Liver transplantation for NASH cirrhosis is not performed at the expense of major post-operative morbidity

BackgroundNon-alcoholic steatohepatitis (NASH) is an emerging indication for liver transplantation (LT) and coexists with multiple comorbidities. Obese and cirrhotic patients experience more perioperative complications. Limited data exist about short-term complications after LT for NASH cirrhosis.AimInvestigate short-term complications in patients transplanted for NASH cirrhosis.MethodsSingle center retrospective cohort study including patients >18 years who underwent LT between 2009–2015. Exclusion criteria were LT for acute liver failure and non-cirrhotic disease. Post-operative complications and severity within 90-days were classified using the Clavien–Dindo classification of surgical complications and comprehensive complication index (CCI). P < 0.05 was significant.ResultsOut of 169 eligible patients, 34 patients (20.1%) were transplanted for NASH cirrhosis. These patients were significantly older (59.2 vs. 54.8 years, P = 0.01), more obese (61.8% vs. 8.1%, P < 0.01), had more diabetes mellitus (73.5% vs. 20%, P < 0.01), metabolic syndrome (83.3% vs. 37.8%, P < 0.01) and cardiovascular disease (29.4% vs. 11.1%, P < 0.01). More grade 1 complications (OR 1.64, 95%CI 1.03–2.63, P = 0.04) and more grade 2 urogenital infections (OR 3.4, 95%CI 1.1–10.6, P = 0.03) were found. Major complications, CCI, 90-day mortality and graft survival were similar.ConclusionDespite significantly increased comorbidities in patients transplanted for NASH cirrhosis, major morbidity, mortality and graft survival after 90 days were comparable to patients transplanted for other indications.     

Infection in cirrhosis: A prospective study

Introduction and objectivesMultidrug-resistant (MDR) infections in cirrhosis are associated with poor outcomes. We attempted a prospective study on infections in patients with cirrhosis evaluating microbiology of these infections and how outcomes depended on factors like bacterial resistance, appropriate antibiotics, stage of liver disease and whether outcomes were significantly different from patients who did not have infections.Materials and methodsThis was a prospective evaluation involving one hundred and fifty nine patients with cirrhosis who were admitted at Peerless Hospitex Hospital and Research Center, Kolkata, West Bengal, India, during a 24 month period. One hundred and nineteen of these patients either had an infection at the time of admission or developed infection during hospitalization. Forty patients did not have an infection at admission and did not acquire infection while admitted. Data was collected about demographics, etiology of cirrhosis, liver and renal function and microbiology.ResultsInfections were community acquired in 27.7% of patients, healthcare associated in 52.9% and nosocomial in 19.3%. Gram negative bacilli (Escherichia coli 47.4% Klebsiella pneumoniae 23%) were common. 84.9% of enterobacteriaceae produced ESBL, AmpC or Carbapenemases. Spontaneous bacteria peritonitis (SBP) and urinary tract infection (UTI) were the most common sites of infection. In hospital mortality was 21.9%. Non-survivors had higher MELD (26 vs 19, p < 0.001) and CTP scores (11.7 vs 10.3, p < 0.001). The control group had lower MELD (16.65 vs. 20.8, p < 0.001) and CTP scores (9.25 vs 10.59, p < 0.001).ConclusionsMDR infections are common in patients with cirrhosis and have serious implications for treatment and outcomes.     

