Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.

BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.

Cirrhotic Patients with Bacterial Infection and Negative Cultures Have a More Advanced Disease and an Increased Short-Term Mortality Rate.

BACKGROUND: The negative clinical impact of bacterial infections (BI) in patients with cirrhosis is well documented. In cirrhotic patients, failure to isolate the pathogen is a frequent event, occurring in 30-40% of cases. AIM: The aim of this study was to compare the clinical characteristics, early (30-day) and short-term (90-day) mortality rates, in a cohort of cirrhotic patients with BI, between those with positive (C-pos) and those with negative (C-neg) microbiological cultures. METHODS: We retrospectively enrolled 279 consecutive hospitalized cirrhotic patients with BI. Survival and predictors of 30-day and 90-day mortality were assessed by Kaplan-Meier curves and logistic regression analysis, respectively. RESULTS: Cultures tested negative in 108/279 (38.7%) patients. C-neg patients were more frequently males (p = 0.035), had higher Child-Pugh-Turcotte (CPT; p = 0.007) and model for end-stage liver disease-sodium (MELD-Na; p = 0.043) scores, and had more frequently decompensated liver disease (p = 0.04). Mortality rate was higher in C-neg than in C-pos patients, both at 30 days (22.2% versus 11.7%, p = 0.024) and 90 days (46.3% versus 33.3%, p = 0.030). MELD-Na score and non-selective beta-blockers (NSBBs) were independent risk factors for 30-day and 90-day mortality. In particular, the use of NSBBs was independently associated with a lower 30-day and 90-day mortality risk (OR 0.41, CI95% 0.17-0.94, p = 0.040; and OR 0.43, CI95% 0.25-0.75, p = 0.003, respectively). CONCLUSIONS: Cirrhotic patients with BI and negative microbiological cultures have significantly higher mortality compared to those with positive cultures. Early mortality and short-term mortality are mainly influenced by the underlying severity of liver disease. In this contest, therapy with NSBBs has a positive impact on short-term survival.

Over time evaluation of glycaemic control in direct-acting antiviral-treated hepatitis C virus/diabetic individuals with chronic hepatitis or with cirrhosis.

BACKGROUND: Data concerning the impact of hepatitis C virus (HCV) cure on type 2 diabetes mellitus (T2DM) are controversial. The aim of the study was to evaluate the effects of anti-HCV direct-acting antiviral (DAA) treatments on long-term glucose control in HCV/T2DM patients with chronic hepatitis C (CHC) or with cirrhosis. METHODS: One hundred and eighty-two consecutive HCV/T2DM patients who achieved a viral clearance by DAA treatment were enrolled. Seventy or 182 of them had CHC, and 112 had cirrhosis. Clinical, biochemical and instrumental parameters were recorded at baseline and at 48, 96 and 120 weeks (48w, 96w and 120w, respectively) after stopping DAA therapy. RESULTS: At baseline, the overall study population had a mean of glycated haemoglobin (HbA1c) value of 7.2% (ranging from 5 to 11.2), without any significant differences between CHC and cirrhosis [7.1 and 7.2, respectively]. Evaluation over time of HbA1c variations showed a significant improvement of glucose control at all post-treatment time points compared with baseline in CHC patients (P = .001). In cirrhotic patients, a significant decrease of HbA1c levels was only found when comparing HbA1c values between baseline and 48w time-point (P = .001), whereas this improvement disappeared at both 98w and 120w (P = .8 and P = .3, respectively). Multivariate logistic regression analysis showed that patients with chronic hepatitis have a 2.5 (CI 1.066-5.945) times greater chance of achieving an improvement of glycaemic values than patients with liver cirrhosis (P = .035). CONCLUSION: DAA-based HCV cure induces a significant and persistent amelioration of glycaemic control in HCV/diabetic patients with chronic hepatitis, whereas cirrhotic HCV/diabetic subjects have only a transient benefit from the virus elimination.

