N. Cañete

Incidence and Prognosis of Different Types of Functional Renal Failure in Cirrhotic Patients With Ascites

BACKGROUND & AIMS Hepatorenal syndrome is a well-characterized type of terminal renal failure that occurs in patients with cirrhosis with ascites. Information about other types of functional renal failure in these patients is scarce. We assessed the incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites and investigated prognostic factors for these disorders. METHODS Consecutive cirrhotic patients (n = 263) were followed for 41 +/- 3 months after their first incidence of ascites. Three types of functional renal failure were considered: pre-renal failure (when renal failure was associated with a depletion of intravascular volume), renal failure induced by infection that did not result in hepatorenal syndrome, and hepatorenal syndrome. RESULTS During the follow-up period, 129 (49%) patients developed some type of functional renal failure. The most frequent was pre-renal failure (27.4%), followed by renal failure induced by infection (14.1%), and then hepatorenal syndrome (7.6%). The 1-year probability of developing the first episode of any functional renal failure was 23.6%. The independent predictors of functional renal failure development were baseline age, Child-Pugh score, and serum creatinine. Although the 1-year probability of survival was 91% in patients without renal failure, it decreased to 46.9% in those patients who developed any functional renal failure (P = .0001). CONCLUSIONS Approximately 50% of the cirrhotic patients with ascites developed some type of functional renal failure during the follow-up period; renal failure was associated with worse prognosis. Efforts should be made to prevent renal failure in cirrhotic patients with ascites.

Long-Term Follow-Up of 1,000 Patients Cured of Helicobacter pylori Infection Following an Episode of Peptic Ulcer Bleeding

OBJECTIVES:To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients.METHODS:Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or 13C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by 13C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up.RESULTS:Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16–1.16%), and the incidence rate of rebleeding was 0.15% (0.05–0.36%) per patient-year of follow up.CONCLUSION:Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C

BACKGROUND & AIMS Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.

Eradication of Helicobacter pylori for the Prevention of Peptic Ulcer Rebleeding

Aim:  To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long‐term study including more than 400 patients.

Rebleeding prophylaxis improves outcomes in patients with hepatocellular carcinoma. A multicenter case-control study.

Outcome of variceal bleeding (VB) in patients with hepatocellular carcinoma (HCC) is unknown. We compared outcomes after VB in patients with and without HCC. All patients with HCC and esophageal VB admitted between 2007 and 2010 were included. Follow‐up was prolonged until death, transplantation, or June 2011. For each patient with HCC, a patient without HCC matched by age and Child‐Pugh class was selected. A total of 292 patients were included, 146 with HCC (Barcelona Classification of Liver Cancer class 0‐3 patients, A [in 25], B [in 29], C [in 45], and D [in 41]) and 146 without HCC. No differences were observed regarding previous use of prophylaxis, clinical presentation, endoscopic findings, and initial endoscopic treatment. Five‐day failure was similar (25% in HCC versus 18% in non‐HCC; P = 0.257). HCC patients had greater 6‐week rebleeding rate (16 versus 7%, respectively; P = 0.025) and 6‐week mortality (30% versus 15%; P = 0.003). Fewer patients with HCC received secondary prophylaxis after bleeding (77% versus 89%; P = 0.009), and standard combination therapy was used less frequently (58% versus 70%; P = 0.079). Secondary prophylaxis failure was more frequent (50% versus 31%; P = 0.001) and survival significantly shorter in patients with HCC (median survival: 5 months versus greater than 38 months in patients without HCC; P < 0.001). Lack of prophylaxis increased rebleeding and mortality. On multivariate analysis Child‐Pugh score, presence of HCC, portal vein thrombosis, and lack of secondary prophylaxis were predictors of death. Conclusions: Patients with HCC and VB have worse prognosis than patients with VB without HCC. Secondary prophylaxis offers survival benefit in HCC patients. (Hepatology 2013; 58:2079–2088)

The addition of a protease inhibitor increases the risk of infections in patients with hepatitis C-related cirrhosis

BACKGROUND & AIMS Antiviral therapy with interferon and ribavirin (double therapy) is associated with a significant risk of developing bacterial infections in patients with hepatitis C-related cirrhosis. The addition of telaprevir or boceprevir seems to increase this risk but there are no studies yet to compare the infection rate between both treatments. We aimed to assess rate, type and predictive factors of infection in cirrhotic patients undergoing triple or double antiviral therapy. METHODS This was a retrospective analysis of prospectively collected data. 167 patients with hepatitis C-related cirrhosis undergoing triple therapy (cohort A) and 81 receiving double therapy (cohort B) were enrolled in the study. Only Child-Pugh A patients were included. RESULTS The infection rate was significantly higher for patients in cohort A as compared to those in cohort B (25% vs. 9%, p=0.001). Interestingly, respiratory tract infections were significantly more frequent in patients in cohort A (12% vs. 1%; p=0.049). The use of triple antiviral therapy was the only predictive factor of infection. Severe infections were also more frequent in patients in cohort A, but the difference did not reach the level of significance (13% vs. 6%, p=0.123). CONCLUSIONS Triple therapy carries a higher risk of infections in patients with cirrhosis and changes the pattern of infection in this subpopulation. Further studies are needed in order to establish the underlying mechanism of this event.

