with Triton X100-trypsin solution (Triton group), or sodium dodecyl sulfate (NaDS) solution (NaDS group), or Sulfobetaine-10 (SB-10) solution (SB group) respectively.

Besides, the relative utility and synergistic effects of these two cell types on the injured liver selleck screening library remain unclear. Methods: MSCs, HSCs and the combination of both cells were obtained from the bone marrow of male mice expressing enhanced green fluorescent protein(EGFP)and injected into the female mice with or without liver fibrosis. The distribution of the stem cells, survival rates, liver function, fibrotic areas, hepatocyte regeneration, growth factors and cytokines of the recipient mice were analyzed.

Results: We found that the liver content of the EGFP-donor cells was significantly higher in the MSCs group than in the HSCs or MSCs + HSCs group. The survival rate for the MSCs group was significantly higher than that of the HSCs or MSCs + HSCs group; all surpassed the control group. After MSC-transplantation, the injured livers were maximally restored, with smaller fibrotic areas and less collagen than the controls. The fibrotic areas had decreased to a lesser extent in the mice transplanted with HSCs or MSCs + HSCs. Compared with mice in the HSCs group, the mice that received MSCs had better improved liver function. MSCs exhibited more remarkable paracrine effects and immunomodulatory properties on hepatic stellate GSK1120212 in vitro cells and

native hepatocytes in the treatment of the liver pathology. Synergistic actions of MSCs and HSCs were most likely not observed because the stem cells in liver were detected mostly as single cells, and single MSCs are insufficient to provide a beneficial niche for HSCs. Conclusion: MSCs exhibited a greater homing capability for the injured liver and modulated fibrosis and inflammation more effectively than did HSCs. Synergistic effects of MSCs and HSCs were not observed MCE公司 in liver injury. Key Word(s): 1. MSC; 2. HSC; 3. Liver injury; Presenting Author: QINGHUA HU Additional Authors: HAITAO ZHU, ZHONGWEI LIU, KUNLUN CHEN, KAIFA TANG, CHUAN QIU Corresponding

Author: QINGHUA HU Affiliations: Department of Medicine, 323 Hospital of PLA; School of Medicine, Xi’an Jiaotong University; Affiliated Hospital of Guiyang Medical College; School of Public Health & Tropical Medicine, Tulane University Objective: Liver tissue engineering and regenerative medicine have emerged as potential alternative therapies for liver failure. Ideal scaffolds are considered as important components for successful tissue engineering. This work aims to assess the structural and biochemical properties of rat liver decellularized bioscaffold (LDB) with different protocols and provide a relatively optimized method. Methods: Livers were immediately harvested after SD rats were sarcrificed. The catheter in the portal veins of liver were attached to a flow pump and then perfused with Triton X100-trypsin solution (Triton group), or sodium dodecyl sulfate (NaDS) solution (NaDS group), or Sulfobetaine-10 (SB-10) solution (SB group) respectively.

The SNPs under discussion are located in the insulin-response element of the APOC3 U0126 cost gene promoter. In one study, the variant promoter was less responsive to the suppressive effect of insulin.13 Thus,

the variant SNPs may modulate the suppressive effect of insulin on APOC3 expression in states of adequate insulin, but become irrelevant in insulin-resistant states, such as obesity and metabolic syndrome. Further studies on these aspects should help clear the air on discrepant findings on the association of APOC3 variants with NAFLD. PNPLA3, also known as adiponutrin, is a gene located on chrome 22q13 that encodes for a 481-aa protein with triacylglycerol lipase activity, which mediates triacylglycerol hydrolysis. Its expression is mainly on the surface of lipid droplets in hepatocytes and adipocytes, and is regulated by insulin. Two SNPs in this gene have been investigated in relation to NAFLD:

