Switching to Regular Diet Partially Resolves Liver Fibrosis Induced by High-Fat, High-Cholesterol Diet in Mice.

The globally prevalent disease, non-alcoholic steatohepatitis (NASH), is characterized by a steatotic and inflammatory liver. In NASH patients, tissue repair mechanisms, activated by the presence of chronic liver damage, lead to the progressive onset of hepatic fibrosis. This scar symptom is a key prognostic risk factor for liver-related morbidity and mortality. Conflicting reports discuss the efficiency of dietary interventions on the reversibility of advanced fibrosis established during NASH. In the present study, the effect of dietary interventions was investigated in the outcome of the fibrosis settled in livers of C57BL/6J mice on a high-fat, high-cholesterol diet (HFHCD) for 5 or 12 consecutive weeks. Various clinico-pathological investigations, including a histological analysis of the liver, measurement of plasma transaminases, steatosis and fibrosis, were performed. To assess the effectiveness of the dietary intervention on established symptoms, diseased mice were returned to a standard diet (SD) for 4 or 12 weeks. This food management resulted in a drastic reduction in steatosis, liver injuries, inflammatory markers, hepatomegaly and oxidative stress and a gradual improvement in the fibrotic state of the liver tissue. In conclusion, our results demonstrated that dietary intervention can partially reverse liver fibrosis induced by HFHCD feeding.

Long-Term Carbohydrate-Containing Late-Evening Snack Significantly Improves the Ratio of Branched Chain Amino Acids to Aromatic Amino Acids in Adults with Liver Cirrhosis due to Hepatitis B.

BACKGROUND: The liver is the primary organ for amino acid metabolism, and metabolic disorder of amino acids is common in liver disease. However, the characteristics of plasma amino acid profiles in patients with HBV-related cirrhosis and the impacts of late-evening snack (LES) on cirrhosis are unclear. OBJECTIVES: To investigate the characteristics of plasma amino acid profiles in patients with HBV-related chronic hepatitis, cirrhosis, and the effects of late-evening snacks on plasma amino acid profiles. METHODS: 86 patients with HBV-related cirrhosis and eighty patients with chronic hepatitis B were included in this study. The plasma amino acid profiles were measured by the amino acid analyzer. Patients were randomly divided into two groups, of which the liver cirrhosis group was to receive daily LES (n = 43) or non-LES (n = 43) for 6 months. Plasma amino acid profiles and biochemical parameters were measured in both groups at baseline and after 1, 3, and 6 months. RESULTS: Compared to healthy controls, the plasma concentration in the liver cirrhosis group of threonine, serine, glycine, glutamine, cysteine, tyrosine, phenylalanine, arginine, and methionine increased significantly (P < 0.05), while the ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA) decreased significantly (P < 0.05). A carbohydrate-predominant LES treatment resulted in a significant increase in BCAA/AAA and decrease in the level of ammonia and glutamine compared with baseline after 6 months of supplementation (P < 0.05). Patients with Child-Pugh B and C are more responsive to changes in amino acid profiles than those with Child-Pugh A. CONCLUSIONS: The application of an LES carbohydrate module for six months in liver cirrhosis patients was associated with increased BCAA/AAA and decreased level of ammonia. Patients with Child-Pugh B and C grades were the most beneficial population.

Usefulness of nutritional therapy recommended in the Japanese Society of Gastroenterology/Japan Society of Hepatology evidence-based clinical practice guidelines for liver cirrhosis 2020.

