Nonalcoholic Cirrhotic Patients Research Articles

WED-380 - Surgical subtype predicts adverse outcomes and costs among non-alcoholic cirrhotic patients

WED-380 - Surgical subtype predicts adverse outcomes and costs among non-alcoholic cirrhotic patients

Surgery in Nonalcoholic Cirrhosis: Clinical Outcomes, Healthcare Utilization, and Cost Analysis.

Patients with cirrhosis are at increased risk of complications following surgery due to multiple factors, including portal hypertension and alterations in hemostasis. Improvements in perioperative management as well as risk stratification scores have helped improve outcomes, but gaps remain in our understanding of the cost and morbidity of cirrhotic patients who undergo surgery. We conducted a case-control study using the IBM Electronic Health Record (EHR) MarketScan Commercial Claims (MSCC) database from January 1, 2007 to December 31, 2017. Nonalcoholic cirrhotic patients who underwent surgery were identified based on International Classification of Diseases,Ninth Revision (ICD-9)/Tenth Revision (ICD-10) codes for multiple surgical categories and matched with controls with cirrhosis who did not undergo surgery in this time period. A total of 115,512 patients were identified with cirrhosis, of whom 19,542 (16.92%) had surgery. Medical history and comorbidities were compiled, and outcomes in the six-month period following surgery were analyzed between matched groups. A cost analysis was performed based on claims data. Nonalcoholic cirrhotic patients who underwent surgery had a higher comorbidity index at baseline compared with controls (1.34 vs. 0.88, P<0.0001). Mortality was increased in the surgery group (4.68% vs. 2.38%, P<0.001) in the follow-up period. The surgical cohort had higher rates of adverse hepatic outcomes, including hepatic encephalopathy (5.00% vs. 2.50%, P<0.0001), spontaneous bacterial peritonitis (0.64% vs. 0.25%, P<0.001), and higher rates of septic shock (0.66% vs. 0.14%, P<0.001), intracerebral hemorrhage (0.49% vs. 0.04%, P<0.001), and acute hypoxemic respiratory failure (7.02% vs. 2.31%, P<0.001). Healthcare utilization analysis revealed increased total claims per patient in the surgical cohort (38.11 vs. 28.64, P<0.0001), higher inpatient admissions (6.05 vs. 2.35, P<0.0001), more outpatient visits (19.72 vs. 15.23, P<0.0001), and prescription claims per patient (11.76 vs. 10.61, P<0.0001) in the postsurgical period. The likelihood of at least one inpatient stay was higher in the surgical cohort (51.63% vs. 22.32%, P<0.0001), and inpatient stays were longer (4.99 days vs. 2.09 days, P<0.0001). The total cost of health services was significantly increased per patient in the postoperative period for patients undergoing surgery ($58,246 vs. $26,842, P<0.0001), largely due to increased inpatient costs ($34,446 vs. $10,789, P<0.0001). Nonalcoholic cirrhotics undergoing surgery experienced worse outcomes with respect to adverse hepatic events and complications, including septic shock and intracerebral hemorrhage. Claims and costanalysis showed a significant increase in health expenditure in the surgical group, largely due to the cost of more frequent and longer inpatient admissions.

The role of myocardial performance index and Nt-proBNP levels as a marker of heart dysfunction in nonalcoholic cirrhotic patients

Objective: Cardiac dysfunction has been reported in both cirrhotic and alcoholic patients. Our aim was to determine the relation of serum N-terminal pro-B-type natriuretic peptide (Nt-proBNP) levels to myocardial performance index (MPI) and disease severity in nonalcoholic cirrhotic patients. Patients and Methods: In this prospective study including 25 cirrhotic patients and 27 healthy controls, MPI was assessed by pulsed-wave tissue Doppler imaging (PW-TDI). The disease severity was determined by Child–Turcotte–Pugh (CTP ) and model for end-stage liver disease (MELD) scores. Results: There were no statistically significant differences in MPI levels between patients and controls (p&amp;lt; 0.246). Nt-proBNP levels (p&amp;lt; 0.0003), cardiac output (CO) (p&amp;lt; 0.0002), left ventricular end-systolic (LVES) volume (p&amp;lt; 0.031) and QT interval (p&amp;lt; 0.0001) increased. Left ventricular systolic function was normal in all cirrhotic patients when compared to controls. Nt-proBNP levels were positively correlated with MELD scores (p&amp;lt; 0.0001, r= 0.59), QT duration (p&amp;lt; 0.0001, r= 0.59), CO (p= 0,001, r= 0.44), right atrial (RA) area (p= 0.026, r= 0.31) and negatively correlated with diastolic BP (p= 0.015, r= -0.34). Conclusion: We conclude that in nonalcoholic cirrhotic patients, left ventricular MPI and systolic function were normal. Nt-proBNP levels were correlated with the disease severity and hyperdynamic circulation.

