Types Of Chronic Liver Disease Research Articles

Etiologic types of end-stage chronic liver disease in adults

Whole native livers from orthotopic liver transplant (LT) recipients provide an ideal resource material for the proper identification and etiologic evaluation of end-stage liver diseases in these patients. This study determined the etiologic types of chronic liver disease (CLD) in adults of our geographic region receiving living donor LT and projected approximate estimates of their current prevalence and temporal changes in these in the general population. The final etiologic categorization of CLD in 372 adult LT recipients was made only after correlating the morphologic findings on explanted whole native livers with all pre-LT data and diagnosis. The final etiologic categorizations of end-stage CLD in the majority (88.4%) of explanted livers in our series were as follows: hepatitis virus related--48.6% [hepatitis C virus (HCV)--31.1%, hepatitis B virus (HBV)--15.9%, HCV and HBV--1.6%]; alcohol related--23.1%; and NALD related--16.7%. Of 84 cases clinically considered as cryptogenic cirrhosis, 57 and nine were finally categorized as nonalcoholic fatty liver disease (NAFLD) cirrhosis and noncirrhotic portal fibrosis, respectively. Hepatocellular carcinoma (HCC) was found in 20.7% of all livers, 81.8% of these tumors developing in HBV-related and/or HCV-related CLD and 9.1% each in alcohol-related and NAFLD-related CLD. The etiology of end-stage CLD in adults of our region has changed over time. HCV, more than HBV, is now the major cause of both CLD and HCC; alcohol-related CLD has increased significantly and several cases of cirrhosis clinically considered as cryptogenic, some of them with HCC, evolve from NAFLD. A proportion of cryptogenic cirrhosis cases that require LT are constituted by the noncirrhotic disease noncirrhotic portal fibrosis.

Review article: the reversibility of cirrhosis

Cirrhosis is the end result of many types of chronic liver diseases. Recent developments in the understanding of the process of hepatic fibrogenesis have revealed that the process is a dynamic one and a capacity for recovery from any degree of fibrosis including those associated with cirrhosis is plausible. To review current evidence of histopathological reversibility following drug therapy of more common aetiologies of cirrhosis. A PubMed search was performed and the evidence for histopathological regression of advanced fibrosis/cirrhosis following drug therapy was reviewed as of the end of February 2012. There is abundant clinical evidence in support of the idea of the reversibility of cirrhosis in patients with different aetiologies of advanced hepatic disease including viral, autoimmune and metabolic/infiltrative liver disease. The concept of cirrhosis has changed from being a form of static and irreversible entity to a dynamic and reversible diseases stage. Novel therapeutic strategies are under investigation to target specific steps in the process of fibrogenesis with the aim of reversing advanced fibrosis/cirrhosis.

Practice Guidelines for Management of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is one of the most common types of chronic liver disease. Now, the American Association for the Study of Liver

Origin of myofibroblasts in liver fibrosis

Most chronic liver diseases of all etiologies result in progressive liver fibrosis. Myofibroblasts produce the extracellular matrix, including type I collagen, which constitutes the fibrous scar in liver fibrosis. Normal liver has little type I collagen and no detectable myofibroblasts, but myofibroblasts appear early in experimental and clinical liver injury. The origin of the myofibroblast in liver fibrosis is still unresolved. The possibilities include activation of endogenous mesenchymal cells including fibroblasts and hepatic stellate cells, recruitment from the bone marrow, and transformation of epithelial or endothelial cells to myofibroblasts. In fact, the origin of myofibroblasts may be different for different types of chronic liver diseases, such as cholestatic liver disease or hepatotoxic liver disease. This review will examine our current understanding of the liver myofibroblast.

Overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis complicated with hepatocellular carcinoma.

