A scoring system for the assessment of the risk of mortality after partial hepatectomy in patients with chronic liver dysfunction

Background/purpose

The aim of this study is to evaluate a new scoring system, called the chronic liver dysfunction (CLD) score, for prediction of the surgical risk of partial hepatectomy in patients with chronic liver damage. Morbidity and mortality rates after gastroenterological surgery are high in patients with hepatic cirrhosis. Accordingly, it is very important to assess the surgical risk in such patients before surgery. Although the Child classification (or Child–Pugh score) has been a standard system, it did not always accurately predict patients at the risk of mortality after gastroenterological surgery, especially partial hepatectomy.

Methods

In 1985, we established a new system called the CLD score, reviewing the patients undergoing gastroenterological operations at one hospital. In the present study, we prospectively used the CLD score in 256 consecutive patients with chronic liver dysfunction who were treated surgically by partial hepatectomy, and investigated the usefulness of the CLD score concerning mortality. The results were compared with those of the Child–Pugh score (C-P score).

Results

After major hepatectomy, all the patients with CLD score exceeding 1.5 died of hepatic failure. After minor hepatectomy, all the patients with CLD score exceeding 2.5 died of hepatic failure. On the other hand, C-P score did not predict the outcome in these patients.

Conclusions

Compared with the C-P score, which was considered the gold standard scoring system for assessing surgical risk for patients with chronic liver dysfunction, our CLD score provides a more reliable assessment of the risk of partial hepatectomy.     

Statin Use in Patients with Cirrhosis: A Retrospective Cohort Study

Background

Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of statins and potentially increased risk for complications. No studies assess mortality in patients with biopsy-confirmed cirrhosis.

Aim

Compare mortality in patients with cirrhosis on statins to those not on statins.

Methods

A retrospective cohort study evaluated patients from 1988 to 2011 at Partners Healthcare Hospitals. The Partners Research Patient Data Registry identified patients with biopsy-proven cirrhosis on statins at biopsy and at least 3 months following. Controls were matched 1:2 by age, gender and Child–Pugh class. Decompensation was defined as ascites, jaundice/bilirubin >2.5 mg/dL, and/or hepatic encephalopathy or variceal hemorrhage. Primary outcome was mortality. Secondary outcome was decompensation in baseline-compensated patients. Chi-square and two-way ANOVA testing compared groups. Cox proportional hazards models for mortality controlled for age, Child–Pugh class, diabetes, coronary artery disease, non-alcoholic steatohepatitis and hepatocellular carcinoma. Kaplan–Meier curves graphed mortality.

Results

Eighty-one statin users and 162 controls were included. Median follow-up: 36 months in statin users and 30 months in controls. 70.4 % of patients were Child–Pugh A. Model for End-Stage Liver Disease (MELD), albumin, varices and beta-blocker use were not significantly different between groups. Statin users had lower mortality on multivariate analysis (HR 0.53, p = 0.01), and Child–Pugh A patients had longer survival on Kaplan–Meier analysis. Cox multivariate analysis for decompensation showed lower risk of decompensation with statins while increased decompensation with low albumin, high MELD score and beta-blocker use.

Conclusions

In patients with cirrhosis, statin therapy is not associated with increased mortality and may delay decompensation.     

Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI

Objectives

Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified.

Methods

Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (C_max, T_max and T_1/2), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM).

Results

Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child–Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child–Pugh scores.

Conclusions

Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels.     

Chemoembolization of intermediate stage hepatocellular carcinomas: Results from a Nordic tertiary liver cancer center

Background

Transarterial chemoembolization (TACE) is used as palliative treatment of hepatocellular carcinoma (HCC). Most publications are from HCC patient populations where viral hepatitis is the primary cause of liver disease. In the Nordic countries, most patients have either alcohol-induced cirrhosis or are noncirrhotic. The aim of this single-center study was to evaluate patient characteristics, survival, and side effects of TACE in a Danish referral center for HCC treatment.