Dual-energy CT quantification of fractional extracellular space in cirrhotic patients: comparison between early and delayed equilibrium phases and correlation with oesophageal varices.

OBJECTIVE: Fractional extracellular space has been validated as a marker of hepatic fibrotic in cirrhotic patients at CT-scan as well as on dual-energy CT, which takes advantage from iodine uptake. Since no consensus still exists between equilibrium phases performed at 3 or 10 min, the first aim of this work is to evaluate performances at the two different time points. Moreover, correlation between fractional extracellular space and oesophageal varices, directly related to liver fibrosis, has been assessed. MATERIALS AND METHODS: Dual-Energy equilibrium phases at 3 and 10 min were performed within a follow-up CT-protocol scan in cirrhotic patients. Oesophageal varices were endoscopically assessed according to their size. At the two different time points, correlation between iodine density of the right and left liver lobes and correlation between the fractional extracellular space values were assessed. Correlation between fractional extracellular space and endoscopic grade of oesophageal varices was calculated. RESULTS: No statistical differences were found between the iodine density values from the two liver lobes at the two time points (p = 0.8 at 3'; p = 0.5 at 10'). No statistical difference about fractional extracellular space estimation was found between the two time points (p = 0.17). Correlation between fractional extracellular space values and oesophageal varices was moderate (ρ = 0.45, IC 0.08-0.71, p < 0.05). CONCLUSION: Fractional extracellular space assessed on dual-energy CT at equilibrium phases with different timing was substantially similar. The moderate correlation found between fractional extracellular space and endoscopic grade of oesophageal varices confirms that CT-scan is not currently reliable as endoscopy.

Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis.

BACKGROUND & AIM: An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. PATIENTS AND METHODS: A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. RESULTS: During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47-6.57: p = 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23-7.51; p = 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05-3.44; p = 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08-4.09; p = 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35-6.09; p = 0.006) were associated with HCC recurrence. CONCLUSION: An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. LAY SUMMARY: This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC.

Dual-source dual-energy CT in the evaluation of hepatic fractional extracellular space in cirrhosis.

BACKGROUND: One of the main features of liver fibrosis is the expansion of the interstitial space. All water-soluble CT contrast agents remain confined in the vascular and interstitial space constituting the fractional extracellular space (fECS). Indirect measure of its expansion can be quantified during equilibrium phase with CT. The goal of this prospective study was to assess the feasibility of dual-energy CT (DECT) with iodine quantification at equilibrium phase in the evaluation of significant fibrosis or cirrhosis. METHODS: Thirty-eight cirrhotic patients (according to Child-Pugh and MELD scores), scheduled for liver CT, were enrolled in the study group. Twenty-four patients undergoing CT urography with a 10-min excretory phase were included in the control group. fECS was calculated as the ratio of the iodine concentration of liver parenchyma to that of the aorta, multiplied by 1 minus hematocrit. RESULTS: Final study and control group were, respectively, composed of 22 and 20 patients. Mean hepatic fECS value was statistically greater in study group (P < 0.05). Positive correlation was observed between hepatic fECS value and MELD score (r = 0.64, P < 0.05). Analysis of variance showed statistical differences between control group and the Child-Pugh grades and between Child-Pugh A and B patients and Child-Pugh C patients (P < 0.05). ROC curves analysis yielded an optimum fECS cutoff value of 26.3% for differentiation of control group and cirrhotic patients (AUC 0.88; 86% sensitivity, 85% specificity). CONCLUSIONS: Dual-source DECT is a feasible, noninvasive method for the assessment of significant liver fibrosis or cirrhosis.

Predictors of Re-bleeding and Mortality Among Patients with Refractory Variceal Bleeding Undergoing Salvage Transjugular Intrahepatic Portosystemic Shunt (TIPS).

