Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy

Background

Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014).

Methods

The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods.

Results

The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (p < 0.001) and with a higher rate of cirrhosis and/or HCC (p < 0.001) than those investigated in 2001. There was a remarkable increase over time in the proportion of male abstainers (36.7% in 2001 and 64.3% in 2014).

Conclusion

This study highlights important inter- and intra-gender differences in the characteristics and etiological factors of patients with CLD in Italy.

     

Clinical Impact of Depression in Cirrhosis

Purpose of Review

Depression is the most commonly diagnosed psychiatric illness. It is prevalent in most chronic medical conditions and is associated with increased morbidity and mortality. Depression is especially common in patients with cirrhosis.

Recent Findings

In this review, we discuss the prevalence, risk factors, diagnosis, clinical impact, and treatment of depression in cirrhosis. We describe various screening tests important for diagnosis, the interaction of depression with hepatic encephalopathy, and its significant impact on medication adherence, mortality, and caregiver burden.

Summary

These findings highlight the importance of appropriate screening, diagnosis, and treatment of depression in patients with cirrhosis.

     

Translation and validation of chronic liver disease questionnaire (CLDQ) in Tamil language

Background

Chronic liver disease questionnaire (CLDQ), a self-administered quality-of-life (QOL) instrument for chronic liver disease (CLD) patients, was originally developed in English language. We aimed to translate and validate CLDQ in Tamil language (CLDQ-T).

Methods

CLDQ-T, prepared by two forward and two backward independent translations by four bilingual (Tamil and English) persons, and repeated iterative modifications, was validated in adult, native-Tamil patients with CLD. CLDQ-T was re-tested in some patients 2 weeks later. Convergent validity was assessed using Spearman’s correlation, and discriminant validity by comparison with World Health Organization’s brief QOL tool (WHOQOL-BREF). Reliability was assessed through internal consistency (Cronbach’s alpha) and test-retest reliability (intra-class correlation). Cutoff used for statistical significance was p<0.05.

Results

The study included 126 patients (age: mean [SD] 46 years [12.5]; male 104; cause: alcohol 42%, HBV 25%, HCV 4%, cryptogenic 29%; CTP class A 47%, B 37%, and C 16%). In convergent validity, all domains except the “abdominal domain” showed significant correlation between CLDQ-T and WHOQOL-BREF. Patients with severe disease had lower scores for all domains of CLDQ-T except the “abdominal” domain, but not for any of the domains for WHOQOL-BREF. Overall Cronbach’s alpha was 0.942, and more than 0.7 for all the individual domains except the “activity” domain. On retesting in 44 (35%) patients, intraclass correlation coefficient was 0.879 for the overall CLDQ-T score and >0.700 for individual domains.

Conclusion

CLDQ-T was easily understood and showed good performance characteristics in assessing QOL in Tamil-speaking patients with CLD.

     

Prothrombotic factors do not increase the risk of recurrent ischemic events after cryptogenic stroke at young age: the FUTURE study

Background

The role of hypercoagulable states and preceding infections in the etiology of young stroke and their role in developing recurrent ischemic events remains unclear. Our aim is to determine the prevalence of these conditions in patients with cryptogenic stroke at young age and to assess the long-term risk of recurrent ischemic events in patients with and without a hypercoagulable state or a recent pre-stroke infection with Borrelia or Syphilis.

Patients and methods

We prospectively included patients with a first-ever transient ischemic attack or ischemic stroke, aged 18–50, admitted to our hospital between 1995 and 2010. A retrospective analysis was conducted of prothrombotic factors and preceding infections. Outcome was recurrent ischemic events.

Results

Prevalence of prothrombotic factors did not significantly differ between patients with a cryptogenic stroke and with an identified cause (24/120 (20.0%) and 32/174 (18.4%) respectively). In patients with a cryptogenic stroke the long-term risk [mean follow-up of 8.9 years (SD 4.6)] of any recurrent ischemic event or recurrent cerebral ischemia did not significantly differ between patients with and without a hypercoagulable state or a recent infection. In patients with a cryptogenic stroke 15-years cumulative risk of any recurrent ischemic event was 24 and 23% in patients with and without any prothrombotic factor respectively.

Conclusions

The prevalence of prothrombotic factors and preceding infections did not significantly differ between stroke patients with a cryptogenic versus an identified cause of stroke and neither is significantly associated with an increased risk of recurrent ischemic events after cryptogenic stroke.