Prioritization for liver transplantation using the MELD score in Chile: Inequities generated by MELD exceptions.: A collaboration between the Chilean Liver Transplant Programs,the Public Health Institute and the National Transplant Coordinator

Introduction and aimThe MELD score has been established as an efficient and rigorous prioritization system for liver transplant (LT). Our study aimed to evaluate the effectiveness of the MELD score as a system for prioritization for LT, in terms of decreasing the dropout rate in the waiting list and maintaining an adequate survival post-LT in Chile.Materials and methodsWe analyzed the Chilean Public Health Institute liver transplant registry of candidates listed from October 15th 2011 to December 31st 2014. We included adult candidates (>15 years old) listed for elective cadaveric LT with a MELD score of 15 or higher. Statistical analysis included survival curves (Kaplan–Meier), log-rank statistics and multivariate logistic regression.Results420 candidates were analyzed. Mean age was 53.6 ± 11.8 years, and 244 were men (58%). Causes of LT included: Liver cirrhosis without exceptions (HC) 177 (66.4%); hepatocellular carcinoma (HCC) 111 (26.4%); cirrhosis with non-HCC exceptions 102 (24.3%) and non-cirrhotic candidates 30 (7.2%). LT rate was 43.2%. The dropout rate was 37.6% at 1-year. Even though the LT rate was higher, the annual dropout rate was significantly higher in cirrhotic candidates (without exceptions) compared with cirrhotics with HCC, and non-HCC exceptions plus non-cirrhotic candidates (47.9%; 37.2% and 24.2%, respectively, with p = 0.004). Post-LT survival was 84% per year, with no significant differences between the three groups (p = 0.95).ConclusionPrioritization for LT using the MELD score system has not decreased the dropout rate in Chile (persistent low donor's rate). Exceptions generate inequities in dropout rate, disadvantaging patients without exceptions.     

Transcatheter arterial chemoembolisation for hepatocellular carcinoma in cirrhosis: Survival rate and prognostic factors

BackgroundThe role of prognostic variables in the treatment of hepatocellular carcinoma (HCC) by transarterial chemoembolisation (TACE) is controversial.AimsTo evaluate the survival of patients with HCC on cirrhosis treated with TACE and to analyse the prognostic factors affecting survival.MethodsFrom 1996 to 2006, 580 consecutive patients with HCC in cirrhosis were observed. Of these 194 patients underwent TACE. The primary end-point was survival. Independent predictors of survival were identified using the Cox model.ResultsThe cumulative 1-year, 3-year, and 5-year survival rates were 96%, 60%, and 41%, respectively. The multivariate analysis showed significant reduction of survival among patients with serum bilirubin values >2 mg/dl compared to patients with values <2 mg/dl (Hazard ratio 3.84; CI 95% 1.70–8.66; p-value = 0.001). Multivariate analysis performed in the group of patients treated with TACE alone showed that elevated serum bilirubin (Hazard ratio 2.96; CI 95% 1.20–7.3; p-value 0.02) and incomplete tumour response (Hazard ratio 2.88; CI 95% 1.18–7.05; p-value 0.02) are correlated with a worse outcome.ConclusionsTACE was well tolerated and overall survival rate was 41% after 5 years. Complete tumour response and serum bilirubin <2 mg/dl were identified as predictors of survival.     

Chromogranin A levels in chronic liver disease and hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the relevant cause of death in patients with compensated cirrhosis. Alpha-fetoprotein (AFP) is used for screening HCC, with limited success.AimWe evaluated plasma chromogranin A (CgA) as a marker of HCC.PatientsCgA plasma levels and AFP serum levels were prospectively measured in 30 patients with HCC, 14 with cirrhosis, 79 with chronic hepatitis and 65 controls.MethodsCgA was measured with an enzyme-linked immunosorbent assay (DAKO A/S Glostrup, Denmark). AFP was measured by electrochemiluminoimmunoassay (Elecsys, Roche S.p.A., Italy).ResultsCgA levels were significantly higher in the three groups of patients than in controls and in patients with HCC they were significantly higher than in chronic hepatitis patients [median 44.5 (interquartile range 21–145.9) U/L vs. 15.3 (10.9–29.25) U/L, p < 0.001]. AFP values were above the upper reference limit in 75% of patients with HCC, 50% of cirrhotic patients and 11% of chronic hepatitis patients (p < 0.005). CgA values significantly correlated with AFP levels (r_s = 0.42, p < 0.0001). The overall diagnostic accuracy of CgA was 75% (CI 66–82), with a sensitivity of 70% (CI 50.6–85.2) and a specificity of 67% (CI 55.9–76.3).ConclusionsDespite the evidence of higher CgA levels in patients with HCC, this test has low-diagnostic accuracy. Its pathophysiological meaning remains unknown, even if it could suggest an endocrine phenotype of HCC.     

