NASH Group Research Articles

Reply

Reply

The Serum Endothelın-1 Level in Steatosıs and NASH, and Its Relatıon wıth Severıty of Lıver Fıbrosıs

Endothelin-1 (ET-1) is known to play an important role in hepatic fibrosis. ET-1 is also a mediator that is elevated in conditions such as insulin resistance, hyperglycemia, oxidative stress, and endothelial cell dysfunction. In this study, we investigated whether ET-1 has a role in determining the severity of liver fibrosis in NASH. Also, the relation between ALT levels, obesity, diabetes, and AST/ALT ratio and fibrosis and ET-1 level was sought. A total of 92 patients were enrolled in the study. The patients were categorized into three groups: group 1, patients with elevated transaminase levels who were diagnosed as NASH by liver biopsy (n=40); group II, patients with only hepatosteatosis determined by biopsy but having elevated transaminase levels (n=12); and group III, patients with hepatosteatosis observed by ultrasonography, having normal transaminase levels (n=40). The serum ET-1 level was measured by an appropriate ELISA kit for all patients. Mean serum ET-1 level was statistically significantly higher in the NASH group compared to the other two groups (15.56+/-4.63 vs 6.75+/-2.46 and 5.74+/-2.34 micromol/L; P < 0.01). Mean serum ET-1 levels in NASH patients with grade I, grade II, and grade IV fibrosis were 14.06+/-0.92, 17.70+/-2.32, and 20.40+/-1.40 micromol/L, respectively. None of the patients were identified as grade III fibrosis. It was found that the serum ET-1 level showed a statistically significant increase as fibrosis severity increased in NASH patients (P < 0.05). In conclusion, the serum ET-1 level is higher in NASH patients compared to patients having only steatosis. There appears to be a correlation between severity of fibrosis and serum ET-1 level in NASH patients. It has been found that NASH patients having a twofold increase in their ALT levels had higher ET-1 levels and a more severe grade of fibrosis.

Hepatic Histopathology of Morbid Obesity: Concurrence of Other Forms of Chronic Liver Disease

Obesity is a chronic inflammatory condition, with related steatohepatitis and liver fibrosis. The authors analyzed the hepatic histopathology in morbidly obese patients and predictors of concurrence of clinical and/ or histopathologic findings of steatohepatitis with other forms of chronic liver disease. The histopathologic findings in the liver of 160 patients who were undergoing laparoscopic gastric bypass or gastric banding for morbid obesity, were examined. Clinical data (gender, age, BMI and associated diseases) and laboratory evaluation were obtained from the patient records. The degree of steatosis, ballooning degeneration, lobular inflammation and fibrosis were determined and scored. Among the patients, 62.5% (n=100) were females and 37.5% (n=60) were males, age 27 +/- 12 years, with mean BMI 43 +/- 5.8 kg/m(2). 63, 54, 26, 15 and 2 patients were diagnosed as non-nonalcoholic steatohepatitis (non-NASH), NASH, chronic hepatitis B (CHB), alcoholic steatohepatitis and chronic hepatitis C (CHC), respectively. The prevalence of NASH was 33.8%, of which 5 patients (9.2%) had bridging fibrosis, but no cirrhosis was found in the NASH group. The prevalence of CHB was 16.3%, of which 3 patients (11.6%) had bridging fibrosis and/or cirrhosis. Multivariate analysis showed an association between steatosis and AST, ALT, GGT, C-peptide, insulin, HOMA-IR and adiponectin. The predictors of ballooning degeneration were serum sugar and AST, whereas the predictors of lobular inflammation were AST and ALT. There was a trend toward a correlation between abnormal liver function, insulin resistance, steatosis, liver cell injury and Mallory body in the NASH population. BMI, C-peptide, steatosis, ballooning degeneration and portal inflammation were significantly different between NASH and CHB groups, but only steatosis and ballooning degeneration were independent factors of NASH compared with CHB group after multivariate analysis. Overall, AST, AST/ALT ratio, uric acid and portal inflammation were independently associated with advanced fibrosis, while only Mallory body (P=0.033) and portal inflammation (P=0.015) were significantly different between mild-moderate fibrosis and advanced fibrosis in the NASH patients. Hepatic steatosis, features of metabolic syndrome and liver cell injuries were common in morbidly obese patients. Abnormal liver function and portal inflammation were related to hepatic fibrosis. The coexistance of clinical and histologic features of steatohepatitis with another chronic liver disease may reflect the biological significance of the chronic inflammatory condition in the obese population, which requires further investigation.

