IL-6 and IL-10 gene polymorphisms and cirrhosis of liver risk from a comprehensive analysis.

BACKGROUND: Different inflammatory and immune cytokines play a key role in the development of cirrhosis of liver (CL). To investigate the association between interleukin-6,10 (IL-6,10) genes polymorphisms and CL risk through comparison of the allele and genotype distribution frequencies by meta-analysis. METHODS: A literature search covered with the PubMed, Embase, Cochrane Library, Web of Science, Google Scholar, SinoMed (CNKI and Wanfang) through 20th April, 2021. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations. RESULTS: After a comprehensive search, three common polymorphisms (rs1800872, rs1800871, rs1800896) in IL-10 gene were selected, and three common polymorphisms (rs1800795, rs1800796, rs1800797) in IL-6 gene were also identified. The important finding was that IL-10 rs1800872 was a risk factor for CL development. For example, there has a significantly increased relationship between rs1800872 polymorphism and CL both in the whole group (OR: 1.30, 95%CI: 1.01-1.67 in heterozygote model), Asian population (OR: 1.40, 95%CI: 1.03-1.88 in heterozygote model) and hospital-based source of control (OR: 1.40, 95%CI: 1.01-1.96 in dominant model). In addition, significant association was found between rs1800896 and primary biliary cirrhosis subtype disease (OR: 1.30, 95%CI: 1.01-1.68 in allelic contrast model). No association was observed in all three polymorphisms in IL-6 gene. CONCLUSION: Our present study suggests that the IL-10 rs1800872 and rs1800896 polymorphisms is potentially associated with the risk of CL susceptibility.

Sofosbuvir based therapy in hepatitis C patients with and without cirrhosis: Is there difference?

OBJECTIVE: To compare sustained viral response to sofosbuvir/ribavirin ±interferon therapy in patients of hepatitis C with and without liver cirrhosis. METHODS: This observational study of chronic hepatitis C patients was carried out at Doctors Hospital and Medical Center (DH&MC). After diagnostic workup, Sofosbuvir/ribavirin for 24 weeks or sofosbuvir/ribavirin/pegylated interferon for 12 weeks were prescribed. Primary outcome was negative HCV RNA by PCR 12 weeks after treatment completion (SVR12). Chi square χ2 and student's t test were used to analyze data. RESULTS: Of 216 patients included, liver cirrhosis was present in 112 (51.9%) patients and 69(31.9%) were treatment experienced. Liver disease was decompensated in 37 (17.1%) patients. Of 206 patient who completed study protocol, 173(83.1%) achieved SVR12, 89.2% (25/28) with triple therapy and 82.2% (148/180) with sofosbuvir/ribavirin therapy. Treatment response was similar between treatment naïve 86.2% (119/138) and treatment experienced 79.4% (54/68) patents. (p value 0.19) SVR12 was inferior in cirrhosis patients 75.4% (80/106) as compared to those with no cirrhosis 93% (93/100) (p value < 0.000). It was even lesser in those with decompensated liver disease 68.8% (24/35) (p value < 0.000). CONCLUSION: Treatment outcome with sofosbuvir/ribavirin combination therapy in cirrhosis patients is suboptimal especially in those with decompensation as compared to patients without liver cirrhosis.

Net time-dependent ROC curves: a solution for evaluating the accuracy of a marker to predict disease-related mortality.

Developing prognostic markers of mortality for patients with chronic disease is important for identifying subjects at high risk of death and optimizing medical management. The usual approach in this regard is the use of time-dependent ROC curves, which are well adapted for censored data. Nevertheless, an important part of the mortality may not be due to the chronic disease, and it is often impossible to individually determine whether or not the deaths are related to the disease itself. In survival regression, one solution is to distinguish between the expected mortality of one general population (from life tables) and the excess mortality related to the disease, by using an additive relative survival model. In this paper, we propose a new estimator of time-dependent ROC curves, which includes this concept of net survival, in order to evaluate the capacity of a marker to predict disease-specific mortality. We performed simulations in order to validate this estimator. We also illustrate this method using two different applications: (i) predicting mortality related to primary biliary cirrhosis of the liver and (ii) predicting mortality related to kidney transplantation in end-stage renal disease patients. For each application, we evaluated a scoring system already established. The results demonstrate the utility of the proposed estimator of net time-dependent ROC curves.