Methods

Fifty-nine consecutive patients with HCC, treated with TACE, either chemoembolization with drug-eluting beads or conventional-TACE with Lipiodol, were included in the study. Their medical records were retrospectively reviewed, computed tomography images analyzed, and biochemical markers recorded. The primary endpoint was overall survival. Analyses were by intention to treat.

Results

Thirty-five patients (59 %) had HCC on a background of liver cirrhosis most often caused by alcohol (60 % of cirrhotics or 35 % overall). Before the first chemoembolization, the patients had a median Child–Pugh score of 6 (5–7) and a median MELD score of 10 (6–21). Median survival after chemoembolization was 18.9 months (13.1–24.7). TACE patients were hospitalized for an average of 3 days (2–30). Prolonged stay was most often due to side effects—eg. pain (31 %), fever (14 %), nausea (10 %), and infection (10 %). Thirty-three patients (56 %) did not have any side effects.

Conclusions

In this cohort, we observed an acceptable survival following TACE without significant side effects.     

Images of Sonazoid-enhanced ultrasonography in multistep hepatocarcinogenesis: comparison with Gd-EOB-DTPA-enhanced MRI

Background

Little is known about the difference in enhancement patterns of hepatocellular carcinoma (HCC) during multistep hepatocarcinogenesis between the post-vascular phase of Sonazoid-enhanced ultrasonography (SEUS) and hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI, as well as uptakes of Sonazoid and Gd-EOB-DTPA by HCC.

Methods

Seventy patients with 73 histologically proven HCCs (33 hypovascular well-differentiated HCCs and 40 progressed HCCs) and 9 dysplastic nodules (DNs) were enrolled. Enhancement patterns of the lesions on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were evaluated. Uptakes of Sonazoid and Gd-EOB-DTPA were assessed by Sonazoid enhancement index and EOB enhancement ratio in relation to immunohistochemistry of CD68 and organic anion transporting polypeptide 8 (OATP8), respectively.

Results

On the post-vascular phase of SEUS, none of the 9 DNs and 3 of 33 hypovascular well-differentiated HCCs (9 %) were hypoechoic, whereas 3 of 9 DNs (33 %) and 31 of 33 hypovascular well-differentiated HCCs (94 %) showed hypointensity on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. Of 31 progressed HCCs, 95 and 93 % were hypoechoic and hypointense on the post-vascular phase of SEUS and hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI, respectively. Sonazoid enhancement indexes decreased in progressed HCCs, correlating with lower Kupffer cell numbers (P < 0.001). EOB enhancement ratios decreased in hypovascular well-differentiated and progressed HCCs, as OATP8 expression declined (P < 0.001).

Conclusions

In stepwise hepatocarcinogenesis, uptake of Sonazoid starts decreasing later than that of Gd-EOB-DTPA. Although signal reductions on the post-vascular phase of SEUS or hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI suggest HCC, hypoechoic appearance on the post-vascular phase of SEUS might be HCC-specific, particularly progressed HCC.     

Area between the hepatic and heart curves of 99mTc-galactosyl-human serum albumin scintigraphy represents liver function and disease progression for preoperative evaluation in hepatocellular carcinoma patients

Background/purpose

We developed software to calculate the pixels of interest in the area between the hepatic and heart curves (ABC) of ^99mTc-galactosyl human serum albumin (GSA) scintigraphy. The aim of this study was to examine the accuracy of the ABC to evaluate liver function before hepatectomy.

Methods

Between January 2005 and December 2010, 205 consecutive patients who underwent initial hepatectomy were enrolled in this study. The ABC was calculated using original computer software. The area under the receiver operating characteristic curve (AUC) was calculated for evaluation of Child–Pugh score grade B (Child B), pathological chronic hepatitis (CH), and liver cirrhosis (LC).

Results

The AUC of any indicator for Child B was more than 0.900 except bilirubin. The AUC of ABC for CH and LC (AUC 0.734 each) was comparable to those of HH15 (clearance index; AUC 0.704 and 0.700, respectively) and LHL15 (receptor index; AUC 0.703 and 0.706, respectively) in multiple receiver operating characteristic comparison.

