Silvia Montoliu

Serum and ascitic fluid bacterial DNA: A new independent prognostic factor in noninfected patients with cirrhosis

We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/μL, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of large‐volume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12‐month follow‐up period. BactDNA was detected in 48 patients. The most prevalent identified bactDNA corresponded to Escherichia coli (n = 32/48 patients, 66.6%). Patients were followed for 12 months after inclusion and in this period 34 patients died: 16 of 108 (15%) bactDNA negative versus 18 of 48 (38%) bactDNA positive (P = 0.003). The most frequent cause of death was acute‐on‐chronic liver failure in both groups (7/16 and 9/18 in patients without or with bactDNA, respectively), although more prevalent in the first month of follow‐up in patients with presence of bactDNA (0 versus 4/7). When considering patients with model for end‐stage liver disease (MELD) score less than 15, mortality was significantly higher in those with presence of bactDNA. Spontaneous bacterial peritonitis developed similarly in patients with or without bactDNA at admission. Conclusion: The presence of bactDNA in a patient with cirrhosis during an ascitic episode is an indicator of poor prognosis. This fact may be related to the development of acute‐on‐chronic liver failure at short term and does not predict the development of spontaneous bacterial peritonitis. (HEPATOLOGY 2008;48:1924‐1931.)

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.

Combining steroids with enteral nutrition: a better therapeutic strategy for severe alcoholic hepatitis? Results of a pilot study

Background Results of a previous randomized controlled trial comparing the outcome of patients with severe alcoholic hepatitis treated with total enteral nutrition (TEN) or corticosteroids suggest that these treatments act through different mechanisms and may be complementary. We report a pilot study of combined treatment with TEN and a shorter course of steroids in patients with severe alcoholic hepatitis. Methods Thirteen patients with severe alcoholic hepatitis were treated with systemic steroids and TEN. Steroid therapy started with 40 mg oral prednisolone daily, and was progressively tapered as soon as both serum bilirubin and prothrombin time decreased below 50% of their baseline values. TEN (2000 kcal, or 8374 kJ, daily) was administered throughout the hospital stay. Patients were followed for at least 12 months or until death. Results Tapering of prednisolone dose could be started after a mean (SD) of 15.4 (3.8) days, whereas TEN was maintained for 22 (3.8) days. TEN was tolerated in 10 of the 13 patients. The major adverse event attributable to therapy was hyperglycemia requiring insulin therapy, which occurred in 12 of 13 patients. Only two patients (15%) died during the treatment period. Another patient died within the first 2 months of follow-up. In no case was the death due to infectious complications, despite two-thirds of patients developing infections during the treatment period. Infections during follow-up occurred only in three patients. Conclusion This pilot study suggests that TEN associated with a short course of steroids could be a good therapeutic strategy for severe alcoholic hepatitis. This possibility deserves investigation in a randomized controlled trial.

Probability of liver cancer and survival in HCV-related or alcoholic-decompensated cirrhosis. A study of 377 patients

Abstract: Background: Although chronic alcohol intake and chronic hepatitis C may progress to cirrhosis and hepatocellular carcinoma (HCC), few data are available about survival and probability of developing HCC in decompensated cirrhosis of both aetiologies.

Clinical usefulness of total hepatitis C virus core antigen quantification to monitor the response to treatment with peginterferon alpha-2a plus ribavirin*.

Summary.  Early virological response may predict outcome following treatment with peginterferon alpha‐2a and ribavirin in patients chronically infected with hepatitis C virus (HCV). As total HCV core antigen may constitute an alternative direct marker to HCV RNA for assessing the levels of viraemia in such patients, we evaluated the correlation between HCV core antigen and HCV RNA, and whether HCV core antigen at baseline, 4 and 12 weeks after treatment could predict sustained virological response (SVR) to combined therapy, in comparison with HCV RNA.

Real-World Effectiveness and Safety of Oral Combination Antiviral Therapy for Hepatitis C Virus Genotype 4 Infection

&NA; Patients with hepatitis C virus (HCV) genotype 4 infection are poorly represented in clinical trials of second‐generation direct‐acting antiviral agents (DAAs). More data are needed to help guide treatment decisions. We investigated the effectiveness and safety of DAAs in patients with genotype 4 infection in routine practice. In this cohort study, HCV genotype 4‐infected patients treated with ombitasvir/paritaprevir/ritonavir (OMV/PTVr) + ribavirin (RBV) (n=122) or ledipasvir/sofosbuvir (LDV/SOF) ± RBV (n=130) included in a national database were identified and prospectively followed up. Demographic, clinical and virologic data and serious adverse events (SAEs) were analyzed. Differences between treatment groups mean that data cannot be compared directly. Overall sustained virologic response at Week 12 post treatment (SVR12) was 96.2% with OMV/PTVr+RBV and 95.4% with LDV/SOF±RBV. In cirrhotic patients, SVR12 was 91.2% with OMV/PTVr+RBV and 93.2% with LDV/SOF±RBV. There was no significant difference in SVR12 according to degree of fibrosis in either treatment group (P = .243 and P = .244, respectively). On multivariate analysis, baseline albumin <3.5 g/dL (OMV/PTVr) and bilirubin >2 mg/dL (both cohorts) were significantly associated with failure to achieve SVR (P < .05). Rates of SAEs and SAE‐associated discontinuation were 5.7% and 2.5%, respectively, in the OMV/PTVr subcohort and 4.6% and 0.8%, respectively, in the LDV/SOF subcohort. DAA‐based regimens returned high rates of SVR12, comparable to limited data from clinical trials, in cirrhotic and non‐cirrhotic HCV genotype 4 patients managed in a realworld setting. Safety profiles of both regimens were good and comparable to those reported for other HCV genotypes.