Alcoholic chronic pancreatitis and liver cirrhosis: Coincidence and differences in lifestyle

Background/objectivesAlcoholic chronic pancreatitis (ACP) and liver cirrhosis (ALC) are sequels of excessive alcohol intake. They develop in a minority of long-term alcohol consumers. Their concomitant occurrence is rare and the organ selection remains unknown. The aim of study was to compare patients with ACP and ALC with respect to their lifestyle.MethodsSixty-six patients with ACP and 80 with ALC were personally interviewed about their lifestyle, drinking, and eating habits.ResultsThe groups of ACP (60 males, 6 females) and ALC (64 males, 16 females) did not differ in the amount of alcohol intake (58 g/day vs. 64 g/day). Significantly more patients with ACP reported first alcohol contact before the age of 15 (28.5% vs. 88%; p = 0.03). ACP patients had the highest alcohol intake between 20 and 30 years of age (43.6% vs. 20.3%; p < 0.01), were more likely to smoke (92.4% vs. 78.7%; p = 0.02) and more likely to start smoking before the age of 15 (16.7% vs. 3.7%; p = 0.04). Patients with ACP had a lower level of education (p < 0.01). We did not observe significant differences between the dietary habits of the groups. The incidence of cirrhosis in ACP patients was 16.7%. The incidence of pancreatitis in the ACL group was 2.5%.ConclusionThe socio-behavioral factors affecting development of either ACP or ALC differed. ACP was associated with an early onset of drinking and smoking, highest alcohol intake at a young age, and a lower level of education. Simultaneous occurrence was unusual. Supported by grant IGAMZ NS/10527-3.     

Echocardiographic assessment of the left ventricular diastolic function in patients with non-alcoholic liver cirrhosis

AimTo assess the left ventricular diastolic function in patients with non-alcoholic liver cirrhosis and correlate the degree of diastolic dysfunction to the severity of liver impairment.MethodsThirty-five patients with non-alcoholic liver cirrhosis in addition to 16 age- and sex-matched healthy controls were studied. Severity of liver impairment was assessed using the Child-Pugh score. All participants were subjected to echocardiographic assessment using both the conventional and tissue Doppler echocardiography. The left ventricular filling pressure was derived from the transmitral and mitral annular velocities.ResultsPatients with non-alcoholic liver cirrhosis (mean age; 53 ± 6) had significantly higher heart rate compared with the controls (86 ± 6.5 vs 72 ± 4 bpm, p = 0.04). Mild degree of left ventricular diastolic dysfunction was detected in 26% of patients using the transmitral diastolic parameters. Compared with controls, the calculated left ventricular filling pressure was statistically significantly higher in patients with non-alcoholic liver cirrhosis (10 ± 3 vs 9 ± 1, p = 0.002). Elevated left ventricular filling pressure was detected in only 4 patients. These patients had more advanced form of liver impairment, and were categorized as having normal left ventricular diastolic function based on the mitral inflow indexes.ConclusionsOne fourth of patients with non-alcoholic liver cirrhosis had mild degree of left ventricular diastolic dysfunction using the conventional echocardiographic parameters. Elevated resting left ventricular filling pressure was detected in 11% of patients. The use of multiple parameters to assess the left ventricular diastolic function in patients with liver cirrhosis could unmask cases with pseudonormal pattern.     