Development of hepatocellular carcinoma (HCC) in patients with autoimmune liver disease is less common than in those with other types of chronic liver disease. Here we report a rare case of overlap syndrome consisting of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) that was subsequently complicated with HCC. A 72-year-old man was initially diagnosed as being in the cirrhotic stage of AIH on the basis of blood chemistry tests and histological examinations. Computed tomography and magnetic resonance cholangiography 20months later showed diffuse stricturing of the intrahepatic bile duct with dilatation of the areas between the strictures, compatible with the findings of PSC, which resulted in a diagnosis of AIH/PSC overlap syndrome. The level of serum protein induced by vitamin K absence or antagonist II increased 22months later, and HCC was diagnosed by radiological examinations. Four cycles of transarterial infusion therapy with cisplatin were performed, but the patient died oneyear later. Sequential overlap of PSC may have played a part in accelerating AIH disease progression, leading to the development of HCC in this patient. Therefore, HCC surveillance may be important in advanced stages of autoimmune disease, especially in the cirrhotic stage.

Sleep Disorders in Chronic Liver Disease

Sleep-related complaints and disturbances are increasingly recognized in the setting of chronic liver disease and have recently been shown to be an important prognostic factor in patients with advanced chronic liver disease. This article reviews the literature surrounding sleep disturbances and disorders in a variety of types of chronic liver disease. This includes the association of sleep disturbances with hepatitis C and antiviral therapy, primary biliary cirrhosis, and Wilson disease as well as the circadian rhythm abnormalities present in cirrhosis and hepatic encephalopathy. The association between chronic liver disease, particularly nonalcoholic fatty liver disease, and sleep-disordered breathing is also reviewed in detail.

Leaky gut and the liver: A role for bacterial translocation in nonalcoholic steatohepatitis

Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments.

Endoglin in liver fibrosis

Liver fibrosis occurs in most types of chronic liver diseases and is characterized by excessive accumulation of extracellular matrix proteins, leading to disruption of tissue function and eventually organ failure. Transforming growth factor (TGF)-β represents an important pro-fibrogenic factor and aberrant TGF-β action has been implicated in many disease processes of the liver. Endoglin is a TGF-β co-receptor expressed mainly in endothelial cells that has been shown to differentially regulates TGF-β signal transduction by inhibiting ALK5-Smad2/3 signalling and augmenting ALK1-Smad1/5 signalling. Recent reports demonstrating upregulation of endoglin expression in pro-fibrogenic cell types such as scleroderma fibroblasts and hepatic stellate cells have led to studies exploring the potential involvement of this TGF-β co-receptor in organ fibrosis. A recent article by Meurer and colleagues now shows that endoglin expression is increased in transdifferentiating hepatic stellate cells in vitro and in two different models (carbon tetrachloride intoxication and bile duct ligation) of liver fibrosis in vivo. Moreover, they show that endoglin overexpression in hepatic stellate cells is associated with enhanced TGF-β-driven Smad1/5 phosphorylation and α-smooth muscle actin production without altering Smad2/3 signaling. These findings suggest that endoglin may play an important role in hepatic fibrosis by altering the balance of TGF-β signaling via the ALK1-Smad1/5 and ALK-Smad2/3 pathways and raise the possibility that targeting endoglin expression in transdifferentiating hepatic stellate cells may represent a novel therapeutic strategy for the treatment of liver fibrosis.

Serum Interleukin-6 Levels Correlate with Resistance to Treatment of Chronic Hepatitis C Infection with Pegylated-Interferon-α2B plus Ribavirin

Interleukin (IL)-6, a pleiotropic cytokine, is increased in various types of chronic liver disease, including chronic hepatitis C (CHC). It was reported recently that IL-6 is associated with insulin resistance, iron metabolism and interferon resistance, which may affect the outcome of antiviral treatment. In this study, we investigated the association of serum IL-6 levels with outcomes of pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. We included 149 CHC patients and measured serum IL-6 levels at baseline and at 4, 8 and 12 weeks, and the end of treatment in 49 patients. We performed univariate and multivariate regression analyses for the association of IL-6 levels and clinical and laboratory parameters and treatment responses. Serum IL-6 levels were significantly higher in CHC patients than healthy subjects. Pretreatment IL-6 levels of male patients were inversely correlated with sustained virological response (SVR) in univariate analysis (P=0.012). In male patients with SVR, serum IL-6 levels decreased significantly at 4 weeks of treatment (P=0.029) and remained significantly lower than those of non-SVR patients after 4, 8 and 12 weeks of PEG-IFN plus RBV therapy. Our results suggest that baseline levels of IL-6, as well as their decrease during treatment, are correlated to outcomes of PEG-IFN plus RBV therapy in male patients. Further analyses of IL-6 may provide new strategies for difficult-to-treat CHC patients and prevention of hepatocarcinogenesis.

