The percentages of patients with PU history (26.1% vs 15.1%, P = 0.004), chronic renal failure (9% vs 1.7%, P < 0.001), or taking non-steroidal anti-inflammatory drugs (NSAIDs) (14.4% vs 3.1%, P < 0.001) in the ulcer group were significantly higher than those in the control group. The percentages of patients Selleckchem Doxorubicin taking cotreatment of anti-acid (histamine H2-receptor antagonists or proton-pump inhibitors) (32.4% vs 70.3%, P < 0.001), ARBs or angiotensin-converting

enzyme inhibitors (ACEIs) (45% vs 58.1%, P = 0.01), or statins (41.4% vs 53.7%, P = 0.02) in the ulcer group were significantly lower than in the control group (Table 1). Similar significant results were observed in the bleeding group, and the same factors for ulcer were significantly different between the bleeding group and the controls. In addition,

the percentage of patients taking β(α)-blocker (17.8% vs 35.5%, P = 0.02) cotreatment was significantly lower than in the control group (Table 1). The candidate 29 SNPs of 24 genes associated with small bowel or ulcer bleeding identified by genome-wide preliminary analysis were evaluated in 593 patients; however, only the CHST2 2082 SNP was significantly associated with ulcer and ulcer bleeding (Table 2). The allele frequencies of SLCO1B1 and CHST2 2082 SNP and the haplotype frequencies of SLCO1B1 are shown in Table 2. The allele frequencies of the polymorphisms did not deviate significantly from those expected under Hardy–Weinberg equilibrium. The frequency of the CHST2 2082 T allele was significantly higher in both the ulcer group (60% vs 46.4%, P = 0.01) and the bleeding group (70.7% vs 46.4%, P = 0.003) compared Sorafenib supplier to the controls (Table 2). The haplotype frequencies of SLCO1B1*1a (388A and 521T, wild type), *1b (A388G and 521T), *5 (388A

and T521C), and *15 (A388G and 521C) in the controls were 10.6, 62.8, 0, and 26.6%, respectively (Table 2). The frequency of the SLCO1B1*1b haplotype was highest and significantly higher in the ulcer group (74.3% vs 62.8%, P = 0.02) compared to the controls (Table 2). Among the patients taking stain, ARB, or ACEI, the frequencies of the SLCO1B1*1b haplotype were significantly higher not only in the ulcer group (77.9% vs 63.1%, P = 0.02) but also in the bleeding group (87.1% vs 63.1%, P = 0.006) N-acetylglucosamine-1-phosphate transferase compared to the controls (Table 3). History of PU (adjusted OR 2.52, 95% CI 1.39–4.55), chronic renal failure (7.63, 2.34–24.9), cotreatment with NSAIDs (6.62, 2.63–16.7), anti-acid (0.18, 0.11–0.31), and SLCO1B1*1b (2.20, 1.24–3.89) were significantly associated with ulcer after adjustment of significant factors in the univariate analysis (Table 4). Age > 80 years (adjusted OR 3.60, 95% CI 1.51–8.59), PU history (4.20, 1.71–10.3), chronic renal failure (6.42, 1.29–32.0), cotreatment with NSAIDs (8.57, 2.20–33.4), anti-acid (0.05, 0.02–0.15), β(α)-blockers (0.33, 0.12–0.90), and CHST2 2082 T allele (2.57, 1.07–6.

Recommendations: For treatment-experienced patients: 10. Re-treatment with boceprevir or telaprevir, together with peginterferon alfa and weight-based ribavirin, can be recommended for patients who had virological relapse or were partial responders after a

prior course of treatment with standard interferon alfa or peginterferon alfa and/or ribavirin (Class 1, Level A). Adverse events occurred more frequently in patients treated with PIs than in those treated with PegIFN and RBV therapy alone. In the BOC trials, anemia and dysgeusia were the most common adverse events, whereas in the TVR trials, rash, anemia, pruritus, nausea, and diarrhea developed more commonly among those who received TVR than who received SOC therapy.12, 16 In the phase 3 TVR trials, a rash of any severity was noted in 56% of patients who received a TVR-based regimen compared to 32% of those who received a PegIFN Selleck LY294002 and RBV regimen.16