Manometric assessment of esophageal motor function in patients with primary biliary cirrhosis

Introduction/aimPrimary biliary cirrhosis is associated with other autoimmune diseases including Sjögren's syndrome, and scleroderma. Esophageal dysmotility is well known in scleroderma, and Sjögren's syndrome. The aim of this study is to investigate whether any esophageal motor dysfunction exists in patients with primary biliary cirrhosis.MethodThe study was performed in 37 patients (36 women, mean age: 56.29 ± 10.01 years) who met diagnostic criteria for primary biliary cirrhosis. Thirty-seven functional dyspepsia patients, were also included as a control group. Patients entering the study were asked to complete a symptom questionnaire. Distal esophageal contraction amplitude, and lower esophageal sphincter resting pressure were assessed.ResultsManometric findings in primary biliary cirrhosis patients vs. controls were as follows: Median lower esophageal sphincter resting pressure (mm Hg): (24 vs 20, p = 0.033); median esophageal contraction amplitude (mm Hg): (71 vs 56, p = 0.050); mean lower esophageal sphincter relaxation duration (sc, x ± SD): (6.10 ± 1.18 vs 8.29 ± 1.92, p < 0.001); and median lower esophageal sphincter relaxation (%) (96 vs 98, p = 0.019); respectively. No significant differences were evident in median peak velocity (sc) (3.20 vs 3.02, p = 0.778) between patients with primary biliary cirrhosis and the functional dyspepsia patients. Esophageal dysmotility was found in 17 (45.9%) primary biliary cirrhosis patients (non-specific esophageal motor disorder in ten patients, hypomotility of esophagus in five patients, nutcracker esophagus in one patient and hypertensive lower esophageal sphincter in one patient).ConclusionEsophageal dysmotility was detected in 45.9% of patients. The study suggests that subclinic esophageal dysmotility is frequent in patients with primary biliary cirrhosis.     

Contrast-enhanced computed tomography and ultrasound-guided liver biopsy to diagnose dysplastic liver nodules in cirrhosis

BackgroundDysplastic nodules in cirrhosis herald a very high risk of transition to hepatocellular carcinoma. A better understanding of the relationships between dysplastic nodules and hepatocellular carcinoma development may help refining strategies of enhanced follow-up.MethodsAll consecutive cirrhotics with a histologically proven de novo dysplastic nodule, were retrospectively identified and underwent alternating abdominal ultrasound and contrast-computed tomography every 3 months. An ultrasound-guided liver biopsy was the diagnostic gold standard, whereas surveillance and recall policies were according to current guidelines.ResultsAmong 36 patients with dysplastic nodule (21 low-grade, 15 high-grade, 17.4 ± 2.6 mm), 17 (47%) showed arterial wash-in, 15 (42%) portal/venous hypodensity whereas 4 (11%) had neither pattern. During 6–128 (median 36) months, 21 patients developed a hepatocellular carcinoma at a rate of 13.8% per year, intranodular = 8.7% vs extranodular = 7.1% per year. Hepatocellular carcinoma occurred more frequently in high-grade than low-grade dysplastic nodules (32.2% vs 9.3% per year, p = 0.0039); the maximum time to hepatocellular carcinoma transformation was 27 months for intranodular vs 67 months for extranodular tumours (p = 0.025). No contrast-computed tomography pattern predicted neoplastic transformation of dysplastic nodules.ConclusionThe histological examination of liver nodules in cirrhosis lacking the imaging hallmark of hepatocellular carcinoma improves both prognostication and outcome of surveillance, since it dictates the intensity of the radiological follow-up.     