Conclusions

We have developed a novel liver function indicator, the ABC, to count radioactivity in sequence. The ABC reflects liver function according to pathological deterioration of the liver. Although the ABC gave no significant advantage compared to HH15 and LHL15, it improved the AUC evaluation by 0.028–0.034.     

Assessment of Gd-EOB-DTPA-enhanced MRI for HCC and dysplastic nodules and comparison of detection sensitivity versus MDCT

Background

We aimed to evaluate gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinomas (HCCs) and dysplastic nodules (DNs) compared with dynamic multi-detector row computed tomography (MDCT), and to discriminate between HCCs and DNs.

Methods

Eighty-six nodules diagnosed as HCC or DNs were retrospectively investigated. Gd-EOB-DTPA-enhanced MRI and dynamic MDCT were compared with respect to their diagnostic ability for hypervascular HCCs and detection sensitivity for hypovascular tumors. The ability of hepatobiliary images of Gd-EOB-DTPA-enhanced MRI to discriminate between these nodules was assessed. We also calculated the EOB enhancement ratio of the tumors.

Results

For hypervascular HCCs, the diagnostic ability of Gd-EOB-DTPA-enhanced MRI was significantly higher than that of MDCT for tumors less than 2?cm (p?=?0.048). There was no difference in the detection of hypervascular HCCs between hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI (43/45: 96%) and dynamic MDCT (40/45: 89%), whereas the detection sensitivity of hypovascular tumors by Gd-EOB-DTPA-enhanced MRI was significantly higher than that by dynamic MDCT (39/41: 95% vs. 25/41: 61%, p?=?0.001). EOB enhancement ratios were decreased in parallel with the degree of differentiation in DNs and HCCs, although there was no difference between DNs and hypovascular well-differentiated HCCs.

Conclusion

The diagnostic ability of Gd-EOB-DTPA-enhanced MRI for hypervascular HCCs less than 2?cm was significantly higher than that of MDCT. For hypovascular tumors, the detection sensitivity of hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI was significantly higher than that of dynamic Gd-EOB-DTPA-enhanced MRI and dynamic MDCT. It was difficult to distinguish between DNs and hypovascular well-differentiated HCCs based on the EOB enhancement ratio.     

Entecavir improves the outcome of acute-on-chronic liver failure due to the acute exacerbation of chronic hepatitis B

Background

The mortality of acute-on-chronic hepatitis B liver failure (ACHBLF) from acute exacerbation of chronic hepatitis B is 30–70 % without liver transplant.

Methods

We conducted an open-label, prospective, 48-week study to evaluate the efficacy of entecavir (ETV) in ACHBLF with 110 patients who received either ETV or no treatment. Primary measurements were survival and improvement in disease severity scores.

Results

Of the 110 patients enrolled, 2 withdrew consent, 108 were treated with 53 ETV, and 55 were untreated. When compared to the patients in the untreated group at week 48, a lower cumulative mortality rate in ETV-treated patients was observed [54.7 % (29/53) vs. 78.2 % (43/55), p < 0.01). ETV treatment significantly improved disease severity scores including Child–Turcotte–Pugh (CTP), model for end-stage liver disease (MELD), and MELD sodium (MELD-Na). All ETV-treated subjects achieved an undetectable HBV DNA level (<500 copies/mL; 100 % vs. 7.9 %, p < 0.001). In univariate analysis, predictors of survival at week 48 included baseline age, total bilirubin, international normalized ratio of prothrombin time, albumin, cholesterol, receiving ETV therapy, CTP, MELD, MELD-Na, and sequential organ failure assessment (SOFA) scores. In multivariate analysis, baseline age, total bilirubin, untreated (with ETV), CTP, and SOFA scores were the independent risk factors for mortality.

Conclusions

Entecavir treatment for patients with ACHBLF significantly improves disease severity scores with a marked reduction in mortality and suppression in HBV DNA to undetectable levels at week 48. Patients’ age, total bilirubin, CTP, and SOFA scores at baseline are independent risk factors for higher mortality without liver transplantation.     