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has proven clinical efficacy as rescue therapy for cirrhotic patients with acute portal hypertensive bleeding who fail endoscopic treatment. AIMS: To investigate predictive factors of 6-week and 1-year mortality in patients undergoing salvage TIPS for refractory portal hypertensive bleeding. METHODS: A total of 144 consecutive patients were retrospectively evaluated. Three logistic regression multivariate models were estimated to individualize prognostic factors for 6-week and 12-month mortality. Log-rank test was used to evaluate survival according to Child-Pugh classes and Bureau's criteria. RESULTS: Mean age 51 ± 10 years, 66% male, mean MELD 18.5 ± 8.3, Child-Pugh A/B/C 8%/38%/54%. TIPS failure occurred in 23(16%) patients and was associated with pre-TIPS portal pressure gradient and pre-TIPS intensive care unit stay. Six-week and 12-month mortality was 36% and 42%, respectively. Pre-TIPS intensive care unit stay, MELD, and Child-Pugh score were independently associated with mortality at 6 weeks. Independent predictors of mortality at 12 months were pre-TIPS intensive care unit stay and Child-Pugh score. CONCLUSIONS: In this large cohort of patients undergoing salvage TIPS, MELD and Child-Pugh scores were predictive of short- and long-term mortality, respectively. Pre-TIPS intensive care unit stay was independently associated with TIPS failure and mortality at 6 weeks and 12 months. Salvage TIPS is futile in patients with Child-Pugh score of 14-15.

Hypergammaglobulinemia is a strong predictor of disease progression, hepatocellular carcinoma, and death in patients with compensated cirrhosis.

BACKGROUND & AIMS: The outcome of compensated cirrhosis may vary considerably and cannot be predicted by routinely performed tests at present. The aim of this study was to evaluate possible predictors of clinical evolution in patients with Child-Pugh (C-P) class A cirrhosis because of untreatable causes by analysing clinical/biochemical/instrumental parameters evaluated at the time of diagnosis and during the subsequent long-lasting follow-up. METHODS: Two hundred and seventy-two consecutive C-P class A cirrhotic patients (155 males; median age 63 years, range 34-81) were analysed. All patients were followed up for a median time of 96 months (range 21-144) through periodically performed clinical/biochemical/ultrasonographic and esophagogastroduodenoscopic examinations. RESULTS: During the follow-up, 97 individuals (36%) were clinically stable, 104 (38%) developed hepatocellular carcinoma (HCC) and 71 (26%) progressed towards C-P class B/C without developing cancer. One hundred and thirty-one patients (48%) died or underwent liver transplantation. Multivariate regression analysis showed that clinical stability was significantly associated with older age (P < .001), the absence of diabetes (P = .04) and of oesophageal varices (P < .001), serum albumin >3.5 gr/dL (P = .01) and gamma globulin <1.8 gr/dL (P = .01). HCC development was significantly associated with younger age (P = .01) and serum gamma globulin values ≥1.8 gr/dL (P < .001). C-P score progression was associated with oesophageal varices (P < .001), lower serum albumin (P = .03) and cholesterol (P = .01) values, and hypergammaglobulinemia (P = .02). Death was associated with younger age (P < .001) and hypergammaglobulinemia (P = .01). Multivariate Cox regression analysis and Kaplan-Meier's survival test confirmed that gammaglobulinemia ≥1.8 g/dL was a significant predictor of death (P < .02, and P < .01 respectively). CONCLUSIONS: Hypergammaglobulinemia identifies C-P class A cirrhotic patients at higher risk of disease progression, HCC development and death.

A combination of different diagnostic tools allows identification of inactive hepatitis B virus carriers at a single time point evaluation.