Strong correlation between ASPM gene expression and HCV cirrhosis progression identified by co-expression analysis

Hepatitis C virus (HCV) cirrhosis is at a high risk of hepatocellular carcinoma (HCC), and its progression is influenced by a complex network of gene interactions. A weighted gene co-expression network was constructed to identify gene modules associated with the seven-stage disease progression from HCV cirrhosis to HCV-related HCC (n = 65). In the significant module (R² = 0.86), a total of 25 network hub genes were identified, half of which were also hub nodes in the protein-protein interaction network of the module genes. In validation, most hub genes showed a moderate correlation with the disease progression, and only ASPM was highly correlated (R² = 0.801). In the test set (n = 63), ASPM was also more highly expressed in HCV cirrhosis with concomitant HCC than in those without HCC (P = 0.0054). Gene set enrichment analysis (GSEA) demonstrated that the gene set of “regulation of protein amino acid phosphorylation” (n = 20) was enriched in HCV cirrhosis samples with ASPM highly expressed (false discovery rate (FDR) = 0.049). In gene ontology (GO) analysis, genes in the enriched set were associated with liver neoplasms and other neoplastic diseases. In conclusion, through co-expression analysis, ASPM was identified and validated in association with the progression of HCV cirrhosis probably by regulating tumor-related phosphorylation.     

Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis

BackgroundChromosomal instability in peripheral blood mononuclear cells has a role in the onset of primary biliary cirrhosis. We hypothesized that patients with primary biliary cirrhosis may harbour telomere dysfunction, with consequent chromosomal instability and cellular senescence.AimTo evaluate the clinical significance of telomerase activity and telomere length in peripheral blood mononuclear cells from patients with primary biliary cirrhosis.Study designIn this population-based case control study, 48 women with primary biliary cirrhosis (25 with cirrhosis), 12 with chronic hepatitis C matched by age and severity of disease, and 55 age-matched healthy women were identified. Mononuclear cells from the peripheral blood of patients and controls were isolated. Telomere length and telomerase activity were measured.ResultsTelomere length and telomerase activity did not differ between cases (5.9 ± 1.5 kb) and controls (6.2 ± 1.4 kb, p_c = 0.164). Telomere shortening and advanced-stage disease strongly correlated with telomerase activity. Patients with advanced disease retained significantly less telomerase activity than those with early-stage disease (0.6 ± 0.9 OD vs. 1.5 ± 3.7 OD, p = 0.03). Telomere loss correlated with age, suggesting premature cellular ageing in patients with primary biliary cirrhosis.ConclusionOur data strongly support the telomere hypothesis of human cirrhosis, indicating that telomere shortening and telomerase activity represent a molecular mechanism in the evolution of human cirrhosis in a selected population of patients.     

Acute kidney injury is associated with higher mortality and healthcare costs in hospitalized patients with cirrhosis

Introduction and ObjectivesAKI is known to be associated with increased risk of mortality, however limited information is available on how AKI impacts healthcare costs and resource utilization in hospitalized patients with cirrhosis. Previous studies have had variable definitions of AKI, resulting in inconsistent reporting of the true impact of AKI in patients with cirrhosis.MethodsData from the Nationwide Inpatient Sample (NIS) which contains data from 44 states and 4378 hospitals, accounting for over 7 million discharges were analyzed. The inclusion data were all discharges in the 2012 NIS dataset with a discharge diagnosis of cirrhosis.ResultsA total of 32,605 patients were included in the analysis, incidence of AKI was 12.12% in patients with cirrhosis. Crude mortality was much higher for patients with cirrhosis and AKI (14.9% vs. 1.8%, OR 9.42, p < 0.001) than for patients without AKI. In addition, mean LOS was longer (8.5 vs. 4.3 days, p < 0.001) and median total hospital charges were higher for patients with AKI ($43,939 vs. $22,270, p < 0.001). In multivariate logistic regression, controlling for covariates and mortality risk score, sepsis, ascites and SBP were predictors of AKI.ConclusionsAKI is relatively common in hospitalized patients with cirrhosis. Presence of AKI results in significantly higher inpatient mortality as well as LOS and resource utilization. Median hospitalization cost was twice as high in AKI patients. Early identification of patients at high risk for AKI should be implemented to reduce mortality and contain costs. Prognosis could be enhanced by utilizing biomarkers which could rapidly detect AKI.     