     

Roles of double-balloon endoscopy in the diagnosis and treatment of Crohn’s disease: a multicenter experience

Background

Double-balloon endoscopy (DBE) examinations are not yet widely accepted as routine procedures for examining the small bowel of patients with Crohn’s disease (CD).

Aim

To evaluate the feasibility and usefulness of DBE for CD in tertiary-care hospitals.

Methods

Between July 2004 and September 2008, 1444 DBE procedures were performed for 704 patients in 6 tertiary-care hospitals. Patient profile, indication, diagnosis and treatment of DBE were evaluated using a multicenter database.

Results

DBE examinations were most frequently performed in 75 patients with CD, corresponding to 10.5% of all the patients examined by DBE. Fifty patients were diagnosed with CD before DBE, while DBE was performed for the diagnosis of 25 new CD patients. Small bowel lesions were often detected even when the terminal ileum was not involved. In the 75 patients, 21 patients were asymptomatic at the time of DBE examinations. Active inflammatory lesions were detected in 51.2% of the CD patients, and were even detected in 33.3% of the asymptomatic CD patients. The treatment was altered in 53.3% of the CD patients after the DBE evaluation. No severe complications were experienced.

Conclusions

DBE procedures can be safely performed in patients with CD and should be considered for the precise evaluation of and to determine the treatment strategy for CD.

     

Raised plasma levels of H<Subscript>2</Subscript>S and nitrate predict intrapulmonary vascular dilations: A preliminary report in patients with cryptogenic cirrhosis

Background and Aims

The role of vasoactive chemicals in the pathogenesis of hepatopulmonary syndrome (HPS), a disorder characterized by intrapulmonary vascular dilation (IPVD), is only vaguely elucidated. We aimed to study the association between plasma H₂S, nitrate levels, and presence and severity of IPVD and HPS.

Methods

Consecutive adult patients with cryptogenic cirrhosis were evaluated for IPVD (by contrast echocardiography) and for hypoxemia (by arterial blood gas analysis). Plasma H₂S and nitrate levels were measured in these patients.

Results

Fifty-eight patients with cryptogenic cirrhosis (male, 45; median age, range, 45, 16–74 years; Child’s class; A, 30; B, 18; C, 10) were enrolled in this study. Thirty-four of the 58 (59%) patients had IPVD and 13 (22%) had HPS (mild, 4; moderate, 5; severe, 2; very severe, 2). Plasma H₂S levels were significantly higher in patients with IPVD (19.6, 5.7–83 μmol/L) as compared to patients who had no IPVD (12.3, 0–47 μmol/L; p-value 0.03) with an area under receiver operating characteristic curve of 0.68 (95% CI 0.53–0.84). Plasma H₂S levels were higher in patients with IPVD irrespective of liver disease severity. There was a trend for higher plasma nitrate levels in patients with IPVD (47, 15.8–126.4 nmol/mL) as compared to patients who had no IPVD (32.3, 6.9–51.4 nmol/mL; p-value 0.1). Raised plasma H₂S and nitrate levels had an additive effect on the presence of IPVD. Neither plasma H₂S nor plasma nitrate levels correlated with the degree of hypoxemia.

Conclusion

Raised plasma H₂S and nitrate levels predict the presence of IPVD in patients with cryptogenic cirrhosis.

     

Effects of a Video on Organ Donation Consent Among Primary Care Patients: A Randomized Controlled Trial

BACKGROUND

Low organ donation rates remain a major barrier to organ transplantation.

OBJECTIVE

We aimed to determine the effect of a video and patient cueing on organ donation consent among patients meeting with their primary care provider.

DESIGN

This was a randomized controlled trial between February 2013 and May 2014.

SETTING

The waiting rooms of 18 primary care clinics of a medical system in Cuyahoga County, Ohio.

PATIENTS

The study included 915 patients over 15.5 years of age who had not previously consented to organ donation.

INTERVENTIONS

Just prior to their clinical encounter, intervention patients (n?=?456) watched a 5-minute organ donation video on iPads and then choose a question regarding organ donation to ask their provider. Control patients (n?=?459) visited their provider per usual routine.

MAIN MEASURES

The primary outcome was the proportion of patients who consented for organ donation. Secondary outcomes included the proportion of patients who discussed organ donation with their provider and the proportion who were satisfied with the time spent with their provider during the clinical encounter.