Association of low serum 25-Hydroxy vitamin D [25(OH) d] with hepatic encephalopathy in patients with decompensated liver cirrhosis.

BACKGROUND AND STUDY AIMS: The mechanism of hepatic encephalopathy is complex and has not been conclusively established. Recent studies support lower serum 25-Hydroxy Vitamin D [25(OH) D] levels in patients with hepatic encephalopathy. This study aimed to evaluate the association between serum 25(OH) D and hepatic encephalopathy in patients with decompensated cirrhosis of liver. PATIENTS AND METHODS: A total of 70 cirrhosis patients (35 cases of hepatic encephalopathy and 35 patients without encephalopathy as control, mean age 53.07 ± 12.99 years, 67 % male) were recruited for this study. Assessment of the severity of cirrhosis was done by using a model for end-stage liver disease(MELD) and Child Turcotte Pugh (CTP) scores, and assessment of the severity of hepatic encephalopathy was done according to West Haven criteria. Serum 25 (OH) D level was measured by Chemiluminescent Microparticle Immuno Assay(CMIA). RESULTS: The mean serum 25(OH) D level among hepatic encephalopathy patients was significantly lower in comparison to the control group without encephalopathy (18.76 ± 8.84 nmol/L vs 31.19 ± 13.9 nmol/L, P<0.0001). 91.4 % of hepatic encephalopathy patients had moderate to severe 25(OH)D deficiency as compared to 51.4 % in the control group. There was a significant correlation observed between the severity of the 25 (OH) D deficiency and the severity of liver disease (r =  - 0.35, P = 0.002). No statistically significant difference in serum 25(OH) D levels was found among patients with different hepatic encephalopathy grades (P = 0.416). CONCLUSION: A significant association was found between a low serum 25(OH) D leveland hepatic encephalopathy. It requires further large-scale multicenter studies to establish it as a risk factor and predictor of hepatic encephalopathy.

Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy.

Background and aims: Chronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in hepatitis B virus (HBV)-suppressed patients. Methods: We conducted a case-control study involving 120 noncirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and Fibrosis-4 (FIB-4)-matched controls. Clinical and laboratory data at viral suppression, including body mass index (BMI), comorbidities, pretreatment HBV viral load, HBe antigen status, hepatitis C virus (HCV) and HIV coinfections, liver chemistries, and AST to Platelets Ratio Index (APRI) values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. Results: Case and control groups had similar ages (51.4 ± 9.9 vs. 51.4 ± 10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, P = 0.01) and more diabetes prevalence (50.0% vs. 26.3%, P = 0.01), while other comorbidities and laboratory parameters were comparable (P > 0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46-6.13), 2.31 (1.23-4.36), and 2.71 (1.05-6.99), P = 0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, P = 0.006), while diabetes showed borderline significance (aHR: 1.99, P = 0.072). Conclusions: In HBV-infected patients achieving viral suppression with therapy, a BMI >23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.

A Prospective Study of Prevalence and Impact of Sarcopenia on Short-term Mortality in Hospitalized Patients with Liver Cirrhosis.

