Prevalence estimation of significant fibrosis because of NASH in Spain combining transient elastography and histology.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. METHODS: This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. RESULTS: From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13-8.75). In the biopsy-proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29-5.98) and 0.70% (95% CI 0.10-4.95) respectively. CONCLUSIONS: These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available.

Let's End HepC: Modelling Public Health Epidemiological Policies Applied to Hepatitis C in Spain.

Background: The WHO has defined international targets toward the elimination of hepatitis C by 2030. Most countries cannot be on track to achieve this goal unless many challenges are surpassed. The Let's End HepC (LEHC) tool aims to contribute to the control of hepatitis C. The innovation of this tool combines the modelling of public health policies (PHP) focused on hepatitis C with epidemiological modelling of the disease, obtaining a unique result that allows to forecast the impact of policy outcomes. The model was applied to several countries, including Spain. Methods: To address the stated objective, we applied the "Adaptive Conjoint Analysis" for PHP decision-making and Markov Chains in the LEHC modelling tool. The tool also aims to be used as an element of health literacy for patient advocacy through gamification mechanisms and country comparability. The LEHC project has been conducted in several countries, including Spain. The population segments comprised in the project are: People Who Inject Drugs (PWID), prisoners, blood products, remnant population. Results: A total of 24 PHP related to hepatitis C were included in the LEHC project. It was identified that Spain had fully implemented 14 of those policies to control hepatitis C. According to LEHC's model forecast, the WHO's Hepatitis C elimination goal on reducing the number of patients living with Hepatitis C to 10% can be achieved in Spain by 2026 if current policies are maintained. The model estimates that the total population in Spain, by 2026, is expected to comprise 26,367 individuals living with hepatitis C. Moreover, if the 24 PHP considered for this study are fully implemented in Spain, the elimination goal may be achieved in 2024, with 29,615 individuals living with hepatitis C by that year. Conclusion: The findings corroborate the view that Spain has set great efforts in directing PHP toward Hepatitis C Virus (HCV) elimination by 2030. However, there is still room for improvement, namely in further implementing 10 of the 24 PHP considered for the LEHC project. By maintaining the 14 PHP in force, the LEHC model estimates the HCV elimination in the country by 2026, and by 2024 if further measures are employed to control the disease.

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

UNLABELLED: 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)/muL, 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.

Pegylated alpha-interferon-2a plus ribavirin compared with pegylated alpha-interferon-2b plus ribavirin for initial treatment of chronic hepatitis C virus: prospective, non-randomized study.

BACKGROUND AND AIM: We assessed whether the two regimens of pegylated alpha-interferon-2b (PEG-IFN-alpha2b) plus ribavirin and pegylated alpha-interferon-2a (PEG-IFN-alpha2a) plus ribavirin showed differences in terms of sustained virological response, withdrawal due to side-effects and dose adjustment requirements in the treatment of naive chronic hepatitis C virus (HCV) patients. METHODS: A prospective non-randomized, open-label comparison was made of naive HCV-infected patients undergoing standard 24- or 48-week treatment with two PEG-IFN combined with weight-based dosing regimen of ribavirin (PEG-IFN-alpha2a/ribavirin, n = 91; PEG-IFN-alpha2b/ribavirin, n = 92). RESULTS: Sustained virological response was similar in PEG-IFN-alpha2a and PEG-IFN-alpha2b (65.9% vs 62%, P = 0.64), without differences according to genotype. In 117 patients with HCV genotype 1, the corresponding rates were 50.8% versus 46.6% (P = 0.713). Rapid virological response at 4 weeks, early virological response at 12 weeks and transient virological response were also similar. In the multivariate analysis, HCV genotype (odds ratio [OR] = 0.076, 95% confidence interval [CI] 0.029-0.198, P = 0.000) and presence of steatosis in the liver biopsy (OR = 2.799, 95% CI 1.362-5.755, P = 0.005) were significantly associated with response to antiviral therapy. The rate of withdrawals due to treatment-related adverse events was 13.2% in the group of PEG-IFN-alpha2a and 10.9% in the group of PEG-IFN-alpha2b. Dose modification of PEG-IFN was necessary in eight patients given PEG-IFN-alpha2a and in seven given PEG-IFN-alpha2b. CONCLUSION: The two PEG-IFN plus ribavirin have comparable anti-HCV activity as shown by similar percentages of patients with sustained virological response.