BACKGROUND & AIMS: Serial evaluation of hepatitis B virus (HBV) DNA and aminotransferase values is required for identification of inactive HBV carriers (ICs). Recently, HBV surface antigen quantification (qHBsAg) and liver stiffness measurement (LSM) have been proposed as diagnostic tools in chronic HBV infection. The aim of this study was to evaluate the efficacy of HBV DNA quantification, qHBsAg and LSM in diagnosing ICs at a single time point. METHODS: Fifty-seven previously characterized ICs and 90 untreated HBsAg-/anti-HBe-positive patients [49 chronic hepatitis (CH), 41 cirrhosis] were enrolled. HBV DNA ≤2000 IU/mL, LSM ≤6.2 kPa and qHBsAg ≤1000 IU/mL were used as cut-offs to evaluate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA). RESULTS: Combined HBV DNA quantification and qHBsAg correctly identified 30/57 (52.6%) ICs showing 94% sensitivity, 96% specificity, 98% PPV, 87% NPV and 95% DA. HBV DNA coupled with LSM identified 40/57 (70.2%) ICs showing 97% sensitivity, 97% specificity, 98% PPV, 95% NPV and 97% DA. Combined LSM and qHBsAg identified 33/57 (57.9%) ICs showing 95% sensitivity, 78% specificity, 89% PPV, 89% NPV and 89% DA. The evaluation of the three parameters altogether allowed the identification of 23/57 (40.3%) ICs showing 100% specificity, 96% sensitivity, 100% PPV, 92% NPV and 97% DA. Similar results were obtained when either CH or cirrhotic patients were excluded from the analysis. CONCLUSIONS: Combined evaluation of HBV DNA amount with LSM and/or qHBsAg is a highly reliable tool allowing the identification of a considerable number of HBV ICs at a single time point evaluation.

Atrial fibrillation in patients with cirrhosis.

BACKGROUND & AIMS: Few information is available regarding atrial fibrillation in cirrhotic patients. The aim of this study was to investigate the occurrence and clinical impact of atrial fibrillation in these patients. METHODS: Three hundred and thirty-five cirrhotic patients (219 males; mean age 65 ± 10.85 years; 196 Child-Pugh class A, 104 class B and 35 class C) were consecutively analysed and followed up for 24 months. Electrocardiograms were available for all patients before starting the study, at basaltime and during the follow-up. Echocardiography was performed in individuals with atrial fibrillation and in 100 randomly chosen patients without it. RESULTS: Atrial fibrillation was observed in 21/335 cirrhotics (mean age 75 ± 7 years, 13 male), six of whom had permanent and 15 had paroxysmal atrial fibrillation. At univariate analysis, atrial fibrillation significantly correlated with older age, history of coronary heart disease, Child-Pugh score, serum albumin, hepatic encephalopathy, treatment with furosemide, QTc prolongation, atrial section areas, increased PAPs and thickness of interventricular septum. Age [odd ratio 1.12, 95% CI (1.05-1.2), P = 0.001], history of coronary heart disease [odd ratio 4.93, 95% CI (1.04-23.54), P = 0.04] and PAPs [odd ratio 1.12, 95% CI (1.02-1.2), P = 0.01] maintained statistical significance at multivariate analysis. Fifty-one of the 335 patients died during the follow-up. At Cox regression analysis, advanced Child-Pugh score [hazard ratio 1.546, 95% CI (1.357-1.762), P = 0.037] and increased heart rate [hazard ratio 1.117, 95% CI (1.021-1.223), P = 0.016] were significantly associated with mortality which was independent of atrial fibrillation occurrence. CONCLUSIONS: Cirrhosis is not a predisposing factor of atrial fibrillation, which in turn has no impact on mortality in cirrhotic patients.

Therapy of occult hepatitis B virus infection and prevention of reactivation.

Occult hepatitis B virus infection (OBI) is highly prevalent worldwide. In some cases, it is a consequence of infection with variant viruses mutated in the S gene and producing a surface antigen not recognized by diagnostic kits. In most cases, OBI is due to a strong inhibition of hepatitis B virus (HBV) activities exerted by host defense mechanisms. OBI may reactivate in patients undergoing immunosuppressive therapy and/or chemotherapy with the possibility of a consequent development of acute hepatitis that may lead to hepatic failure. Hematological malignancies and therapeutic schedules including rituximab are the conditions most frequently associated with OBI reactivation. However, this event may occur in a large number of additional clinical and therapeutic settings. Identification of patients prone to undergo reactivation is of great importance for promptly starting a proper antiviral therapy that may stop the HBV reactivation and prevent its clinical sequelae.