Background: Sarcopenia is common in chronic advanced liver disease and is associated with poor prognosis. There is paucity of Indian data regarding sarcopenia in chronic advanced liver disease & its impact on prognosis. The aim of this study was to study the prevalence of sarcopenia in Indian patients with chronic advanced liver disease and its impact on morbidity and short-term mortality. Methods: Patients with chronic advanced liver disease were prospectively evaluated for the presence of sarcopenia using computerized tomography (CT) abdomen. The cross-sectional area of the right psoas muscle was measured at the third lumbar vertebra (L3) and the Psoas muscle index (PMI) was calculated. Sarcopenia was defined as PMI <295 mm2/m2 for females and <356 mm2/m2 for males. The normative values of PMI were obtained from patients undergoing CT scan for non-specific abdominal pain who had no confounding factor which could result in sarcopenia. All patients were followed up for 6 months or until death, whichever was earlier. The impact of sarcopenia on mortality and rate of readmission has been assessed at the end of 6 months. Results: Of the 156 patients with chronic advanced liver disease, 74 (47.4%) patients had sarcopenia. Sarcopenia was more commonly seen in males (M: F = 61:13) and in patients with alcohol-related liver disease. There was a linear correlation (negative) between the PMI and severity of liver disease as assessed by Child-Pugh and model for end-stage liver disease (MELD) scores (r = -0.591 and -0.465, respectively). Patients with encephalopathy, ascites, and coagulopathy had higher prevalence of sarcopenia. On six months follow-up, sarcopenic patients had higher readmission rates (74.3% vs. 22%; P = 0.0001) and higher mortality (24.3% vs. 3.7%; P = 0.002). MELD score and PMI were independent predictors of mortality. The cut-off value of PMI 305.9 mm2/m2 predicted mortality with a sensitivity of 76.2% and a false positivity of 22.2% (area under curve was 0.805; 95% confidence interval: 0.69-0.91, P = 0.001). Conclusion: Sarcopenia is seen in about half of the patients with chronic advanced liver disease. It is commoner in males, patients with alcoholic liver disease, and those with advanced liver disease. Patients with sarcopenia have worse prognosis, require more frequent hospitalization and it negatively impacts short-term survival.

Predictors Of Re-Bleeding After Oesophageal Variceal Banding In Cirrhotic Patients At 4 Weeks.

BACKGROUND: Acute upper gastrointestinal bleeding is a serious complication in cirrhotic patients. Without recommended management, recurrent bleeding happensin 30-40% within the next 2-3 days, and up to 60% within 1 week. Aim was to determine predictors of re-bleeding after oesophageal variceal banding in cirrhotic patients for 4 weeks. It was a descriptive study, conducted at the Department of Medicine, Sheikh Zayed Hospital, Rahim Yar Khan. Six months from June 21 to December 21, 2021. METHODS: A total of 93patients with active oesophageal variceal bleeding were included in this study. Upper gastrointestinal (UGI) endoscopy was performed to look for bendable varices (grades 1-4) and band ligation was applied. Patients were followed for 4 weeks for the history of hematemesis or Malena, fall in haemoglobin of 2 grams per decilitre or more and endoscopic rebleeding findings. RESULTS: Out of 93 patients, 67(72.0%) were males, while 26(28.0%) were females. The Mean age of the patients was 45.66±16.61 years. According to Child Pugh Classification, the majority of the patients 45(48.4%) had Child-Pugh Class-A, while 33 (35.5%) were Child B and 15 (16.1%) patients belonged to Child-Pugh Class C. Red wale sign was noted in 22 patients (23.7%). Among 93 cirrhotic patients who presented with variceal bleeding, 9 (9.7%) had re-bleeding within 4 weeks. Amongst 9 patients, 8 patients (88.9%) had red wale sign, grade II or above oesophageal varices and belonged to severe liver disease with child class B or C. CONCLUSIONS: Endoscopic variceal band Ligation is an effective treatment modality for the control of oesophageal variceal bleeding. Re-bleeding after band ligation was 9.7%. The major contributing factors to re-bleeding were the severity of cirrhosis, grades and columns of oesophageal varices, number of bands ligation and findings of red wale sign. Increasing age and duration of cirrhosis were contributing predictors of increased re-bleeding risk.

Serum kallistatin as a marker of severity of liver fibrosis in cirrhosis: A cross-sectional observational study.