BACKGROUND: The JSGE/JSH guidelines for the management of patients with liver cirrhosis revised in 2020 recommends new strategies for nutritional assessment and intervention, although their usefulness in daily clinical practice is unclear. METHODS: A total of 769 patients with cirrhosis were classified into low-, intermediate-, and high-risk groups according to hypoalbuminemia and sarcopenia, the criteria established for initiating the nutritional therapy algorithm in the guidelines. The association between these groups and mortality was analyzed using a Cox proportional hazards model. The effect of branched-chain amino acids (BCAAs) on survival was evaluated using propensity score matching. RESULTS: Of the enrolled patients, 495 (64%) were men with a median age of 73 years, 428 (56%) had hypoalbuminemia, 156 (20%) had sarcopenia, and 288 (37%) were receiving BCAAs. During a median follow-up period of 1.5 years, 276 (36%) patients died. The intermediate-risk [hazard ratio (HR), 1.60; 95% confidence interval (CI), 1.18-2.18] and high-risk (HR, 2.85; 95% CI, 1.92-4.23) groups independently predicted mortality. Among the propensity score-matched 250 patients, 49 (39%) BCAA-treated and 58 (46%) untreated died. Overall survival was higher in BCAA-treated patients than in untreated patients (HR, 0.67; 95% CI, 0.46-0.98). The survival benefit of BCAAs was pronounced in the intermediate-risk (HR, 0.50; 95% CI, 0.31-0.80) and high-risk (HR, 0.38; 95% CI, 0.16-0.91) groups. CONCLUSIONS: The 2020 JSGE/JSH guidelines for liver cirrhosis are useful in stratifying the mortality risk and providing effective nutritional interventions for malnourished patients with cirrhosis.

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5-7%) can already have a beneficial effect on NASH. However, the underlying molecular mechanisms of exercise and diet interventions remain largely elusive, and it is unclear whether they exert their health effects via similar or different pathways. METHODS: Ldlr-/-.Leiden mice received a high fat diet (HFD) for 30 weeks to establish a severe state of NASH/fibrosis with simultaneous atherosclerosis development. Groups of mice were then either left untreated (control group) or were treated for 20 weeks with exercise (running wheel), diet change (switch to a low fat chow diet) or the combination thereof. The liver and distant organs including heart, white adipose tissue (WAT) and muscle were histologically examined. Comprehensive transcriptome analysis of liver, WAT and muscle revealed the organ-specific effects of exercise and diet and defined the underlying pathways. RESULTS: Exercise and dietary change significantly reduced body weight, fat mass, adipocyte size and improved myosteatosis and muscle function with additive effects of combination treatment. WAT inflammation was significantly improved by diet change, tended to be reduced with exercise, and combination therapy had no additive effect. Hepatic steatosis and inflammation were almost fully reversed by exercise and diet change, while hepatic fibrosis tended to be improved with exercise and was significantly improved with diet change. Additive effects for the combination therapy were shown for liver steatosis and associated liver lipids, and atherosclerosis, but not for hepatic inflammation and fibrosis. Pathway analysis revealed complementary effects on metabolic pathways and lipid handling processes, thereby substantiating the added value of combined lifestyle treatment. CONCLUSIONS: Exercise, diet change and the combination thereof can reverse established NASH/fibrosis in obese Ldlr-/-.Leiden mice. In addition, the lifestyle interventions had beneficial effects on atherosclerosis, WAT inflammation and muscle function. For steatosis and other parameters related to adiposity or lipid metabolism, exercise and dietary change affected more distinct pathways that acted complementary when the interventions were combined resulting in an additive effect for the combination therapy on important endpoints including NASH and atherosclerosis. For inflammation, exercise and diet change shared several underlying pathways resulting in a net similar effect when the interventions were combined.

Sarcopenic Obesity in Liver Cirrhosis: Possible Mechanism and Clinical Impact.

The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle-liver-adipose tissue axis. Here, we overview the current knowledge of Sa-O, especially focusing on LC.

Microbiota, Fiber, and NAFLD: Is There Any Connection?

Gut microbiota can contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD). In fact, some specific changes of gut microbiota are observed in patients in what is called dysbiota. There has been a lot of investigation by using a variety of interventions, including diet, showing the possibility to modify components of gastrointestinal dysbiota towards healthy and multivariate microbiota to restore physiologic status. One of the main focuses has been dietary fiber (DF), in which most of its variants are prebiotics. The highest effective treatment for NAFLD is, so far, weight loss achieved by caloric restriction. DF supplementation with oligofructose facilitates weight loss, enhances the production of beneficial metabolites, decreases some pathogenic bacteria population by increasing Bifidobacteria, and has effects on intestinal barrier permeability. DF use has been associated with improvement in diverse metabolic diseases, including NAFLD, by modifying gut microbiota. Additionally, it has been shown that a higher insoluble fiber consumption (≥7.5 g/day) revealed improvements in 3 different scores of liver fibrosis. Further research is needed, but given the evidence available, it is reasonable to prescribe its consumption in early stages of NAFLD in order to prevent disease progression.