KEY RESULTS

Intervention patients were more likely than control patients to consent to donate organs (22 % vs. 15 %, OR 1.50, 95%CI 1.10–2.13). Intervention patients were also more likely to have donation discussions with their provider (77 % vs. 18 %, OR 15.1, 95%CI 11.1–20.6). Intervention and control patients were similarly satisfied with the time they spent with their provider (83 % vs. 86 %, OR 0.87, 95%CI 0.61–1.25).

LIMITATION

How the observed increases in organ donation consent might translate into a greater organ supply is unclear.

CONCLUSION

Watching a brief video regarding organ donation and being cued to ask a primary care provider a question about donation resulted in more organ donation discussions and an increase in organ donation consent. Satisfaction with the time spent during the clinical encounter was not affected.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01697137

     

The Assessment and Management of Pain in Cirrhosis

Purpose of Review

The treatment of pain in patients with cirrhosis is complicated by unpredictable hepatic drug metabolism and a higher risk of adverse drug reactions. We aimed to conduct a scoping review regarding pain management in cirrhosis.

Recent Findings

Despite the high prevalence of pain in patients with cirrhosis, there is little literature to guide the management of pain in this population. Complex pain syndromes and disease-specific pain etiologies are common in patients with cirrhosis. There are numerous contraindications and limitations when considering pharmacotherapy for analgesia in cirrhosis, specifically with nonsteroidal anti-inflammatory drugs and opioid medications. Non-pharmacologic therapies for pain have not been specifically assessed in this population.

Summary

As with other populations, a multi-dimensional treatment approach to pain with a focus on physical, behavioral, procedural, and pharmacologic treatment is recommended when caring for patients with cirrhosis and pain. However, more research is needed to evaluate opioid-sparing and non-pharmacologic analgesia in this population.

     

Fettleberdiagnostik bei Diabetes mellitus Typ 2

Definition of terms

Under the term non-alcoholic fatty liver disease (NAFLD) both simple hepatic fat accumulation and non-alcoholic steatohepatitis (NASH) are combined. NASH is associated with liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC).

Epidemiological importance

In 2020, NAFLD will be the leading cause for liver transplantation in the USA, with rising financial costs for the healthcare system.

Comorbidities, diagnosis, and treatment

Type 2 diabetes (T2D) and metabolic syndrome (MetS) are important risk factors for the development of NAFLD, whereby these three diseases share similar pathophysiologic conditions, e.g., insulin resistance, obesity, and metabolic inflammation. Due to the rising number of patients with T2D and MetS, clinicians should aim to diagnose NAFLD early in this patient population and if necessary start treatment.

Goal

The aim of this work is to give an overview over the topic of NAFLD and diagnostic approaches in patients with T2D.

     

Hepatitis C Cure Is Associated with Decreased Healthcare Costs in Cirrhotics in Retrospective Veterans Affairs Cohort

Background

Approximately 233,898 individuals in the Veterans Affairs healthcare network are hepatitis C virus (HCV)-infected, making the Veterans Affairs the single largest provider of HCV care in the USA. Direct-acting antiviral treatment regimens for HCV offer high cure rates. However, these medications pose an enormous financial burden, and whether HCV cure is associated with decreased healthcare costs is poorly defined.

Aims

To measure downstream healthcare costs in a national population of HCV-infected patients up to 9 years post-HCV antiviral treatment, to compare downstream healthcare costs between cured and uncured patients, and to assess impact of cirrhosis status on cost differences.

Methods

This is a retrospective cohort study (2004–2014) of hepatitis C-infected patients who initiated antiviral treatment within the United States Veterans Affairs healthcare system October 2004–September 2013. We measured inpatient, outpatient, and pharmacy costs after HCV treatment.

Results

For the entire cohort, cure was associated with mean cumulative cost savings in post-treatment years three–six, but no cost savings by post-treatment year nine. By post-treatment year nine, cure in cirrhosis patients was associated with a mean cumulative cost savings of $9474 (? 32,666 to 51,614) per patient, while cure in non-cirrhotic patients was associated with a mean cumulative cost excess of $2526 (? 12,211 to 7159) per patient.

Conclusions

Among patients with cirrhosis at baseline, cure is associated with absolute cost savings up to 9 years post-treatment compared to those without cure. Among patients without cirrhosis, early post-treatment cost savings are counterbalanced by higher costs in later years.