Diurnal Corrected QT Interval and QT Dispersion Variation in Non-alcoholic Cirrhotic Patients and Healthy Control: A Case-Control Study, Iran

Background: Cirrhosis could lead to a long corrected QT (QTc) interval in a subgroup of patients, but there are spare data on its diurnal variation. Objectives: The present study aimed to determine the diurnal variation of QTc interval and its relationship to heart rate and blood pressure variation during 24-hour Holter-monitoring in non-alcoholic cirrhosis in comparison with the healthy controls. Methods: The study population comprised 15 patients with non-alcoholic cirrhosis and 15 healthy subjects, undergoing 24-hour electrocardiogram (ECG), heart rate, and blood pressure monitoring. The mean QT interval, mean QTc, maximum and minimum QT, QT dispersion (QT disp), heart rate, and mean arterial blood pressure were measured for each person for 24 hours. Liver stiffness measurement (LSM) was performed by FibroScan® 502 machine (EchoSense, Paris, France, 5 MHz). The results were demonstrated as percentages and mean ± SD. P value ≤ 0.05 was considered significant. Results: Mean QTc was significantly higher in cirrhosis (438 ms) than healthy controls (401.7 ms) (P = 0.03). The mean heart rate was significantly different in cirrhotic patients (79.6 ± 2.9/bpm) compared to healthy controls (72.47 ± 2.0/bpm) (P = 0.05). Conclusions: In this study, QTc was prolonged and increased with the severity of cirrhosis, and its diurnal variation in cirrhosis was different from healthy subjects.

Favorable clinical outcome of nonalcoholic liver cirrhosis patients with coronary artery disease: A population-based study.

AIMTo elucidate the prevalence and risk of mortality of nonalcoholic liver cirrhosis (LC) patients with coronary artery disease (CAD).METHODSThe study cohort included newly diagnosed nonalcoholic LC patients age ≥ 40 years old without a diagnosis of CAD from 2006 until 2011 from a longitudinal health insurance database. The mean follow-up period for the study cohort was 1152 ± 633 d. The control cohort was matched by sex, age, residence, and index date. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and the Kaplan-Meier method.RESULTSAfter exclusion, a total of 3409 newly diagnosed nonalcoholic cirrhotic patients were identified from one million samples from the health insurance database. We found that CAD (5.1% vs 17.4%) and hyperlipidemia (20.6% vs 24.1%) were less prevalent in nonalcoholic LC patients than in normal subjects (all P < 0.001), whereas other comorbidities exhibited an increased prevalence. Among the comorbidities, chronic kidney disease exhibited the highest risk for mortality (adjusted HR (AHR) = 1.76; 95%CI: 1.55-2.00, P < 0.001). Ascites or peritonitis exhibited the highest risk of mortality among nonalcoholic cirrhotic patients (AHR = 2.34; 95%CI: 2.06-2.65, P < 0.001). Finally, a total of 170 patients developed CAD after a diagnosis of nonalcoholic LC. The AHR of CAD in nonalcoholic LC patients was 0.56 (95%CI: 0.43-0.74, P < 0.001). The six-year survival rates for nonalcoholic LC patients with and without CAD were 52% and 50%, respectively (P = 0.012).CONCLUSIONWe conclude that CAD was less prevalent and associated with a reduced risk of mortality in nonalcoholic cirrhotic patients.

Both α-1-antitrypsin Z phenotypes and low caeruloplasmin levels are over-represented in alcohol and nonalcoholic fatty liver disease cirrhotic patients undergoing liver transplant in Ireland.

Alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) are steatotic liver diseases and major causes of cirrhosis. Only a minority of patients with risk factors develop cirrhosis and genetic cofactors may be important in pathogenesis. Mutations in the Wilson's and α-1-antitrypsin genes are not uncommon and we speculated that they may act as cofactors. We investigated α-1-antitrypsin phenotyes and caeruloplasmin levels in patients undergoing elective liver transplantation. We compared patients with alcohol and NAFLD with nonsteatotic liver disease patients: viral hepatitis B or C, autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. Two hundred and thirty-one patients were included in the study. Pretransplant caeruloplasmin levels and α-1-antitrypsin phenotypes were available in 197 and 112 patients, respectively. α-1-Antitrypsin Z phenotypes were significantly more common in the alcohol and NAFLD group: 12/56 versus 3/56 (P<0.05). Serum caeruloplasmin (0.3±0.01 vs. 0.39±0.01 g/l, P<0.01) and serum copper levels (13.5±0.9 vs. 19.3±0.9 μmol/l, P<0.01) were significantly lower in the alcohol and NAFLD patients compared with the viral and autoimmune patients. In this study, we found the α-1-antitrypsin Z phenotype was more common, and serum caeruloplasmin and copper levels were lower in patients with fatty liver diseases. We suggest that mutations in the α-1-antitrypsin and Wilson's genes may act as cofactors in the pathogenesis of fatty liver diseases.

Increased serum interleukin‐6, not minimal hepatic encephalopathy, predicts poor sleep quality in nonalcoholic cirrhotic patients

Sleep-wake disturbances are common in patients with cirrhosis and have a considerable effect on health-related quality of life; however, the underlying mechanism behind the phenomenon is unclear. Cytokines are involved in the mediation of signalling pathways regulating fibrogenesis, leading to cirrhosis. In addition, increased cytokines could contribute to sleep disturbances. To determine the relationship between pro-inflammatory cytokines and sleep disturbance in cirrhotic patients. Ninety-eight nonalcoholic cirrhotic patients without overt hepatic encephalopathy were enrolled in this cross-sectional study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The Psychometric Hepatic Encephalopathy Score (PHES) was used to examine cognitive performance and define minimal hepatic encephalopathy (MHE). The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the mood status of the patients. Pro-inflammatory cytokines that include interleukin 6 (IL-6) and tumour necrosis factor-α, as well as HBV-DNA or HCV-RNA levels were determined in patients. A total of 56 (57%) cirrhotic patients were identified as 'poor' sleepers (PSQI > 5). After multivariate analysis, IL-6 (P = 0.001) and HADS scores (P = 0.002) were found to be independent predictive factors of poor sleep quality. No significant relationships were observed between the sleep indices and the presence of MHE. HCV-RNA, but not HBV-DNA, viraemia was associated with sleep disturbance in cirrhotic patients. Sleep disturbance is found commonly in cirrhotic patients and a high serum IL-6 level is predictive of poor sleep quality. Minimal hepatic encephalopathy by itself may not contribute to sleep dysfunction in cirrhotic patients.

Different Models of Decompensation in Alcoholic versus Nonalcoholic Cirrhotic Patients

Different Models of Decompensation in Alcoholic versus Nonalcoholic Cirrhotic Patients

Long-and short-range functional connectivity density alteration in non-alcoholic cirrhotic patients one month after liver transplantation: A resting-state fMRI study

PurposeTo longitudinally evaluate long- and short-range functional connectivity density (FCD) alteration in cirrhotic patients one month after liver transplantation (LT) and their correlation with cognitive changes by using resting-state functional magnetic resonance imaging (rs-fMRI). MethodsTwenty seven candidates awaiting LT and 24 age-, gender-, and education-matched healthy controls (HCs) were studied. All 27 patients and HCs performed rs-fMRI examinations. Of 27 cirrhotic patients, 13 patients received LT underwent the repeated rs-fMRI examinations one month after LT. Laboratory and psychometric tests were carried out. The long- and short-range FCD maps derived from degree centrality calculation were compared. Correlations between FCD alteration and laboratory/psychometric changes were evaluated as well. ResultsIn cirrhotic patients, most of the brain areas with altered long- and short-range FCD could reverse one month after LT, which was accompanied with cognitive and liver functional improvement. The reduced long-range FCD in right posterior cingulate cortex (PCC) and Left middle frontal gyrus (MFG), and reduced short-range FCD in right precuneus (PCu) persisted in the early period after LT. In addition, one month after LT, the post-LT group showed reduced long-range FCD in right rectus gyrus (REC) and left medial prefrontal cortex (MPFC), and reduced short-range FCD in left middle temporal gyrus (MTG), when compared with the pre-LT group. We found Δdigital symbol test (ΔDST) score positively correlated with long-range ΔFCD in right precentral gyrus (preCG) (r=0.72, P<0.01) and right supplementary motor area (SMA) (r=0.59, P<0.05). ConclusionLT results in favorable effect on cognitive function in cirrhotic patient, which can be reflected by FCD alteration. However, persistence of PCC/PCu functional connectivity disturbance one month after LT indicates complete cognitive function restoration may need a longer time.