Coffee and nonalcoholic fatty liver disease: A review.

Nonalcoholic fatty liver disease (NAFLD) is widely prevalent globally and has no effective treatment. Coffee is one of the most popular beverages in the world and can therefore have a significant impact on public health on account of its health-promoting properties. Evidence from observational, clinical, and animal studies suggests that coffee may play an important role in human health. This article summarizes the effects of coffee on liver health, especially on nonalcoholic fatty liver disease (NAFLD) and its progression: liver fibrosis, cirrhosis and hepatocellular carcinoma. In addition, this article describes the pathogenesis, prevalence, diagnosis, and nutrition guidelines relating to NAFLD. Possible mechanisms responsible for the effects of coffee on the liver are also suggested.

Japan's Practical Guidelines for Zinc Deficiency with a Particular Focus on Taste Disorders, Inflammatory Bowel Disease, and Liver Cirrhosis.

Zinc deficiency is common in Japan, yet awareness on this disorder is lacking. The Japanese Society of Clinical Nutrition recently issued the Japan's Practical Guideline for Zinc Deficiency 2018 setting forth criteria for diagnosing zinc deficiency, i.e., (a) one or more symptoms of zinc deficiency or low serum alkaline phosphatase, (b) ruling out other diseases, (c) low serum zinc, and (d) alleviation of symptoms upon zinc administration. Serum zinc <60 µg/dL and 60-80 µg/dL indicate zinc deficiency and marginal deficiency, respectively. Zinc deficiency symptoms vary and include dermatitis and taste disorders among others. Zinc administration improves taste in 50-82% of patients suffering from taste disorders (a common symptom of zinc deficiency). Effects of zinc administration do not appear immediately, and therapy should be continued for at least three months. Zinc deficiency often accompanies various diseases and conditions. Here, we focus on inflammatory bowel diseases and liver cirrhosis. As zinc deficiency enhances intestinal inflammation via macrophage activation, we discuss the pathological mechanism for inflammation and zinc deficiency in the context of IBD. Zinc deficiency can also lead to a nitrogen metabolic disorder in patients with liver cirrhosis. Zinc supplementation can improve not only the ammonia metabolism, but also the protein metabolism. We also discuss directions for future studies of zinc deficiency.

Home-Based Physical Activity and Diet Intervention to Improve Physical Function in Advanced Liver Disease: A Randomized Pilot Trial.

INTRODUCTION: A decline in physical function is highly prevalent and a poor prognostic factor in cirrhosis. We assessed the benefits of a home-based physical activity program (HB-PAP) in patients with cirrhosis with a randomized pilot trial. METHODS: All participants received a personal activity tracker to monitor daily activities and were given 12 g/day of an essential amino acid supplement. The HB-PAP intervention consisted of biweekly counseling sessions to increase physical activity for 12 weeks. Six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) assessed changes in aerobic fitness. Different anthropometric measuring tools were used for skeletal muscle and adiposity assessment. RESULTS: Seventeen patients (60% male; 29% nonalcoholic steatohepatitis/cryptogenic, 29% hepatitis C, 24% alcohol, 18% other) were randomized, 9 to HB-PAP group. There were no significant differences in MELD-sodium between HB-PAP and controls at baseline or after the 12-week intervention. By the end of study, there was a significant between-group difference in daily step count favoring the active group (2627 [992-4262], p = 0.001), with less sedentary patients in the active group (33-17% vs. 25-43%, p = 0.003). The 6MWT improved in the HB-PAP group (423 ± 26 m vs. 482 ± 35 m), while the controls had a nonsignificant drop (418 ± 26 m vs. 327 ± 74 m) with a significant between-group difference. CPET did not change. Other than an improvement in psoas muscle index, there were no differences in anthropometry, or in quality of life. CONCLUSIONS: HB-PAP maintained physical performance and improved aerobic fitness according to 6MWT but not CPET, supporting the use of personal activity trackers to monitor/guide home-based prehabilitation programs in cirrhosis.