Study of adiponectin in chronic liver disease and cholestasis

Purpose

Adiponectin is an adipocytokine suggested to have a hepatoprotective effect. To date, little information is available in the literature regarding changes in serum adiponectin levels in cirrhosis and cholestasis and the associated metabolic disturbances. In order to elucidate the role of adiponectin in chronic liver disease our aim was to determine serum adiponectin in patients with different grades of cirrhosis and cholestasis and to correlate it with markers of liver injury, inflammation and cholestasis. We also aimed to correlate adiponectin with markers of metabolic syndrome such as body mass index and insulin resistance.

Methods

Forty patients with cirrhosis; 30 patients with cirrhosis and cholestasis; and 20 matched controls were studied. They were subjected to clinical assessment, laboratory investigations: serum bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, C-reactive protein, prothrombin activity, fasting blood sugar, insulin. HOMA index was calculated. Abdominal ultrasonography and upper GI endoscopy were performed.

Results

Adiponectin was elevated in patients with cirrhosis and cirrhosis/cholestasis and was significantly higher in Child A and B. Adiponectin showed correlation with liver cell injury, marker of inflammation, synthetic liver function and markers of cholestasis. Adiponectin did not correlate with complications of cirrhosis as ascites and esophageal varices nor did it correlate with BMI or HOMA.

Conclusions

Adiponectin is elevated in cirrhosis and shows correlation with degree of hepatocellular injury and cholestasis. Finally, adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function.     

Waiting list mortality of patients with primary biliary cirrhosis in the Japanese transplant allocation system

Background

The present study aimed to evaluate etiology-based differences in the risk of waiting list mortality, and to compare the current Japanese transplant allocation system with the Child–Turcotte–Pugh (CTP) and the Model for End-Stage Liver Disease (MELD) scoring systems with regard to the risk of waiting list mortality in patients with primary biliary cirrhosis (PBC).

Methods

Using data derived from all adult candidates for deceased donor liver transplantation in Japan from 1997 to 2011, we assessed factors associated with waiting list mortality by the Cox proportional hazards model. The waiting list mortality risk of PBC patients was further estimated with adjustment for each scoring system.

Results

Of the 1056 patients meeting the inclusion criteria, 743 were not on the list at the end of study period; waiting list mortality was 58.1 % in this group. In multivariate analysis, increasing age and PBC were significantly associated with an increased risk of waiting list mortality. In comparison with patients with hepatitis C virus (HCV) infection, PBC patients were at 79 % increased risk and had a shorter median survival time by approximately 8 months. The relative hazard of PBC patients was statistically significant with adjustment for CTP score and medical point score, which was the priority for ranking candidates in the Japanese allocation system. However, it lost significance with adjustment for MELD score. Stratification by MELD score indicated a comparable waiting list survival time between patients with PBC and HCV.

Conclusions

PBC patients are at high risk of waiting list mortality in the current allocation system. MELD-based allocation could reduce this risk.     

Study of the sleep quality and psychological state of patients with hepatitis B liver cirrhosis

Aim

We aimed to investigate sleep quality, mild hepatic encephalopathy, anxiety, and depression in patients with hepatitis B cirrhosis by using a variety of scales and questionnaires.

Method

A cohort of 341 patients with hepatitis B liver cirrhosis were categorized by Child–Pugh grading (A, B, and C) in this cross‐sectional study. Pittsburgh Sleep Quality Index (PSQI), Number Connection Test‐A (NCT‐A), and Hospital Anxiety and Depression (HAD) evaluated the questionnaires and statistically analyzed the intrinsic correlation. The control group included 50 healthy individuals. Of 341 patients, 213 had a PSQI index >5 points.

