Gut microbiota and the liver.

Nowadays liver diseases represent one of major healthy problems in the world in terms of morbidity and mortality. The high prevalence of liver pathologies represents the key point to understand the necessity to identify the pathogenetic mechanisms that support these disorders in order to nurse them. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Gut microbiota is considered both as a promoting factor and as a potential therapeutic target of a large number of liver pathologies due to the connection between intestine and liver: the gut-liver axis. This connection influences absorption and deposition of nutrients into the liver, but also induces the activation of toll-like receptors due to the passage of pathogen-associated molecular patterns in the portal blood and therefore may start both the development of liver damage and its consequent progression to more advanced stages, including cirrhosis and hepatocarcinoma. The gut liver axis also includes the intestinal permeability (IP) degree. It is very variable and interconnected to several factors, most of them dependent from gut microbiota, that is the "lead" in the control of IP. This revue is aimed to report the more recent knowledges about gut microbiota and chronic liver disease, from liver steatosis to cirrhosis and its complications, including hepatocellular carcinoma. For these reasons, it could be useful to intervene, through suitable therapeutic approaches, on the interruption of mechanisms that underlie dysbiosis, IP increase, activation of liver inflammasome, hepatic stellate cells and hepatocarcinogenic processes in order to reduce the liver damage.

Endocan Serum Levels in Patients with Non-Alcoholic Fatty Liver Disease with or without Type 2 Diabetes Mellitus: A Pilot Study.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is emerging as an independent cardiovascular risk factor. Recently, Endocan has been studied as an early marker of endothelial dysfunction. Our aim was to evaluate Endocan serum levels in patients with NAFLD with or without type 2 diabetes mellitus. METHOD: We enrolled 56 patients: 19 with NAFLD and 37 with type 2 diabetes mellitus with or without NAFLD, and compared them to 25 healthy controls. Endocan serum level was measured by using the ELISA EndoMark assay. RESULTS: Endocan level was significantly higher in NAFLD subjects, compared to controls (1.23+/-1.51 vs 0.68+/-0.4 ng/mL; p=0.016). It was higher in patients with non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH) (1.12+/-1.11, 1.49+/-2.16 and 0.68+/-0.4 ng/ml vs controls, respectively), independently from presence of type 2 diabetes mellitus. The increase was more marked in patients with NASH and in those with NAFL versus controls (p=0.001 and p=0.004, respectively), but not statistically different between the two groups (p=0.448). Finally, we found a statistically relevant increase of this marker in diabetic NAFLD patients compared to those non diabetic (1.56+/-0.81 vs 0.72+/-0.58 ng/ml; p=0.01). CONCLUSION: We demonstrated an increased Endocan serum level in NAFLD patients, higher in those with type 2 diabetes mellitus and/or NASH because of an endothelial dysfunction in these pathologies.

Urotensin-II Receptor: A Double Identity Receptor Involved in Vasoconstriction and in the Development of Digestive Tract Cancers and other Tumors.

Urotensin II and Urotensin-II receptors are important molecular factors that regulate vasoconstriction and all the diseases that are linked to abnormalities in blood pressure regulation (i.e.: hypertension, kidney diseases, cirrhosis etc.). Recently, Urotensin II and its receptor have also been involved in metabolic syndrome, diabetes and schizophrenia. Recent strong findings suggest that Urotensin II and its receptor are involved in the onset and development of different epithelial cancers. Indeed, it was reported that cell growth, motility and invasion in human breast, bladder, prostate, colorectal and glioblastoma cancer cells were regulated by Urotensin II and Urotensin-II receptor axis. This axis also regulated focal adhesion kinase and small Guanosine-5'-triphosphate binding proteins that likely had a role in motility and invasion mediated by Urotensin-II receptor. Additionally, its expression on tumour tissues is variably associated to the prediction of the clinical outcome of the patients and it can be considered an alternative molecular marker to be used as prognostic factor in human cancers. In conclusion, a new weapon in the treatment of human cancers is highlighting a new scenario for the future.

Reactivation of hepatitis B virus in cancer patients treated with chemotherapy for solid tumors. Is the prophylaxis really required?