Risk of Depressive Disorder following Non-Alcoholic Cirrhosis: A Nationwide Population-Based Study

Background & AimsTo evaluate the risk of depressive disorders among non-alcoholic patients by using the Taiwan National Health Insurance Research Database (NHIRD).MethodsWe conducted a retrospective study of a matched cohort of 52 725 participants (10 545 non-alcoholic cirrhotic patients and 42 180 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 11 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in cirrhotic patients.ResultsDuring the 11-year follow-up period, 395 (3.75%) non-alcoholic cirrhotic patients and 1 183 (2.80%) control patients were diagnosed with depressive disorders. The incidence risk ratio of depressive disorders between non-alcoholic cirrhotic patients and control patients was 1.76 (95% CI, 1.57–1.98, P<.001). After adjusting for age, sex, and comorbidities, non-alcoholic cirrhotic patients were 1.75 times more likely to develop depressive disorders (95% CI, 1.56–1.96, P<.001) compared with the control patients. The hazard ratios for patients younger than 60 years old (1.31) and female (1.25) indicated that each is an independent risk factor for depressive disorders in non-alcoholic cirrhotic patients.ConclusionsThe likelihood of developing depressive disorders is greater among non-alcoholic cirrhotic patients than among patients without cirrhosis. Symptoms of depression should be sought in patients with cirrhosis.

S11 * ALCOHOL AS A MODULATOR OF LIVER DISEASE PROGRESSION ESBRA &amp; EASL JOINT SYMPOSIUM

S11 * ALCOHOL AS A MODULATOR OF LIVER DISEASE PROGRESSION ESBRA &amp; EASL JOINT SYMPOSIUM

Diastolic Dysfunction and Severity of Cirrhosis in Nonalcoholic Cirrhotic Patients

Background. In this study, we evaluated the association between diastolic dysfunction severity and severity of cirrhosis in nonalcoholic cirrhotic patients. Methods. This cross-sectional study was conducted on all nonalcoholic cirrhotic patients who were admitted in Rasht Razi hospital the Cancer of Guilan Province, north of Iran, from January 2011 to March 2012. Severity of cirrhosis was evaluated by Child-Pugh score. A 12-lead surface ECG and echocardiographic studies were performed. We used a HDI 3000 (Philips ATL, Bothell, WA, USA) equipped with 2 to 4 MHz probes. Diastolic function was determined by an expert cardiac sonographer. Data were analyzed by SPSS for win (version16). A P value less than 0.05 was considered significant. Results. Sixty-tree percent of patients were male. The mean age of patients was 52.78 ± 15.2 years. 22%, 38%, and 40% of patients were considered as child class A, B, and C, respectively. There was a significant relation between diastolic dysfunction and disease duration (P = 0.001), female gender (P = 0.004), age > 60 years (P = 0.045), and severity of cirrhosis (P = 0.048). On multivariate analysis, decreased E/A ratio (P = 0.03) and disease duration (P = 0.02) showed an independent significant relation. Conclusion. According to the relation between severity of cirrhosis and diastolic dysfunction, we recommend cardiac assessment in all child B and C cirrhotic patients.

Effects of low dose zinc supplementation on biochemical markers in non-alcoholic cirrhosis: a randomized clinical trial.