Results

The PSQI, NCT‐A, anxiety scale (HAD [a]), and depression scale (HAD [d]) of the patients were significantly different. The NCT‐A‐positive patients revealed 214 cases of possible minimal hepatic encephalopathy (MHE) during a preliminary screening of patients. The PSQI score of NCT‐A‐positive patients was significantly elevated compared to NCT‐A‐negative patients (P < 0.001). HAD (a) and HAD (d) were significantly different between the NCT‐A‐positive and NCT‐A‐negative groups (P = 0.002 and P = 0.006, respectively). Univariate Pearson's correlation analysis found that NCT‐A and HAD (a) were positively correlated with PSQI (P < 0.001 and P = 0.045, respectively); however, Child–Pugh score and HAD (d) were not correlated with PSQI (P = 0.061 and P = 0.059, respectively).

Conclusion

These results indicated that patients with hepatitis B liver cirrhosis have a disturbed sleep, which might be an MHE symptom, further causing considerable anxiety. Thus, the evaluation of sleep quality and psychological state of patients with hepatitis B liver cirrhosis necessitates further investigation to guide positive intervention.     

Portal Hypertensive Gastropathy: Correlation with Portal Hypertension and Prognosis in Cirrhosis

Background

Portal hypertensive gastropathy (PHG) is a common endoscopic finding in patients with cirrhosis. However, the relationship between PHG and portal hypertension is controversial. Furthermore, nothing is known regarding the correlation between PHG and prognosis in patients with cirrhosis.

Methods

The hepatic venous pressure gradient (HVPG), endoscopic PHG grade, Child–Pugh score, and model for end-stage liver disease (MELD) score were assessed at baseline and were followed prospectively in 331 cirrhotic patients (284 males, 85.8%; mean age, 52.16 ± 9.05 years) from January 2001 to April 2009. The relationship between PHG with HVPG and survival was investigated.

Results

The HVPG was significantly higher in patients with severe PHG than in those with mild or no PHG (absent, 4.9 ± 1.7 mmHg; mild, 10.7 ± 4.1 mmHg; severe, 15.6 ± 4.6 mmHg; P < 0.001). During follow-up, 28 patients (8.5%) died from liver-related disease. In the Cox regression analysis, severe PHG (none and mild vs. severe) (hazard ratio 1.153, 95% confidence interval: 1.048–1.269) showed a significantly high relative risk of mortality, and in the Kaplan–Meier analysis, severe PHG showed a significantly shorter expected survival time than none or mild PHG (median survival time, 77.6 ± 9.6 months in severe PHG; log-rank test, P = 0.030).

Conclusions

PHG was associated with portal hypertension severity and prognosis in patients with cirrhosis.     

Assessment of hepatic reserve for indication of hepatic resection: decision tree incorporating indocyanine green test

Preoperative assessment of liver function and prediction of postoperative remaining functional liver parenchymal mass and reserve is of paramount importance to minimize surgical risk, especially in patients with hepatocellular carcinoma (HCC), the majority of whom have liver cirrhosis as a complication. We have established a decision tree for deciding the safe limit of hepatectomy based on three variables: whether ascites is present, the serum total bilirubin level, and the indocyanine green retention rate at 15 minutes (ICGR-15), an indicator of sinusoidal capillarization. In patients who show a sign of decompensated cirrhosis as reflected by an elevated bilirubin value or uncontrollable ascites, hepatectomy is not indicated. In patients without ascites and with normal bilirubin level, the ICGR-15 value becomes the main determinant for the resectability and hepatectomy procedure. Incorporation of ICGR-15 into the decision tree enables patients conventionally classified into Child–Turcotte–Pugh class A or score 5–6 to be subdivided into several groups in which various hepatectomy procedures are feasible: enucleation, limited resection, segmentectomy, mono- to bisectoriectomy, and trisectriectomy. During strict application of this decision tree to 1429 consecutive hepatectomies, of which 685 were performed on HCC patients, during the last 10 years, we encountered only a single mortality.     

Portal Hypertensive Enteropathy Diagnosed by Capsule Endoscopy in Cirrhotic Patients: A Nationwide Multicenter Study

Background and Aim

Due to the limited data on portal hypertensive enteropathy (PHE), the prevalence of and clinical factors related to PHE remain unclear. This study determined the prevalence of PHE using capsule endoscopy (CE) and PHE-related clinical factors.