BACKGROUND: Reactivation of hepatitis B virus during cancer chemotherapy for non-hematological tumors is not fully clear. AIM: To evaluate the risk of hepatitis B virus reactivation in carriers of hepatitis B virus cancer patients treated with chemotherapy for solid tumors. METHODS: Two hundred sixty-seven patients with solid tumors were consecutively enrolled: 13 (4.8%) were hepatitis B s-antigen positive, of whom 6 were documented inactive carriers and 7 had chronic liver disease. Thirty-two patients (12%) were hepatitis B s-antigen negative/hepatitis B c-antibody positive. Hepatitis B virus inactive carriers were followed every 3 months by alanine aminotransferases, hepatitis B virus-DNA; whereas hepatitis B virus occult carriers were followed every 3 months by alanine aminotransferases and hepatitis B s-antigen. RESULTS: None of the 38 total patients with inactive or occult B infection who did not receive prophylaxis presented hepatitis B virus reactivation during the follow-up period. CONCLUSION: This study suggests that, in hepatitis B s-antigen negative patients who undergo chemotherapy for solid tumors, hepatitis B and c-antibody screening results are not relevant to clinical decision and can be avoided. Larger studies are needed to establish whether the risk of reactivation of HBV during chemotherapy is negligible in this subset of patients and they could not be monitored for HBV reactivation.

Postoperative Changes in Fecal Bacterial Communities and Fermentation Products in Obese Patients Undergoing Bilio-Intestinal Bypass.

We assessed the gut microbial ecology of 11 severely obese patients before and after bilio-intestinal bypass (BIB). Fecal samples were evaluated for microbial communities using 16S rDNA Illumina sequencing, real-time PCR targeting functional genes, and gas chromatography of short chain fatty acids (SCFAs). At 6 months after surgery, subjects exhibited significant improvements in metabolic markers (body weight, glucose, and lipid metabolism) compared with baseline. The fecal microbiota of post-surgery individuals was characterized by an overall decrease of bacterial diversity, with a significant reduction in Lachnospiraceae, Clostridiaceae, Ruminococcaceae, Eubacteriaceae, and Coriobacteriaceae. On the contrary, there were significant increases of genera Lactobacillus, Megasphaera, and Acidaminococcus and the family Enterobacteriaceae. The pH was decreased in fecal samples from patients after BIB and SCFA profiles were altered, with lower percentages of acetate and propionate and higher levels of valerate and hexanoate. Some changes in the bacterial populations were associated with variations in the patients' metabolic health parameters, namely Gemmiger and glucose, Lactobacillus and glucose, and Faecalibacterium and triglycerides. The results from this study of BIB patients furthers our understanding of the composition of gut microbiota and the functional changes that may be involved in improving obesity-related conditions following weight-loss surgery.

Alcoholic Liver Disease and Hepatitis C Chronic Infection.

Alcoholic and virus C hepatitis currently represent the main causes of chronic liver disease worldwide. Every year many people die and are subjected to complex hospitalization and medical assistance due to these pathologies. Alcoholic liver disease and hepatitis C virus chronic infection are often present in the same patient. These two pathologies sinergically act in determining the onset and progression of liver damage that, from the chronic hepatitis staging, may rapidly progress to fibrosis, cirrhosis and hepatocellular carcinoma. In this review we analysed physiopathological aspects and biomolecular interactions that relate ethanol and hepatitis C virus in determining liver damage; moreover we took into account the effect on the natural history of liver disease deriving from the co-presence of these pathologies. Therefore we paid particular attention to the ability of ethanol and hepatitis C virus to in inducing oxidative stress or lipid accumulation, and analyzed the basic mechanisms of fibrogenesis that both diseases have got, amplified by their co-presence in the same patient. Finally we paid attention to the oncogenetic mechanisms inducing hepatocellular carcinoma and variability of response to antiviral therapy that derives from alcohol abuse in a subject affected by C hepatitis.

Silybin-Phosphatidylcholine Complex Protects Human Gastric and Liver Cells from Oxidative Stress.