     

Transjugular liver biopsy in severe alcoholic hepatitis

Background

Alcoholic hepatitis and cirrhosis although part of spectrum of alcoholic liver disease can have overlapping features, and differentiating them using clinical, biochemical, and imaging features is not always possible. Standard therapy for each differs, and steroid therapy while beneficial in alcoholic hepatitis may be detrimental in cirrhosis due to high infectious complications. We analyzed our experience with liver biopsy in patients with severe alcoholic hepatitis.

Methods

Male patients in the age group of 25–65 years who were clinically diagnosed with severe alcoholic hepatitis (DF > 32) were retrospectively analyzed and included in this study. All of them had undergone transjugular liver biopsy within the first 7 days of hospitalization.

Results

Thirty patients were included. Most were in the 35–55 age group. Jaundice was present in all patients with fever and tender hepatomegaly also being common. On histopathological evaluation, 33.3% (n = 10) suspected clinically to have alcoholic hepatitis had underlying cirrhosis.

Conclusion

Cirrhosis is found in one third of patients with severe alcoholic hepatitis. This may alter our approach to management of this condition.

     

Non-HFE iron overload as a surrogate marker of disease severity in patients of liver cirrhosis

Background

Decompensated liver cirrhosis is an important cause of mortality worldwide. Various modifiable and non-modifiable factors are involved in the pathogenesis of cirrhosis and its complications. This study was aimed to evaluate the association of iron overload and disease severity in patients of liver cirrhosis and its association with HFE gene mutation.

Methods

Forty-nine patients with decompensated liver cirrhosis were recruited. Clinical and laboratory parameters were compared in patients with and without iron overload. C282Y and H63D gene mutation analysis was performed in all patients with iron overload.

Results

Iron overload was found in 20 (40.82 %) patients. A significant positive correlation of transferrin saturation with Child-Turcotte-Pugh (CTP) score (r?=?0.705, p?<?0.001) and model for end-stage liver disease (MELD) score (r?=?0.668, p?<?0.001) was found. Transferrin saturation was also independently associated with high CTP and MELD score on multivariate analysis. Mortality over 3 months was significantly more common in iron-overloaded patients (p?=?0.028). C282Y homozygosity or C282Y/H63D compound heterozygosity was not found in any of the patients with iron overload.

Conclusion

Iron overload was significantly associated with disease severity and reduced survival in patients of decompensated liver cirrhosis.

     

Functional Defects of Treg Cells: New Targets in Rheumatic Diseases,Including Ankylosing Spondylitis

Purpose of review

This study aims to review the advances of Treg cell biology, the functional defects of Treg cells, and the potential strategies for the experimental, preclinical or clinical application of Treg cell therapy in the context of autoimmune/immune-mediated rheumatic diseases.

Recent findings

CD4⁺CD25⁺ regulatory T (Treg) cells are a phenotypically and functionally heterogeneous subset of lymphocytes that prevent a variety of autoimmune diseases. As in many autoimmune diseases, the functional defects of Treg cells are supposed to play relevant roles in the pathogenesis and development of systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, and other autoimmune/immune-mediated rheumatic diseases. Consequently, manipulation and modulation of Treg cells represent a potent strategy for therapeutic benefit in many such diseases.

Summary

A further understanding of the functional defects of Treg cells in rheumatic diseases will contribute to find new targets and therapies in rheumatic diseases, including ankylosing spondylitis.

     

Non-variceal upper gastrointestinal bleeding in cirrhotic patients in Nile Delta

Background and Study Aims

Acute upper gastrointestinal bleeding (AUGIB) in cirrhotic patients occurs mainly from esophageal and gastric varices; however, quite a large number of cirrhotic patients bleed from other sources as well. The aim of the present work is to determine the prevalence of non-variceal UGIB as well as its different causes among the cirrhotic portal hypertensive patients in Nile Delta.

Methods

Emergency upper gastrointestinal (UGI) endoscopy for AUGIB was done in 650 patients. Out of these patients, 550 (84.6 %) patients who were proved to have cirrhosis were the subject of the present study.

Results

From all cirrhotic portal hypertensive patients, 415 (75.5 %) bled from variceal sources (esophageal and gastric) while 135 (24.5 %) of them bled from non-variceal sources. Among variceal sources of bleeding, esophageal varices were much more common than gastric varices. Peptic ulcer was the most common non-variceal source of bleeding.