Review article: malnutrition/sarcopenia and frailty in patients with cirrhosis.

BACKGROUND: Malnutrition/sarcopenia and frailty are common in patients with cirrhosis and are associated with poor outcomes. AIM: To provide an overview of data on the importance, assessment and management of malnutrition/sarcopenia and frailty in cirrhosis. METHODS: A literature search was conducted in PubMed and other sources, using the search terms "sarcopenia," "muscle," "malnutrition," "cirrhosis," "liver" and "frailty" from inception to April 2019, to identify the relevant studies and international guidelines. RESULTS: The prevalence of malnutrition/sarcopenia in cirrhosis is 23%-60%. Frailty generally overlaps with malnutrition/sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition/sarcopenia in cirrhosis is complex/multifactorial and not just reduction in protein/calorie intake. Hyperammonemia appears to be the main driver of sarcopenia in cirrhosis through several molecular signalling pathways. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, they, and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. CONCLUSIONS: Malnutrition/sarcopenia and frailty are unique, inter-related and multi-dimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.

Omega-3 polyunsaturated fatty acids prevent progression of liver fibrosis and promote liver regeneration after partial hepatectomy in cirrhotic rats.

OBJECTIVE: To assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on liver regeneration of rats with liver cirrhosis after hepatectomy and antifibrosis. MATERIALS AND METHODS: Omega-3 polyunsaturated fatty acids were intravenously injected in n-3 PUFA group 3 days before the operation to 1 day after partial hepatectomy. 70% hepatectomy was performed in rats, which were subsequently divided into 4 groups, namely normal and hepatectomy group (PH); liver cirrhosis and hepatectomy group (LC+PH); liver cirrhosis, n-3 PUFA (1 mL/kg), and hepatectomy group (LC+n-3 PUFA+PH); liver cirrhosis, n-3 PUFA (2 mL/kg) and hepatectomy group (LC+n-3PUFA*+PH). Body/liver weight ratios, serum parameters, histopathological examination, immunostaining, inflammatory cytokine and quantification of mRNA expression were also investigated. RESULTS: Liver regeneration was significantly delayed compared with PH group 7 days after hepatectomy (PH) in LC+PH group. Besides, liver regeneration of LC+n-3 PUFA*+PH group increased significantly compared with LC+PH group 7 days after PH. In LC+PH group, liver cirrhotic was significantly higher compared with LC+n-3 PUFA+PH group 7 days after PH. In the meantime, liver cirrhosis of LC+n-3 PUFA*+PH group was significantly reduced compared with LC+n-3 PUFA+PH group 7 days after PH. Anti-inflammatory cytokine IL-10 was increased and pro-inflammatory cytokine IL-6 was decreased in LC+n-3 PUFA*+PH group compared with LC+PH group. N-3 PUFA also suppressed increments in mRNA expression for transforming growth factor-ß and up-regulated the expression of matrix metalloproteinase-9 and matrix metalloproteinase-1 in the liver. CONCLUSIONS: The mentioned results clearly show that n-3 PUFA reduces liver fibrosis and promotes liver regeneration, even under cirrhotic conditions. This could be a potentially useful treatment for liver cirrhosis.

Mastiha (Pistacia lentiscus) Improves Gut Microbiota Diversity, Hepatic Steatosis, and Disease Activity in a Biopsy-Confirmed Mouse Model of Advanced Non-Alcoholic Steatohepatitis and Fibrosis.