BACKGROUND/AIM: Silybin is the main component of silymarin with antioxidant, anti-inflammatory and cytoprotective actions. Our aim was to compare the effect of silybin used as single substance, silybin-phosphatidylcholine complex (SilPho), and derivatives of silybin (MannpSil, GalpSil, GlcpSil, LactpSil) on MKN28 and HepG2 cell viability and cell death, in vitro, after induction of oxidative stress. MATERIALS AND METHODS: Oxidative stress was induced by incubating HepG2 and MKN28 cells with xanthine oxidase in the presence of its substrate xanthine. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide assay. Determination of Malondialdehyde (MDA) in MKN28 cells was performed by high-performance liquid chromatography. Quantitative analysis of apoptotic cells was carried-out using annexin. RESULTS: SilPho and new silybin glycoconjugates did not affect cell viability, while silybin induced about 50% cell death in both MKN28 and in HepG2 cells. Pre-treatment of cells with silybin and new silybin glycoconjugates (before oxidative stress induction) did not affect cell viability, while SilPho had a protective effect. Exposure of MKN28 cells to oxidative stress caused a two-fold increase in cellular MDA concentration compared to untreated cells. Moreover, pre-treatment with SilPho, but not with silybin, significantly prevented oxidative stress-induced increase in cellular Malondialdehyde. Moreover, silybin induced apoptosis potentiated by oxidative stress, while SilPho did not induce any effect. Oxidative stress caused cell death primarily by necrosis, antagonized by SilPho. CONCLUSION: The protective effect of SilPho is partially due to inhibition of radical oxidative species.

Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma and Child-Pugh A or B cirrhosis.

Sorafenib confers a survival benefit for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) A liver cirrhosis. At present, limited data exists with regard to the safety and efficacy of sorafenib in treating CP-B HCC patients. The present study describes the use of sorafenib in patients with HCC and CP-A or -B cirrhosis. Clinical data was obtained from patients with HCC who were treated with sorafenib at the Department of Clinical and Experimental Medicine, Second University of Naples (Naples, Italy) and were analyzed retrospectively in terms of tumor response, tolerance and survival. The treatment outcomes were analyzed according to the respective CP status. The adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events, version 3.0, and the tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.2. In total, 26 patients received sorafenib at 400 mg twice daily. The median age was 69 years (range, 58-81 years) and the ratio of males to females was 18:8. Overall, 15 patients were infected with the hepatitis C virus (HCV), eight with HBV and three were co-infected with HCV/HBV. In total, 20 (77%) patients presented with an underlying CP-A (CP-A5 and CP-A6) cirrhosis and six (23%) with CP-B (CP-B7). Previous treatments included surgery (n=4), transarterial chemoembolization (n=5) and percutaneous ethanol injection or radiofrequency interstitial thermal ablation (n=12). A partial response was observed in three patients (12%), a stable disease lasting at least 12 weeks in 13 patients (50%) and a progression of disease in 10 patients (38%). The median overall survival (OS) time was 7.4 months [95% confidence interval (CI), 3.2-11.6) and the median progression-free survival (PFS) time was 3.7 months (95% CI, 1.9-5.5). The median OS and PFS times differed between patients with CP-A and CP-B, with a trend (P=0.06) toward a worse outcome in those with CP-B, although this was not statistically significant. The CP-A and CP-B groups experienced a similar incidence in the majority of AEs. A reduction in dose was required in 59% of the patients. The CP-A5, CP-A6 and CP-B7 patients tolerated sorafenib similarly, and derived comparable clinical and survival benefits.

Focus on emerging drugs for the treatment of patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules.

New silibinin glyco-conjugates: synthesis and evaluation of antioxidant properties.

New silibinin glyco-conjugates have been synthesized by efficient method and in short time. Exploiting our solution phase strategy, several structurally diverse silibinin glyco-conjugates (gluco, manno, galacto, and lacto-) were successfully realized in very good yields and in short time. In preliminary study to evaluate their antioxidant and neuroprotective activities new derivatives were subjected to DPPH free radical scavenging assay and the Xanthine oxidase (XO) inhibition models assay. Irrespective of the sugar moiety examined, new glyco-conjugates are more than 50 times water-soluble of silibinin. In the other hand they exhibit a radical scavenging activities slightly higher than to silibinin and XO inhibition at least as silibinin.

Non alcoholic fatty liver: epidemiology and natural history.

Non Alcoholic Fatty Liver Disease (NAFLD), defined as the presence of a significant amount of lipid accumulation in the liver (at least in 5% of hepatocytes), represents a challenging issue for the Hepatologists. NAFLD is not represented by a single entity, but rather by two different entities that have different natural history and evolution that range from simple fat accumulation in the liver (without any consequence), to necroinflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The reason of these differences has to be found in the host characteristics and associated risk factors. Globally, its prevalence among liver diseases, and in the general population, is rising in the recent years along with its associated conditions: obesity, insulin resistance, metabolic syndrome and diabetes. This increment, together with the reported clinical conditions, may be accounted for changes in dietary habits and the increase of sedentary lifestyle. Its diffusion seems to be pandemic, given that it is beginning to affect the populations in the developing world due to the spread of Western lifestyle. This is particularly worrying in young adults and children in what seems to have become the main cause of liver disease. Even if the real rate of global incidence of NAFLD are not known, its worldwide prevalence in general population is estimated to be 20-30% in Western Countries and 5-18% in Asia and it is increasing over time. In this review we will report on the global and regional prevalence of NAFLD, the principal risk factors and the natural history of its different presentations.