Plasma proteosome level as a potential marker for hepatocellular carcinoma

Background and study aimsHepatocellular carcinoma (HCC) is a fatal malignancy. Effective curative surgery is achieved when HCC is detected earlier. Proteosomes, the main non-lysosomal proteolytic structures organising the cellular mechanisms of cleaving proteins, can be considered a tumour marker in many kinds of malignancies.The aim of this study was to assess the plasma proteosome level in HCC and cirrhosis and, accordingly, evaluate its potential diagnostic ability in the detection of HCC in cirrhosis.Patients and methodsThis study included 60 patients, divided into two groups: the HCC group and the liver cirrhosis group. Twenty normal subjects served as a control group. Serum levels of proteosome and alpha-foetoprotein (AFP) were measured using the enzyme-linked immunosorbent assay (ELISA) technique.ResultsPlasma proteosome levels were significantly higher in patients with HCC and in patients with cirrhosis without HCC when compared to controls individually (p > 0.002 and p > 0.001, respectively) but did not reach a significant differentiating level between them (area under curve (AUC) = 0.641, p = 0.061). Moreover, the plasma proteosome level was not correlated with the severity of HCC by the Milan criteria or with AFP level. In addition, it was not significantly related to laboratory or Child-Pugh scoring. Moreover, the combined use of plasma proteosome level and AFP measurements for the diagnosis of HCC was not effective.ConclusionsIn this study, the plasma proteosome level was comparably recorded in both patients with cirrhosis and patients with HCC (mean value ± standard deviation were 5.796 ± 1.46 and 7.176 ± 2.48 μg ml^?1, respectively), not reaching a significant differentiating level between them, although predictability of HCC using the plasma proteosome level was significant (p = 0.017).     

Electrocardiographic findings in hepatic cirrhosis and their association with the severity of disease

Purpose/aimPrevious studies reported prolongation of QT interval in cirrhotic patients. We aimed to investigate the electrocardiographic changes and their correlation with the disease severity in cirrhotic patients.MethodsSixty-nine cirrhotic patients were examined. The prolongation of corrected QT interval and low-voltage QRS in electrocardiography were cross-examined for clinical and biochemical data. The association of electrocardiographic findings with the severity of cirrhosis, as determined by both Child–Pugh and model for end-stage liver diseases (MELD) scores, was investigated.ResultsQT-interval prolongation was detected in 63.5% patients and 57.7% met the criteria for low-voltage QRS. Patients with prolonged QT-interval had higher Child scores (9.58 ± 2.5 vs. 8.16 ± 2.29 respectively, P = 0.04) but model for end-stage liver diseases scores was similar in those with prolonged QT and low-voltage electrocardiogram. The frequency of prolonged QT interval and low-voltage QRS were similar among patients with different Child–Pugh classes. Heart rate was also higher in patients with low-voltage electrocardiogram (89 ± 15 beats/min vs. 79 ± 16 beats/min, P = 0.01). Mean QRS voltage in precordial leads was lower in those with ascites (8.5 ± 2.6 mV vs. 11.8 ± 3.4 mV, P = 0.006).ConclusionElectrocardiographic changes are common in cirrhosis regardless of the disease severity. Low-voltage QRS may be related to anthropomorphic changes and development of ascites in these patients.     

Liver transplanted patients with preoperative autoimmune hepatitis and immunological disorders are at increased risk for Post-Transplant Lymphoproliferative Disease (PTLD)