The present study aimed to evaluate the effects of low dose zinc (Zn) supplementation on biochemical markers and underlying disease status in non-alcoholic cirrhotic patients. We enrolled 60 cirrhotic patients in a double-blind, placebo-controlled, randomized clinical trial. All patients in the interventional group (n = 30) received long-term, low dose Zn supplementation (50 mg elemental Zn sulfate daily). The control group (n = 30) received placebo (starch). Child-Pugh scores and biochemical markers were assessed for both interventional and control groups at the first day and the end of the 90th day of the interventional period. A per-protocol analysis was performed after excluding all participants who did not receive or complete the randomized intervention. The mean differences of quantitative variables between and within groups were evaluated by independent samples t-test and paired-samples t-test, respectively. SPSS version 13.00 was used for statistical analysis. In the initial evaluation, 16 (53.30%) patients from the interventional group had a Child-Pugh score of 5-8 and 14 (46. 70%) had a score of 9-12. In the control group 18 (60.00%) had a Child-Pugh score of 5-8 and 12 (40.00%) scored 9-12. After three months the mean Child-Pugh score in the interventional group showed a significant improvement (from 6.56 ± 0.21 to 5.72 ± 0.22, P = 0.001) whereas in the control group despite no significant decline, the mean Child-Pugh score increased slightly (from 6.25 ± 0.27 to 6.67 ± 0.31, P = 0.14). Zn supplementation significantly decreased copper (Cu; P = 0.01) and creatinine (Cr; P < 0.0001) levels. In this study, we determined that low dose Zn supplementation could prevent deterioration of clinical status of cirrhosis and prevent excess Cu accumulation in non-alcoholic cirrhotic patients. Zn supplementation produces metabolic effects and trends towards improvements in liver function, hepatic encephalopathy, and nutritional status. Registration ID in IRCT: IRCT201106122017N4.

Anatomical cardiac alterations in liver cirrhosis: An autopsy study

Background. It has been suggested that liver cirrhosis (LC), regardless of etiology, may be associated with anatomical cardiac alterations.Objective. To describe the frequency and type of macroscopical anatomic cardiac abnormalities present in alcoholic and non-alcoholic cirrhotic patients in an autopsy series.Material and methods. The autopsy records performed at our institution during a 12-year period (1990-2002) were reviewed. All cases with final diagnosis of LC were included, their demographic characteristics as well as cirrhosis etiology and macroscopic anatomical cardiac abnormalities (MACA) analyzed. Patients with any known history of heart disease prior to diagnosis of cirrhosis were excluded.Results. A total of 1,176 autopsies were performed, of which 135 cases (11.5%) were patients with LC. Two patients with cardiac cirrhosis were excluded. Chronic alcohol abuse (29%) and chronic hepatitis due to hepatitis C virus (HCV) infection (20%) were the most common causes of cirrhosis. The etiology was not identified in 35% of the cases, even after exhaustive clinical, serological and/or radiological assessment. In the postmortem analysis, 43% of the cases were informed to have MACA (47% in the group of patients with alcoholic cirrhosis and 41% in other types of cirrhosis); this rate increased to 62% in patients with ascites. The most frequent alterations were cardiomegaly and left ventricular hypertrophy (LVH).Conclusion. The results confirm the high frequency of cardiac abnormalities in patients with cirrhosis, regardless of cirrhosis etiology.

Induction of blood lymphocyte cytochrome P450 2E1 in early stage alcoholic liver cirrhosis

To validate the induction of blood lymphocyte cytochrome P450 2E1 (CYP2E1) expression in alcoholic liver cirrhosis and mRNA and protein expression of CYP2E1 in freshly prepared blood lymphocytes of alcoholic liver cirrhotic (ACP), nonalcoholic cirrhotic patients (NACP), alcoholic controls (ACs), and nonalcoholic controls (NACs) were investigated. Registered ACP and NACP patients at Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India along with NACs and ACs were included in the study. Real time polymerase chain reaction, enzyme-linked immunosorbent assay, and CYP2E1-dependent enzyme activity were determined in blood lymphocytes isolated from cases and controls. Significant increases in CYP2E1 mRNA and protein expression were observed in freshly prepared blood lymphocytes isolated from ACs and ACP patients as compared with respective NACs or NACP patients. A concomitant increase in N-nitrosodimethyamine demethylase activity was evident in the blood lymphocytes of ACs and ACP patients. Interestingly, the comparative increase observed in CYP2E1 expression was of greater magnitude in the blood lymphocytes isolated from ACP patients, although they abstained from alcohol drinking. Findings suggest that significant increase in the CYP2E1 mRNA and protein expression in the blood lymphocytes, isolated from early stage ACP patients, can be used to predict alcohol-induced toxicity.