Clinical significance of abdominal lymphadenopathy in chronic liver disease.

The possibility of assessing the relationship of ultrasound (US)-detected abdominal lymphadenopathy with etiology, biochemical findings, and histologic data in patients with chronic liver disease was evaluated. US examination of the upper abdomen was performed in 321 consecutive patients with various chronic liver disorders and 56 control patients. The prevalence of lymphadenopathy in chronic liver disease was 38%. This prevalence varied according to etiology of liver disease, from 50% in chronic hepatitis C virus (HCV) to less than 10% in alcoholic cirrhosis and hepatitis B-virus (HBV)-related chronic liver disease. Patients with lymphadenopathy showed significantly higher serum levels of AST and ALT, as well as greater histopathological severity on liver biopsy specimens. In anti-HCV positive patients, there were no differences in the prevalence of lymphadenopathy according to HCV genotypes, whereas lymphadenopathy occurred less frequently in responders to interferon therapy than in nonresponders.

Changing prevalence, clinical features, and outcome of acute hepatitis in Spain (1982-2003).

BACKGROUND: Diagnostic and preventive measures have contributed to a change in the epidemiology of acute hepatitis. The purpose of the present paper was to assess the changing prevalence of acute hepatitis from 1982 to 2003. METHODS: Trends in the epidemiology, clinical findings, and outcome of acute viral hepatitis from 1982 to 2003 were examined. A total of 548 episodes of acute hepatitis diagnosed between 1982 and 2003, the clinical course of which was monitored up to the year 2003, were included. Annual changes as well as for the intervals 1982-1992 and 1993-2003 were compared. RESULTS: Severe infections occurred in 1.3% of cases, with a mortality of 0.6%, with progression into chronicity in 25.1%. The annual incidences of acute hepatitis and the comparative intervals 1982-1992 and 1993-2003 showed a decline of parenterally -B, delta and C virus- transmitted infections, unchanged number of cases of acute hepatitis A, an increase in the number of cases of drug-induced hepatitis, increase in median ages, and a decrease in the proportion of hepatitis in injecting drug users. Ages of patients with hepatitis A tended to increase. CONCLUSIONS: A decline of parenterally transmitted acute hepatitis was documented throughout a 22-year period, while the number of cases of hepatitis A was unchanged and that of drug-induced hepatitis increased. Evaluation of the current targeted hepatitis A vaccination approach and adequate pharmacovigilance measures are required in the near future.

Effect of hepatitis C virus infection and abstinence from alcohol on survival in patients with alcoholic cirrhosis.

GOALS: We assessed the effect of HCV infection and abstinence from alcohol on survival in a cohort of patients with alcoholic cirrhosis. BACKGROUND: Hepatitis C virus (HCV) infection may be an important cofactor for liver disease in chronic alcoholics. STUDY: The study population consisted of 213 patients with the diagnosis of alcoholic cirrhosis, 72 of these patients were infected by HCV. Complete alcohol abstinence after diagnosis of alcoholic cirrhosis was recorded in 86 patients. The reference group consisted of 89 patients with anti-HCV positivity who had never consumed alcohol. Survival was analyzed by the Kaplan and Meier method and predictors of survival by the Cox's multiple regression model. RESULTS: HCV infection was not a determinant factor for survival in alcoholic cirrhosis. Age and Child-Pugh grade at the time of diagnosis of cirrhosis and persistence of alcohol consumption after diagnosis were independent predictors of poor outcome. The cumulative survival curve in abstinent alcoholics was significantly different from that of alcoholics who maintained the same pattern of alcohol consumption (log-rank = 4.30, p = 0.0381). Moreover, the cumulative survival in patients with anti-HCV-positive cirrhosis who stopped drinking after diagnosis was similar to that in patients with HCV-positive cirrhosis who had never consumed alcohol (log-rank 0.26, p = 0.61). CONCLUSIONS: Cumulative survival in alcoholic cirrhosis does not seem to be influenced by the presence or absence of markers of HCV infection. Once liver cirrhosis has been diagnosed in the alcoholic patient, complete alcohol abstinence should be strongly recommended.

Risk factors for nonhepatic surgery in patients with cirrhosis.

Cirrhosis of the liver appears to have an unfavorable prognosis in the surgical patient. The aim of this study was to determine risk factors for morbidity and mortality in patients with cirrhosis undergoing nonhepatic surgery. We studied 135 patients with liver cirrhosis undergoing nonhepatic procedures and 86 controls matched by age, sex, and preoperative diagnosis. Preoperative, intraoperative, and postoperative variables associated with 30-day mortality and morbidity were assessed by univariate and multivariate analyses. Patients with cirrhosis showed higher blood transfusion requirements, longer length of hospital stay, and a higher number of complications than controls. The mortality rate was 16.3% in cirrhotics and 3.5% in controls. By univariate analysis, the need for transfusions, prothrombin time, and Child-Pugh score were significantly associated with postoperative liver decompensation, whereas duration of surgery, prothrombin time, Child-Pugh score, cirrhosis-related complications, and general complications were significantly associated with mortality. In the multivariate analysis, Child-Pugh score (odds ratio [OR] 24.4; 95% confidence interval [CI] 5.5 to 106); duration of surgery (OR 5; 95% CI 1.2 to 15.6), and postoperative general complications (OR 3.7; 95% CI 3.4 to 6.4) were independent predictors of mortality. Patients with cirrhosis undergoing nonhepatic operations are at significant risk of perioperative complications leading to death. Independent variables associated with perioperative mortality include preoperative Child-Pugh score, the duration of surgery, and the presence of postoperative general complications.

Mitochondrial oxidative stress and CD95 ligand: a dual mechanism for hepatocyte apoptosis in chronic alcoholism.

Apoptosis plays an important role in the progression of alcohol-induced liver disease to cirrhosis. Oxidative stress is an early event in the development of apoptosis. The major aim of this study was to study the conditions in which oxidative stress occurs in chronic alcoholism and its relationship with apoptosis of hepatocytes. We have found that oxidative stress is associated with chronic ethanol consumption in humans and in rats, in the former independently of the existence of alcohol-induced liver disease. Ethanol or acetaldehyde induces apoptosis in hepatocytes isolated from alcoholic rats, but not in those from control rats. Inhibition of aldehyde dehydrogenase, but not of cytochrome P450 2E1, prevents ethanol-induced cell death. Ethanol-induced apoptosis is caused by increased reactive oxygen species (ROS) driven by increased availability of the reduced form of nicotinamide-adenine dinucleotide (NADH) owing to mitochondrial acetaldehyde metabolism and it is prevented by blocking the opening of mitochondrial permeability transition (MPT) pores with cyclosporine A. Inhibition of nitric oxide (NO) synthase or addition of antioxidant vitamins C and E completely prevented ethanol-induced apoptosis. Mitochondrial oxidative stress, which occurs during chronic alcoholism, renders hepatocytes susceptible to apoptosis. On the other hand, the CD95 ligand expression was up-regulated by acetaldehyde. In conclusion, ethanol induces apoptosis via 2 different pathways: MPT and up-regulation of the expression of CD95-Fas ligand. The overproduction of ROS by mitochondria, driven by acetaldehyde metabolism, is a common trigger of both mechanisms.