Eradication of Helicobacter pylori infection: which regimen first?

Helicobacter pylori (H. pylori) is a well-known human pathogen that plays an essential role in the pathogenesis of chronic gastritis, peptic ulcer disease, and gastric malignancies. Although H. pylori is susceptible to several antimicrobials, this infection has proven challenging to cure because of the increasing prevalence of bacterial strains that are resistant to the most commonly used antimicrobials, particularly clarithromycin. An effective (i.e., > 90%) first-line therapy is mandatory for avoiding supplementary treatments and testing, and more importantly for preventing the development of secondary resistance. This study reviews the recent literature on first-line therapies for H. pylori. The eradication rates following standard triple therapy (a proton pump inhibitor plus amoxicillin and clarithromycin) for H. pylori infection are declining worldwide. Several first-line strategies have been proposed to increase the eradication rate, including extending the treatment duration to 14 d, the use of a four-drug regimen (bismuth-containing quadruple, sequential, and concomitant treatments), and the use of novel antibiotics, such as fluoroquinolones. However, the efficacy of these regimens is controversial. A first-line eradication regimen should be based on what works best in a defined geographical area and must take into account the prevalence of antimicrobial resistance in that region.

Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

BACKGROUND: Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. METHODS: We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. RESULTS: Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. CONCLUSIONS: UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer.

Percutaneous endoscopic gastrostomy for critically ill patients in a general intensive care unit.

BACKGROUND AND AIM: percutaneous endoscopic gastrostomy (PEG) is an effective way of providing enteral feeding to patients with functionally normal gastrointestinal tract who cannot meet their nutritional needs because of inadequate oral intake. This retrospective study evaluated the clinical outcome of critically ill patients with high assistance level undergoing PEG in a general ICU over a 12 year period. PATIENTS AND METHODS: we studied a cohort of 82 patients who underwent PEG over a 12-year period between 1 January 1999 and 31 December 2010. Patients were followed-up for 1 year after PEG placement. RESULTS: There were no complications related either to the procedure or to the management of PEG, even in house nursing.In one patient, PEG with a collapsible bumper was successfully removed because the patient fully recovered from his neurological problem. Catheter substitution was necessary in three patients during the first year, because of stoma inflammation due to enteric reflux between the stoma and the catheter. One year after PEG, 66 patients were still alive while 16 patients died from the underlying disease during hospitalization. None of the patients with PEG had aspiration pneumonia. CONCLUSIONS: PEG, in expert hands, is a safe and effective procedure for enteral nutrition. Moreover, catheters should be chosen in relation to the duration of enteral feeding and as to whether the patient is likely to recover from his underlying disease.

Secondary Extramedullary Plasmacytoma of the Duodenum: An Unusual Endoscopic Presentation.

We describe an unusual case (a 79-year-old woman) of secondary extramedullary plasmacytoma (EMP) involving the duodenum. While all the previously reported cases of duodenal involvement by EMP (namely 20 cases) were characterized by the presence of ulcerative masses or ischemic necrotic lesions, in our case EMP led to the unusual finding of several non-polypoid lesions with a depressed central area. The final diagnosis was multiple myeloma IgA lambda, stage II A, with secondary duodenal EMP. To our knowledge this is the first report showing duodenal involvement by EMP with the aspect of multiple non-polypoid lesions.

Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

AIM: Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. RESULTS: CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P < 0.001 in all cases). Circulating levels of pro-inflammatory cytokine TNF-α were significantly increased in rats with liver fibrosis as compared with normal rats, while symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-ß, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. CONCLUSIONS: Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis.

Intestinal permeability in patients with chronic liver diseases: Its relationship with the aetiology and the entity of liver damage.