BackgroundLong term immunosuppression and therapy of acute rejections result in a 20–120-fold increased risk to develop Non Hodgkin lymphoma (NHL). Since immunosuppressive therapy and immunological disorders are major risk factors for the development of NHL in the non-transplant population we aimed to analyze risk factors for PTLD in our cohort of liver transplanted (LT) patients.MethodsWe analyzed retrospectively 431 patients liver transplanted between 1998 and 2008.ResultsPTLD was diagnosed in eleven of 431 patients (2.6%). PTLD, especially late PTLD, was significantly more frequent in patients who received steroids before LT (Kaplan–Meier: p < 0.001). Moreover PTLD in immunocompromised patients with preoperative steroid treatment occurred at a significantly younger age (49.5 ± 4.7 years) compared to patients without steroids (60.6 ± 5.1 years; p = 0.006). Multivariate analysis revealed pretransplant steroid treatment and liver transplantation for autoimmune hepatitis as main risk factors for the development of PTLD after liver transplantation (p < 0.001).ConclusionLiver transplanted patients who received steroids before LT due to immunological disorders and patients with autoimmune hepatitis seem to be at particular high risk to develop PTLD. Prospective cohort studies including immunoepidemiologic investigations of abnormalities of cellular, humoral and innate immunity should be carried out to identify predictive factors and patients at risk.     

Acute kidney injury and chronic kidney disease after liver transplant: A retrospective observational study

Background and rationaleChronic kidney disease remains an important risk factor for morbidity and mortality among LT recipients, but its exact incidence and risk factors are still unclear.Material and methodsWe carried out a retrospective cohort study of consecutive adults who underwent liver transplant (January 2009–December 2018) and were followed (at least 6 months) at our institution. CKD was defined following the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guidelines. Long-term kidney function was classified into 4 groups: no CKD (eGFR, ≥60 mL/min/1.73 m²), mild CKD (eGFR, 30–59 mL/min/1.73 m²), severe CKD (eGFR, 15–29 mL/min/1.73 m²), and end-stage renal disease (ESRD).ResultsWe enrolled 410 patients followed for 53.2 ± 32.6 months. 39 had CKD at baseline, and 95 developed de novo CKD over the observation period. There were 184 (44.9%) anti-HCV positive, 47 (11.5%) HBsAg positive, and 33 (8.1%) HBV/HDV positive recipients. Recipient risk factors for baseline CKD were advanced age (P = 0.044), raised levels of serum uric acid (P < 0.0001), and insulin dependent DM (P = 0.0034). Early post-transplant AKI was common (n = 95); logistic regression analysis found that baseline serum creatinine was an independent predictor of early post-LT AKI (P = 0.0154). According to our Cox proportional hazards model, recipient risk factors for de novo CKD included aging (P < 0.0001), early post-transplant AKI (P = 0.007), and baseline serum creatinine (P = 0.0002). At the end of follow-up, there were 116 LT recipients with CKD – 109 (93.9%) and 7 (6.1%) had stage 3 and advanced CKD, respectively. Only two of them are undergoing long-term dialysis.ConclusionThe incidence of CKD was high in our cohort of LT recipients, but only a slight decline in kidney function over time was recorded. Prevention of post-transplant AKI will improve kidney function in the long run. We need more studies to analyze the function of kidneys among LT recipients over extended follow-ups and their impact on mortality.     

Systemic inflammatory response syndrome in patients with liver cirrhosis

Background and study aimsPatients with liver cirrhosis present an increased susceptibility to the systemic inflammatory response syndrome (SIRS), which is considered the cause of hospital admission in about 10% of patients and is present in about 40% of those admitted for ongoing complications. We tried to assess the prevalence of the SIRS with the possible effects on the course of the disease during hospital stay.Patients and methodsTwo hundred and three patients with liver cirrhosis were examined and investigated with close monitoring during hospital stay. The main clinical endpoints were death and the development of portal hypertension-related complications.ResultsEighty-one patients met the criteria of SIRS (39.9%). We found significant correlations between SIRS and jaundice (p = 0.005), bacterial infection (p = 0.008), white blood cell count (p < 0.001), low haemoglobin concentration (p = 0.004), high serum creatinine levels (p < 0.001), high alanine aminotransferase levels (p < 0.001), serum bilirubin levels (p < 0.001), international normalised ratio (p < 0.001), serum albumin levels (p = 0.033), high Child-Pugh score (p < 0.001). During the follow-up period, 26 patients died (12.8%), 15 developed portal hypertension-related bleeding (7.3%), 30 developed hepatic encephalopathy (14.7%), and 9 developed hepatorenal syndrome type-1 (4.4%). SIRS showed significant correlations both to death (p < 0.001) and to portal hypertension-related complications (p < 0.001).ConclusionThe systemic inflammatory response syndrome occurs in patients with advanced cirrhosis and is associated with a bad prognosis.     