The rash was typically eczematous and maculopapular in character, consistent with a drug-induced eruption. In most patients, the rash was mild to moderate in severity but was severe (involving >50% of the body surface area) in 4% of cases. The development of rash necessitated discontinuation of TVR in 6% and of the entire regimen in 1% of the cases. The Stevens Johnson Syndrome or Drug-Related Eruption with Systemic Symptoms (DRESS) occurred in <1% of subjects but at a higher frequency than generally observed for other drugs. The response of the rash to local or systemic treatment with corticosteroids Obeticholic Acid and oral antihistamines is uncertain. Pruritus, commonly but not always associated with rash, was noted in ∼50% of patients who received TVR therapy.16 Anemia developed among recipients of both PIs. Hemoglobin decreases below 10 g/dL (grade 2 toxicity) occurred in 49% of patients Adenosine who received a BOC regimen compared to 29% of those who received the SOC regimen, whereas 9% had a hemoglobin decline of <8.5 g/dL (grade 3 toxicity).12 Among patients treated with T12PR, hemoglobin levels of <10 g/dL were observed

in 36% of patients compared to in 14% of patients who received SOC, and 9% had hemoglobin decreases to <8.5 g/dL.16 Because hematopoietic growth factors were not permitted during the TVR trials, there was a 5%-6% higher rate of treatment discontinuation among those who developed anemia than among those who did not. However, neither anemia nor RBV dose reduction adversely affected the SVR rate. Of note is that in the BOC trial, SVR rates in patients managed by RBV dose reduction alone were comparable to those in patients managed with erythropoietin therapy.23 Similarly, in the TVR trials, dose reduction of RBV had no effect on SVR rates, and therefore dose reduction should be the initial response to management of anemia.

As the favourable polymorphism has a substantially higher frequency in European than African populations (75% vs. 40% respectively) this factor has been estimated to contribute to approximately half the difference in response rates between these racial groups. Testing for the IL28B polymorphism is not yet routinely available. However, future treatment regimens may be influenced and individualized according to the presence or absence of the polymorphism. HCV RNA should be assessed in

all HIV-positive persons as approximately 6% of these individuals fail to develop detectable HCV antibodies selleck kinase inhibitor so a negative antibody test result should not be interpreted as indicating that the patient does not have HCV infection [27]. Patients coinfected Kinase Inhibitor Library research buy with HIV and HCV have an approximately twofold greater risk of developing cirrhosis and progress more rapidly to liver failure compared with HCV monoinfected individuals [29]. The importance

of the need to treat HCV in this patient group should therefore be emphasized. To optimize response to anti-HCV treatment HIV infection should be fully suppressed using HAART. HAART regimens should not include zidovudine (AZT) as this is contraindicated with ribavirin because of the potential for severe anaemia [30]. Didanosine and stavudine should also be avoided because of the interaction with ribavirin and the risk of potentially fatal lactic acidosis [31]. There is oxyclozanide evidence that abacavir may be associated with poor treatment responses to HCV combination therapy because of an inhibitory effect on ribavirin so this should be considered if it is to be included in HAART regimens [32]. HIV non-progressors who are maintaining normal CD4 counts not on HAART should also be encouraged to undertake HCV treatment. Co-infected patients have lower SVRs with PegIFN/ribavirin treatment compared with monoinfected individuals. In the meta-analysis reported by Franchini co-infected patients had an overall SVR of 29% [26]. The indications for liver transplantation in HCV infected bleeding disorder patients who have progressed to end-stage

liver disease or have developed HCC are no different from other patients. HIV co-infected patients with non-progression of HIV infection or with stable disease on HAART should also be considered for transplantation [33]. All patients undergoing transplantation will acquire HCV infection in the new liver with a variable outcome in time. However, co-infected patients have a more rapid progression to fibrosis and a lower survival rate following liver transplantation than HCV monoinfected individuals [34]. New antiviral therapies including HCV nucleoside protease inhibitors (Telaprevir, Boceprevir), polymerase inhibitors and non-nucleoside polymerase inhibitors have been developed for use against genotype 1 virus and should become an integral part of eradication regimens in the near future [35].

