Diabetes as a Risk Factor for Infections in Cirrhosis. Authors' reply

Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.

Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives

Objectives We aimed to evaluate recompensation factors among patients with decompensated cirrhosis. Design A multicentre retrospective case-control study was conducted. Data were collected from and compared between groups of patients with recompensated and acute decompensated cirrhosis. Univariable and multivariable logistic regressions were used to select indicators associated with recompensation among patients with decompensated cirrhosis with different complications. A decision tree with 10-fold cross-validation was used to develop the model to identify patients with recompensation. We followed the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guideline for development and reporting of the new model. Setting The study was conducted in six tertiary public hospitals in Chongqing, China. Participants This study included 3953 patients with decompensated cirrhosis. Results In the total sample of included patients, there were 553 patients with recompensation and 3400 patients with acute decompensation, including 1158 patients with gastrointestinal bleeding, 1715 patients with a bacterial infection, 104 patients with hepatic encephalopathy and 423 patients with ascites. The most relevant indicator of recompensation selected by the decision tree model was albumin, with a threshold of 40 g/L. Total protein, haemoglobin, basophil percentage, alanine aminotransferase, neutrophil-to-lymphocyte ratio and diabetes were also selected to subsequently distinguish patients. The terminal nodes with a probability of recompensation was 0.89. The overall accuracy rate of the model was 0.92 (0.91-0.93), and it exhibited high specificity (86.9%) and sensitivity (92.6%). Conclusions The occurrence of recompensated cirrhosis could be identified by albumin, total protein, haemoglobin, basophil percentage, alanine aminotransferase, neutrophil-to-lymphocyte ratio and diabetes. These simple variables may help clinicians develop a treatment plan to encourage patients with decompensated cirrhosis to recompensate.

https://bmjopen.bmj.com/content/bmjopen/11/6/e043083.full.pdf

Recompensation factors for patients with decompensated cirrhosis: a multicentre retrospective case-control study.

Background: Liver cirrhosis (LC) is largely associated with diabetes mellitus (DM). More than 80% of patients with LC manifest glucose intolerance and about 30% have type 2 DM. A particular and yet unrecognized entity is hepatogenous diabetes (HD), defined as impaired glucose regulation caused by altered liver function following LC. Numerous studies have shown that DM could negatively influence liver-related outcomes. Aim: We aimed to investigate whether patients with LC and DM are at higher risk for hepatic encephalopathy (HE), variceal hemorrhage (VH), infections and hepatocellular carcinoma (HCC). The impact of DM on liver transplant (LT) outcomes was also addressed. Methods: Literature search was performed in PubMed, Ovid, and Elsevier databases. Population-based observational studies reporting liver outcomes in patients with LC were included. Results: Diabetics are at higher risk for HE, including post-transjugular intrahepatic portosystemic shunt HE. DM also increases the risk of VH and contributes to elevated portal pressure and variceal re-bleeding, while uncontrolled DM is associated with increased risk of bacterial infections. DM also increases the risk of HCC and contributes to adverse LT outcomes. Conclusions: Patients with DM and LC may benefit from close follow-up in order to reduce readmissions and mortality. Due to the heterogeneity of available research, prospective multicenter clinical trials are needed to further validate these findings.

https://www.mdpi.com/2077-0383/10/2/262/pdf

Association between Liver Cirrhosis and Diabetes Mellitus: A Review on Hepatic Outcomes.

The diabetogenic potential of liver cirrhosis (LC) has been known for a long time, and the name "hepatogenous diabetes" (HD) was coined in 1906 to define the condition. Diabetes mellitus (DM) that develops as a consequence of LC is referred to as HD. In patients with LC, the prevalence rates of HD have been reported to vary from 21% to 57%. The pathophysiological basis of HD seems to involve insulin resistance (IR) and pancreatic β-cell dysfunction. The neurohormonal changes, endotoxemia, and chronic inflammation of LC initially create IR; however, the toxic effects eventually lead to β-cell dysfunction, which marks the transition from impaired glucose tolerance to HD. In addition, a number of factors, including sarcopenia, sarcopenic obesity, gut dysbiosis, and hyperammonemia, have recently been linked to impaired glucose metabolism in LC. DM is associated with complications and poor outcomes in patients with LC, although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research. In fact, there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC. Currently, T2DM and HD are being treated in a similar manner although no standardized guidelines are available. The different pathophysiological basis of HD may have an impact on treatment options. This review article discusses the existence of HD as a distinct entity with high prevalence rates, a strong pathophysiological basis, clinical and therapeutic implications, as well as widespread skepticism and knowledge gaps.

Aarti Ravikumar

Papers

Uncontrolled diabetes mellitus increases risk of infection in patients with advanced cirrhosis.