Transforming growth factor-β1 gene expression in hepatocellular carcinoma: A preliminary report

Background and study aimsThe transforming growth factor (TGF)-β signalling pathway plays a dual role in hepatocarcinogenesis. It has been recognised for its role as a tumour suppressor as well as a tumour promoter depending on the cellular context.The aim of this study was to investigate the clinical significance of serum TGF-β1 level and TGF-β1 messenger RNA (mRNA) in the peripheral blood of liver cirrhosis and hepatocellular carcinoma (HCC) patients as noninvasive biomarkers in diagnosing HCC.Patients and methodsTwenty patients were allocated to each of the liver cirrhosis and HCC groups, in addition to 20 healthy volunteers. TGF-β1 gene expression in peripheral blood was quantitated using real-time polymerase chain reaction (PCR), while serum TGF-β1 was analysed using enzyme-linked immunosorbent assay (ELISA).ResultsTGF-β1 gene expression was significantly lower in HCC patients (median 0.401 (0.241–0.699) fold change) than in liver cirrhosis patients (median 0.595 (0.464–0.816)) (p = 0.042) and normal controls (median 1.00 (0.706–1.426) fold change) (p = 0.001). TGF-β1 gene expression showed significant positive correlation with serum TGF-β1 (r = 0.272, p = 0.036) and significant negative correlation with alpha-fetoprotein (AFP) (r = −0.528, p = 0.001). Receiver operating characteristic (ROC) analysis was conducted for TGF-β1 gene expression in comparison with AFP. The area under the curve for TGF-β1 gene expression was 0.688 (95% CI = 0.517–0.858) (p = 0.042) and AFP was 0.869 (95% CI = 0.761–0.976) (p = 0.001). The sensitivity and specificity of TGF-β1 gene expression were 65% and 75%, respectively, at a cutoff value of 0.462 fold change.ConclusionTGF-β1 gene expression in the peripheral blood may be used as a molecular marker for the diagnosis of HCC. Additional studies on a large-scale population are necessary to gain greater insight into the impact of TGF-β1 gene expression in the pathogenesis of HCC.     

Long-term outcome of early gastric cancer after endoscopic submucosal dissection: Expanded indication is comparable to absolute indication

BackgroundEndoscopic submucosal dissection has become widely used for early gastric cancer with an expanded indication, although there is no strong consensus. We aimed to compare the clinical and long-term oncological outcome after endoscopic submucosal dissection according to indication.MethodsRetrospective review of 1152 patients with 1175 lesions who had undergone endoscopic submucosal dissection for early gastric cancer at tertiary educational hospital in Korea, between March 2005 and November 2011. Of these, 366 and 565 lesions were included in the absolute and expanded indication groups, respectively.ResultsEn bloc resection rates were not significantly different between the absolute and expanded indication groups. The complete resection rate was higher in the absolute indication group versus the expanded indication group (94.8% vs. 89.9%, respectively; P = 0.008). In the expanded indication group, complete resection rate was higher in the differentiated versus undifferentiated tumour subgroups (92.9% vs. 78.4%, respectively; P < 0.001). Recurrence rates were 7.7% in the absolute indication group vs. 9.3% in the expanded indication group (P = 0.524). Disease-free survival was not significantly different between the two indication groups (P = 0.634).ConclusionsEndoscopic submucosal dissection for early gastric cancer with expanded indication is a feasible approach to disease management. Periodic endoscopic follow-up is necessary to detect cancer recurrence.