46, 47 This study undoubtedly has some limitations. In the current version of the ITA.LI.CA database, data regarding tumor recurrence after treatment are not

available, and therefore in this study the influence of alpha-fetoprotein levels on some important composite selleck compound endpoints such as recurrence plus death could not be assessed. Furthermore, as expected in our country, hepatitis virus infection was the cause of cirrhosis in most cases, and therefore it remains to be established whether these results can be generalized to HCC patients with other etiologies.48, 49 Lastly, although the ITA.LI.CA database includes more than 3,000 HCC patients, the selection Bortezomib chemical structure criteria for this study were very strict, and therefore the study population was limited to 205 patients. A post-hoc analysis shows that this sample size had a statistical power of 22% to detect a difference between the observed 5-year survival rates of patients with alpha-fetoprotein below (61%) and above (55%) 20 ng/mL. With such survival rates, a sample size

of 2,118 patients with compensated cirrhosis and single, small HCC treated with curative intent, derived from a population of more than 30,000 patients with HCC, would have been needed to achieve a power of 80%. All in all, we feel that even these figures, if framed in the context of clinical practice, confirm the bland prognostic potential of alpha-fetoprotein in the subset of patients we selected. In conclusion, we found that serum alpha-fetoprotein has no prognostic role in compensated cirrhosis patients with a single, small HCC diagnosed during surveillance and treated with curative intent. These findings emphasize the futility of serum alpha-fetoprotein determination in a clinical setting where surveillance for HCC may provide its maximal benefit in terms of amenability to curative treatment and patients survival. New, more accurate markers are therefore needed to improve our current ability

to predict the outcome of patients diagnosed with early HCC. Other members of the ITA.LI.CA group: Dipartimento di Medicina Clinica, Alma Mater Studiorum, this website Università di Bologna, Italy: Mauro Bernardi, Maurizio Biselli, Romina Cassini, Paolo Caraceni, Marco Domenicali, Virginia Erroi, Marta Frigerio, Annagiulia Gramenzi, Barbara Lenzi. Dipartimento di Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche, Azienda Ospedaliero-Universitaria di Bologna, Italy: Donatella Magalotti. Divisione di Medicina, Azienda Ospedaliera Bolognini, Seriate, Italy: Claudia Balsamo, Maria Di Marco, Elena Vavassori. Divisione di Medicina, Ospedale Treviglio-Caravaggio, Treviglio, Italy: Lodovico Gilardoni, Mario Mattiello.

pylori eradication on the development of new neoplasms. Second, we classified the extent of atrophic fundic gastritis into open and closed type in this study. Further studies are needed to determine cut-off levels that could identify patients at high risk for developing metachronous EGC, by AFI. Third, all metachronous EGCs were small intramucosal carcinomas that were classified as Category 4: mucosal high grade neoplasia in the revised Vienna classification.14 There is a question as to whether EGC is a pseudo-cancer PLX-4720 and not a truly lethal disease.28 Therefore, whether detection of metachronous neoplasm would affect the prognosis of EGC patients who are treated by ESD warrants further

investigation. In conclusion, patients with extensive atrophic fundic gastritis diagnosed by AFI are at high risk for developing metachronous gastric cancer after ESD for EGC, even

though they have achieved successful eradication of H. pylori. Scheduled surveillance endoscopy is strongly endorsed in such patients. “
“For more than a century and a half, the description of a liver as “cirrhotic” was sufficient to connote both a pathological and clinical status, and to assign the prognosis of a patient with liver disease. However, as our interventions to treat advanced liver disease have progressed (e.g., antiviral therapies), the inadequacy of a simple one-stage description for advanced fibrotic liver disease has become increasingly evident. Mirabegron Until recently, Lenvatinib refining the diagnosis of cirrhosis into more than one stage hardly seemed necessary when there were no interventions available to arrest its progression.

Now, however, understanding the range of potential outcomes based on the severity of cirrhosis is essential in order to predict outcomes and individualize therapy. This position paper, rather than providing clinical guidelines, attempts to catalyze a reformulation of the concept of cirrhosis from a static to a dynamic one, creating a template for further refinement of this concept in the future. We already make the clinical distinction between compensated and decompensated cirrhosis, and are incrementally linking these clinical entities to quantitative variables such as portal pressure measurements and emerging noninvasive diagnostics. Moreover, mounting evidence suggests that cirrhosis encompasses a pathological spectrum which is neither static nor relentlessly progressive, but rather dynamic and bidirectional, at least in some patients. Thus, there is a pressing need to redefine cirrhosis in a manner that better recognizes its underlying relationship to portal hypertension and related circulatory changes, and more faithfully reflects its progression, reversibility and prognosis, ultimately linking these parameters to clinically relevant outcomes and therapeutic strategies.