Methods

This was a retrospective multicenter study using the Capsule Endoscopy Nationwide Database Registry. From 2,879 cases that underwent CE, 45 cirrhosis patients with portal hypertension (PH) were enrolled and divided into PHE (n = 18) and non-PHE (n = 27) groups. From computed tomography (CT) images, six secondary changes due to PH were scored to give a total CT score of 0–6. The main outcome variable was the prevalence of PHE and PHE-related clinical factors.

Results

The prevalence of PHE was 40 %. Comparing the PHE and non-PHE groups, the most common findings were angiodysplasias in 55.7 % (vs. 7.4 %, p = 0.001) and varices in 38.9 % (vs. 0 %, p = 0.001). Active bleeding was observed in 16.6 and 3.7 %, respectively, but this difference was not significant. In the univariate analysis, Child–Turcotte–Pugh class C (p = 0.002) and a high CT score (≥3 vs. <3, p = 0.004) were significantly associated with PHE. However, only a high CT score was significant in the multivariate analysis (odds ratio 11.19; 95 % confidence interval, 1.59-infinity; p = 0.040).

Conclusions

The prevalence of PHE was 40 %, and it might be more prevalent in cirrhosis patients with PH who have a high CT score. CE is a useful diagnostic tool for evaluating PHE in cirrhosis patients with PH.     

Hepatogenous Diabetes in Cirrhosis Is Related to Portal Pressure and Variceal Hemorrhage

Background and Aim

The clinical impact and complications of hepatogenous diabetes (HD) on cirrhosis have not been elucidated. This study aimed to evaluate the relationship of HD with portal hypertension (PHT) and variceal hemorrhage and to assess the prevalence of HD.

Methods

From July 2007 to December 2009, 75-g oral glucose tolerance test and insulin resistance (IR) were evaluated for 195 consecutive cirrhotic liver patients (M:F = 164:1, 53.0 ± 10.2 years) who had no history of diabetes mellitus. IR was calculated using the homeostasis model of assessment-insulin resistance (HOMA-IR) formula. Endoscopy for varices, hepatic venous pressure gradient (HVPG), and serologic tests were also conducted.

Results

HD was observed in 55.4 % (108/194) of the patients. Among them, 62.0 % required OGTT for diagnosis because they did not show an abnormal fasting plasma glucose level. The presence of HD showed a significant correlation with high Child–Pugh’s score, variceal hemorrhage, and HVPG (p = 0.004, 0.002, and 0.019, respectively). In multivariate analysis, Child–Pugh’s score (OR 1.43, 95 % CI 1.005–2.038) and HVPG (OR 1.15, 95 % CI 1.003–2.547) had significant relationships with HD. Patients with recent variceal hemorrhages (within 6 months) exhibited significantly higher glucose levels at 120 min in OGTT compared to patients without hemorrhages (p = 0.042). However, there was no difference in fasting glucose levels. The 120-min glucose level and HOMA-IR score were significantly and linearly correlated with HVPG (r ² = 0.189, p < 0.001 and r ² = 0.033, p = 0.011, respectively).

Conclusion

HD and IR have significant relationships with PHT and variceal hemorrhage. Postprandial hyperglycemia in particular had a significant relationship with variceal hemorrhage.     

Fungal translocation measured by serum 1,3-ß-D-glucan correlates with severity and outcome of liver cirrhosis—A pilot study

Background & Aims

On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host–pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier.

Methods

Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3-β-D-glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease.

Results

Patients with cirrhosis Child–Pugh class (CPC)-B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2–25.2) compared to patients with cirrhosis CPC-A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon-gamma-induced protein). Mortality differed significantly between patients with positive versus negative BDG (log-rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8–26.3).

Discussion

We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in-depth knowledge about (fungal-)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host–pathogen interactions and potentially introduce points of application for therapeutic interventions.     

