Alessandro Redaelli

Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus–induced cirrhosis. A 12-year prospective follow-up study†

The incidence of de novo development of esophageal varices (EV) in patients with compensated liver cirrhosis has been determined by few studies in the short term and never in the long term. The aims of the present study were to determine the incidence and the risk factors associated with the development of EV and to assess whether antiviral treatment and achievement of sustained virologic response (SVR) may prevent de novo EV development in patients with HCV‐induced cirrhosis. We studied 218 patients with compensated EV‐free, HCV‐induced cirrhosis consecutively enrolled between 1989 and 1992 at three referral centers in Milan, Italy. Endoscopic surveillance was performed at 3‐year intervals according to international guidelines. SVR was defined as undetectable serum HCV‐RNA 24 weeks after treatment discontinuation. During a median follow‐up of 11.4 years, 149/218 (68%) patients received antiviral treatment and 34 (22.8%) achieved SVR. None of the SVR patients developed EV compared with 22 (31.8%) of the 69 untreated subjects (P < 0.0001) and 45 (39.1%) of the 115 non‐SVR patients (P < 0.0001). On multivariate analysis, HCV genotype 1b (hazard ratio [HR] 2.40; 95% confidence interval [CI] 1.17‐4.90) and baseline model for end‐stage liver disease (MELD) score (HR 1.20; 95% CI 1.07‐1.35 for 1 point increase) were independent predictors of EV. Conclusion: In the long term, the achievement of SVR prevents the development of EV in patients with compensated HCV‐induced cirrhosis. Therefore, in these patients, endoscopic surveillance can be safely delayed or avoided. Genotype 1b infection and MELD score identify the subset of patients at higher risk of EV development who need tailored endoscopic surveillance. Hepatology 2010

Predicting Mortality Risk in Patients With Compensated HCV-Induced Cirrhosis: A Long-Term Prospective Study

OBJECTIVES:The identification of prognostic factors associated with mortality is crucial in any clinical setting.METHODS:We enrolled in a prospective study 352 patients with compensated hepatitis C virus (HCV)-induced cirrhosis, consecutively observed between 1989 and 1992. At entry, patients underwent upper endoscopy to detect esophageal varices, and were then surveilled by serial clinical and ultrasonographic examination. The model for end-stage liver disease (MELD) score was calculated with information collected at enrollment. Baseline predictors and intercurrent events associated with mortality were assessed using the Cox regression model.RESULTS:During a median follow-up of 14.4 years, 194 subjects received a single course of interferon monotherapy, 131 patients developed decompensation (ascites, bleeding, hepatic encephalopathy), 109 patients had hepatocellular carcinoma (HCC), 9 had liver transplant, and 158 died. Esophageal varices were associated with development of decompensation (hazard ratio (HR), 2.09; 95% confidence interval (CI), 1.33–3.30) and liver-related death (HR, 2.27; 95% CI, 1.41–3.66). A MELD score of 10 predicted overall mortality (HR, 2.15; 95% CI, 1.50–3.09). Overall survival of patients with MELD ≤10 was 80% at 10 years. HCC occurrence increased the risk of decompensation fivefold (HR, 5.52; 95% CI, 3.77–8.09). Hepatic and overall mortality hazard ratios were 8.62 (95% CI, 5.57–13.3) and 3.80 (95% CI, 2.67–5.42), respectively, for patients who developed HCC, and 16.9 (95% CI, 9.97–28.6) and 7.08 (95% CI, 4.88–10.2) for those who experienced decompensation.CONCLUSIONS:In patients with compensated HCV-induced cirrhosis, the presence of esophageal varices at baseline predicted decompensation and mortality. The development of HCC during follow-up strongly hastens the occurrence of decompensation, which is the main determinant of death. Patients with a MELD score ≤10 at study entry had a prolonged life expectancy.

Hepatocyte proliferation and risk of hepatocellular carcinoma in cirrhotic patients.