Malnutrition was associated with active H. pylori infection. Helicobacter pylori (H. pylori) is a gram-negative, curved-shaped bacterium, classified in Group I carcinogen, clinically associated with gastritis, peptic ulcer disease

and PS-341 cell line gastric cancer [1, 2]. In developing countries, more than 80% of adults and 50% of children are colonized by H. pylori compared to 30% of adults and 10% of children in developed countries [3]. In Mexico, in 1988 a seroepidemilogical survey estimated H. pylori prevalence of 66% [4, 5]. Twenty percent of infants of 1 year and younger were colonized by H. pylori, and colonization had reached 50% in children before they reached 10 years of age [6]. In a study carried out in 2001 in boarding schools of the National Indigenous Institute of Hidalgo State in Mexico, prevalence of active H. pylori infection was 52% [7]. In a population study, in Mexico City, 38% of school children had active H. pylori. Children with H. pylori infection this website averaged 1.32 cm (CI 95% −2.22 to −0.42) less in height than children without infection [8]. In the same population, the colonization by H. pylori was a dynamic phenomenon, with an incidence rate of 64 new cases/year/1000 school children and a spontaneous infection clearance rate of 47 cases/year/1000 school children [9]. There are different

H. pylori strains with genetic variability. Bacterial characteristics, host characteristics, and environmental factors determine the degree of damage that the infection can cause in the gastric mucosa [10]. H. pylori displays factors that determine its virulence; one of them is the cytotoxin-associated gene A (cagA) [11]. In many most populations, approximately 50% of H. pylori strains have this virulence

factor. The cagA island encodes a bacterial type IV secretion system that translocates CagA into host cells. Intracellular CagA affects multiple pathways that alter host cell morphology, signaling, and inflammatory responses [11]. H. pylori infection with this virulence factor has been associated with the development of severe diseases such as gastric and duodenal ulcer, gastric atrophy, and gastric cancer [12-14]. The infection by H. pylori in children has also been associated with extra-gastric manifestations such as lower growth rate and iron deficiency (ID) or iron deficiency anemia (IDA) [15-21]. Some authors suggest that a chronic infection is a prerequisite for the development of diseases such as symptomatic gastritis, gastric and duodenal ulcers, gastric cancer [22], ID or IDA [23, 24]. Studies on the effect of active infection on the speed of child growth have shown that there is a greater negative effect in the months after the onset of the infection. This effect is maintained and affects infected children’s growth cumulatively throughout time [18, 19, 21]. The majority of H. pylori-infected people remain asymptomatic; thus, the infection is not detected in the acute phase.

Italian patients with severe haemophilia aged ≥65 years born in the 1940s or earlier were compared with men without bleeding disorders matched for age and geography. HRQoL was assessed via generic and disease-specific questionnaires. Potential associations with concomitant illnesses, orthopaedic status, physical functioning, Ibrutinib mw cognitive status and depression were evaluated. In addition, the newly adapted HRQoL questionnaire specific for elderly persons with haemophilia (Haem-A-QoLEldlery)

was psychometrically tested and validated. Thirty-nine patients, aged 65–78 years, were investigated, 33 with haemophilia A and six with haemophilia B, and compared to 43 controls, aged 65–79 years. Chronic blood borne viral infections, hypertension and arthropathy

were more FK506 concentration frequent in patients, whereas hypercholesterolemia and cardiovascular diseases were more frequent in controls. Psychometric characteristics of Haem-A-QoLElderly showed good to excellent values for reliability and validity. HRQoL was worse in patients at EQ-VAS, WHOQOL-BREF and WHOQOL-Old. The highest impairments were found in patients by means of the haemophilia-specific Haem-A-QoLElderly in such dimensions as ‘physical activity & leisure’, ‘physical health’ and ‘view’. A poor orthopaedic status was negatively associated with HRQoL. Compared to age-matched controls elderly patients with haemophilia had an impaired HRQoL in association with their health status. The newly developed Haem-A-QoLElderly proved to be a reliable and valid instrument for HRQoL assessment in elderly haemophilia patients. “
“This

chapter contains sections titled: Musculoskeletal assessment: outcome measurement Musculoskeletal outcome: the body—assessment of structure and function Musculoskeletal outcome: the person—assessment of activities and functional independence in hemophilia Musculoskeletal outcome: in society—assessment Liothyronine Sodium of participation and quality of life Conclusion Acknowledgment References “
“Summary.  Recurrent haemarthroses leading to chronic synovitis and arthropathy remain a major cause of morbidity in patients with haemophilia. Radioactive synovectomy (RS) is considered the first choice of treatment for chronic haemophilic synovitis. The aim of this study was to evaluate the effect of RS with Yttrium90 citrate (C-Y90) in the joints of patients with chronic haemophilic synovitis. From 2003 to 2007, 245 joints (118 knees, 76 elbows, 49 ankles and two shoulders) of 190 patients with haemophilia or von Willebrand disease were submitted to RS with C-Y90 at Hemocentro de Mato Grosso, Brazil. Forty joints had radiographic Pettersson scores above 8. There were 36 joints of 22 patients with inhibitors to factor VIII. The procedure was safe with low occurrence of adverse events. The main effect was the overall reduction in joint bleeding frequency, from 19.

