Top PDF Insulin resistance and steatosis in chronic hepatitis C

Insulin resistance and steatosis in chronic hepatitis C

Insulin resistance and steatosis in chronic hepatitis C

changed IR in non responders, despite a decrease in BMI. 32-34 Steatosis Although the estimated prevalence of hepatic steato- sis in the general population is 20%, in patients with chronic hepatitis C it may vary from 40-80%, depending on alcohol consumption, obesity, diabetes and other risk factors to fatty liver. 35-43 If all steatogenic co-factors are excluded, the prevalence of steatosis remains 50% (al- though present in less than 30% of the hepatocytes in about two thirds of the patients), 38,40 resulting in a 2.5 fold increased prevalence as compared with the general population and other forms of chronic liver disease, 44-46 particularly HBV infection, in which the prevalence of steatosis is 18%. 47 In chronic hepatitis C, although hepat- ic steatosis can be related to metabolic factors like obesi- ty, dyslipidaemia and DM, 38-42,48,49 as much as one third of the patients with steatosis do not have any metabolic im- pairment. 44 Also, steatosis is more frequent in HCV as compared to HBV infected subjects, even after adjust- ment to BMI. As shown in Table I. 37
Show more

9 Read more

Prevalence of insulin resistance in chronic hepatitis C genotype 1 and 3 patients

Prevalence of insulin resistance in chronic hepatitis C genotype 1 and 3 patients

Our data contradicts some studies that have found a more severe degree of liver steatosis and fibrosis among HCV genotype 3 patients. 28-35 Indeed, HCV genotype 3 seems to have a direct cytopathic effect, which has been shown to decrease and disappear upon successful treatment with antivirals. 36,37 However, despite inducing more steatosis and fibro- sis, it is not clear whether HCV genotype 3 is linked or not to a higher degree of IR. In this regard, data is controversial, with some authors showing higher IR among HCV genotypes 1 and 4, 27 while others found it to be increased in patients infected with HCV genotype 3. 3 Finally, a more recent multicen- tre study found that HCV genotype does not affect IR in non diabetic patients with chronic hepatitis C. 38 Our results corroborate these later findings.
Show more

5 Read more

Leptin ameliorates insulin resistance and hepatic steatosis in Agpat2 / lipodystrophic mice independent of hepatocyte leptin receptors

Leptin ameliorates insulin resistance and hepatic steatosis in Agpat2 / lipodystrophic mice independent of hepatocyte leptin receptors

DISCUSSION The worldwide epidemic of obesity and related meta- bolic diseases has fueled new adipose tissue biology re- search. Among the most important advances in the fi eld has been the discovery of the hormonal actions of WAT ( 2 ). In CGL patients, the lack of WAT determines insulin resistance, diabetes mellitus, hepatic steatosis, and hyper- lipidemia. In these patients ( 28 ) as well as in all tested mu- rine models of CGL ( 27, 50, 51 ), leptin infusion ameliorates all metabolic complications of lipodystrophy, in spite of persistent WAT defi ciency, indicating that leptin secretion by adipocytes is necessary for normal metabolic regula- tion. Importantly, the understanding of the mechanism by which leptin ameliorates the metabolic disturbances CGL is still incomplete.
Show more

13 Read more

PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C

PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C

DISCUSSION We reported an association between PNPLA3 rs738409 allele-G and liver steatosis in a large co- hort of chronic hepatitis C patients. Indeed, the im- pact of PNPLA3 polymorphisms on steatosis depends on viral and IL28B genotypes. Steatosis is known to negatively impact on the natural history of HCV infection as it accelerates the progression to cirrhosis. Metabolic, enviromental, genetic and viral factors have been implicated on steatosis develop- ment. However, the weight of each of them in a de- terminate patient remains elusive. Patients with PNPLA3 allele-G, overweight, HOMA > 4 and viral genotype 3a were independently associated with st- eatosis. PNPLA3 allele-G was associated with stea- tosis in patients infected by HCV-genotype 1, showed a trend in genotype 2 and genotype 4, but was not related to steatosis in genotype 3a. A link between this gene and steatosis was reported by Trépo, et al., but genotype 3 patients were not in- cluded. 12 Our data confirm previous results reported by Valenti, et al. 13 and Cai, et al. 14 that evaluated the effect of PNPLA3 on liver fat and fibrosis in HCV patients. The rs738409 GG genotype was close- ly associated with steatosis across all viral geno-
Show more