Impact of hepatitis B virus (HBV) preS/S genomic variability on HBV surface antigen and HBV DNA serum levels.

UNLABELLED: To evaluate whether hepatitis B virus (HBV) preS/S gene variability has any impact on serum hepatitis B surface antigen (HBsAg) levels and to analyze the replication capacity of naturally occurring preS/S variants, sera from 40 untreated patients with HBV-related chronic liver disease (hepatitis B e antigen [HBeAg]-positive, n = 11; HBeAg-negative, n = 29) were virologically characterized. Additionally, phenotypic analysis of three different preS/S variant isolates (carrying a 183-nucleotide deletion within the preS1 region, the deletion of preS2 start codon, and a stop signal at codon 182 within the S gene, respectively) was performed. HBV infecting 14 (35%) patients had single or multiple preS/S genomic mutations (i.e., preS1 and/or preS2 deletions, preS2 start codon mutations, C-terminally truncated and/or "a" determinant mutated S protein). Presence of preS/S variants negatively correlated with HBsAg titers (r = -0.431; P = 0.005) and its prevalence did not significantly differ between HBeAg-positive and HBeAg-negative patients. No correlation was found between HBsAg and HBV DNA levels in patients infected with preS/S mutants, whereas a significant correlation was found between HBsAg and viremia levels (r = 0.607; P = 0.001) in patients infected with wild-type HBV strains. HepG2 cells replicating the above-mentioned three preS/S variants showed significant reduction of HBsAg secretion, retention of envelope proteins in the endoplasmic reticulum, less efficient virion secretion and nuclear accumulation of significantly higher amounts of covalently closed circular DNA compared with wild-type HBV replicating cells. CONCLUSION: In patients infected with preS/S variants, HBV DNA replication and HBsAg synthesis/secretion appear to be dissociated. Therefore, the use of HBsAg titer as diagnostic/prognostic tool has to take into account the frequent emergence of preS/S variants in chronic HBV infection.

Antibody to hepatitis B virus core antigen positivity is a predictor of non-alcoholic fatty liver disease severity.

Insufficient information is available about co-factors favoring the progression of non-alcoholic fatty liver disease (NAFLD) toward cirrhosis. We aimed to evaluate the impact of a limited alcohol intake and of occult hepatitis B virus (HBV) infection (OBI) on the severity of NAFLD. Three-hundred-seventy-four alcohol non-abusers and HBV surface antigen negative NAFLD patients (223 males; mean age 55.4 years), consecutively admitted to the outpatients clinic of a referral liver unit from January 1st, 2018 to December 31st, 2019, were studied. Anti-HBV core antigen antibody [(anti-HBc), a surrogate marker of OBI] was assessed in all patients. Patients were distinguished between teetotal and moderate alcohol consumers (intake of less than 30 g and 20 g if males or females, respectively). Liver fibrosis was non-invasively assessed by FIB-4 and transient elastography. Uni- and multivariate analyses were performed to identify predictors of advanced fibrosis. Patients had a mean BMI of 28.5 kg/m2, and the majority presented metabolic and cardio-vascular comorbidities [258 patients (69%) had insulin resistance/diabetes, 249 (66.6%) dyslipidemia, 200 (53.5%) arterial hypertension]. Multivariate analysis showed that anti-HBc positivity (p = 0.046, OR 2.153) was a factor associated with advanced fibrosis at FIB-4 score testing, whereas moderate alcohol intake was not associated with severe NAFLD both at FIB-4 and transient elastography evaluations. The study showed that a moderate alcohol intake has no impact on NAFLD severity and suggested that OBI might negatively affect the NAFLD outcome.

Fibroscan: a new noninvasive method for evaluation of liver dysfunction in Turner syndrome.