(i) a G-to-C change leading AP24534 mouse to substitution of isoleucine with methionine at codon 148 (I148M; rs738409), and (ii) a G-to-T change leading to substitution of serine with isoleucine at codon 453 (S453I; rs6006460). In contrast to the APOC3 variants, association of PNPLA3 I148M variant with NAFLD is much clearer, with most studies showing an increased risk though the strength of association has varied. In a large genome-wide association the study of subjects included in the Dallas Heart study, the mutant allele was a major determinant of increased MCE公司 hepatic fat content and hepatic inflammation, independent of BMI, diabetes status, ethanol use and ancestry; further, this allele was most common in Hispanics, the subgroup most susceptible to NAFLD.14 In another study from Italy and the UK, this variation was associated with severity of steatosis and liver fibrosis, independent of age, BMI, and diabetes.15 A recent meta-analysis showed that the I148M polymorphism exerts a strong influence not only on liver fat

accumulation (73% higher lipid content with GG genotype than with CC genotype) but also on disease severity at histology (3.24-fold greater risk of high necro-inflammatory scores and 3.2-fold higher risk of liver fibrosis with GG than CC genotype).16 These data clearly indicate that this SNP is a strong modifier of occurrence and natural history of NAFLD irrespective of ethnic origin.16 In fact, even in the study by Petersen et al.5 that showed association of APOC3 variants with NAFLD in Indian men, the presence of GG genotype of PNPLA3 was associated with higher liver triglyceride content. Furthermore, the association of this PNPLA3 variant with NAFLD begins in early childhood, and is present in both obese and non-obese persons, and in those with and without diabetes.17,18 Hence, the finding of Hyysalo et al.10 that Finnish carriers of PNPLA3 GG genotype had a 2.7-fold higher hepatic fat than those with CC genotype is no surprise.

The SNPs under discussion are located in the insulin-response element of the APOC3 Protein Tyrosine Kinase inhibitor gene promoter. In one study, the variant promoter was less responsive to the suppressive effect of insulin.13 Thus,

the variant SNPs may modulate the suppressive effect of insulin on APOC3 expression in states of adequate insulin, but become irrelevant in insulin-resistant states, such as obesity and metabolic syndrome. Further studies on these aspects should help clear the air on discrepant findings on the association of APOC3 variants with NAFLD. PNPLA3, also known as adiponutrin, is a gene located on chrome 22q13 that encodes for a 481-aa protein with triacylglycerol lipase activity, which mediates triacylglycerol hydrolysis. Its expression is mainly on the surface of lipid droplets in hepatocytes and adipocytes, and is regulated by insulin. Two SNPs in this gene have been investigated in relation to NAFLD:

(i) a G-to-C change leading click here to substitution of isoleucine with methionine at codon 148 (I148M; rs738409), and (ii) a G-to-T change leading to substitution of serine with isoleucine at codon 453 (S453I; rs6006460). In contrast to the APOC3 variants, association of PNPLA3 I148M variant with NAFLD is much clearer, with most studies showing an increased risk though the strength of association has varied. In a large genome-wide association the study of subjects included in the Dallas Heart study, the mutant allele was a major determinant of increased MCE公司 hepatic fat content and hepatic inflammation, independent of BMI, diabetes status, ethanol use and ancestry; further, this allele was most common in Hispanics, the subgroup most susceptible to NAFLD.14 In another study from Italy and the UK, this variation was associated with severity of steatosis and liver fibrosis, independent of age, BMI, and diabetes.15 A recent meta-analysis showed that the I148M polymorphism exerts a strong influence not only on liver fat

accumulation (73% higher lipid content with GG genotype than with CC genotype) but also on disease severity at histology (3.24-fold greater risk of high necro-inflammatory scores and 3.2-fold higher risk of liver fibrosis with GG than CC genotype).16 These data clearly indicate that this SNP is a strong modifier of occurrence and natural history of NAFLD irrespective of ethnic origin.16 In fact, even in the study by Petersen et al.5 that showed association of APOC3 variants with NAFLD in Indian men, the presence of GG genotype of PNPLA3 was associated with higher liver triglyceride content. Furthermore, the association of this PNPLA3 variant with NAFLD begins in early childhood, and is present in both obese and non-obese persons, and in those with and without diabetes.17,18 Hence, the finding of Hyysalo et al.10 that Finnish carriers of PNPLA3 GG genotype had a 2.7-fold higher hepatic fat than those with CC genotype is no surprise.