8 Read more

Serum lipids and chronic hepatitis C genotype 4: interaction and significance

Serum lipids and chronic hepatitis C genotype 4: interaction and significance

noted in clinical cases. 8 These data suggest how mo- lecules targeting lipid metabolism could improve HCV therapy. 9 Different HCV genotypes are shown to have diffe- rent associations with hepatic steatosis. In particu- lar, in patients infected with genotype 3, steatosis is mostly virus-induced and often severe, correlates with intrahepatic viral load, and resolves after suc- cessful antiviral therapy. 10,11 In contrast, in patients infected with genotype 1, 4 steatosis is mainly asso- ciated with host metabolic factors and correlates with body mass index (BMI) and central adiposity. 12 Moreover, recent clinical data suggest that HCV associated IR is genotype-dependent (1 and 4). 13 Ta- king these lines of evidence together, we hypothesi- zed that there exist genotypic differences on the association of lipid profiles and HCV. Unfortunately, HCV-4 has simply not been the subject of wides- pread research and, the differential association of li- pid profiles with HCV viral load and histology between genotypes 4 infections remain largely unk- nown and deserves to be studied. We therefore con- ducted this prospective study to determine the serum lipid profile in patients with chronic HCV-4 infection, and to detect if there is any correlation between serum lipid levels and viral load, HCV geno- type or liver histology.
Show more

10 Read more

Recreational Drug and Psychosocial Profile in Chronic Hepatitis C Patients Seeking Antiviral Therapy

Recreational Drug and Psychosocial Profile in Chronic Hepatitis C Patients Seeking Antiviral Therapy

rehabilitation facilities or support programs facilitating supervised drug consumption associated with a lower re- infection rates. Alcohol is considered to be the most used and abused psychoactive drug worldwide. 33 In agreement with this statement, more than 85% of our study population report- ed alcohol use, of whom nearly half had harmful/hazard- ous alcohol use. Notably, 28% of patients were current drinkers. Alcohol abuse also contributes to risky behavior patterns 34,35 and is associated with higher incidence 36 and prevalence of HCV infection compared to the general population. 37 It is well known that alcohol plays a major role on liver disease. Recently, even moderate alcohol consumption was linked to cirrhosis in a nationwide Dan- ish study. 38 Marijuana is another widely used recreational drug and almost 80% of our patients were either past or current THC consumers. The role of cannabinoids in cir- rhosis is a widely debated topic. There is experimental ev- idence linking CB1 overexpression to increased steatosis, 39 whereas, THC inhibits alcohol-induced in- flammation and steatosis via CB2, 40 in addition to sup- pressing proliferation and inducing apoptosis of hepatic myofibroblasts resulting in an antifibrotic and hepatopro- tective effect. 41 Although a retrospective study indicated daily THC use independently predicted fibrosis progres- sion, 42 more evidence is needed to clarify final effects of smoking marijuana on hepatic fibrogenesis. In what re- spects to regression of fibrosis, alcohol use in HCV-relat- ed cirrhosis would negate patients from the full benefits of viral eradication by perpetuating the fibrogenic proc- ess. 43 To date, there is no data on the mechanism of THC in fibrosis regression after viral eradication. Whereas it is crucial to identify HCV patients with alcohol use disorder and refer them to effective de-addiction and rehabilitation programs to reduce future liver damage, the same cannot be said about THC yet, but arguably evidence points in the same direction.
Show more

9 Read more

Risk factors for liver fibrosis progression in patients with chronic hepatitis C

Risk factors for liver fibrosis progression in patients with chronic hepatitis C

Steatosis and metabolic factors Steatosis occurs in more than 50% of patients with chronic hepatitis C and is associated with increased he- patic fibrosis. In many of these patients the pathophysiol- ogy of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease-that is, related to visceral adiposity and obesity. 62 This suggest that increas- ing body mass index has an important role in the patho- genesis of steatosis in the chronic hepatitis C. Weight loss in patients with chronic hepatitis C may be associated with a reduction in steatosis and abnormal liver enzymes and an improvement in fibrosis, despite the persistence of the virus. Weight reduction may provide an important ad- junct treatment strategy for patients with chronic hepatitis C. 66,67 Recently we have confirmed that genotype 3 HCV infection was associated with significantly more steatosis than other genotype, with lower cholesterol levels and that this “viral” steatosis disappeared in sustained re- sponders. Therefore any studies on steatosis in patients with chronic hepatitis C must separate the genotype 3 population from other patients.
Show more