239例肝硬化失代偿期患者的短期预后评估

目的评价终末期肝病模型（MELD）、MELD-Na、Child—Turcotte—Pugh（CTP）和包含血肌酐值的CTP（CrCTP）评分对肝硬化患者短期预后的评估意义。方法回顾性收集自2005年1月-2007年12月我院收治的239例肝硬化失代偿期患者的病例资料,分别应用CTP、CrCTP、MELD和MELD—Na模型进行评分,并了解其3个月内的病死率。以受试者工作特征曲线（ROC）下面积（AUC）衡量各评分系统预测肝硬化失代偿期患者短期预后的能力,并运用Z检验比较各系统的预测能力。结果30例患者在3个月内死亡。死亡组患者的CTP、CrCTP、MELD和MELD—Na分值（分别为11．47±2．46、12,47±2．05、19．70±6．71、27．97±10．79）与生存组（分别为8．73±2．03、8．95±2．13、10．92±4．74、14．48±6．55）相比差异有统计学意义（P〈0．001）。CTP、CrCTP、MELD和MELD-Na评分对肝硬化失代偿期患者3个月预后评估的ROC曲线下面积分别为0．799、0．822、0．873、0．870。结论CTP、CrCTP、MELD和MELD-Na模型均可有效预测我国肝硬化失代偿期患者的短期预后;MELD评分在判断肝硬化失代偿期患者的短期预后方面优于CTP;在CTP中引入血肌酐值即CrCTP评分可以提高对肝硬化失代偿患者短期预后的判断准确性;MELD-Na模型未显示比MELD更佳的预测能力。     

Two cases of hepatopulmonary syndrome with improved liver function following long-term oxygen therapy

Hepatopulmonary syndrome (HPS) is a complication of liver disease that is characterized by hypoxemia and intrapulmonary vascular dilatations. The only established therapy for this disorder is liver transplantation. Here, we report two patients (a 63-year-old woman and a 72-year-old man) with HPS associated with hepatitis C virus-related cirrhosis. We gave the patients low-dose oxygen supplementation to improve their respiratory symptoms. Surprisingly, their liver function improved from Child Pugh class C to class A, and ascites disappeared after a year of oxygen supplementation. We believe that long-term oxygen therapy contributed to the improvement of liver function in these two cases. Long-term oxygen therapy might offer a new therapeutic approach to improve liver function in patients with cirrhosis with hypoxemia.     

Advanced Disease, Diuretic Use, and Marital Status Predict Hospital Admissions in an Ambulatory Cirrhosis Cohort

Background and Aims

Hospital admissions in cirrhotic patients are a source of significant health care expenditure. Most studies to date have focused on readmissions in patients with decompensated cirrhosis. We sought to describe predictors of hospital admissions in an ambulatory cirrhosis cohort consisting of both compensated and decompensated patients to identify patients who could benefit from intensified outpatient chronic disease management.

Methods

We performed a retrospective cohort study of 395 cirrhotic patients followed at an academic medical center liver clinic. Inclusion criteria were documented cirrhosis and longitudinal care at our center during 2006–2008. Patients were followed until December 2011, death, or liver transplantation. The primary outcomes were non-elective cirrhosis-related hospital admissions within 1 year and time to admission. The secondary outcome was 2-year cirrhosis-related mortality. The study was approved by the Partners Human Research Committee (protocol 2012P001912).

Results

Seventy-eight patients (19.7 %) had at least one cirrhosis-related hospital admission within 1 year. The following were significant predictors in the multivariable model: model for end-stage liver disease score ≥15 [OR 2.22, 95 % CI (1.21–4.07), p = 0.01], diagnosis of hepatocellular carcinoma [3.64 (1.42–9.35), 0.007], diuretic use [2.27 (1.23–4.17), 0.008], at least one cirrhosis-related admission during the baseline year [2.17 (1.21–3.89), 0.01], and being unmarried [1.92 (1.10–3.35), 0.02].

Conclusions

Advanced disease, diuretic use, and marital status were associated with cirrhosis-related hospital admissions in patients followed at an academic medical center liver clinic. Our findings suggest that patients with inadequately or overzealously treated ascites, as well as those with limited social supports, could benefit from intensified outpatient management.