It is a general experience that the colitis associated with PSC usually is extensive.13, 79, 82 This observation also includes CD in PSC, that typically manifests as extensive colitis.76 CD confined to the small bowel is not associated with PSC.76, 78 Interestingly, it has been noted that the CD colitis may not always have features strongly suggestive of CD.77, 84 A definite classification

of the IBD in PSC may be difficult and can vary between centers. The presence of rectal sparing or ileal involvement may for example be interpreted by some centers as CD or indeterminate colitis, rather than UC.77, 84 IBD in children with PSC is also characterized by extensive colitis, often with rectal sparing, and mild clinical symptoms.84 Although learn more symptoms of IBD in PSC cannot be distinguished from those of IBD without PSC,76 the bowel disease in PSC tends to run a more quiescent course.77, 85 The IBD can also have a prolonged subclinical course.79 In a follow-up study of 27 PSC patients with IBD, 12 patients (44%) reported disease activity during the first time after diagnosis of IBD, followed by a quiescent phase.81 Seven (26%) Bcl-2 inhibitor patients had intermittent disease activity. Follow-up colonoscopy revealed mild or inactive disease in the majority

of cases (16 patients; 76%), however, 16 patients had experienced some complication of IBD during the observation period. PSC patients who have an ileal pouch anal anastomosis (IPAA) after colectomy have an increased risk of pouchitis compared to patients with UC without PSC.77, 86, 87 Predisposing factors for this complication are unknown. Although one report suggests that patients with PSC and IPAA run an increased risk of development of dysplasia in the ileal pouch mucosa compared with UC

patients without PSC and that these patients consequently should undergo regular screening,88 studies in larger cohorts of patients should be carried out to confirm the findings. UC is associated with an increased risk of colorectal cancer (CRC).89–93 Indeed, a thorough meta-analysis including 11 studies, indicates that patients with UC and PSC are at an increased risk of CRC and dysplasia compared with patients with UC alone, with OR 4.79 (95% CI 3.58–6.41).94 medchemexpress In a recent study, PSC patients with IBD and CRC were found to be younger at onset of IBD than patients who had IBD and CRC without PSC (19 versus 29 years; P = 0.04).95 The time interval from onset of colitis until diagnosis of CRC was, however, similar in the two groups (17 versus 20 years; P = 0.02). Given the increased risk of CRC in patients with PSC, surveillance colonoscopy at one to two year intervals from the time of diagnosis of PSC in patients with UC as recommended by several experienced centers.77, 79, 96, 97 Colorectal neoplasia associated with PSC appears to have a predilection for the proximal colon, with up to 76% having a right-sided distribution.

Methods: A total of 21 Patients with Portal hypertension from the First Affiliated Hospital of Nanchang University were exeeuted TIPS with Covered Stent in rencent 2 years and

were followed up for 4 to 14 months. The portal venous pressure pertosystemic pressure gradients, alimentary tract hemorrhage, stent reocclusion, hepatic encephalopath, blood coagulation, hepatic function, blood ammonia, iconography and endoscopy results were monitored before and after Tips treatment. Results: In all of the 21 Patients,18 cases were sueeessfully completed the operation. The rate of hemostatsis in 24 hours was 1 00%. HVPG dropped from (41.9 ± 15.9)cm H20 to (25.5 ± 13.5)cm H20, there was significant http://www.selleckchem.com/products/AZD2281(Olaparib).html statistical signifieance. During in the 4 months–14 months of follow-up, GS-1101 in vitro The relapse rate of rehaemorrhagia was 26.7% (4/15), and occurred in 1, 2, 6, 8 month after the operation. Esophageal varices of 11 cases release, another 6 cases did not change significantly. Stent reocclusion rate 16.7% (3/18), and the total of 3 cases rehaemorrhagia. The incidence rate of hepatic encephalopathy was16.7% (3/18), symptoms of every cases disappear after symptomatic