Background: Liver cirrhosis is among the leading causes of morbidity and mortality worldwide. Although liver biopsy is the gold standard for the assessment of liver fibrosis in cirrhosis, it has its own limitations. Therefore, noninvasive methods to detect liver fibrosis are widely preferred. However, they also have their own limitations. Thus, there is always a need to extend the battery of serum-based assays. Kallistatin is a protein synthesized primarily in the liver. As it is a negative acute-phase protein, its blood level decreases with a decline in liver function. In our study, we explored the relationship between serum kallistatin and radiological evidence of liver fibrosis by transient elastography to determine if kallistatin levels can be used as a diagnostic marker of liver fibrosis. Materials and Methods: A cross-sectional study of 1-year duration was conducted at a leading tertiary care hospital in northern India. Patients between 15 and 75 years of age having evidence of chronic liver disease were enrolled. All enrolled patients were evaluated by detailed history, physical examination, and relevant investigations. Serum kallistatin levels were quantified using the ELISA method. Grading of liver fibrosis was done using transient elastography. A FibroScan scoring card was used to convert FibroScan results measured in kPa into the Metavir scale F1-F4. Results: A total of 128 subjects, including 64 patients with cirrhosis and 64 healthy controls, were enrolled. Our study suggested that FibroScan values were significantly higher in cases as compared to controls. The kallistatin level of cases was significantly lower than that of controls. An inverse correlation was found between FibroScan value and kallistatin level among cases. Conclusion: We conclude that serum kallistatin levels are low in patients with liver fibrosis and can be used as a potential marker of liver fibrosis.

The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study.

BACKGROUND AND AIMS: Liver cancer is a detrimental complication in patients with chronic viral hepatitis and alcoholic or nonalcoholic fatty liver disease (NAFLD). However, metabolic risk factors underlying NAFLD usually cause substantial differences in their clinical outcomes. Recently, several studies have used a novel definition of metabolic dysfunction-associated fatty liver disease (MAFLD) to reassess patients with NAFLD and pointed out the importance of metabolic risk factors. Since patients with NAFLD, MAFLD, or metabolic syndrome (MetS) have different burden of metabolic risk factors, it is crucial to decipher the risk of developing hepatic complications in these populations. METHODS: Through a longitudinal nationwide cohort study, the risk of liver cancer was investigated in patients with MetS alone, NAFLD alone, overlap NAFLD/MAFLD, and coexisting MetS and NAFLD. The general characteristics, comorbidities, and incidence of liver cancer were also compared. RESULTS: Intriguingly, patients diagnosed with MetS alone did not have a significant risk of developing HCC compared to control individuals, while patients with NAFLD alone, NAFLD/MAFLD, and coexisting NAFLD and MetS exhibited 6.08-, 5.81-, and 15.33-fold risks of developing HCC, respectively. Apart from metabolic risk factors, renal function status and liver cirrhosis were the independent risk factors for the development of HCC among these groups. CONCLUSION: Our data emphasize that metabolic dysfunction has a significant impact on hepatocarcinogenesis in patients with NAFLD. Moreover, coexisting multiple metabolic risk factors would dampen the risk of developing HCC in patients with NAFLD. Closely tracing HCC formation through laboratory examination or imaging is crucial in these patients.

Safety Assessment of Autologous Stem Cell Combination Therapy in Patients With Decompensated Liver Cirrhosis: A Pilot Study.

BACKGROUND: Haematopoietic stem cell (HSC) infusion has demonstrated short-term improvement in liver functions in patients with chronic liver disease. The combination of HSC with mesenchymal stem cells (MSCs), which has an immunomodulatory effect, may augment the effects and enhance the duration of improvements on liver functions. The aim of the present study was to assess the safety of infusing the combination of autologous HSCs and MSCs in decompensated liver cirrhosis. METHODS: In phase I of the study, in vitro assessment was performed to observe the effect of coculturing MSCs with HSCs on their viability and cytokine profiles. Phase II of the study was to assess the safety of combination of stem cell infusions. Bone marrow (50 ml) was aspirated for MSC isolation and expansion using standard protocol. Patients received subcutaneous doses (n = 5) of granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization followed by leukapheresis for harvesting HSCs using CliniMacs. HSCs and MSCs were infused through the hepatic artery under fluoroscopic guidance and were monitored for any adverse effects. RESULTS: In vitro studies revealed 94% viable HSCs in coculture similar to monoculture. HSCs released only interleukin (IL)-8, whereas MSCs secreted IL-8 and IL-6 in monocultures, and both IL-8 and IL-6 were secreted in coculture. G-CSF administration- and bone marrow aspiration-related complications were not observed. Infusion of the cells through the hepatic artery was safe, and no postprocedural complications were noted. CONCLUSION: The combination of autologous HSC and MSC infusion is a safe procedure in patients with decompensated liver cirrhosis, and the outcomes needed to be assessed in larger studies. TRIAL NUMBER: NCT04243681.