SCOPE: As a result of the obesity epidemic, the prevalence of non-alcoholic steatohepatitis (NASH) is increasing. No drug is approved for the treatment of NASH. In this study, the effect of a nutritional supplement, Mastiha or Chios mastic gum, on metabolic and histological parameters and on the gut microbiome in mice with NASH and fibrosis was investigated. METHODS AND RESULTS: Advanced NASH was induced by feeding C57BL/6J mice a diet rich in fat, sucrose, and cholesterol for 41 weeks. After randomization, animals received the NASH-inducing diet with or without 0.2% (w/w) Mastiha for a further 8 weeks. Disease activity was assessed by liver histology and determination of plasma transaminase activities. Fecal microbiota DNA extraction and 16S rRNA amplicon sequencing were used to determine the composition of the gut microbiome. Mastiha supplementation led to a significant reduction in circulating alanine aminotransferase (ALT) activity, improvement in hepatic steatosis and collagen content, and a reduction in NAFLD activity score. Furthermore, it resulted in a partial but significant recovery of gut microbiota diversity and changes in identity and abundance of specific taxa. CONCLUSION: This is the first study demonstrating an improvement in disease activity in mice with advanced NASH with fibrosis by a diet containing Mastiha.

[Nutrition in Liver Cirrhosis: Clinical Practice Recommendations]. / Ernährung bei Leberzirrhose: wichtige Tipps für Klinik und Praxis.

Liver disease and nutritional status affect each other mutually. Hepatic function is impaired by malnutrition and can be improved by nutrition therapy. Liver cirrhosis leads to prognostically relevant malnutrition in a stage dependent manner. Protein depletion and sarcopenia are its key features. Patients with liver cirrhosis should undergo systematic screening for risk of malnutrition and if positive sarcopenia should be assessed and a nutrition plan devised. In cirrhotic patients, spontaneous food intake frequently does not meet requirements and prolonged (> 12 h) periods of fasting must be avoided. In a stepwise fashion nutritional counseling, oral nutritional supplements, enteral tube feeding and parenteral nutrition as third-line-therapy should be used. In cirrhotic patients, nutrition therapy can improve morbidity and mortality by ensuring the adequate provision of energy, protein and micronutrients.

A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease.

Currently, there is no effective therapy for non-alcoholic fatty liver disease (NAFLD), although intensive calorie restriction is typically recommended but dietary adherence is an issue. The current study aimed to determine the effectiveness and adherence of eight weeks of modified alternate-day calorie restriction (MACR) in the control of NAFLD activity. This was a randomized controlled trial with MACR as the intervention and normal habitual diet as control. The outcome measures were body mass index (BMI), blood lipids, fasting blood sugar (FBS), liver enzymes (ALT and AST), and ultrasonographic measurements of liver steatosis and shear wave elastography (SWE). Per-protocol (PP) and intention-to-treat (ITT) analysis were performed within and between-groups with P < 0.05 as significant. 43 individuals with NAFLD satisfied study entry criteria, 33 were randomized to MACR and 10 to control group, and, 30 from MACR and 9 from control group completed PP. In between-group analysis of MACR vs. control, BMI were reduced in PP (P = 0.02) and ITT (P = 0.04). Only ALT was reduced in between-group analysis of MACR vs. control, both PP and ITT (P = 0.02 and 0.04 respectively). No reductions in all lipid parameters and FBS were found in between-group analyses (PP and ITT, all P > 0.22). Both liver steatosis grades and fibrosis (SWE) scores were reduced in between-group analyses of MACR vs. controls (PP and ITT, all P < 0.01). Adherence level remained between 75-83% throughout the study. As conclusion, 8 weeks of MACR protocol appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate.

Nutritional support in cirrhotic patients with sarcopenia.

Sarcopenia has been linked to oncologic and chronic diseases such as liver cirrhosis. In fact, sarcopenia is present in 25-70% of patients with liver cirrhosis. Furthermore, sarcopenia is an independent predictor of poor prognosis in many diseases. Currently cirrhotic patients are recommended to adopt a high protein diet (1.5 g/kg/day) with 30-40 kcal/kg/day and several meals throughout the day, being late evening snack intake with at least 50 g of carbohydrates of special importance. Despite the growing interest in the impact of sarcopenia in cirrhotic patients, there are still gaps in knowledge in the appropriate diagnostic criteria for this syndrome, the role of gut microbiota, as well as the most appropriate nutritional therapy.

Mechanistic evaluation of AMPK/SIRT1/FXR signaling axis, inflammation, and redox status in thioacetamide-induced liver cirrhosis: The role of Cichorium intybus linn (chicory)-supplemented diet.