treatment. Refractory ascites of all cases remission obviously and even disappear. The difference of hepatic function and platelet between before and after operation was not significant statistically (P > 0.05). Conclusion: The curative effect of TIPS in treating portal hypertension caused by liver cirrhosis

is exact, and is worthy of clinical application. Key Word(s): 1. TIPS; 2. Portal HyPenension; 3. Liver cirrhosis; Presenting Author: CHAO DU Additional Authors: MINGDE JIANG Corresponding Author: CHAO DU Affiliations: Chengdu Military Command Objective: Liver fibrosis is the pathological basis of chronic liver disease and it must lead to the cirrhosis. There is still no effects of drugs to reverse the liver fibrosis. In recent years medchemexpress numerous studies have confirmed that bone marrow-derived mesenchymal stem cells in the the body and outward have the potential of differentiation to liver cell, it is expected to repair or reverse the process of liver fibrosis. The genetically modified stem cells maintain the directly differentiation characteristics, while corresponding factor can improve the efficacy and is compensate for the lack of simple MSCs transplantation therapy. Matrix metalloproteinases in the liver was expressed and secreted by hepatic stellate cells (HSC) and Kupffer cell. It was zinc – calcium-dependent family of endogenous proteolytic enzymes involved in extracellular matrix degradation. It was the only enzyme that breaks down collagen fiber and almostly breaks down the ECM components outside the polysaccharide, it plays an important role in physiological and pathological processes.

Methods: A total of 21 Patients with Portal hypertension from the First Affiliated Hospital of Nanchang University were exeeuted TIPS with Covered Stent in rencent 2 years and

were followed up for 4 to 14 months. The portal venous pressure pertosystemic pressure gradients, alimentary tract hemorrhage, stent reocclusion, hepatic encephalopath, blood coagulation, hepatic function, blood ammonia, iconography and endoscopy results were monitored before and after Tips treatment. Results: In all of the 21 Patients,18 cases were sueeessfully completed the operation. The rate of hemostatsis in 24 hours was 1 00%. HVPG dropped from (41.9 ± 15.9)cm H20 to (25.5 ± 13.5)cm H20, there was significant Navitoclax mouse statistical signifieance. During in the 4 months–14 months of follow-up, CHIR-99021 supplier The relapse rate of rehaemorrhagia was 26.7% (4/15), and occurred in 1, 2, 6, 8 month after the operation. Esophageal varices of 11 cases release, another 6 cases did not change significantly. Stent reocclusion rate 16.7% (3/18), and the total of 3 cases rehaemorrhagia. The incidence rate of hepatic encephalopathy was16.7% (3/18), symptoms of every cases disappear after symptomatic

treatment. Refractory ascites of all cases remission obviously and even disappear. The difference of hepatic function and platelet between before and after operation was not significant statistically (P > 0.05). Conclusion: The curative effect of TIPS in treating portal hypertension caused by liver cirrhosis

is exact, and is worthy of clinical application. Key Word(s): 1. TIPS; 2. Portal HyPenension; 3. Liver cirrhosis; Presenting Author: CHAO DU Additional Authors: MINGDE JIANG Corresponding Author: CHAO DU Affiliations: Chengdu Military Command Objective: Liver fibrosis is the pathological basis of chronic liver disease and it must lead to the cirrhosis. There is still no effects of drugs to reverse the liver fibrosis. In recent years MCE numerous studies have confirmed that bone marrow-derived mesenchymal stem cells in the the body and outward have the potential of differentiation to liver cell, it is expected to repair or reverse the process of liver fibrosis. The genetically modified stem cells maintain the directly differentiation characteristics, while corresponding factor can improve the efficacy and is compensate for the lack of simple MSCs transplantation therapy. Matrix metalloproteinases in the liver was expressed and secreted by hepatic stellate cells (HSC) and Kupffer cell. It was zinc – calcium-dependent family of endogenous proteolytic enzymes involved in extracellular matrix degradation. It was the only enzyme that breaks down collagen fiber and almostly breaks down the ECM components outside the polysaccharide, it plays an important role in physiological and pathological processes.