Abstract 1408A: Estrogen can stimulate cholangiocarcinoma cells proliferation and invasion and associate with poor prognosis

Abstract Cholangiocarcinoma is defined as a cancer arising from bile duct epithelial cell. The prevalence of cholangiocarcinoma is low among worldwide, however it was raised each year. Moreover, this kind of cancer is endemic in Thailand which associated with liver fluke infection, Opisthorchis viverrini. In Thailand, the prevalence of cholangiocarcinoma was about 20-time higher than in western country and may be more than 400-time in endemic area (northeastern part). Cholangiocarcinoma has poor prognosis with low 5-year survival rate due to its high metastasis rate which caused inadequate surgery while chemotherapy and radiotherapy are resisted. It is a type of chronic liver disease with altered estrogen metabolizing enzyme that could leading to the accumulation of estrogen in plasma. Estrogen was known as a promoting factor in progression of some cancer, eg. breast cancer and endometrial cancer. Our finding indicated the increasing of serum estrogen level in male cholangiocarcinoma patients and correlated with serum alkaline phosphatase and bilirubin and inverse correlated with albumin. The high level of serum estrogen could be determined as poor prognostic factor for survival of cholangiocarcinoma patients with statistically significant. In vitro studies demonstrated the effect of estrogen on cell proliferation and invasion of cholangiocarcinoma cell lines. Real time proliferative assay indicated the growth stimulated effect of estrogen on 4 cholangiocaricinoma cell lines (KKU-100, KKU-M055, KKU-M156 and KKU-M213) in dose dependent manner up to 10 nM. Results from in vitro invasion assay showed the effect of estrogen on cholangiocarcinoma cell invasion with highest effect at concentration 1 nM and this effect could be inhibited by tamoxifen. Metastasis genes expression of KKU-M213 cholangiocarcinoma cell induced by estrogen was measured by RT2 ProlifilerTM PCR array system. Total 84 metastasis genes expression were compared with non-induced cell, 24 genes showed change in expression level more than twice which were 11 genes increased and 13 genes decreased. The pathway of estrogen induced metastasis genes in cholangiocarcinoma cells should be analyzed. The results should indicate the mechanism and control of cholangiocarcinoma invasion and metastasis, which may be introduced to the new therapeutic guideline. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1408A. doi:10.1158/1538-7445.AM2011-1408A

Changes in the Prevalence of the Most Common Causes of Chronic Liver Diseases in the United States From 1988 to 2008

Chronic liver diseases (CLDs) are major causes of morbidity and mortality worldwide. We assessed changes in the prevalence of different types of CLD in the United States. National Health and Nutrition Examination Surveys conducted between 1988 and 2008 were used to estimate changes in the prevalence and predictors of CLDs. Serologic and clinical data were used to establish the diagnoses of CLDs in 39,500 adults. Statistical analyses were conducted with SUDAAN 10.0 (SAS Institute, Inc, Cary, NC). The prevalence rates for CLD were 11.78% (1988-1994), 15.66% (1999-2004), and 14.78% (2005-2008). During the same period, the prevalence of hepatitis B virus infection (0.36%, 0.33%, and 0.34%), hepatitis C virus (1.95%, 1.97%, and 1.68%), and alcoholic liver disease (1.38%, 2.21%, and 2.05%) remained generally stable. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD) increased from 5.51% to 9.84% to 11.01%. From 1988 to 1994, NAFLD accounted for 46.8% of CLD cases; from 1994 to 2004 its prevalence increased to 62.84%, and then to 75.1% from 2005 to 2008. During these time periods, steady increases were observed in obesity (21.74%, 30.02%, and 33.22%), visceral obesity (35.18%, 48.16%, and 51.43%), type II diabetes (5.55%, 7.88%, and 9.11%), insulin resistance (23.29%, 32.50%, and 35.00%), and hypertension (22.68%, 33.11%, and 34.08%). A multivariate analysis showed that during all time periods, obesity was an independent predictor of NAFLD. National Health and Nutrition Examination Surveys data collected from 1988 to 2008 show that the prevalence of major causes of CLD remained stable, except for NAFLD, which increased steadily, along with the prevalence of metabolic conditions. Given the increasing rates of obesity, NAFLD prevalence is expected to contribute substantially to the burden of CLD in the United States.