8 Read more

Factors associated with the severity of liver damage in chronic hepatitis C

Factors associated with the severity of liver damage in chronic hepatitis C

and methods: Retrospective study of 84 liver biopsies of patients with chronic infection with hepatitis C virus were studied. The pathological appearance was classified as stage I when chronic hepatitis with mild activity without fibrosis was observed; as stage II when moderate chronic hepatitis with mild fibrosis was observed and as stage III when there was a moderate chronic hepatitis with fibrosis or cirrhosis. The amount of steatosis and iron deposition in the biopsy were also assessed. Results: Forty one percent of patients were in stage I, 32% in stage II and 27% in stage III. Patients in stage I were younger than those in stages II and III (40.7 and 52.2 years respectively, p <0,001). No association between the severity of liver damage and the degree of steatosis, hemosiderosis, body mass index or alcohol intake, was observed. The frecuency of diabetes mellitus increased along with pathological staging (3, 15 and 30% in stages I, II and III, respectively, p <0,05). Conclusions: This study confirms that severity of chronic hepatitis C is associated with age and the presence of diabetes mellitus.
Show more

6 Read more

Role of insulin-degrading enzyme (IDE) in diabetes mellitus and insulin resistance

Role of insulin-degrading enzyme (IDE) in diabetes mellitus and insulin resistance

Despite the intuitive appeal of this idea, we need to take into account that different studies suggested that a strong decrease of IDE activity will not have a beneficial impact in whole metabolism of T2DM patients. In theory, if IDE is involved in insulin clearance, than chronic inhibition of IDE might result in persistent hyperglycemia, which could in turn further increase insulin resistance 176 . Chronic hyperinsulinemia can also lead to up-regulation of cell proliferation 177 . Moreover, numerous side effects are expected after IDE inhibition, due to IDE degradation activity on other metabolic substrates as glucagon, Aβ and amylin. In the case of Aß, which accumulates abnormally in the brains of Alzheimer’s patients, it has been shown that inhibitors of IDE that do not cross the blood-brain barrier do not effect Aß 173 . However, with regard to amylin, which accumulates in the pancreas, there is controversy about possible exacerbation of amylin deposition due to IDE inhibition. On the one hand, using a weak inhibitor of IDE, bacitracin, which is also not very selective Bennett et al. 178 reported that prolonged IDE inhibition leads to amyloid deposition 178 in 2.6.3 Pharmacological therapies against T2DM based on inhibition of IDE
Show more

155 Read more

Diagnostic performance of controlled attenuation parameter for predicting steatosis grade in chronic hepatitis B

Diagnostic performance of controlled attenuation parameter for predicting steatosis grade in chronic hepatitis B

between S0/S1 and S2/S3 would be advantageous for a screening tool. Although LB remains the gold standard for as- sessing steatosis it is subject to limitations as dis- cussed briefly in the introduction. 19,20 Most importantly, due to the invasive nature of the tech- nique it cannot be performed on all patients, repeat- ed regularly or used as a screening tool. Hence, other non-invasive methods have been developed to diagnose steatosis. 20,41-44 Of the imaging techniques, ultrasonography is the most frequently used for liv- er imaging and steatosis can be assessed by compar- ing parenchymal echogenicity with kidney echogenicity. 41,44,45 However, use of this method for assessing steatosis in clinical practice is controver- sial as it is highly operator and machine depend- ent. 41,44-46 Other imaging techniques can also detect steatosis, but have limitations such as being ionis- ing (CT), lacking sensitivity and specificity, 41,44,45 lacking validation or standardization (MRI and magnetic resonance spectroscopy), 44,47,48 and/or be- ing costly. 44,49 Similarly, the use of serum markers for predicting steatosis has been investigated, but found to have low performance. 42-44,50
Show more

11 Read more

Prevalence and resistance pattern of genotype G and H in chronic hepatitis B and HIV co infected patients in Mexico

Prevalence and resistance pattern of genotype G and H in chronic hepatitis B and HIV co infected patients in Mexico