Factors Predicting Cardiac Dysfunction in Patients with Liver Cirrhosis.

BACKGROUND Left ventricular diastolic dysfunction (LVDD) is the earliest cardiac dysfunction noted in patients with liver cirrhosis, which increases the morbidity and mortality in such patients. There are sparse studies from India evaluating the predictive factors of LVDD in patients with cirrhosis. Hence we undertook this prospective study with an aim to evaluate the factors predicting the development of LVDD in liver cirrhosis. METHODS 104 patients with cirrhosis were enrolled in this prospective study. A detailed cardiac evaluation was done by 2 D echocardiography with tissue Doppler imaging by an experienced senior cardiologist. The severity of liver disease was defined by Model For End-Stage Liver Disease (MELD) and Child-Pugh score. RESULTS The prevalence of LVDD was 46% in our study. Multivariate logistic regression analysis revealed that serum albumin, MELD score, and presence of ascites (OR = 0.1, 95%CI 0.03-0.3, p < 0.001; Or = 1.12, 95%CI 1.03-1.22, p < 0.001; OR = 4.19, 95%CI 1.38-12.65, p < 0.01, respectively) were independent predictors of LVDD in patients with cirrhosis. Diastolic dysfunction was unrelated to age, sex, and etiology of cirrhosis. The patients with cirrhosis and LVDD had significantly higher child Pugh score, MELD score, and lower serum albumin than patients without LVDD. The echocardiographic parameters like E/e' ratio, Deceleration time (DT), and Left atrial volume index (LAVI) were significantly different in cirrhotic patients with higher MELD and child Pugh score than lower. CONCLUSION The present study showed a significant correlation of diastolic dysfunction with the severity of the liver disease. Low serum albumin, high MELD score, and presence of ascites significantly predict the development of LVDD in patients with cirrhosis.

Comparison of clinical and metabolic profiles of lean versus non-lean nonalcoholic fatty liver disease.

BACKGROUND: Data on nonalcoholic fatty liver disease (NAFLD) in the Philippines are scarce. We aimed to compare the clinical and biochemical profiles of lean (BMI<23) vs. non-lean (BMI≥23) NAFLD patients. METHODS: Consecutive patients diagnosed with NAFLD on ultrasound in two outpatient hepatology clinics from February 2007-January 2017 were included. Patients with significant alcohol intake, alternative causes of steatosis, and incomplete data were excluded. RESULTS: A total of 663 patients (57.9% male) were included. Most patients were non-lean (88.1%) and had an elevated alanine aminotransferase (ALT) (63%). Cirrhosis or hepatocellular carcinoma (HCC) were already present in 8.4% on initial consultation. Concomitant hepatitis B was equally common in patients with and without cirrhosis (20.7% vs. 17.5%; p=0.660) or HCC (17.9% vs. 12.8%; p=0.415). Independent factors associated with HCC/cirrhosis on initial consultation were older age (OR=1.038), low albumin (OR=0.428), high BARD score (BMI, AST/ALT ratio, T2 diabetes mellitus; OR=2.548) and the presence of symptoms (OR=1.808). Compared to lean NAFLD patients, non-lean patients were more likely to be younger (51.5±14.4 vs. 55±14.3; p=0.003), have DM (47.9% vs. 29.1%; p=0.002), hypertension (57.5% vs. 38%; p=0.001), dyslipidemia (73.1% vs. 54.4%; p=0.001) and metabolic syndrome (60.3% vs. 30.4%; p<0.0001), abnormal metabolic parameters (LDL-C, HDL-C, triglycerides, uric acid and FBS), and with elevated ALT (65.2% vs. 46.8%; p=0.002) and AST (41.1±29.6 vs. 35.3±28.3; p=0.008). CONCLUSIONS: The proportion of lean NAFLD was 11.9%. Although metabolic derangements and its clinical consequences were present in about a third of lean patients, these were still more common in non-lean NAFLD. Cirrhosis or HCC were already present in a significant proportion (8.4%) of NAFLD patients on initial presentation.

A Study on the Temporal Trends in the Etiology of Cirrhosis of Liver in Coastal Eastern Odisha.