Interferon-Free Therapy in Elderly Patients With Advanced Liver Disease

Objectives:Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice.Methods:Retrospective analysis of hepatitis C virus (HCV) patients aged ≥65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C).Results:Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65–74 years, 211 (17%) were aged 75–79 years, and 86 (7%) were aged ≥80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin ≤3.5 g/dl was the only independent negative predictor of response (0.25 (0.15–0.41); P<0.01). Regarding tolerability, the rate of severe adverse events increased with age category (8.8, 13, and 14%; P=0.04). In addition, the main predictors of mortality (2.3%) were age ≥75 years (2.59 (1.16–5.83); P =0.02) and albumin ≤3.5 (17 (6.3–47); P <0.01).Conclusions:SVR rates with interferon-free regimens in elderly patients are high and comparable to the general population. Baseline low albumin levels (≤3.5 g/dl) was the only predictor of treatment failure. Importantly, the rate of severe adverse events and death increased with age. Elderly patients (≥75 years) or those with advanced liver disease (albumin ≤3.5) presented higher mortality. Thus a careful selection of patients for antiviral treatment is recommended.

Presentación atípica de metástasis a distancia de hepatocarcinoma

Resumen El hepatocarcinoma (HCC) es el tumor primario maligno de higado mas frecuente. Habitualmente asienta sobre un higado cirrotico, lo que justifica su cribado mediante determinacion de las concentraciones de alfafetoproteina y ecografia abdominal de forma semestral en todo paciente cirrotico con funcion hepatocelular preservada. Esto permite la deteccion precoz de tumores, lo que incrementa la proporcion de casos potencialmente curables. La diseminacion metastasica mas frecuente del HCC es la trombosis de la vena porta, mientras que es poco frecuente la diseminacion a distancia. Presentamos 3 casos de HCC con metastasis de localizacion infrecuente y sintomas inespecificos, que motivaron una orientacion diagnostica inicial erronea. Dada la mayor supervivencia actual de este tipo de pacientes, debe considerarse la posibilidad de metastasis a distancia ante la aparicion de sintomas inespecificos en pacientes portadores de HCC.

Enterococcus gallinarum bacteriascites in a patient with active tuberculosis and HCV cirrhosis

TO THE EDITOR: In the January issue, Maxwell et al. (1) describe an intriguing relationship between the use of antibiotics and the development of functional bowel symptoms likened to irritable bowel syndrome (IBS). They determined that in their cohort of subjects, 4 months after the use of antibiotics, there was an increased incidence of functional GI symptoms relative to controls. There are, however, some concerns with the study, and the authors may have overlooked other interpretations of their data. First, the authors provide background to suggest that when infectious diarrhea is treated with antibiotics, the incidence of IBS symptoms is higher (82%) than in controls (68%), based on a study by Gwee et al. (2). What is not adequately quoted is that this difference was not significant and that it likely represented a more severe infectious illness in the IBS group. In fact, the reported degree of diarrhea and abdominal pain during the infectious illness was higher among those subjects who ultimately developed IBS and likely determined the increased (albeit not significantly) level of antibiotic use. Another concern about Maxwell and colleagues’ article is the timing of their questionnaire (1). Clearly, it was first administered after the subjects had already received the antibiotics. Although there appeared to be a similar preantibiotic prevalence of IBS described in Table 1, there also appeared to be a lower median number of functional symptoms in the preceding month in antibiotic-treated subjects versus controls (0.5 vs 2.0). The authors later describe results suggesting that at the time of the first questionnaire (after antibiotics) more IBS subjects had no functional symptoms. In fact, 50% of antibiotic-treated subjects reported no functional bowel symptoms, compared with 33% of the controls (p 0.09). Four months after antibiotic use this trend reversed but was more statistically equal to controls (p 0.2). Based on these results, the authors need at least to consider the possibility that the antibiotic use may have initially diminished functional symptoms, with return/ exacerbation of these symptoms 4 months later. There are a number of ways the authors could have sorted this out. First, they could have administered a questionnaire just before the use of antibiotics in addition to immediately after. Second, they could track the initial bowel habits (e.g., the 1st wk after antibiotics) and again compare bowel symptoms to controls to determine if there was an initial detrimental or beneficial effect of treatment. Third, the course of symptoms could have been tracked over time. Why was 4 months chosen? Why would there be less IBS symptoms initially upon completion of antibiotics and yet a worsening later? This needs to be discussed. There are other data supporting this alternative explanation whereby antibiotics may produce a beneficial effect in IBS. The first is an article by Nayak et al. (3) suggesting that metronidazole given in a double-blind placebo-controlled fashion actually improved IBS symptoms in subjects relative to controls. The second is an article by our group (4) suggesting a role of intestinal flora in IBS whereby antibiotics resulted in a significant improvement of IBS symptoms. Although both studies are recognized to have their limitations, the authors fail to discuss this possibility and have not adequately ruled it out. Despite the criticisms, this article is important, as it again hints at the potential relationship between functional symptoms and enteric bacteria as influenced by antibiotics. We look forward to any follow-up studies the authors have that may rule in or out any initial beneficial effects of antibiotics as a confounding factor.

Paritaprevir/r/Ombitasvir + Dasabuvir 8 weeks in HCV-genotype 1b with mild-moderate fibrosis: Results from a Real World Cohort

The interferon‐free regimen paritaprevir/ritonavir, ombitasvir + dasabuvir (PTV/r/OBV/DSV) has shown high efficacy in patients with hepatitis C virus (HCV) genotype 1b infection when administered for 8 or 12 weeks, but data regarding the 8‐week treatment are scarce. The aim of our study was to assess the efficacy and safety of the 8‐week administration of PTV/r/OBV/DSV in a real‐world cohort.