Conclusions

Non-variceal bleeding in cirrhosis was not frequent, and sources included peptic ulcer, portal hypertensive gastropathy, and erosive disease of the stomach and duodenum.

     

Assessment and Management of Sleep Disturbance in Cirrhosis

Purpose of Review

This review presents an in-depth overview of the sleep–wake phenotype of patients with cirrhosis, together with available pharmacological and non-pharmacological treatment strategies. A set of simple, practical recommendations is also provided.

Recent Findings

The understanding of the pathophysiology of sleep disorders in this patient population has improved over the past decade, especially in relation to the interplay between homeostatic and circadian sleep regulation. In addition, new tools have been utilised for both screening and in-depth investigation of the sleep–wake profile of these patients. Finally, a number of studies have evaluated the efficacy of novel treatment strategies, often with encouraging results.

Summary

Since sleep disturbances are common in patients with cirrhosis, more so than in patients with other chronic diseases of similar severity, their assessment should become routine hepatological practice, along with the initiation of adequate treatment.

     

Diagnostik bei Verdacht auf Systemerkrankungen

Background

Systemic diseases often affect the kidneys and are important differential diagnoses in nephrology. Connective tissue diseases and vasculitis are of major relevance as the degree of kidney involvement determines the clinical course of the disease and thereby limits the prognosis.

Aim

This review discusses relevant diagnostic steps in patients with systemic diseases.

Conclusion

The diagnostic procedure in patients with systemic autoimmune diseases is complex. The medical history should be taken, physical examination and specific laboratory tests should be tailored to the suspected diagnosis. Making an accurate and timely diagnosis has therapeutic implications and differential diagnoses should be carefully considered.

     

Intensive Care Management of Patients with Cirrhosis

Purpose of review

Cirrhosis is a major worldwide health problem which results in a high level of morbidity and mortality. Patients with cirrhosis who require intensive care support have high mortality rates of near 50%. The goal of this review is to address the management of common complications of cirrhosis in the ICU.

Recent findings

Recent epidemiological studies have shown an increase in hospitalizations due to advanced liver disease with an associated increase in intensive care utilization. Given an increasing burden on the healthcare system, it is imperative that we strive to improve our management cirrhotic patients in the intensive care unit.

Summary

Large studies evaluating the management of patients in the intensive care setting are lacking. To date, most recommendations are based on extrapolation of data from studies in cirrhosis outside of the ICU or by applying general critical care principles which may or may not be appropriate for the critically ill cirrhotic patient. Future research is required to answer important management questions.

     

Quality of Life in Patients with Cirrhosis—Measurement and Clinical Impact

Purpose of the Review

As understanding of liver disease progression to cirrhosis has expanded, there has also been an acceleration in clinical trials and treatment options for the different underlying causes of cirrhosis to include chronic viral hepatitis, alcoholic and non-alcoholic fatty liver disease. It is imperative that healthcare practitioners fully appreciate the impact of liver disease and treatment from the patients’ and society perspective.

Recent Findings

An important aspect of patient-reported outcomes (PROs) is assessment of health-related quality of life (HRQL) completed using generic or disease-specific instruments. In the past decades, substantial evidence has been complied that demonstrates development of cirrhosis which has a significant negative impact on a patients’ HRQL while effective treatment leads to significant gains in HRQL especially for patients with decompensated cirrhosis.

Summary

Clinicians and clinical investigators must understand the importance of PROs for inclusion in clinical trials to fully assess the impact of cirrhosis on patients and the society.

     

Ethical Issues in Patients with Cirrhosis

Purpose of Review

To briefly summarize topical ethical issues in patients with cirrhosis.

Recent Findings

The “four quadrants” framework is ideally suited to address ethical issues in patients with cirrhosis. The presence of hepatic encephalopathy complicates any ethical analysis and stresses the importance of advanced directives and end of life planning, both of which appear to be poorly applied. Organ allocation in liver transplantation (LT) based on survival benefit, a “not unreasonable standard” to assess live donor LT (LDLT) in patients removed from the wait list, LT in patients with acute alcoholic hepatitis, and LT in undocumented immigrants are supported by sound ethical principles.

Summary

Significant ethical issues remain challenging and unresolved for patients with cirrhosis. Further research must be done to assess how frequently ethical problems occur in individual patients. Clear, detailed policies, based on strong ethical platforms, must be developed to further address these significant ethical challenges.