Depression in Patients with Nonalcoholic Fatty Liver Disease and Chronic Viral Hepatitis B and C

Patients with chronic liver disease (CLD) and depression may be at a higher risk for various complications, including impaired quality of life and more advanced liver disease. The purpose of this study was to determine the prevalence of depression in CLD patients (non-alcoholic fatty liver disease (NAFLD), Hepatitis B (HBV), and Hepatitis C (HCV)) and to identify potential clinical and laboratory correlates of depression in these patients. We used a database of CLD patients that contains extensive clinical (including self-reported depression) and laboratory data for each patient. We compared the prevalence of depression in patients with HBV, HCV, and NAFLD. We also used regression models to find independent predictors of depression in these patients. Of 878 CLD patients, 207 (23.6%) had a diagnosis of depression (NAFLD 27.2%, HCV 29.8%, and HBV 3.7%). Examination of predictors of depression differed by the type of chronic liver disease. For NAFLD, independent predictors of depression were the presence of hypertension, smoking, history of lung disease, being female, and non-African-American. For HBV patients, the only independent predictor of depression was excessive alcohol consumption (defined as >10 g/d), while for HCV patients, independent predictors were being female and non-Asian, presence of fatigue, and excessive alcohol intake. This study demonstrates that individuals with NAFLD and HCV have a higher prevalence of depression than HBV patients and the rates of depression reported for the general population. The most consistent correlates of depression status in CLD patients are being female and excessive alcohol consumption.

Comparative Evaluation of Trace Metals in the Blood of Hepatitis C Patients and Healthy Donors

Hepatitis C is one of the common types of chronic liver disease, and its plausible association with trace metal imbalance has been investigated in the present study. The blood samples of hepatitis C patients and healthy donors were analysed for trace metals (Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Pb, and Zn) by flame atomic absorption spectrophotometry after wet acid digestion. In the blood of the hepatitis patients, mean concentrations of essential metals, Na, K, Fe, Ca, Mg, and Zn, were 918.7, 361.0, 102.5, 20.00, 24.66, and 9.429ppm, respectively, while the mean metal levels in the blood of healthy donors were 1509, 406.8, 232.5, 28.35, 24.59, and 8.799ppm, respectively. On the average, Cr was significantly higher, while Na, Fe, Ca, Cu, Mn, Pb, and Cd were comparatively lower in the blood of the patients. The correlation study manifested significantly divergent mutual relationships of trace metals in the blood of the patients and healthy donors. Multivariate statistical methods revealed considerably diverse distribution of trace metals in the two groups. Dissimilarity in the trace metal distribution was also noted with the gender and residential location of the donors in both groups.

Serum 25-hydroxy-vitamin D3 in chronic liver disease: a transient elastography- based study

Background: Low serum 25-hydroxy-vitamin D3 (vit. D) levels have been associated with advanced liver fibrosis and unfavorable outcome of chronic viral hepatitis C (HCV) treatment. Lately, transient elastography (TE) has gained wide acceptance as a non-invasive tool to assess liver fibrosis. Here we investigate serum vit. D levels in relation to TE values in patients with different types of chronic liver diseases (CLD).

Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years

BackgroundLiver stiffness measurement (LSM) has been used to measure fibrosis in patients with various types of chronic liver diseases. However, its usefulness as a screening procedure in apparently healthy people...