BACKGROUND: Alteration in intestinal permeability may be an important factor in the pathogenesis of both the progression of some chronic liver diseases and the onset of some complications in patients with liver cirrhosis. AIMS: To investigate the relationships between intestinal permeability, portal hypertension, alcohol use, plasma levels of pro-inflammatory cytokines, and nitric oxide, expressed as s-nitrosothiols, and nitrite levels in patients with various types and degrees of chronic liver diseases. METHODS: 134 healthy volunteers and 83 patients with chronic liver damage entered the study. Intestinal permeability was assessed with the lactulose/mannitol test. Plasma levels of tumour necrosis factor-alpha, interleukin-6, and nitrite and total s-nitrosothiols were determined. RESULTS: Intestinal permeability was altered in patients with advanced liver disease and impaired in 15-35% of patients without cirrhosis. Independent factors for intestinal permeability alteration were age, portal hypertension, alcohol use, and diabetes. Plasma levels of inflammatory cytokines and nitrosothiols were significantly higher in patients with altered intestinal permeability. CONCLUSIONS: An intestinal permeability evaluation in patients with chronic liver diseases might clarify the significance of intestinal permeability in the pathophysiology of both the progression of liver damage, and the occurrence of complications that accompany liver cirrhosis.

Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells.

BACKGROUND/AIMS: Hepatic fibrogenesis, a consequence of chronic liver tissue damage, is characterized by activation of the hepatic stellate cells (HSC). Silybin has been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the fine cellular and molecular events responsible for this effect. The aim of this study was to assess the mechanisms regulating the anti-fibrogenic and anti-inflammatory activity of Silybin. METHODS: Experiments were performed on HSC isolated from human liver and activated by culture on plastic. RESULTS: Silybin was able to inhibit dose-dependently (25-50 microM) growth factor-induced pro-fibrogenic actions of activated human HSC, including cell proliferation (P < 0.001), cell motility (P < 0.001), and de novo synthesis of extracellular matrix components (P < 0.05). Silybin (25-50 microM), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01) and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkBalpha phosphorylation. In addition, Silybin was confirmed to act as a potent anti-oxidant agent. CONCLUSION: The results of the study provide molecular insights into the potential therapeutic action of Silybin in chronic liver disease. This action seems to be mostly related to a marked inhibition of the production of pro-inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct and indirect pro-fibrogenic potential of HSC.

The impact of diet on liver fibrosis and on response to interferon therapy in patients with HCV-related chronic hepatitis.

BACKGROUND AND AIMS: A deranged metabolic status and alcohol intake may trigger induction and progression of chronic hepatitis C virus (HCV) liver disease. The aim of this study was to evaluate whether dietary composition affects the severity of liver damage and response to therapy in patients with HCV-related chronic hepatitis. METHODS: We enrolled 1,084 patients with biopsy-proven HCV-related chronic hepatitis (432 treated with interferon plus ribavirin) and 2,326 healthy subjects in this prospective study conducted in a university hospital. Dietary habits were recorded in enrolled individuals, and their alcohol consumption was evaluated with a questionnaire (AUDIT). Body mass index, and plasma levels of blood glucose, nitrogen, creatinine, cholesterol, and triglycerides were also measured. All individuals underwent routine liver tests and HCV genotyping. RESULTS: At study onset, there were no differences in metabolic status or alcohol consumption between patients and controls. About 50% of each group was overweight, and about 60% consumed alcohol. Patients and controls had similar dietary habits. Intake of carbohydrates, lipids and polyunsaturated fatty acids, and alcohol consumption were independent factors of liver damage at histology (logistic regression analysis). Some dietary components (unsaturated fatty acids, iron, zinc, vitamin A, and niacin) and alcohol intake differed significantly (P < 0.05 and P 0.01, respectively; univariate analysis) between responders and nonresponders to interferon therapy. Genotype, age, body mass index, steatosis, and fibrosis were independent predictors of therapy outcome (P < 0.02; multivariate analysis). CONCLUSIONS: The severity of HCV-related chronic hepatitis depends on a variety of factors. Our results show that dietary composition is related to the extent of liver damage. Although traditional risk factors independently affected treatment response, some dietary components were associated with nonresponse to therapy in our patients. This suggests that HCV patients may benefit from instructions regarding their diet.

Emerging drugs for non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a condition of emerging relevance that includes different forms of chronic liver damage, from a simple fatty infiltration (steatosis) of hepatocytes to steatohepatitis (NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma. OBJECTIVE: To discuss therapeutic management of NAFLD. Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. Differentiation between steatosis and NASH currently requires a liver biopsy. METHODS: We discuss different therapeutic approaches proposed in literature for patients with NAFLD. RESULTS: The treatment of associated conditions leads to an improvement of NAFLD and NASH. No specific drug is actually present to treat liver steatosis or NASH. CONCLUSIONS: The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercise may be considered a basal universal approach. Future research will discover possible specific liver drugs.