BACKGROUND: The etiology of cirrhosis of liver is known to change with time due to various factors including awareness, preventive interventions, and lifestyle changes in society. However, there is scarce Indian data available about temporal trends in etiology of cirrhosis of liver. Hence, the aim of this study was to study the temporal trends in the etiology of cirrhosis of liver. MATERIALS AND METHODS: This is a retrospective study conducted in the Department of Gastroenterology, Srirama Chandra Bhanja Medical College and Hospital, Cuttack, from January 2005 to December 2017. Data were collected from hospital records of all patients admitted to the Gastroenterology unit. A Poisson regression model was used to compare the hospitalization rate for different etiologies of cirrhosis of liver. All data were analyzed using Stata version 5.1 software. RESULTS: A total of 4,331 hospitalized patients of cirrhosis of liver were included in the analysis, of whom 2,742 (63.3%) had alcohol-related cirrhosis, 858 (19.8%) had viral hepatitis-related cirrhosis, and 731 (16.9%) had cirrhosis of liver due to nonalcohol and nonviral causes. The proportion of alcohol-related cirrhosis was increased by 26% from 2005 to 2017 (RR 1.26, p for trend <0.001). Though there were minimal ups and downs observed in the admission rate of viral hepatitis-related liver cirrhosis during later years, this was remarkably reduced by 73% (RR 0.27, p for trend <0.001) in the year 2017 at the end of the study. Similarly, the proportion of cirrhosis due to nonalcohol and nonviral causes decreased by 26% (RR 0.74, p for trend <0.001) by 2017. CONCLUSION: Alcohol is the most common cause of cirrhosis of liver and the burden of alcohol-related cirrhosis is significantly increasing in comparison to other causes including viral infection, nonalcoholic steatohepatitis (NASH), and autoimmune hepatitis. HOW TO CITE THIS ARTICLE: Mishra D, Dash KR, Khatua C, et al. A Study on the Temporal Trends in the Etiology of Cirrhosis of Liver in Coastal Eastern Odisha. Euroasian J Hepato-Gastroenterol 2020;10(1):1-6.

Utility of Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) in Decompensated Cirrhosis.

BACKGROUND AND AIMS: Renal failure occurring in the setting of cirrhosis increases mortality by more than threefold. Serum creatinine, the conventional marker for renal dysfunction has inherent limitations in identifying and categorizing renal dysfunction in patients with chronic liver disease (CLD). Neutrophil gelatinase associated lipocalin (NGAL) is a novel biomarker which gets upregulated as early as 2-6 hours following the insult to renal tubules. In this study, we aim to check the utility of uNGAL to identify the different phenotypes of renal dysfunction in patients with CLD. We also intend to assess the utility of NGAL to predict 90-day transplant-free survival in patients with CLD. METHODS: A total number of 120 adult patients, with cirrhosis of liver were recruited. Those with pre-existing renal parenchymal disease, receiving nephrotoxic medications, spontaneous bacterial peritonitis, septic shock, proteinuria, hematuria, urinary tract infection and anuria were excluded. Urine samples for NGAL was measured at admission and at 48 hours thereafter. Patients were followed up for 90 days post admission. RESULTS: Among the study population, 16 patients (13.3%) had normal kidney function, 43 (35.8%) had prerenal azotemia and 54 (45%) had Hepatorenal Syndrome (HRS - AKI) and 7 (5.8%) had acute tubular necrosis (ATN). Urinary NGAL (uNGAL) levels were considerably lower in patients with normal kidney function and prerenal azotemia. An uNGAL level of 124 ng/ml on admission could distinguish severe forms of renal injury, with a sensitivity of 86% and specificity of 84%. The non survivors had higher uNGAL levels at admission [209.6 ng/ml (118.7-376.8) vs. 123 (33.6-344.3); P = 0.013].The receiver operated curves for uNGAL and serum creatinine at admission did not show any significant difference for predicting 90 day mortality (AUC for uNGAL: 0.632 vs 0.580 for serum creatinine; difference in AUC 0.053, P value 0.17). CONCLUSION: uNGAL levels are elevated in patients with HRS-AKI and ATN. A higher uNGAL level at admission was suggestive of severe renal dysfunction. An elevated uNGAL on admission is associated with inferior survival. However, uNGAL is not superior to serum creatinine in predicting 90-day mortality.