Angiogenesis and experimental hepatic fibrosis

Angiogenesis is a basic change occurring during repair by granulation tissue. This process seems to precede fibrosis formation in most types of chronic liver disease. To examine its presence and significance in different types of hepatic insults, this paper sought to identify the presence, evolution and peculiarities of angiogenesis in the most common experimental models of hepatic fibrosis. The characterization of cells, vessels and extracellular matrix and the identification of factors associated with endothelium (factor VIII RA), vascular basement membrane, other components of the vascular walls (actin, elastin) and the presence of the vascular-endothelial growth factor were investigated. The models examined included Capillaria hepatica septal fibrosis, whole pig serum injections, carbon tetrachloride administration, main bile duct ligation and Schistosoma mansoni infection. The first four models were performed in rats, while the last used mice. All models studied exhibited prominent angiogenesis. The most evident relationship between angiogenesis and fibrosis occurred with the C. hepatica model due to circumstances to be discussed. Special attention was paid to the presence of pericytes and to their tendency to become detached from the vascular wall and be transformed into myofibroblasts, which is a sequence of events that explains the decisive role angiogenesis plays in fibrosis.

The role of adiponectin in the pathogenesis and treatment of non‐alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries and the leading cause of cryptogenic cirrhosis. Insulin resistance (IR) is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of IR or metabolic syndrome (MetS). Although the pathogenesis of NAFLD is not fully elucidated, a complex interaction between adipokines and cytokines produced by adipocytes and/or inflammatory cells infiltrating adipose tissue appears to play a crucial role in MetS and NAFLD. Adiponectin is the most abundant and adipose-specific adipokine. In the liver, adiponectin acts through the activation of 5-AMP-activated protein kinase and peroxisome proliferator-activated receptor-alpha pathways and inhibition of toll-like receptor-4 mediated signalling. There is an evidence that adiponectin decreases hepatic and systematic IR and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and severity of NAFLD, but it remains to be addressed to what extent this is a direct effect or related to the presence of more severe IR. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. Weight loss, through diet, lifestyle changes and/or medications including orlistat, sibutramine, rimonabant or bariatric surgery, increase adiponectin and may improve liver histology. Insulin sensitizers, including pioglitazone and rosiglitazone, and lipid-lowering agents, including statins and fibrates, also upregulate adiponectin and ameliorate liver histology. The wider use of new treatment approaches appears to signal the dawn of a new era in the management of NAFLD. In this adiponectin-focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are systematically analysed.

End-stage nonalcoholic fatty liver disease: evaluation of pathomorphologic features and relationship to cryptogenic cirrhosis from study of explant livers in a living donor liver transplant program

In a proportion of liver cirrhosis, the etiology continues to remain elusive. It is uncertain whether and to what extent cirrhosis evolving from nonalcoholic fatty liver disease contributes to this group of cryptogenic cirrhosis because the clinicopathologic features of nonalcoholic fatty liver disease cirrhosis are largely unknown. We explored these facets by examining the explant livers and clinical data in living donor liver transplant recipients. Among 103 adult liver transplant recipients with different types of chronic liver disease, 30 had a pre-liver transplant diagnosis of cryptogenic cirrhosis. A final categorization of the native liver disease was attempted in these cases on the basis of detail pathomorphological findings in adequately sampled explant liver correlated with careful review of pre-liver transplant clinical data. Of the 30 cryptogenic cirrhosis cases, 19 (63.3%) finally labeled as nonalcoholic fatty liver disease cirrhosis showed histologic features in several respects different from those reported for the early and established phases of nonalcoholic fatty liver disease. Steatosis was infrequent and focal or even absent, whereas variable grades of Mallory hyaline and inflammation were consistently present. Ductular proliferation and hydropic change of hepatocytes were also frequent. Only 9 (47%) of the 19 cases had nonalcoholic fatty liver disease associated risk factors like diabetes and obesity. It was concluded that appreciation of quantitative and qualitative differences in hepatic morphology between the cirrhotic and the early/established stage of nonalcoholic fatty liver disease will help in making a correct diagnosis of nonalcoholic fatty liver disease cirrhosis in the proper clinical setting. When appropriate criteria are used, nonalcoholic fatty liver disease appears to account for close to two thirds of cases currently labeled as cryptogenic cirrhosis.