BACKGROUND: Raised liver enzyme value is frequently detected in patients with Turner syndrome (TS), but its clinical importance is still unclear. OBJECTIVE: To investigate the entity of liver involvement in TS and to avoid the invasiveness of liver biopsy, we planned to measure liver stiffness by transient elastography (TE). DESIGN: Cross-sectional study. PATIENTS AND METHODS: Twenty-five consecutive patients with TS and a chronological age ≥ 12·5 years (mean age = 21·7 years), full pubertal development and final height's achievement were enrolled and investigated by blood biochemical analyses [glucose, insulin, aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), gamma-glutamil transferase (GGT), alkaline phosphatase, cholesterol, triglyceride, HDL-cholesterol], ultrasonography and TE of the liver. RESULTS: Of 25, 7 subjects (28%) showed liver enzyme levels higher than the normal upper limit. Mean liver stiffness value in the entire study group was 4·5 ± 1·7 kPa, being significantly higher in patients with abnormal liver enzymes than in those with normal liver biochemistry (6·0 ± 2·9 vs. 4·0 ± 0·9, P < 0·05). Strong correlations were found between TE values and ALT (P < 0·005), GGT (P < 0·0001), Body mass index (P < 0·05), HOMA index (P < 0·05), HDL-cholesterol (P < 0·05) and triglycerides (P < 0·0001). CONCLUSIONS: We can assert that (i) liver stiffness, measured by TE, strongly correlates with liver enzyme levels in patients with TS ; (ii) the increased liver stiffness in patients with TS with biochemical signs of liver dysfunction is significantly related to metabolic syndrome parameters; (iii) TE may be an useful tool to select among patients with TS with elevated liver enzymes or other metabolic risk factors, those who deserve more invasive diagnostic procedures, namely liver biopsy, for the best characterisation of liver damage.

Rate of hepatocellular carcinoma diagnosis in cirrhotic patients with ultrasound-detected liver nodules.

Ultrasound (US) detection of liver nodules in cirrhotic patients requires further radiological examinations and often a follow-up with repeated short-term evaluations to verify the presence of hepatocellular carcinoma (HCC). Aims of the study were to assess the rate of HCC diagnosis and to identify HCC predictors in a cohort of cirrhotics followed-up after US detection of the liver nodule(s). One-hundred-eighty-eight consecutive cirrhotic patients (124 males, mean age 64.2 years) with liver nodule(s) detected by US were enrolled. All patients underwent second-level imaging [computed tomography (TC) or magnetic resonance (MR)], and those without a definite diagnosis of HCC were followed-up with TC and/or RM repeated every 3-6 months up to 18 months if HCC was not diagnosed. After 18 months, non-HCC patients came back to routine US surveillance. HCC was diagnosed in 73/188 cases (38.8%). In 66/73 patients (90.4%) HCC was identified at first radiological evaluation after US, while in the remaining seven subjects it was diagnosed at the subsequent imaging examination. Age (p = 0.001) and nodule dimension (p = 0.0001) were independent predictors of HCC at multivariate analysis. Fourty-nine/188 patients were lost at follow up after 18 months. Twenty/139 remaining patients developed HCC and 3/139 cholangiocarcinoma; 77 died between 3 and 110 months from the beginning of the study (61 for end-stage liver disease, 8 for extrahepatic causes, eight for unknown causes). Patients who developed liver cancer earlier during the follow up had the shortest overall survival. US-detected liver nodules are not neoplastic in more than half of cirrhotic patients. A definite diagnosis may be obtained at the time of the first radiologic evaluation after US in the vast majority of the cases. Patients in whom nodules are found not to be tumoral may return to the US surveillance program routinely applied to all cirrhotics.

Computer-assisted image analysis of liver collagen: relationship to Ishak scoring and hepatic venous pressure gradient.

UNLABELLED: Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG (r = 0.62; P < 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more (P < 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher (P < 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P < 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P = 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies. CONCLUSION: CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis.