'Alarming' New Numbers on Bacterial Infection in Cirrhosis
Neil Osterweil
April 12, 2018

Infections caused by multidrug-resistant bacteria, which are common in patients with cirrhosis, are associated with a significant elevation in risk for in-hospital mortality, results from a global study show. "The efficacy of first-line treatment is crucial to improve the survival of cirrhotic patients with bacterial infections," said Paolo Angeli, MD, PhD, from the University of Padova in Italy. For their study, Angeli and his colleagues followed 1302 patients with cirrhosis and bacterial or fungal infections until death, liver transplantation, or discharge. All were treated at one of 46 centers in North and South America, Europe, Africa, and Asia, and bacteria were considered multidrug-resistant if they were impervious to at least one agent in three or more antibiotic classes.

Angeli presented the results here at the International Liver Congress 2018.

In the study cohort, mean Model for End Stage Liver Disease (MELD) score was 21, 77% of the patients had ascites, and 35% had acute-on-chronic liver failure. Cirrhosis was caused by alcohol in 52% of patients, by hepatitis C virus in 20%, by hepatitis B virus in 8%, and by nonalcoholic steatohepatitis in 10%; the remaining 10% of patients had cirrhosis of unspecified origin. Of the infections, 48% were deemed to be community-acquired, 26% were nonhospital healthcare-associated, and 26% were nosocomial. The most common infections were spontaneous bacterial peritonitis (27%), urinary tract infections (22%), and pneumonia (19%). The most prevalent infectious organisms were Escherichia coli, Klebsiella pneumonia, Enterococcus, Staphylococcus aureus, and Pseudomnoas areuginosa.

Of the 959 micro-organisms isolated from the 740 patients with at least one positive culture, 58% were Gram-negative, 38% were Gram-positive, and 4% were fungi.

The global prevalence of multidrug-resistant bacteria was 34%, and the prevalence of extensively drug-resistant bacteria — Gram-negative bacteria resistant to nearly all available agents — was 8%. The risk for infection with multidrug-resistant bacteria was especially high in India (odds ratio [OR], 7.94; P < .001), Asia (OR, 2.79; P = .017), and South America (OR, 2.23; P = .053).

Multidrug-resistant bacterial infections were less likely than other bacteria to respond to empiric antibiotic therapy (40% vs 68%; P < .001). And patients with multidrug-resistant infections were significantly more likely to experience septic shock (27% vs15%; P < .001) and new organ failure (42% vs 31%; P = .001). Additionally, multidrug-resistant infections were less likely to be resolved and were associated with a significantly higher rate of in-hospital death (31% vs 21%; P = .004).

"These are very alarming data: more than 30% of multidrug resistance anywhere, more or less, in the world is really alarming," said Annalisa Berzigotti, MD, PhD, from the University of Bern in Switzerland, who was not involved in the study. "At the moment, we are awaiting new antibiotic therapy that could overcome these bugs, but meanwhile, we should all be aware of the measures to prevent infectious disease," she said during a briefing held in advance of the presentation. Isolation of these patients could have reduced the number of infections, she said. "As Angeli suggested, there must be active screening of patients who might have been in contact with these bacteria," Berzigotti said. "Whenever they are admitted to the hospital from another hospital or from the intensive care unit, where there is a much greater distribution of these bacteria, they should be actively screened, and as soon as they are identified, they should be isolated," she said.

International Liver Congress (ILC) 2018: Abstract GS-001. Presented April 12, 2018. ... See more

Difficult-to-Treat Sclerosing Cholangitis Eased With Statins.
Neil Osterweil

April 13, 2018

Statins can significantly reduce the risk for complications and death from primary sclerosing cholangitis, results from a Swedish registry study show. Primary sclerosing cholangitis is progressive, with no known therapy to prevent cirrhosis, liver transplant, or progression to cholangiocarcinoma, said Annika Bergquist, MD, PhD, from the Karolinska Institute in Stockholm.

However, recent evidence suggests that statins can be beneficial for patients with chronic and cholestatic liver disease, and might play a protective role in primary sclerosing cholangitis, she explained here at the International Liver Congress 2018. Bergquist and her colleagues drew on comprehensive birth-to-death Swedish registry data to explore the effects of different drugs, including statins, on the risk for death, liver transplantation, liver cancer, and variceal bleeding in patients with primary sclerosing cholangitis.

The team identified 2914 primary sclerosing cholangitis patients with data available on drug prescriptions, cancer status, general health, and death.

Drug exposure from the time of first prescription fulfillment was assessed on multivariate Cox regression analysis, with adjustments for age at diagnosis of primary sclerosing cholangitis, date of diagnosis, date of diagnosis of inflammatory bowel disease, and sex. The association with inflammatory bowel disease is strong. In Sweden, approximately 80% of primary sclerosing cholangitis patients have inflammatory bowel disease, Bergquist reported. In the study cohort, 58.3% of the patients also had a diagnosis of ulcerative colitis, 12.4% had a diagnosis of Crohn's disease, and 29.2% had mixed presentation of the two conditions.

The Swedish registry data were very high quality. Follow-up was nearly complete and the team was able to eliminate all patients with sclerosing cholangitis secondary to other conditions. However, they were unable to capture drug indications or the clinical status of patients, and information was lacking on potential confounding factors, such as alcohol use and smoking, and on compliance, Bergquist acknowledged. After the briefing during which Bergquist presented the findings, Medscape Medical News asked whether these data suggest that azathioprine also has a protective effect.

"Azathioprine is used very much in inflammatory bowel disease and, therefore, it is difficult to say whether this has an impact on the primary sclerosing cholangitis itself," she explained.

The specific statins used might have had an influence on outcomes, said briefing moderator Annalisa Berzigotti, MD, PhD, from the University of Bern in Switzerland. "Simvastatin, in studies that have been done on cirrhosis, which are quite extensive, and also in vitro, has a particular pharmacokinetic and pharmacodynamic effect, and it is able to penetrate better into cells," she told Medscape Medical News. Bergquist said she agrees, noting that simvastatin has anti-fibrotic, anti-angiogenic, and anti-vasoconstrictive effects, which help to improve portal hypertension. This early work is "not the basis for treating everyone with statins," Bergquist emphasized. But "it is a class effect - what we observe with statins in liver disease - and it is possible that simvastatin is slightly superior."

International Liver Congress (ILC) 2018. Abstract PS-128. Presented April 12, 2018. ... See more

Poverty Harms Patients With Diabetes and Fatty Liver
Neil Osterweil

April 17, 2018
Medscape Medical News © 2018 WebMD, LLC

For patients with diabetes and nonalcoholic fatty liver disease (NAFLD), the risk for advanced hepatic fibrosis increases nearly three times when patients cannot consistently afford a healthy diet, results from a cross-sectional survey suggest. In fact, food insecurity — limited or uncertain availability of nutritionally adequate foods — is a better predictor of advanced fibrosis than other socioeconomic variables, said investigator Russell Rosenblatt, MD, from the New York Presbyterian Hospital in New York City.

"We recommend that hepatologists now think of screening these patients for food insecurity," he said here at the International Liver Congress 2018.

In the United States, food insecurity began to rise around 2008, coinciding with the Great Recession. It is estimated that nearly 50 million Americans are at risk of going hungry at least some of the time. In Europe, a similar trend began to emerge in 2010, with the advent of austerity measures, Rosenblatt reported. The link between food insecurity and diabetes, a major risk factor NAFLD, stems from the fact that calorie-dense but nutritionally poor foods tend to be considerably cheaper than healthy foods. People with food insecurity tend to have poor nutrition and higher levels of obesity, metabolic syndrome, and diabetes.

The American Diabetes Association has made screening for food insecurity when patients with diabetes are evaluated a class A recommendation.

To explore the strength of the association between food security and advanced fibrosis in patients with diabetes and NAFLD, Rosenblatt and his colleagues analyzed data on adults with diabetes from the 2005 to 2014 cycle of the National Health and Nutrition Examination Survey.

National Health and Nutrition Examination Survey
The team used a validated algorithm to identify patients with NAFLD and exclude people with viral hepatitis, women who consume more than two alcoholic drinks per day and men who consume more than three, people with liver transaminase levels above 500 IU/L, and pregnant women.

Study participants completed a 10-question validated food insecurity survey that assessed whether, in the previous year, they had worried about running out of food, worried about not having enough food until the next paycheck, skipped meals because they could not afford them, or lost weight because they did not have enough to eat. Respondents were considered to have very low food security when they answered at least six questions in the affirmative, and full food security when they answered no questions in the affirmative.

The NHANES data indicate that the proportion of people with very low food security grew from 2005 to 2014. In the final study cohort, 1,289,057 people were deemed to have very low food security and 16,344,991 to have full food security. People with very low food security were significantly younger than those with full food security, and significantly more likely to be female, to have a higher mean BMI, to have a higher level of haemoglobin A1c, to be insulin-dependent, and to have metabolic syndrome.

Food insecurity might be exacerbated by poor health habits, such as the consumption of sugary beverages and lack of exercise, said briefing moderator Markus Cornberg, MD, PhD, from Hannover Medical School in Germany. When evaluating patients for fibrosis, "I think we look more to overweight and overeating, but part the problem, in fact, is that they may not have the money to buy the good stuff," he told Medscape Medical News.

International Liver Congress (ILC) 2018: Abstract PS-060. Presented April 12, 2018. ... See more