Secondly, we examined variations of these four variables throughout the depth buy CHIR-99021 range experienced during transits. This enabled us to investigate

how penguins may anticipate the nature of the dive they are going to undertake in terms of transit rates. The study was carried out on Possession Island, Crozet Archipelago (46.4°S, 51.8°E) from December 2003 to March 2004. Birds used in the study were king penguins breeding at La Baie du Marin, a colony of approximately 16 000 pairs (Delord, Barbraud & Weimerskirch, 2004). The procedures received the approval of the ethics committee of the French Polar Institute (IPEV) and of the French Ministry of the Environment. Detailed description of the general surgical and handling procedure are given in Froget et al. (2004). Six breeding male king penguins were captured while brooding an egg and immediately subjected HKI-272 mw to isoflurane-anaesthesia, during which they were fitted with data loggers. SMAD data loggers (DEPE-IPHC, Strasbourg, France; 80 × 25 × 10 mm, 54 g) were externally attached to the lower-back feathers of each animal to diminish hydrodynamic drag (Bannasch, Wilson & Culik, 1994) and recorded depth every 2 s. SMAD were also programmed to measure tail-to-head (surge) and ventral-to-dorsal (heave) accelerations during two 1-h high-frequency sessions per day when penguins performed deep dives, and stored these measurements 32 times

per second. Cross-sectional area (CSA) of the external logger (2.5 cm2) represented less than 1% of the smallest bird’s CSA. Modified Mk7 data loggers (Wildlife Computers, Redmond, WA, USA) were also implanted subcutaneously for a study

of peripheral temperatures; these results have been described previously in Schmidt (2006). Together, the mass of both loggers (87 g) represented less than 0.8% of the smallest bird’s mass. The penguins undertook a foraging trip at sea 15–18 days later, after being relieved by their partners. After their return to the colony, the birds were recaptured and anaesthetized using the same procedure, and the loggers 上海皓元 were removed. All the loggers were recovered, of which five had recorded usable data. Data from these loggers were extracted, prepared and analysed using purpose-written computer programs in Matlab 6.0 (The MathsWorks, Natick, MA, USA). Dives >50 m, hereafter called ‘deep dives’, were used for analysis as they represent the majority of the foraging dives of king penguins (Charrassin et al., 1998). For each dive analysed, the following parameters were calculated: maximum dive depth (m), dive duration (s), subsequent surface interval duration until the next dive of any depth (s), subsequent time interval until the next deep dive (s), rank of the dive in a bout (i.e. sequence of successive dives), number of wiggles during the bottom phase or the entire dive. Wiggles are a particular, undulation-like pattern in the dive profile over time.

Secondly, we examined variations of these four variables throughout the depth selleck kinase inhibitor range experienced during transits. This enabled us to investigate

how penguins may anticipate the nature of the dive they are going to undertake in terms of transit rates. The study was carried out on Possession Island, Crozet Archipelago (46.4°S, 51.8°E) from December 2003 to March 2004. Birds used in the study were king penguins breeding at La Baie du Marin, a colony of approximately 16 000 pairs (Delord, Barbraud & Weimerskirch, 2004). The procedures received the approval of the ethics committee of the French Polar Institute (IPEV) and of the French Ministry of the Environment. Detailed description of the general surgical and handling procedure are given in Froget et al. (2004). Six breeding male king penguins were captured while brooding an egg and immediately subjected www.selleckchem.com/products/midostaurin-pkc412.html to isoflurane-anaesthesia, during which they were fitted with data loggers. SMAD data loggers (DEPE-IPHC, Strasbourg, France; 80 × 25 × 10 mm, 54 g) were externally attached to the lower-back feathers of each animal to diminish hydrodynamic drag (Bannasch, Wilson & Culik, 1994) and recorded depth every 2 s. SMAD were also programmed to measure tail-to-head (surge) and ventral-to-dorsal (heave) accelerations during two 1-h high-frequency sessions per day when penguins performed deep dives, and stored these measurements 32 times