Acute kidney injury in patients with cirrhosis of liver: Clinical profile and predictors of outcome.

BACKGROUND: Acute kidney injury (AKI) is a common complication of liver cirrhosis and is associated with poor survival. We studied the clinical profile and predictors of in-hospital mortality in patients with cirrhosis of the liver with AKI. METHODS: This retrospective cohort study examined patients at a tertiary care hospital. AKI staging was done based on the new 2015 Ascites Club Criteria. Patients were grouped into three types of AKI: pre-renal azotemia (PRA), hepatorenal syndrome (HRS), and acute tubular necrosis (ATN). RESULTS: Data of 123 patients with cirrhosis and AKI were analyzed. Most patients had AKI stage 3 (57.7%). ATN (42.3%) and HRS (43.9) were the predominant types of AKI followed by PRA (13.8%). The overall in-hospital mortality in our study was 44.7%. The mortality increased with increasing severity of AKI (p = 0.0001) and was the highest in AKI stage 3 (p = 0.001) and those who required hemodialysis (p = 0.001). There was a significant in-hospital mortality in patients with ATN and HRS in comparison to PRA (p = 0.001). On multivariate analysis, the factors predicting in-hospital mortality were AKI stage 3, and oliguria (p = 0.0001). CONCLUSIONS: Acute kidney injury in cirrhosis of liver carries high in-hospital mortality. Pre-renal AKI has a better survival compared to ATN and HRS. The higher stage of AKI at presentation and the presence of oliguria are two important predictors of in-hospital mortality.

Resolution of refractory hepatic hydrothorax in patients with hepatitis C virus cirrhosis after treatment with direct-acting antiviral agents.

Hepatic hydrothorax (HH) is a transudative pleural effusion that complicates advanced liver cirrhosis. Cases refractory to medical treatment in the form of salt restriction and diuretics are labeled refractory hepatic hydrothorax (RHH) and may require transjugular intrahepatic portosystemic shunts (TIPSS) or even liver transplantation. Renal impairment is common in advanced liver disease, worsens its prognosis, and makes the management of HH more challenging. Successful antiviral therapy reduces some of the complications of cirrhosis secondary to hepatitis C virus (HCV) infection. We herein report two cirrhotic patients with chronic kidney disease who developed RHH which resolved after the successful treatment of their HCV infection with direct-acting antivirals (DAAs). In cases of RHH associated with HCV cirrhosis, a trial of DAAs is warranted before resorting to TIPSs or liver transplantation.

Prevalence of and Factors Associated With Minimal Hepatic Encephalopathy in Patients With Cirrhosis of Liver.

BACKGROUND/OBJECTIVES: Minimal hepatic encephalopathy (MHE), though highly prevalent, is a frequently underdiagnosed complication of cirrhosis of the liver. Because lack of time is reported as the major reason for non-testing, identifying patients at high risk of MHE would help in targeting them for screening. We aimed to determine the factors associated with MHE to help identify patient subgroups with a higher risk of MHE for targeted screening. METHODS: Patients with cirrhosis of liver presenting between April 2015 and November 2016 were included. Those with a Psychometric Hepatic Encephalopathy Score (PHES) of ≤-5 points on psychometric testing were diagnosed to have MHE. Various demographic, clinical and laboratory parameters were included in a univariate and later multiple logistic regression models. RESULTS: Of the 180 (male = 166, 92.2%) patients included 94 (52.2%) had MHE. Though serum albumin, serum total bilirubin, serum aspartate aminotransferase, international normalized ration, Child-Turcotte-Pugh and Model-For-End-Stage-Liver-Disease scores were significant on univariate analysis, only CTP score was found to be significantly associated with MHE (P = 0.002) on multivariate analysis. A higher CTP class was associated with a higher risk of the presence of MHE. The Odds ratio for having MHE was higher with CTP classes of B (P ≤ 0.001) and C (P ≤ 0.001) compared to class A. CONCLUSIONS: MHE is a common complication in patients with cirrhosis of liver and higher CTP scores independently predict the presence of MHE. Patients with CTP class B and C have a higher risk of suffering from MHE than CTP class A. Screening of patients in CTP class B and C is likely to increase the MHE detection rates while saving time, although select CTP class A patients may also need screening in view of public safety or poor quality of life.

