Hepatocellular carcinoma in chronic hepatitis B patients under antiviral therapy

Patients with chronic hepatitis B are at increased risk of hepatocellular carcinoma(HCC),while the inhibition of viral replication can represent a reasonable target for HCC prevention.Interferon-αtherapy results in decreased HCC risk,which is more evident in patients with high baseline HCC risk.The majority of chronic hepatitis B patients are treated with a nucleos(t)ide analogue(NA)for several reasons including the nonsustained response after interferon-α.The effect of the first licensed and low genetic barrier NA,lamivudine,on HCC incidence,has been repeatedly evaluated.Lamivudine,compared to no treatment,reduces the HCC incidence,which may increase again in cases with lamivudine resistance.Emerging data with the currently first-line NAs,entecavir and tenofovir,suggest that they also reduce the HCC incidence.The treatment benefit in reduction of the HCC incidence is always greater in patients with high baseline HCC risk,particularly cirrhotics,and without virological remission under entecavir/tenofovir.However,the HCC risk is not eliminated even in the vast majority of patients who remain in virological remission under entecavir/tenofovir.Therefore,patients at increased baseline HCC risk should continue to undergo HCC surveillance even if they have achieved complete long-term inhibition of viral replication and improvements in liver histology.

Serum leptin and ghrelin in chronic hepatitis C patients with steatosis

AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infected with hepatitis C virus(HCV)genotype-1 and 40 with HCV genotype-3.Patients with decompensated cirrhosis,and those with other causes of chronic liver disease,were excluded.Serum HCV-RNA concentra-tions were measured before the initiation of treatment;at weeks 12(for genotype 1 patients),24 and 48 during treatment;and 24 wk after the end of treatment.Genotype was determined using INNO-LIPA HCV as-says,and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay.Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild,moderate,or severe,according to the Brunt classif ication.RESULTS:Overall,SVR was positively related to the presence of genotype-3,to biopsy-determined lower histological stage of liver disease,and lower grade of steatosis.Patients ≥ 40 years old tended to be less responsive to therapy.In genotype-1 infected pa-tients,SVR was associated with a lower grade of liver steatosis,milder fibrosis,and an absence of insulin resistance.Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concen-trations at baseline,with significant increases as the severity of steatosis worsened,whereas those who achieved SVR had higher ghrelin concentrations.In genotype-3 infected patients,SVR was associated only with fibrosis stage and lower homeostasis model as-sessment insulin resistance at baseline,but not with the degree of steatosis or leptin concentrations.Geno-type-3 infected patients who achieved SVR showed signif icant decreases in ghrelin concentration at end of treatment.Baseline ghrelin concentrations were elevat-ed in responders of both genotypes who had moderate and severe steatosis.CONCLUSION:Increased serum leptin before treat-ment may predict non-SVR,especially in HCV geno-type-1 infected patients,whereas increased ghrelin may predict SVR in genotype-1.

Fecal calprotectin measurement is a marker of shortterm clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease

AIM To evaluate the utility of fecal calprotectin(FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease(IBD) cohort.METHODS All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term(6 mo) course of the disease were extracted from the medical files. Exclusion criteria were defined as:(1) An established flare of the disease at the time of FC measurement,(2) Loss to follow up within 6 mo from baseline FC measurement, and,(3) Insufficient data on file. Statistical analysis was performed to evaluate whether baseline FC measurement could predict the short term clinical relapse and/or the presence of mucosal healing.RESULTS We included 149 [Crohn's disease(CD) = 113, Ulcerative colitis(UC) = 36, male = 77] IBD patients in our study. Within the determined 6-month period post-FC measurement, 47(31.5%) had a disease flare. Among 76 patients who underwent endoscopy, 39(51.3%) had mucosal healing. Baseline FC concentrations were significantly higher in those who had clinical relapse compared to those who remained in remission during follow up(481.0 μg/g, 286.0-600.0 vs 89.0, 36.0-180.8, P < 0.001). The significant predictive value of baseline median with IQR FC for clinical relapse was confirmed by multivariate Cox analysis [HR for 100μg/g: 1.75(95%CI: 1.28-2.39), P = 0.001]. Furthermore, lower FC baseline values significantly correlated to the presence of mucosal healing in endoscopy(69.0 μg/g, 30.0-128.0 vs 481.0, 278.0-600.0, in those with mucosal inflammation, median with IQR, P < 0.001). We were able to extract cut-off values for FC concentration with a high sensitivity and specificity for predicting clinical relapse(261 μg/g with AUC = 0.901, sensitivity 87.2%, specificity 85.3%, P < 0.001) or mucosal healing(174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P < 0.001). FC was better than CRP in predicting either outcome; nevertheless, having a pathological CRP(> 5 mg/L) in addition to the cutoffs for FC, significantly enhanced the specificity for predicting clinical relapse(95.1% from 85.3%) or endoscopic activity(100% from 87.2%). CONCLUSION Serial FC measurements may be useful in monitoring IBD patients in remission, as FC appears to be a reliable predictor of short-term relapse and endoscopic activity.

Serum zonulin levels in patients with liver cirrhosis:Prognostic implications

BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis.Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.AIM To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications.METHODS Consecutive cirrhotic patients who attended our liver clinic were included in the study.Serum zonulin levels,clinical,radiological and biochemical data were collected at baseline.Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo.RESULTS We enrolled 116 cirrhotics[mean Child-Turcotte-Pugh(CTP)score:6.2±1.6;model for end-stage liver disease score:11±3.9].The causes of cirrhosis were viral hepatitis(39%),alcohol(30%),non-alcoholic fatty liver disease(17%),and other(14%).At baseline,53% had decompensated cirrhosis,48% had ascites,and 32% had history of hepatic encephalopathy.Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class(4.2±2.4 ng/dL vs 3.5±0.9 ng/dL,P=0.038),with than without ascites(P=0.006),and with than without history of encephalopathy(P=0.011).Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year(P=0.039),with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation.Higher CTP score(P=0.021)and portal vein diameter(P=0.022)were independent predictors of mortality.CONCLUSION Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.