Association of polymorphism in alcohol dehydrogenase and interaction with other genetic risk factors with alcoholic liver cirrhosis

The association of polymorphism of alcohol dehydrogenase ( ADH) and its interaction with genes involved in the generation and detoxification of free radicals such as cytochrome P4502E1 ( CYP2E1) and glutathione S-transferases M1 ( GSTM1) were studied with alcoholic liver cirrhosis. The study included 175 alcoholic cirrhotic patients, 140 non-alcoholic cirrhotic patients, 255 non-alcoholic controls and 140 alcoholic controls. Our data revealed that the ADH1C*1/*1 genotype exhibited significant association with alcoholic liver cirrhosis while ADH1B genotypes did not show any significant association. A much higher risk to alcoholic liver cirrhosis was observed in patients carrying a combination of wild genotypes of ADH1C ( ADH1C*1/*1) and variant genotype of ADH1B ( ADH1B*2/*2) or CYP2E1 ( CYP2E1*5B) or null genotype of GSTM1. Our data suggest a role for the interaction amongst the genes involved in metabolizing alcohol and in generating and detoxifying free radicals with susceptibility to alcoholic liver cirrhosis.

Polymorphism in cytochrome P450 2E1 and interaction with other genetic risk factors and susceptibility to alcoholic liver cirrhosis

The association of polymorphism in cytochrome P450 2E1 (CYP2E1), the major microsomal ethanol metabolizing enzyme and its interaction with genes, involved in detoxification of reactive oxygen species, such as glutathione-S-transferases M1 (GSTM1) and alcohol intake, gamma-aminobutyric acid receptor γ2 (GABRG2) was studied with the risk to alcoholic cirrhosis in a case–control study. A total of 160 alcoholic cirrhotic and 125 non-alcoholic cirrhotic cases, visiting the OPD facility of Gastroenterology Department of Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India and 250 non-alcoholic and 100 alcoholic controls having no evidence of liver disease were included in the study. PCR-based RFLP methodology was followed for genotyping studies. Our data revealed that the variant genotypes of CYP2E1*5B exhibited significant association with the alcoholic liver cirrhosis when compared to non-alcoholic controls (OR: 4.3; 95%CI: 1.5–12.4; p: 0.003) or non-alcoholic cirrhosis patients (OR: 5.4; 95%CI: 1.2–24.5; p: 0.01) or alcoholic controls (OR: 4.3; 95%CI: 0.95–19.62; p: 0.04). Haplotype approach revealed that haplotype T–A–T was found to be associated with more than 5-fold increase in risk for alcoholic cirrhosis. Likewise, combination of variant genotype of CYP2E1*5B with null genotype of GSTM1, a phase II detoxification enzyme, resulted in several fold increase in risk in alcoholic cirrhotic patients when compared with non-alcoholic controls or non-alcoholic cirrhotic patients. Further, the combination of variant genotype of CYP2E1*5B with GABRG2, significantly increased the risk upto 6.5-fold in alcoholic cirrhotic patients when compared with non-alcoholic controls thereby suggesting the role of gene–gene interaction in alcoholic cirrhosis.

Low Bone Mineral Density and Impaired Bone Metabolism in Young Alcoholic Patients Without Liver Cirrhosis: A Cross‐Sectional Study

Osteoporosis is regularly mentioned as a consequence of alcoholism. Ethanol's direct effect on bone-modeling cells as well as alcoholism-related "life-style factors" such as malnutrition, lack of exercise, hormonal changes, and liver cirrhosis are discussed as potential causative factors. In a cross-sectional study, we have examined 57 noncirrhotic alcoholic patients (37 male, 20 female) aged 27 to 50 years. Patients suffering from comorbid somatic diseases and with co-medication known to have an influence on bone mineral density (e.g., glucocorticoids, heparin, anticonvulsant agents, oral contraceptives) were excluded. We determined bone mineral density (BMD) by dual x-ray absorptiometry (DXA) in the lumbar spine (L1-L4) and the proximal right femur (femoral neck, total hip) as well as parameters of bone metabolism. In males but not females, BMD was significantly reduced in the lumbar region, as well as in the proximal femur (femoral neck, total hip). Nine male patients (24.3% of men) and 1 female patient (5% of women) had low BMD (defined as Z-score < or = -2.0). As expected, there was a positive correlation between body mass index (BMI) and BMD. Alcohol-related factors (e.g., duration of abuse, consumed amount of alcohol per day) as well as smoking were not associated with a significant effect on BMD. All of the 20 women examined showed elevated estradiol levels, which may have served as a protective factor. In this study, 75.7% of the men and 90% of the women had vitamin D insufficiency or deficiency (plasma levels of 25-hydroxy-vitamin D < 30 ng/ml). Our study indicates that younger alcoholic patients without other diseases may suffer from an increased risk to develop low BMD and a disturbance of vitamin D metabolism. Nutritional factors or less exposure to sunlight may play an important role in bone loss in young alcoholic patients. BMD measurement and assessment of bone metabolism should be considered in all patients with chronic alcoholism.