Endotheliitis in Chronic Viral Hepatitis

Endotheliitis is an important histologic feature of acute cellular rejection (ACR) in the liver allograft. This change is not specific, however, and has been suggested to be associated with various liver diseases. End-stage liver disease owing to chronic hepatitis C is the leading indication for transplantation in North America, and its recurrence in allograft recipients is common. Because the presence of endotheliitis remains a diagnostic and therapeutic dilemma in transplant pathology, we investigated the prevalence and severity of endotheliitis in chronic liver diseases including hepatitis C. Endotheliitis was evaluated in 128 nontransplant liver biopsies of chronic liver diseases before therapy, including hepatitis C (HCV, n=62), hepatitis B (HBV, n=17), and nonalcoholic steatohepatitis (NASH, n=49). Eighty posttransplant biopsies with ACR were also reviewed. Subendothelial and supraendothelial endotheliitis were separately scored in the portal and central regions using a semiquantitative scoring system from 0 to 4. Pathologists were blinded to the clinical histories, and each biopsy was independently scored by 2 pathologists. Histologic activity index was also scored subsequently for cases of chronic HCV and HBV, using the modified Knodell (Ishak) score. Mean endotheliitis scores>1 were seen in 60%, 35%, and 6% of HCV, HBV, and NASH patients, respectively. The scores for portal subendotheliitis and supraendotheliitis were significantly higher in the viral hepatitis group than in the NASH group (P<0.01). There was no significant difference in the scores of endotheliitis comparing HCV to HBV. ACR group showed significantly higher scores in both portal and central subendotheliitis than any other group (P<0.00005). In the HBV and HCV groups with mean scores of portal subendotheliitis>1 (n=44), mean Ishak scores for portal inflammation and periportal injury were 2.43 and 2.34, respectively; whereas in those with less severe portal subendotheliitis (<or=1, n=35), Ishak scores were 1.66 and 1.37, respectively (P=0.00001 for portal inflammation and P=0.00001 for periportal injury, respectively). Our results suggest that minimal to mild subendotheliitis is common in portal veins in chronic hepatitis C and B, but is significantly less intense than that seen in ACR. The degree of endotheliitis correlates with inflammatory activity. These observations may help minimize the risk of overdiagnosing ACR when the patient has recurrent viral hepatitis, and may help clinicians avoid exposing patients to unnecessary immunosuppressive regimens when patients do not have cellular rejection.

Comparison of Liver Histology Between Patients with Non‐Alcoholic Steatohepatitis and Patients with Alcoholic Steatohepatitis in Japan

This study compared the liver histology of patients with NASH and patients with ASH. Subjects consisted of 79 patients (41 in the NASH group and 38 in the ASH group). We performed physical and laboratory examinations as well as liver biopsy in all subjects, and we evaluated the differences between the NASH and ASH groups. In addition, we compared the liver histology of patients with obesity, diabetes or hyperlipidemia within the NASH group. BMI was significantly higher in the NASH group than in the ASH group. Steatosis and nuclear vacuoles were more prevalent in the NASH group than in the ASH group. On the other hand, ballooning hepatocytes, lipogranuloma, focal necrosis, acidophilic bodies and fibrosis were more remarkable in the ASH group than in the NASH group. The degrees of steatosis and lipogranuloma gradually decreased as the stage of liver fibrosis progressed. Necro-inflammation and fibrosis tended to be more remarkable in the ASH group than in the NASH group. In the NASH group, ballooning hepatocytes and acidophilic bodies were significantly higher in the group with diabetes than in that without diabetes. Perivenular fibrosis, pericellular fibrosis and portal fibrosis were also higher in the NASH group with diabetes than in the NASH group without diabetes. These findings suggested that diabetes is deeply involved in the development and progression of NASH.