RVR rates for rs12979860 genotypes in Caucasians were: CC 28% versus selleck chemical CT 5% versus TT 5%; complete EVR rates were CC 87% versus CT 38% versus TT 28%, translating to an overall intent-to-treat SVR rate of 69% in good-response CC patients versus 33% and 27% in CT and TT patients).10 Subsequent studies have shown that this is largely the result of improved phase 1 viral kinetics, with the degree of

viral load reduction clearly different by IL28B genotype as early as 24 h following the first injection of peg-IFN.11,12 Tanaka and colleagues used a two-stage testing approach for their GWAS. They defined their primary response phenotype as virological non-response (VNR; < 2 log reduction in HCV—RNA at 12 weeks) in 80% adherent patients (n = 142). The study used the Affymetrix 6.0 GWAS chip (Santa Clara, CA, USA). The discovery phase identified two significant SNPs that satisfied

criteria after correction for multiple testing (VNR vs SVR, rs12980275 odds ratio [OR]: 26.7, P = 7.41 × 10−13, and rs8099917 OR: 36.5, P = 5.00 × 10−14). XAV 939 These associations were replicated in a second cohort (n = 172); in a combined analysis, the strongest genetic association signal arose from rs8099917 (combined cohorts OR: 27.2, P = 1.11 × 10−27). The large OR in this GWAS likely reflects the relatively extreme phenotype investigated, as shown in the IDEAL dataset: > 97% of Caucasian good-response patients achieve an early virological response,

which inflates the OR. This study did not identify an association between rs12979860 and IFN response. Importantly, this was not a negative result, but reflected the fact that the Affymetrix 6.0 genotyping chip did not include rs12979860 as a tag SNP. Suppiah and colleagues conducted an initial GWAS for SVR in a clinically, well-characterized discovery cohort of patients of European—Australian ancestry (n = 293). Only rs8099917 was found to be genome-wide significant (P = 7.06 × 10−8). A Fossariinae total of 172 SNPs with suggestive association and biological plausability were then assessed in a validation cohort of similar ethnic background (n = 555), confirming the significance of the association between rs8099917 and SVR (combined cohort OR: 1.98, P = 9.25 × 10−9). The strongest association signal in the combined cohort was from another IL28B haplotype SNP (rs12980275, P = 7.74 × 10−10). This GWAS phase used a combination of genotyping platforms (Illumina Infinium Human Hap300 or CNV370-Quad BeadChip; Illumina, USA). Again, data for rs12979860 were not presented. A fourth large European GWAS cohort provided further validation that the IL28B genotype was associated with both treatment-induced and spontaneous viral clearance in a more heterogenous cohort, including patients with prior non-response, non-1 genotypes, and HIV co-infection.

In this analysis sample, 42% of patients achieved SVR, 23% relapsed, 10% had breakthrough, and 24% were nonresponders. Approximately one-third of the breakthrough and nonresponder patients completed at least 44 weeks of treatment. Of the four trials included in this selleck analysis, epoetin alfa use was only allowed in the Latino study and was received by 10.4% of patients in the Latino group and 18% of patients in the non-Latino Caucasian group.8 The mean ± SD maximum decrease from baseline was 2.5 ± 1.3 × 109/L for neutrophils, 93.6 ± 44.9 × 109/L for platelets, 3.9 ± 1.5 g/dL for hemoglobin, and 6.3% ± 4.7% for weight. The mean maximum decreases in hematologic parameters and weight by virologic response category are shown in Fig. 1. Cirrhosis

was associated with smaller declines in neutrophils and platelets and was therefore included in the final models. The analysis indicated that there was a correlation between virologic response and maximum decreases from baseline in each parameter. Patients with a virologic response (SVR, relapse, and breakthrough) experienced greater declines in neutrophil count, platelet count, hemoglobin level, and weight than nonresponders (P < 0.01 for all parameters except Ku-0059436 supplier for the difference in hemoglobin decline between breakthrough and nonresponders, which was not significant). Among virologic responders, the mean total dose of PEG-IFN alfa-2a was 7,202.8 μg and the mean total dose of ribavirin was 3,803.8 mg/kg.