Polymorphism in glutathione-S-transferases: A risk factor in alcoholic liver cirrhosis

In a case-control study, association of polymorphism in glutathione-S-transferases ( GSTM1, GSTT1, GSTP1), involved in detoxification of reactive oxygen species (ROS), was studied with alcoholic liver cirrhosis. The study included 175 alcoholic cirrhotic patients (ACPs), 140 non-alcoholic cirrhotic patients (NACPs), visiting Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India, 255 non-alcoholic controls and 140 alcoholic controls. The data showed an increase in risk to alcoholic cirrhosis in ACPs with GSTM1 ( null) genotype when compared with non-alcoholic controls (OR: 1.7; 95% CI: 1.15–2.56) or alcoholic controls (OR: 1.7; 95% CI: 1.07–2.73). Significant increase in risk was also observed in ACPs with variant genotype of GSTP1 when compared with non-alcoholic controls (OR: 1.65; 95% CI: 1.12–2.43). A much higher risk to alcoholic liver cirrhosis was observed in patients carrying combination of null genotypes of GSTM1 and GSTT1 (OR: 2.8; 95% CI: 1.3–6.06) or variant genotype of GSTP1 and null genotype of GSTM1 (OR: 2.8; 95% CI: 1.58–4.90) or GSTT1 (OR: 2.16; 95% CI: 1.08–4.28). Likewise, greater risk for alcoholic cirrhosis was observed in patients carrying combination of GSTM1, GSTT1 ( null) and variant genotype of GSTP1 (OR: 5.8; 95% CI: 2.17–15.80). Our data further showed that interaction of GSTs with variant genotype of manganese superoxide dismutase ( MnSOD), which detoxifies free radicals, or cytochrome P450 2E1, which generates free radicals, resulted in several fold increase in risk to alcoholic liver cirrhosis in ACPs when compared with non-alcoholic controls thus demonstrating the role of gene–gene interactions in modulating the risk to alcoholic liver cirrhosis.

Patients With Minimal Hepatic Encephalopathy Have Poor Insight Into Their Driving Skills

Minimal hepatic encephalopathy (MHE) is associated with impaired driving skills. It is not clear whether patients have insight into this. The Driving Behavior Survey (DBS) is a validated self- or observer-administered questionnaire. DBS consists of a total score (maximum, 104) and an attention-related driving skills section (maximum, 40). DBS was used to compare self-assessment with observer-assessment of driving skills in cirrhotic patients tested for MHE. Forty-seven nonalcoholic cirrhotic patients and 40 controls underwent psychometric tests, DBS, and driving simulation with navigation/driving tasks. An adult familiar with the subject's driving completed the DBS independently. Simulator performances, total DBS scores, and driving skill scores were compared between/within groups (MHE+, MHE-, and controls) with respect to self-assessment and observer assessment. Thirty-six patients were MHE+ and 11 were MHE-. MHE+ had a significantly higher simulator crash (MHE+, 3; MHE-, 1.2; controls, 1.7; P = .001) and illegal turn rate (MHE+, 1.2; MHE-, 0.3; controls, 0.1; P = .0001). Despite this worse performance, MHE+ patients rated themselves similar to MHE- patients and control groups on total (P = .28) and driving skills scores (P = .19). Observer assessment in MHE+ was significantly lower for total (P = .0001) and driving skills (P = .0001) compared with observer assessment for MHE- patients and control groups. MHE+ patients were rated significantly lower on driving skills (34 vs 37; P = .02) and trended lower in the total score (P = .08) by observers compared with self-ratings. In contrast, MHE- and control groups rated themselves similar to their observers on driving skills and total DBS scores. MHE patients have poor insight into their driving skills. A part of the MHE patient's clinical interview should be to increase awareness of this driving impairment.