Abstract OBJECTIVES: High hepatocyte proliferation has been recently proposed as a risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess whether hepatocyte proliferation is an independent risk factor for HCC when considered together with clinical and demographic characteristics. METHODS: We retrospectively evaluated 97 consecutive patients with a histological diagnosis of cirrhosis and preserved liver function, enrolled in a surveillance program for early diagnosis of HCC. Hepatocyte proliferation was evaluated by flow-cytometric analysis in liver samples collected at the time of histological diagnosis of cirrhosis. All patients were followed with abdominal US and serum α-fetoprotein (AFP) assays every 6 months. RESULTS: During a mean follow-up of 53 months (range, 12–120 months), 12 patients developed HCC, giving an annual incidence of 2.8%. The mean S-phase fraction was 2.5% ± 1.6 in patients who developed HCC and 0.9% ± 0.6 in those who did not ( p p p p p p CONCLUSIONS: Patients with high S-phase fraction and/or above-normal serum AFP are at higher risk of developing HCC and should be offered a close surveillance program.

Depression during interferon therapy for chronic viral hepatitis : early identification of patients at risk by means of a computerized test

Objectives At the doses used for the treatment of chronic viral hepatitis, interferon (IFN)‐related side‐effects are usually modest, even though in some cases they require the interruption of therapy. Neuropsychiatric disturbances that range from modest depression and irritability to forms of manic‐depressive psychosis and attempted or successful suicides are among the most important sideeffects. The aim of our study was to determine whether the Minnesota Multiphasic Personality Inventory (MMPI) is a sensitive and reliable test for the early identification of patients at risk of depression before IFN therapy is commenced, and whether it could be useful for the monitoring of these patients during treatment. Methods We prospectively studied 67 patients with chronic active liver diseases, consecutively enrolled in open studies and treated with r‐IFN&agr;2. Before starting therapy and after 3 months of treatment, all patients underwent a clinical neurological evaluation and MMPI. Results At baseline, the correlation between the clinical evaluation and the score of the depression scale of the MMPI was statistically significant (P < 0.0001). Nine of 14 (64.3%) patients with a baseline score ⩾ 60/100 showed a depressive mood after 3 months of therapy. Five of 44 patients (11.3%) with a baseline score < 60/100 showed a depression of medium level after 3 months of treatment. This difference was highly significant (P < 0.0001). Conclusions According to our results, the MMPI is a reliable and sensitive test for the early identification of patients at risk of depression before and during IFN therapy for chronic viral liver diseases. Eur J Gastroenterol Hepatol 12:505‐509

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C : Influence of HCV genotype

Objective To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2307 patients. Results The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P < 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P < 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P < 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P < 0.01) and a lower cumulative hazard for HCC (P < 0.01). Conclusions Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Fibrosis is associated with adiponectin resistance in chronic hepatitis C virus infection.

Eur J Clin Invest 2011; 41 (8): 898–905

First clinical experiences with a novel endoscopic over-the-scope clip system

We describe our experience with a new over-the-scope clip (OTSC) system (Padlock Clip?) in the treatment of 14 patients. Eight of the 14 patients were treated for closure of gastrointestinal fistulas (n?=?4), iatrogenic gastrointestinal perforations (n?=?2), or hemostasis of post-polypectomy bleeding (n?=?2). The site of clipping was the lower gastrointestinal tract in five patients and the upper gastrointestinal tract in three patients. The clip was successfully delivered in seven out of the eight patients and clinical success was achieved in all patients. Endoscopic full thickness resection (EFTR) was performed to treat six patients: four with recurrent adenoma (n?=?4), one with ulcerated nodules at ileorectal anastomosis, and one with a neuro-endocrine tumor of the rectum. A complete intestinal wall resection was achieved in three of the six patients (50?%) and an R0 resection in five of the six patients (83.3?%). No complications related to the procedure and no recurrence at endoscopic follow-up were observed in any patient. The novel Padlock Clip seems to be an effective and safe tool to treat gastrointestinal fistulas, perforations or post-polypectomy bleeding, and to perform EFTR.