Other associated mutations as T1762/A1764 asso- ciated with genotype F and hepatocelluar carcinoma could not be determined in our study. 10 Studies of long-term treatment with lamivudine in patients with HBeAg positive chronic hepatitis B re- veal 11 and 14% with lamivudine resistance in 1 year, and 6 to 27% in HBeAg negative chronic hepati- tis B. 20,21 All our patients who developed resistance mutations had more than one year with lamivudine experience. As well, we found similar pattern muta- tions that Lai et al., with lamivudine resistance ba- sed on the signature mutations rtM204I and rtM204V which in the case of rtM204V was frequently accom- panied by the rtL180M secondary mutation. 22
Show more

5 Read more

Treatment of chronic hepatitis C virus infection in the near future

Treatment of chronic hepatitis C virus infection in the near future

open-label, single-arm study, enrolled 327 treatment naïve patients with HCV genotypes 1,4,5 and 6. There was fixed treatment duration of 12 weeks, without use of response guided therapy. Overall, 17% of the patients were cirrhotics and 29% had IL28B CC. Results showed an SVR of 89% for HCV genotype 1 patients and 97% for the 35 patients with genotypes 4,5 and 6. There was no actual control group, however the study used a calculated historical, with an estimated SVR of 60%. Patients with cir- rhosis had an SVR of 80%, which was the highest rate reported thus far for a population of patients with cirrhosis in any study. The few failures were relapses. No sofosbuvir resistance was detected, con- firming the high genetic barrier of this compound.
Show more

6 Read more

Role of metabolic endotoxemia in insulin resistance and obesity. The Buffering Efficiency Hypothesis

Role of metabolic endotoxemia in insulin resistance and obesity. The Buffering Efficiency Hypothesis

The evidences reviewed here led us to propose the buff- ering effi ciency hypothesis (fi gure 1). LPS is an impor- tant factor that might produce insulin resistance and obesity in humans. Chronic low-grade infl ammation and associated insulin resistance might be viewed in the con- text of an unbalanced innate immune system. A de- creased production of anti-LPS proteins and peptides were associated with insulin resistance, obesity, vascular dysfunction, hepatic dysfunction and dyslipidemia. A partial lost in the buffering effi ciency of LPS could in- crease its negative effects on metabolism. Furthermore, insulin resistance might result in a decreased concentra- tion of those proteins that buffer LPS. It is well known that adiponectin production by the adipose tissue is de- creased under insulin resistance and infl ammatory con- ditions. Neutrophils also lose antimicrobial effi ciency in insulin resistant conditions, decreasing the production of lactoferrin, BPI and other antimicrobial proteins. Neu- trophil activity may be restored by controlling hypergly- cemia using insulin. 80,81
Show more

8 Read more

Insulin resistance and erectile dysfunction  Effect of treatment with metformin

Insulin resistance and erectile dysfunction Effect of treatment with metformin

Aims: To evaluate in ED patients: 1) the presence of IR; 2) the degree of severity of ED according to the presence of IR; 3) the effect of treatment with metformin on erectile function in patients with ED and IR. Methods: Prospective, randomized, controlled, double-blind placebo study. We included 81 patients with ED and 20 men without ED (control group). Exclusion criteria: pharmacologic, anatomic or endocrine ED (hypogonadism or hyperprolactinemia), DM2, prior prostatic surgery or chronic illnesses. The erectile function was rated according the International Index of Erectile Function 5. IR was measerud by HOMA index. Thirty patients with ED, IR and poor response to sildenafil were randomized to receive metformin or placebo.
Show more

8 Read more

Insulin resistance in overweight and obese adolescents

Insulin resistance in overweight and obese adolescents

Overweight and obesity were determined by Must et al. criteria: overweight between 85 and 95 percentile and obesity overt the 95 percentile. Glycemia and basal insulin were determined in serum obtained by vein puncture. IR was determined by HOMA’s index considering Keskin diagnosis value of 3,1. Results: There was no biochemical statistical difference between the overweight and obesity groups; 14% showed IR, 16,2% in the obese children and 12,3% in those overweight. Average insulin and HOMA in obese