Applicability and accuracy improvement of transient elastography using the M and XL probes by experienced operators

Transient elastography (TE) is the reference method to obtain liver stiffness measurements (LSM), but no results are obtained in 3.1% and unreliable in 15.8%. We assessed the applicability and diagnostic accuracy of TE re‐evaluation using M and XL probes. From March 2011 to April 2012 868 LSM were performed with the M probe by trained operators (50–500 studies) (LSM1). Measurements were categorized as inadequate (no values or ratio <60% and/or IQR/LSM >30%) or adequate. Inadequate LSM1 were re‐evaluated by experienced operators (>500 explorations) (LSM2) and inadequate LSM2 using XL probe (LSMXL). Inadequate LSM1 were obtained in 187 (21.5%) patients, IQR/LSM >30% in 97 (51%), ratio <60% in 24 (13%) and TE failed to obtain a measurement in 67 (36%). LSM2 achieved adequate registers in 123 (70%) of 175 registers previously considered as inadequate. Independent variables (OR, 95%CI) related to inadequate LSM1 were body mass index (1.11, 1.04–1.18), abdominal circumference (1.03, 1.01–1.06) and age (1.03, 1.01–1.04) and to inadequate LSM2 were skin‐capsule distance (1.21, 1.09–1.34) and abdominal circumference (1.05, 1.01–1.10). The diagnostic accuracy (AUROC) to identify significant fibrosis improved from 0.89 (LSM1) to 0.91 (LSM2) (P = 0.046) in 334 patients with liver biopsy or clinically significant portal hypertension. A third evaluation (LSMXL) obtained adequate registers in 41 (93%) of 44 patients with inadequate LSM2. Operator experience increases the applicability and diagnostic accuracy of TE. The XL probe may be recommended for patients with inadequate values obtained by experienced operators using the M probe. http://clinicaltrials.gov (NCT01900808).

Ability of treatment week 12 viral response to predict long-term outcome in genotype 1 hepatitis C virus/HIV coinfected patients.

Objective:Guidelines recommendation to extend treatment duration in genotype 1 hepatitis C virus (HCV)/HIV-coinfected patients who clear the virus later than treatment week 4 is not evidence-based. Our main objective was to study the ability of week 12 viral response [early virologic response (EVR)] to predict long-term outcome in patients treated for 48 weeks. Design:Multicenter retrospective cohort analysis. Methods:Genotype 1 HCV treatment-naive, HIV-coinfected adult patients with compensated liver disease who started combination therapy with fixed-dose pegylated-interferon (pegIFN) alfa-2a or weight-based pegIFN alfa-2b plus ribavirin were included. Univariate and forward stepwise logistic regression analysis were used to identify predictors of sustained viral response (SVR) and relapse. Results:By intention-to-treat analysis, 31.3% (87/278) of patients achieved an SVR. SVR rate was more than three-fold higher in patients who cleared the virus by week 12 of treatment compared with late responders. Among 123 end-of-treatment responders, 36 (29.3%) relapsed. Relapse risk increased in patients with cirrhosis, in those with ribavirin dose reductions and in late responders: more than 65% of patients who cleared the virus between weeks 12 and 24 relapsed following 48 weeks of treatment compared with 10% of those attaining a complete EVR (<15 IU/ml) at treatment week 12 (risk ratio 6.4, 95% confidence interval 2.9–14.4). Conclusion:Viral response at treatment week 12 is a strong predictor of long-term outcome. Genotype 1 HCV/HIV-coinfected patients who achieve a complete EVR (<15 IU/ml) are at low risk of viral relapse after completing the standard 48 weeks of therapy.

Hepatitis aguda C en España: estudio retrospectivo de 131 casos

BACKGROUND AND AIMS The management of acute hepatitis C (AHC) is controversial. We have conducted a retrospective study to determine the epidemiological and biochemical aspects, the genotypes, the spontaneous clearance of HCV (SVC), and the treatment responses in patients with AHC. METHODS We have retrospectively collected data from 131 patients with AHC from 18 Spanish hospitals. RESULTS The mean age was 43 ± 16 years (17-83), 69% were symptomatic. The causes of infection were nosocomial in 40% and intravenous drug users in 20%. Eighty two percent had genotype 1. The delay from symptoms-onset to HCV-RNA confirmation was 50 ± 68 days (range, 11-350 days) and to treatment (in 59%) 14±1 3 weeks (range, 2-58 days). In the treated group, 80% achieved sustained virological response (SVR) versus 57% SVC in untreated patients (p = 0.004). Up to 96% of those treated within the first 12 weeks had SVR versus 86% of those treated later (p = 0.04). Patients with HCV-RNA(-) at week 4 resolved with or without treatment more frequently than those HCV-RNA(+) (98% versus 69%, p = 0.005). The treatment was not beneficial if HCV-RNA was undetectable at week 12. No differences in SVR were found in genotype 1 patients treated for 24 or 48 weeks. Patients with low baseline viral load achieved higher SVC and SVR. The SVC in patients with bilirubin > 5 mg/dL was 78 versus 40% in those with lower values (p = 0.004). CONCLUSIONS The most common transmission route was nosocomial. SVR was higher in patients treated than SVC in non-treated.Early treatment (before week 12) achieved the highest response rate. SVC and SVR were more common in patients with a low baseline viral load. Undetectable HCV-RNA at week 4 was associated with high SVR and SVC rates. Jaundice was related with SVC.

Impact of Anthropometric Features on the Applicability and Accuracy of FibroScan® (M and XL) in Overweight/Obese Patients.

Transient elastography is the reference method for liver stiffness measurement (LSM) in the general population, having lower applicability in obese patients. We evaluated the applicability and diagnostic accuracy of the M and XL probes in overweight/obese patients to establish the most appropriate approach.