Among nonresponders, the mean total dose of PEG-IFN alfa-2a was 5,074.3 μg and the mean total dose of ribavirin was 2,474.0 mg/kg. After

adjusting Flavopiridol (Alvocidib) for total PEG-IFN and ribavirin received (Fig. 2A), the differences between virologic responders and nonresponders in neutrophil and platelet count declines remained statistically significant; however, the decreases in hemoglobin level and weight were no longer consistently associated with virologic response. An additional sensitivity analysis that included only a subset of patients who completed at least 44 weeks of therapy (Fig. 2B) showed that after adjusting for drug exposure and taking into consideration duration of therapy, only neutrophil decline was independently associated with virologic response. The mean changes in pharmacodynamic parameters after adjusting for drug exposure from baseline to weeks 4, 12, and 24 for virologic responders and nonresponders are shown in Fig. 3. Following the initiation of combination therapy, rapid decreases in neutrophil count, platelet count, and hemoglobin level were observed, with most of the decline occurring by week 4 for both responders and nonresponders. Significantly greater declines in neutrophil count (P < 0.0001) and platelet count (P < 0.005) were seen at all time points in virologic responders compared with nonresponders. The mean decreases from baseline in hemoglobin level were similar between virologic responders and nonresponders at all time points after adjusting for drug exposure.

Overall there were 69 bleeds(52 patients).In total 437 OGDs were performed. Complications were seen in 3% of OGDs(pain/fever). Non-selective beta-blockers (NSBB) were used as adjunctive therapy in 21 group B patients. During 42mo median follow up progression of varices was recorded in 25% and 39% in group A and B, respectively. Conclusion: The prediction of severe GE varices remains challenging from existing non-invasive markers. PVT patients have higher variceal progression. 27% of patients presented with bleeding. During the current follow-up

primary and PD0325901 order secondary prophylaxis were successful in 95% and 74% of patients, respectively. Disclosures: The following people have nothing to disclose: Anastasios Grammatikopoulos, Peter Witters, Dominic A. Hughes, Palaniswamy Karthikeyan, Somashekara H Ramakrishna, Mark Davenport, Anil Dhawan The hepatocyte plays a central role in hepatic lipid homeostasis PF-02341066 molecular weight and storage by regulating the formation and utilization of lipid droplets (LDs), spherical organelles composed of triacylglyc-erol (TG) and cholesteryl esters surrounded by a phoshophlipid monolayer. Aberrant accumulation of hepatic lipids occurs when the synthesis of LDs exceeds catabolism, leading to steatosis. Autophagy is a major process used by the hepatocyte to catabolize LDs, although the central mechanisms supporting the autophagic digestion of LDs, or “lipophagy,” are poorly defined.

Proteomic studies have indicated that Rab7, a small GTPase best known for regulating the late endosomal pathway, resides on LDs, although its function in LD metabolism remains elusive. We have found that GFP-tagged Rab7 associates prominently with LDs in live hepatocytes and that this interaction is significantly increased when cells are placed under nutrient stress. From these findings, the GOAL of this study was to determine whether Rab7 might act as a regulator of lipophagy in hepatocytes. We demonstrate that Rab7 is indispensable for LD breakdown in hepatocytes subjected to nutrient deprivation. Importantly, Rab7 is dramatically activated in cells placed under nutrient stress. This activation is required for the association of both multivesicular bodies (MVBs) and lysosomes with the

LDs during autophagic catabolism. Rapamycin in vivo Depletion of Rab7 leads to gross morphological changes of the MVB, lysosomal, and autophagosomal compartments, while the physical interactions between these compartments and the LD are markedly reduced thereby attenuating hepatocellular lipophagy. These findings provide additional support for the role of autophagy in LD catabolism in the hepatocyte and implicate the small GTPase Rab7 as a key regulatory component of this essential process, thus providing a potential therapeutic target for liver steatosis. This study was supported by grants 5R37DK044650 (MAM), 5RO1AA020735 (MAM and CAC), NIH Challenge Grant AA19032 (MAM and CAC), and the Optical Morphology Core of the Mayo Clinic Center for Cell Signalling in Gastroenterology (MIDDK P30DK084567).