per second. Cross-sectional area (CSA) of the external logger (2.5 cm2) represented less than 1% of the smallest bird’s CSA. Modified Mk7 data loggers (Wildlife Computers, Redmond, WA, USA) were also implanted subcutaneously for a study

of peripheral temperatures; these results have been described previously in Schmidt (2006). Together, the mass of both loggers (87 g) represented less than 0.8% of the smallest bird’s mass. The penguins undertook a foraging trip at sea 15–18 days later, after being relieved by their partners. After their return to the colony, the birds were recaptured and anaesthetized using the same procedure, and the loggers MCE were removed. All the loggers were recovered, of which five had recorded usable data. Data from these loggers were extracted, prepared and analysed using purpose-written computer programs in Matlab 6.0 (The MathsWorks, Natick, MA, USA). Dives >50 m, hereafter called ‘deep dives’, were used for analysis as they represent the majority of the foraging dives of king penguins (Charrassin et al., 1998). For each dive analysed, the following parameters were calculated: maximum dive depth (m), dive duration (s), subsequent surface interval duration until the next dive of any depth (s), subsequent time interval until the next deep dive (s), rank of the dive in a bout (i.e. sequence of successive dives), number of wiggles during the bottom phase or the entire dive. Wiggles are a particular, undulation-like pattern in the dive profile over time.

8 Here we refer to NAFLD/NASH when the discussion is about the pathologically more significant form of

NAFLD, present in 20–30% of cases.3–5 In this review, we first consider the rationale for considering NAFLD as a distinct entity, where NASH fits into that concept, and the mechanistic implications of what appear to be inextricable connections between over-nutrition and insulin Selleckchem LY2109761 resistance; visceral adiposity and steatosis; adipose restriction, inflammation and failure and worsening insulin resistance. We then discuss newer aspects that now seem relevant to NASH pathogenesis, distinguishing between what is known and key questions that remain unanswered (Table 1). Since this field is now extensive, we will confine the first part of the review to metabolic factors, which we believe lead to steatohepatitis—not just steatosis. In Part 2 of the review, we will consider mechanisms whereby lipotoxicity leads to hepatocellular injury,

inflammation and fibrosis, the pathological features of NASH. To the extent that NASH has neither a single cause, unique and reproducible clinicopathological hallmarks or an accepted treatment, it is not a disease. But neither is high arterial blood pressure, cigarette smoking, expanded waistline nor hypercholesterolemia! Yet who would dispute the health implications ABT-199 mw of these pathophysiological measurements, MCE公司 behaviors or changes in body composition? When they are combined, the implications for

cardiovascular health, T2D and cancer risk are strongly supported by epidemiological evidence, albeit there remains debate about the utility of combining them as a defined ‘metabolic syndrome’.12 Likewise, NAFLD is a condition in which hepatocytes, which normally contain only small amounts of storage lipid, contain supra-physiological amounts of fat. This can be observed by light microscopy as ‘steatosis.’10,11 With NAFLD, the amount of hepatic storage triglyceride varies from just above normal (5% liver mass) to greater than ten-fold normal levels.13–15 Whether there is more in NASH is important to establish, although with development of cirrhosis steatosis decreases. Variability in free fatty acids (FFA) and other lipid molecules is greater and may be more relevant to steatohepatitis pathogenesis, as discussed in part 2. The increased susceptibility of fatty livers to injury (after surgical resection,16 during ischemia-reperfusion,17 or with hepatitis C virus infection18) is one piece of evidence that NAFLD is not a healthy state, although with simple steatosis (SS), progression to cirrhosis or hepatocellular carcinoma (HCC) is rare.19,20 When hepatocytes leak their intracellular contents into serum, evident by a rise in serum alanine aminotransferase (ALT), ferritin, etc.