7 Read more

Glucose metabolism and insulin resistance in dogs

Glucose metabolism and insulin resistance in dogs

Glukagon utsöndras från pankreas α-celler och är ett viktigt hormon i den postabsorptiva fasen då det motverkar hypoglykemi. Glukagon frisätts när blodglukoskoncentrationen sjunker och har motsatt effekt mot insulin. Hormonet verkar för att öka glukosnivån i blodet vilket främst görs genom att öka glykogenolysen och glukoneogenesen. Lipolysen i fettvävnaden stimuleras också av glukagon. Även den sjunkande koncentrationen av insulin är avgörande för övergången till ett katabolt tillstånd i den postabsorptiva fasen. Det är förhållandet mellan nivåerna av insulin och glukagon som avgör om metabolismen blir anabol eller katabol. Under fysisk aktivitet kommer glukagon dominera över insulin eftersom det centrala nervsystemet hämmar insulin men stimulerar glukagon. Detta gör att blodglukoskoncentrationen bibehålls trots att mycket glukos förbrukas. I skelettmuskulatur verkar insulinoberoende mekanismer för att förse vävnaden med glukos i tillräcklig mängd.
Show more

18 Read more

Vitamin D deficiency and vitamin D therapy in chronic hepatitis C

Vitamin D deficiency and vitamin D therapy in chronic hepatitis C

Data on the stage of liver fibrosis measured with transient elastography performed in the previous 6 months were available on 89 patients. The IL28B rs12979860C/T polymorphism was determined in 95 patients. Methods to determine HCV load in plasma, HCV genotype and subtype and IL28B rs12979860C/T genotype have been described elsewhere. 19 Haemato- logical and biochemical analysis were performed by standard tests. Sixty patients were naïve for antivi- ral therapy whereas the remaining 48 had received unsuccessful interferon-based therapy more than a year before their inclusion in the study.
Show more

6 Read more

Chronic Hepatitis C and HCC : What is new?

Chronic Hepatitis C and HCC : What is new?

Liver Angiopoietin-2 Predicts De Novo and Recurrent HCC after DAA Therapy of HCV Fallaci F et al Hepatology 2018 Recurrent and de novo HCCs had significantly higher liver fibrosis scores, portal pressure, and systemic inflammation than non-recurrent HCC or patients never developing HCC

49 Read more

Alcoholic intake predisposes to more interface hepatitis in chronic hepatitis C

Alcoholic intake predisposes to more interface hepatitis in chronic hepatitis C

MF Gomes de Sá Ribeiro et al. Alcoholic intake predisposes to more interface hepatitis in chronic hepatitis C 181 edigraphic.com Discussion This study shows that histopathological parameters like fibrosis, lobular inflammation and portal infiltrate in candidates for blood donation with hepatitis C did not differ when alcohol abstainers, light drinkers and heavy drinkers were compared. Only periportal inflam- mation was more severe in heavy drinkers. The most commonly used parameter to evaluate the progression of liver disease is fibrosis, 18 and many studies have indicat- ed an increased risk of progression of chronic hepatitis C with increasing levels of alcohol consumption. 14,19 As some of these studies have included higher percentages of cirrhotic patients than ours, our results may reflect an earlier phase of disease progression. 20 As the inflamma- tory process precedes fibrosis development, it is under- standable that there was a statistically significant differ- ence for inflammation but not for fibrosis. The histo- pathological finding of periportal inflammation cannot be associated with isolated alcohol abuse. In fact, the most common histopathological alcoholic alterations predominate in zone 3 of the Rappaport acinus. 21 On the other hand, we are dealing with an association of hepati- tis C and alcohol, and the histopathological parameters, suggestive of alcoholic damage, are different from those of viral hepatitis. 22 Another possibility which explains no differences in fibrosis, when abstainers were com- pared to light or heavy drinkers, is a beta error. In fact, the greater degree of histological architectural alter- ations was found in only 13 patients, the majority of them (61.5%) being heavy drinkers. One can speculate that, in a larger population, a significant difference would appear, as shown by other authors. 6,14
Show more

9 Read more

Obesity, insulin resistance and type 2 diabetes mellitus in adolescents

Obesity, insulin resistance and type 2 diabetes mellitus in adolescents

RI se han basado en la distribución en una población de referencia, pero como consecuencia de la influencia que ejer- cen muchos factores como la pubertad, las diferencias étnicas, y los estados nu- tricionales, es que estos valores varían y no existe uno reconocido y aceptado in- ternacionalmente. Diversos autores han propuesto puntos de corte para identifi- car la RI. En ese sentido, Keskin demostró en niños obesos que el punto de corte para diagnosticarla fue de 3,16, dada su alta sensibilidad y especificidad 19 . Recien- temente Garcia-Cuartero, en niños sanos y con un estado nutricional normal, en- contraron que el valor del 90 percentil fue de 3,43 23 .
Show more

6 Read more

Show all 10000 documents...

Related subjects