Susana Coll

Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial

BACKGROUND There is no standard treatment for unresectable hepatocellular carcinoma. Arterial embolisation is widely used, but evidence of survival benefits is lacking. METHODS We did a randomised controlled trial in patients with unresectable hepatocellular carcinoma not suitable for curative treatment, of Child-Pugh class A or B and Okuda stage I or II, to assess the survival benefits of regularly repeated arterial embolisation (gelatin sponge) or chemoembolisation (gelatin sponge plus doxorubicin) compared with conservative treatment. 903 patients were assessed, and 112 (12%) patients were finally included in the study. The primary endpoint was survival. Analyses were by intention to treat. FINDINGS The trial was stopped when the ninth sequential inspection showed that chemoembolisation had survival benefits compared with conservative treatment (hazard ratio of death 0.47 [95% CI 0.25-0.91], p=0.025). 25 of 37 patients assigned embolisation, 21 of 40 assigned chemoembolisation, and 25 of 35 assigned conservative treatment died. Survival probabilities at 1 year and 2 years were 75% and 50% for embolisation; 82% and 63% for chemoembolisation, and 63% and 27% for control (chemoembolisation vs control p=0.009). Chemoembolisation induced objective responses sustained for at least 6 months in 35% (14)of cases, and was associated with a significantly lower rate of portal-vein invasion than conservative treatment. Treatment allocation was the only variable independently related to survival (odds ratio 0.45 [95% CI 0.25-0.81], p=0.02). INTERPRETATION Chemoembolisation improved survival of stringently selected patients with unresectable hepatocellular carcinoma.

S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial.

BACKGROUND/AIM The efficacy of S-adenosylmethionine (AdoMet) in the treatment of liver cell injury has been demonstrated in several experimental models. The aim of this study was to investigate the effects of AdoMet treatment in human alcoholic liver cirrhosis. METHODS A randomized, double-blind trial was performed in 123 patients treated with AdoMet (1200 mg/day, orally) or placebo for 2 years. All patients had alcoholic cirrhosis, and histologic confirmation of the diagnosis was available in 84% of the cases. Seventy-five patients were in Child class A, 40 in class B, and 8 in class C. Sixty-two patients received AdoMet and 61 received placebo. RESULTS At inclusion into the trial no significant differences were observed between the two groups with respect to sex, age, previous episodes of major complications of cirrhosis, Child classification and liver function tests. The overall mortality/liver transplantation at the end of the trial decreased from 30% in the placebo group to 16% in the AdoMet group, although the difference was not statistically significant (p = 0.077). When patients in Child C class were excluded from the analysis, the overall mortality/liver transplantation was significantly greater in the placebo group than in the AdoMet group (29% vs. 12%, p = 0.025), and differences between the two groups in the 2-year survival curves (defined as the time to death or liver transplantation) were also statistically significant (p = 0.046). CONCLUSIONS The present results indicate that long-term treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic liver cirrhosis, especially in those with less advanced liver disease.

Risk factors for spontaneous bacterial peritonitis in cirrhotic patients with ascites

BACKGROUND This study was performed to investigate the risk factors for a first episode of spontaneous bacterial peritonitis in cirrhotic patients. METHODS One hundred ten cirrhotics with sterile ascites, without previous spontaneous bacterial peritonitis (SBP), were included from March 1988 to October 1989 and followed up until October 1990 (follow-up, 46 +/- 3.5 weeks; range, 4-120 weeks). RESULTS Twenty-eight patients (25.45%) suffered SBP. In multivariate analysis (Coxs regression model) including only variables commonly used in clinical practice, ascitic fluid protein concentration and serum bilirubin level independently correlated with first SBP development. Using these two variables the relative risk of a first SBP episode was calculated for each patient. According to the median relative risk coefficient (1.2), a low-risk group (relative risk, < 1.2) and a high-risk group (relative risk, > 1.2) were established. Kaplan-Meier estimates of patients free of SBP were significantly higher in the low-risk group. CONCLUSIONS The probability of a first SBP episode is significantly influenced by the antimicrobial capacity of ascitic fluid and hepatic function.

Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage

Introduction. The need to detect pancreatic cancer at earlier stages is undisputed. We recorded the signs and symptoms of patients presenting with exocrine pancreatic cancer and evaluated their association with clinical characteristics such as tumour site and disease stage.Patients and methods. All patients (n=185) with exocrine pancreatic cancer newly diagnosed at five general hospitals in Eastern Spain were prospectively recruited over 3 years. Symptoms were elicited through personal interviews and signs were recorded by the attending physician on admission.Results. At diagnosis, one third of tumours of the pancreas head were in stage I and another third in stage IV. None of the tumours of the body and tail were in stage I, and over 80% were in stage IV (p<0.001). At presentation, the most frequent symptoms were asthenia (86%), anorexia (83%), weight-loss (85%), abdominal pain (79%), and choluria (59%). Cholestatic symptoms were more common in tumours affecting only the pancreatic head (p<0.001). There was a clear trend towards more localized tumours with increasing numbers of cholestatic signs (p<0.001). Asthenia, anorexia and weight-loss were unrelated to stage. An increased symptom-to-diagnosis interval was associated with more advanced stage (p=0.048).Conclusions. Proper attention to signs and symptoms, especially cholestasis, may help identify patients with pancreatic cancer at an earlier stage. Results also provide a current picture of the semiology of pancreatic cancer which could be of use in studies on the potential of proteomic tests in the early detection of this neoplasm.

Pre-treatment with prednisolone does not improve the efficacy of subsequent alpha interferon therapy in chronic hepatitis C

BACKGROUND/AIMS Alpha interferon administration is quite disappointing as a single therapy in chronic hepatitis C. A brief course of corticosteroid therapy might increase the effectiveness of subsequent alpha interferon administration, but data on this issue are controversial. METHODS One hundred and fifty-six consecutive patients with chronic hepatitis C were randomly assigned to be treated blind with tapering doses of oral prednisolone or placebo for 4 weeks. Two weeks after cessation of therapy, patients received alpha interferon (3 MU t.i.w.) for 48 weeks and were followed for 24 additional weeks. Response was defined by the presence of normal alanine aminotransferase (ALT) and negative HCV-RNA in serum. RESULTS ALT activity decreased during prednisolone administration and rebounded upon withdrawal in 38% of the patients treated with this drug. Significant changes in serum bilirubin were not observed. HCV-RNA serum concentration tended to increase during prednisolone administration and to decrease upon withdrawal. ALT and HCV-RNA did not change during administration of placebo. At the end of interferon administration, 33% of patients treated with prednisolone and 25% of those treated with placebo presented biochemical and virological response. At the end of post-treatment follow-up, response was maintained in 12% and 13% of patients treated with prednisolone or placebo respectively. Response was not related to ALT or HCV-RNA changes observed during the pre-interferon phase of the study. No adverse events related to prednisolone administration were observed. CONCLUSIONS Prednisolone administration and withdrawal induced a rebound in ALT activity and a decrease in HCV-RNA serum concentration in about one third of the patients with chronic hepatitis C. However, these changes did not enhance the effectiveness of subsequent alpha interferon therapy.

Quantification of HBsAg to predict low levels and seroclearance in HBeAg-negative patients receiving nucleos(t)ide analogues

Background HBeAg-negative chronic hepatitis B patients require long-term nucleos(t)ide analogues(NAs) because loss of surface antigen (HBsAg) is unusual. Low quantitative HBsAg (qHBsAg) levels can identify patients with higher probability of seroclearance. The aim of our study was to evaluate qHBsAg in HBeAg-negative patients receiving NAs to predict a reduction of HBsAg levels and seroclearance. Methods Retrospective analysis of qHBsAg in HBeAg-negative patients before and at years 1, 3, 5, 8 and over of NAs treatment. Results From 1999 to 2015, HBsAg was quantified in 358 serum samples from 95 HBeAg-negative patients. Low qHBsAg (<120 IU/mL) was identified at baseline or during follow-up in 14% of patients and HBsAg loss in 4%. No baseline variables predicted seroclearance and only treatment duration predicted low qHBsAg. The annual decline of qHBsAg was -0.102 log IU/mL and the median time to HBsAg loss was 6.04 years. The decline was greater in patients achieving low HBsAg levels (-0.257) than in those who did not (-0.057)(p<0.001). The diagnostic accuracy (ROC curve, 95%CI) of qHBsAg delta at year 3 was 0.89 (0.81–0.97), with cut-off >0.3 log IU/mL showing a positive and negative predictive value of 42% and 100% to identify patients achieving low levels of HBsAg. Conclusions Reduction of qHBsAg is slow in HBeAg-negative patients receiving NAs, although low levels or faster qHBsAg decline may occur in 14%. A qHBsAg reduction >0.3 log IU/mL at year 3 can identify patients with a higher probability of achieving low levels and HBsAg seroclearance.