Liver cirrhosis is a scene profitable to the advance of hepatocellular carcinoma (HCC). The current work was engrossed to weigh the potential role of Cichorium intybus linn against thioacetamide (TAA)-induced liver cirrhosis and their probable underlying biochemical and molecular mechanisms. farnesoid-X-receptor (FXR) expression, proliferating cell nuclear antigen (PCNA) immunoreactivity, and activated AMP protein kinase (pAMPK), sirtuin-1 (SIRT1), and interleukin-6 (IL6) levels were estimated in hepatic tissue by real-time PCR, immunohistochemistry, and immunoassay, respectively. C. intybus linn supplementation caused a significant improvement in serum liver enzymes, albumin, bilirubin levels, tissues redox status and hepatic histological features in addition to decreased IL6 level, hydroxylproline content, and PCNA immunoreactivity. On contrary, increased pAMPK/SIRT1 levels and upregulated FXR gene expression were observed. C. intybus linn could feasibly protect against TAA-induced hepatic damage, fibrosis, and cirrhosis by relieving oxidative stress and by interruption of the inflammatory pathway via AMPK/SIRT1/FXR signaling. PRACTICAL APPLICATIONS: No specific therapies are available until now to target the underlying mechanisms for protection against liver diseases. Herbal protection is widely available and cheap with no side effect. Cichorium intybus linn, a natural supplement, is proved in this current work to have the potential of being hepatoprotectant, antioxidant, and anti-inflammatory agents, thus reducing the risk of hepatic cirrhosis.

Nutrition in Cirrhosis.

PURPOSE OF REVIEW: This review discusses the prevalence of malnutrition in cirrhosis, metabolic functions of the liver and alterations in cirrhosis, malnutrition screening tools, and common macronutrient and micronutrient deficiencies encountered in individuals with chronic liver disease and their impact on morbidity and mortality. RECENT FINDINGS: Several meta-analyses and international society guidelines recommend malnutrition screening and nutrition interventions to improve outcomes in all patients with chronic liver disease given their high risk of malnutrition which is often under recognized. Malnutrition is common in individuals with chronic liver disease and has a significant impact on patient outcomes. Thus, it is critical that validated malnutrition screening tools are used routinely in this patient population in order to identify high-risk patients and implement nutrition and exercise interventions early.

Pentraxin 3 Detects Clinically Significant Fibrosis in Patients with Chronic Viral Hepatitis C.

Pentraxin 3 (PTX3) plays a pathogenic role in experimental models of chronic liver injury and contributes to the progression of fibrosis. The detection of advanced fibrosis (METAVIR F≥3) is important to identify patients who are in urgent need of antiviral treatments versus those whose treatment could be deferred (F≥2). The aim was to assess the diagnostic value of PTX3 as a potential biomarker for clinically significant and advanced fibrosis. PTX3 associations with biochemical and histological parameters of inflammatory activity and fibrosis were investigated in 138 patients with chronic viral hepatitis C (HCV) before antiviral treatment. METAVIR histological scores of activity and fibrosis were obtained. PTX3 was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of serum PTX3 levels was compared to that of other fibrosis markers, including transforming growth factor-ß 1 (TGF-ß 1), hyaluronic acid (HA), aspartate transaminase to platelet ratio index (APRI), fibrosis score based on four factors (FIB4), gamma-glutamyltranspeptidase to platelet ratio (GPR), and the liver stiffness measurement (LSM) by transient elastography (FibroScan®). In HCV patients the PTX3 level increased in parallel with the METAVIR histological score of activity, being independently associated with the METAVIR fibrosis score (P < 0.001). Using the receiver operating characteristics analysis, the best marker for detecting F≥2 and F≥3 was PTX3 with AUC = 0.802 and AUC = 0.867, respectively. The area under the curve of PTX3 for predicting significant fibrosis (F≥2) was significantly greater than those for the GPR ratio (AUC = 0.648) and FIB-4 score (AUC = 0.770) and similar to that for APRI index (AUC = 0.831). PTX3 provided clinically relevant diagnostic accuracy as a single marker of significant fibrosis.