Adiponectin changes in HCV‐Genotype 4: relation to liver histology and response to treatment

Recently, attention has been focussed on adiponectin and its changes in different types of chronic liver disease. Its relation to hepatic fibrosis and insulin resistance in post-hepatitis liver disease is not clear. The aim of this study was to clarify the adiponectin changes in genotype 4 hepatitis C virus (HCV)-infected patient in relation to liver histology and insulin resistance, and its usefulness as a predictor of hepatic fibrosis and response to treatment. Total adiponectin and its high molecular weight (HMW) form as well as insulin levels were studied in 92 chronic HCV, genotype 4 and 66 healthy control volunteers. Neither total adiponectin (r = 0.101, P = 0.220) nor HMW adiponectin (r = 0.081, P = 0.328) correlated with viral load. Total and not HMW adiponectin was significantly correlated with hepatic fibrosis and inflammation (r = 0.267, P = 0.002, r = 0.278, P < 0.001, respectively).In addition, total adiponectin (r = 0.224, P = 0.002) and HMW adiponectin (r = 0.266, P < 0.0006) significantly correlated with insulin resistance. As fibrosis did not correlate with insulin resistance (r = 0.081, P = 0.204), the correlation between total adiponectin and fibrosis was not mediated by insulin resistance. Multivariable regression analysis, (including pretreatment cases and controls) revealed that total adiponectin was significantly associated with gender, being lower among male subjects (X(2) = 13.04, P = 0.0001). The multivariable regression model supported the lack of association between insulin resistance and total adiponectin levels (X(2) = 1.88, P = 0.171), while non cirrhotics had significantly lower total adiponectin levels than cirrhotics (X(2) = 10.90, P = 0.004) and lower level of inflammation significantly lower total adiponectin levels than more severe inflammation (X(2) = 8.95, P = 0.003). Total or HMW adiponectin did not yield receiver operating characteristic (ROC) curves with area under the curve (AUC) >75%, thus the cutoff points have poor sensitivity/specificity as predictors of fibrosis. However, as a predictor of end-of-treatment response, the ROC curve of adiponectin index gave yield an AUC = 81.4%. We can conclude that total adiponectin level, in HCV genotype 4 patients, increases with progression of hepatic fibrosis regardless of insulin resistance. Its high molecular form does not have such correlation. The adiponectin changes are not related to viral load, insulin resistance or other demographic data suggesting that this change is histologically related. In spite of this, no adiponectin cutoff level had reasonable sensitivity/specificity for predicting hepatic fibrosis stage, while this may be used as a predictor for antiviral response possibly reflecting improvement in hepatic inflammation post treatment.

Effect of pentoxifylline on serum hyaluronic acid in patients with non-alcoholic fatty liver disease

Abstract: Background and study aims Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver diseases. Non-alcoholic fatty liver disease (NAFLD) can be associated with progressive hepatic fibrosis. In this study we evaluated the effect of pentoxifylline (PTX) on serum hyaluronic acid (HA) levels as a marker of fibrosis. Patients and methods In this study we included 30 subjects (14 males and 16 females), divided into three groups. The NAFLD group included 20 patients with fatty livers as shown by ultrasound examination. Patients were randomised into a placebo group of 10 patients who received a placebo, and a pentoxifylline PTX group of 10 patients who received pentoxifylline at 400 mg/day for 6 months. The control group included 10 normal individuals. Results In the NAFLD group the mean value of the base line serum HA was 133 ± 150.48, while in the control group it was 33.5 ± 10.01; the difference between the groups was statistically significant ( p p = 0.007). In the placebo treated group the mean value of the base line serum HA was 96.5 ± 143.004, while after 6 months of treatment it was 59.7 ± 44.29; this difference was not statistically significant ( p = 0.594). Conclusion Our results showed that, when administered for 6 months, PTX caused a significant decline in HA levels, which may be an index reflecting improvement of hepatic fibrosis. Further investigations should be conducted with a large number of patients to confirm our results and correlate this with histological findings.