Elevated urine neopterin levels in nonalcoholic steatohepatitis

Objectives: The aim of this study was to relate urine levels of neopterin, a marker of activation of the cellular immune system, with grading and staging of NASH. Design and methods: Urine concentrations of neopterin, routine tests, insulin and C-peptide levels were assessed in 50 patients with NASH, 25 patients with chronic viral hepatitis (CVH), and in 26 healthy controls. Results: Urine neopterin levels were found elevated in the NASH and CVH groups compared with controls. There was no significant correlation between urine neopterin levels and inflammation grade in the liver. Conclusions: Urine neopterin levels are a marker of cellular immunity and are higher in patients with NASH. However, neopterin levels were not significantly associated with histopathological grade and stage of disease.

Axenic cultivation and characterization of Giardia lamblia isolated from humans in Korea.

Inoculating of human fecal cysts to suckling Mongolian gerbils, two Giardia lamblia isolates, K1 and K2, were established as axenic cultures. Using this in vitro culture, both isolates were characterized as a "medium-rate grower" upon its growth pattern. These two Giardia isolates were grouped by using two genetic analysis. With genetic analysis of SSU-rDNA sequences, both K1 and K2 were found as members of Hopkins' group 1, despite some nucleotide differences noticed in K2 (5 differences/292 bases). The other genetic study used PCR-RFLP of the tim (triose phosphate isomerase) gene. Both of K1 and K2 were found to belong to Nash's group 2. Our results suggest that Nash's group 2 can not be a separate group, but a part of Hopkins' group 1.

EQUIVARIANT EXPONENTIALLY NASH VECTOR BUNDLES

Let $G$ be a compact affine exponentially Nash group and let $\eta$ be a $C^\infty G$ vector bundle over a compact affine exponentially Nash $G$ manifold $X$. We prove that $\eta$ admits a unique strongly exponentially Nash $G$ vector bundle structure $\zeta$, and that $\eta$ admits a non-strongly exponentially Nash $G$ vector bundle structure if dim $X\geq 1$, rank $\eta\geq 1$ and $X$ has a 0-dimensional orbit. Moreover we show that every exponentially Nash $G$ vector bundle structure of $\eta$ which is not necessarily strongly exponentially Nash is exponentially Nash $G$ vector bundle isomorphic to $\zeta$ if the action on $X$ is transitive.

EQUIVARIANT EXPONENTIALLY NASH VECTOR BUNDLES

Let $G$ be a compact affine exponentially Nash group and let $\eta$ be a $C^\infty G$ vector bundle over a compact affine exponentially Nash $G$ manifold $X$. We prove that $\eta$ admits a unique strongly exponentially Nash $G$ vector bundle structure $\zeta$, and that $\eta$ admits a non-strongly exponentially Nash $G$ vector bundle structure if dim $X\geq 1$, rank $\eta\geq 1$ and $X$ has a 0-dimensional orbit. Moreover we show that every exponentially Nash $G$ vector bundle structure of $\eta$ which is not necessarily strongly exponentially Nash is exponentially Nash $G$ vector bundle isomorphic to $\zeta$ if the action on $X$ is transitive.

Groups definable in local fields and pseudo-finite fields

Using model-theoretic methods we prove: If G is a Nash group over the real or p-adic field, then there is a Nash isomorphism between neighbourhoods of the identity of G and of the set of F-rational points of an algebraic group defined over F. Let G be a connected affine Nash group over ℝ. Then G is Nash isogeneous with the (real) connected component of the set of real points of an algebraic group defined over ℝ. Let G be a group definable in a pseudo-finite field F. Then G is definably virtually isogeneous with the set of F-rational points of an algebraic group defined over F.

Correction to: “One-dimensional Nash groups”

Correction to: “One-dimensional Nash groups”

One-dimensional Nash groups

One-dimensional Nash groups

On groups and fields definable in o-minimal structures

The structure M = ( M, <, R 1, R 2,…) is o-minimal if every definable set X ⊂ M is a finite union of intervals ( a, b) and points. Let G be a group definable in M (i.e. G is a definable subset of M n and the graph of multiplication is also definable). We show that G can be definably equipped with the structure of a ‘manifold’ over M in which multiplication and inversion are continuous. In the special case M = ( R , <, +, ·) our construction gives G the structure of a Nash group. These results are also used to show that an infinite field definable in an o-minimal structure is real closed or algebraically closed.