Role of Helicobacter pylori and hyperammonemia in subclinical hepatic encephalopathy in cirrhosis of liver.

In a prospective study of 47 patients of subclinical hepatic encephalopathy in cirrhosis of liver, aged between 23 and 60 years, 49% showed Helicobacter pylori positivity by rapid urease test. The baseline characters of patients (mean age, serum creatinine, sereum albumin, serum bilirubin, prothrombin time) were similar among patients with and without Helicobacter infection in all the patients. There was no statistically significant difference in blood ammonia levels in either group of patients. Blood ammonia values showed good correlation with the functional state of liver function but they did not show statistically significant difference between two groups of patients in any of Child Pugh classes. It is concluded that Helicobacter pylori does not contribute significantly to blood ammonia levels and the severity of hepatic encephalopathy.

Non-Invasive Predictors of Gastro-Oesophageal Varices.

INTRODUCTION: The worldwide accepted tool for screening and monitoring gastro-oesophageal varices in patients with liver cirrhosis is upper gastrointestinal endoscopy. Endoscopy needs clinical expertise and has got its own procedure related complications. Repeated endoscopies may be expensive and patients tend to develop poor compliance. This study was undertaken to establish the role of noninvasive parameters in predicting gastro-esophageal varices. METHODS: Two hundred patients with clinical features, laboratory and sonological findings suggestive of cirrhosis of liver and endoscopic evidence of portal hypertension were included in the study. Blood parameters like serum albumin, international normalized ratio (INR), platelets count and ultrasonography assessments of portal vein diameter and spleen size were compared with presence of gastro-oesophageal varices. RESULTS: At cutoff point of 2.55g/dl, serum albumin had high specificity of 99% whereas platelets count <1,44,000/mm3 had 87.9% sensitivity for presence of oesophageal varices. Sensitivities of 92.72% and 94.5% while specificities of 90% and 75% were detected for presence of oesophageal varices when the cutoff values for portal vein diameter and spleen size were 12.25 mm and 13.9 cm respectively. CONCLUSIONS: Measurements of serum albumin, platelets count, portal vein diameter and spleen size by ultrasonography can be recommended as a non-invasive predictor for gastro-oesophageal varices in cirrhosis of liver. All these non-invasive parameters could be useful to patients with liver cirrhosis with portal hypertension in predicting presence of varices as well as in long-term clinical monitoring and management.

Long Term Outcomes of Patients with Significant Biliary Obstruction Due to Portal Cavernoma Cholangiopathy and Extra-Hepatic Portal Vein Obstruction (EHPVO) With No Shuntable Veins.

AIMS: The natural history of portal cavernoma cholangiopathy (PCC) in patients with significant biliary obstruction (SBO) who cannot undergo shunt surgery, is not known. We therefore, analyzed data of patients of extra-hepatic portal venous obstruction (EHPVO) with PCC. METHODS: Prospectively recorded details of 620 (age 21.2 [11.4] years; 400 [65%] males) patients with primary EHPVO were reviewed. Outcomes (hepatic decompensation/mortality) of patients with PCC and SBO without shuntable veins were noted at follow up of 7 [4-11] years. RESULTS: Ninety-seven of 620 (15.6% [60 men]) EHPVO patients had PCC-SBO. Of these 57 did not have shuntable veins. The median duration from any index symptom to symptomatic PCC was 7 (0-24) years and from index bleed to symptomatic PCC was and 12 (5-24) years, respectively. Thirteen patients underwent endoscopic retrograde cholangiography; nine repeatedly over 7 (4-10) years. Decompensation was seen in 5 patients. Presentation other than variceal bleed was associated with hepatic decompensation (5/19 versus 0/38, P = 0.003). CONCLUSIONS: Majority of patients with PCC-SBO do not have shuntable veins, and may have good long-term outcomes. Patients presenting with variceal bleed have low chance of decompensation. Symptomatic PCC appears to be a late event in EHPVO.