Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores. CONCLUSION: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.

Comparison of virtual computed tomography enteroscopy using carbon dioxide with small-bowel enteroclysis and capsule endoscopy in patients with small-bowel tuberculosis.

OBJECTIVE: Comparison of virtual CT enteroscopy (VCTE) using carbon dioxide with small-bowel enteroclysis (SBE) and capsule endoscopy (CE) in small-bowel tuberculosis (SBTB). METHODS: This prospective study comprised consecutive patients suspected to have SBTB. VCTE and SBE were performed on the same day and evaluated by independent radiologists. CE was performed within 2 weeks. VCTE was performed following insufflation of carbon dioxide via catheters in the jejunum and anorectum. A contrast-enhanced CT was followed by a delayed non-contrast CT. Image processing was done using virtual colonoscopy software. Findings on VCTE, SBE, and CE were compared. The final diagnosis of SBTB was based on either histopathological or cytological findings, response to antitubercular treatment, or a combination of these. RESULTS: Of the 55 patients in whom VCTE was performed, complete data was available in 52 patients. A final diagnosis of SBTB was established in 37 patients. All patients had VCTE and SBE. CE was performed in 34 patients. Adequate luminal distension was achieved in all patients with SBE and 35 patients with VCTE. SBE showed more strictures in jejunum (10.8%) and ileum (75.7%) compared with VCTE (jejunum, 8.1%, and ileum, 64.9%) and CE (jejunum, 5.9%, and ileum, 61.8%). However, difference was not statistically significant. VCTE revealed a greater length of strictures in both the jejunum and ileum compared with SBE and CE. CONCLUSION: VCTE allows adequate evaluation of the bowel in most patients with SBTB. It allows detection of greater length of abnormality in jejunum and ileum compared with SBE and CE. KEY POINTS: • The use of VCTE using CO2 bowel insufflation in patients with SBTB should be considered. • VCTE allows detection of a greater length of abnormality in the jejunum and ileum.

Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Prediction of 28-day mortality in acute decompensation of cirrhosis through the presence of multidrug-resistant infections at admission.

BACKGROUND AND AIM: The aim of this study is to evaluate the epidemiology and impact of bacterial infections at admission in patients with acute decompensation (AD) of cirrhosis. METHODS: A cohort with AD of cirrhosis (European Association for the Study of the Liver criteria) admitted at a tertiary center was evaluated between 2013 and 2014 for the presence of bacterial infections at admission. Clinical, demographic, and microbiological data were collected prospectively till death, transplant, or 90 days. RESULTS: Of 179 patients with AD, 102 (56.9%) had bacterial infections at admission. The commonest infections were spontaneous bacterial peritonitis (SBP) (n = 65; 63.7%), spontaneous bacteremia (n = 10; 9.8%), pneumonia (n = 9; 8.8%), urinary tract infection (n = 8; 7.8%), spontaneous bacterial empyema (n = 4; 3.9%), and cellulitis (n = 2; 1.9%). The commonest source was community acquired (n = 85; 83.3%). Serum albumin and sodium levels were lower in infected as compared with non-infected cohort (P = 0.015; for both). Escherichia coli was the commonest organism isolated from SBP (n = 14; 21.5%), urinary tract infection (n = 5; 45.5%), and bacteremia (n = 3; 20%). There was a trend toward higher 28-day mortality in infected cohort as compared with non-infected cohort (48 [52.7%] vs 28 [32%]; P = 0.152). Multidrug-resistant organisms (MDROs) were isolated in 63% of all culture-positive infections. The presence of MDRO was an independent predictor of 28-day mortality. CONCLUSIONS: Infections are the leading reason for the occurrence of AD; SBP is the most common infection, and E. coli is the commonest microorganism based on this single-center study of Indian patients with AD of cirrhosis. There is a high prevalence of MDROs among culture-positive infections that independently predict 28-day mortality in AD of cirrhosis.

Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients.

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Invasive fungal infections amongst patients with acute-on-chronic liver failure at high risk for fungal infections.

AIMS: To study the prevalence, risk factors, role of serum biomarkers for diagnosis and impact of invasive fungal infections (IFIs) in patients with acute-on-chronic liver failure (ACLF). METHODS: An analysis of IFI in patients with ACLF (EASL criteria) was conducted retrospectively. The diagnosis of IFI in clinically suspected patients was based on EORTC/MSG criteria. The demographical, clinical, laboratory details and outcomes were analysed. RESULTS: Out of 264 patients with ACLF, 54 (20.4%) patients with suspicion of IFI were evaluated and IFI was diagnosed in 39 (14.7%). Invasive candidiasis was documented in 25 (64.1%) and invasive aspergillosis in 14 (35.8%). The most common source of infection was respiratory (n = 13) followed by renal (n = 7) and spontaneous fungal peritonitis (n = 6). On univariate analysis, diabetes mellitus, hemodialysis, prior antibiotic use, cerebral and respiratory organ failures, Chronic Liver Failure Consortium (CLIF-OF and CLIF-C ACLF) scores were predictors for development of IFI (P < 0.05). On multivariate analysis, hemodialysis and prior antibiotics use predicted the development of IFI (P < 0.05). Non-survivors were more likely to have IFI (P = 0.029), high CLIF-OF and CLIF-C ACLF scores (P < 0.001; for both) and higher 1,3-ß D Glucan (BDG) levels (P = 0.009). The sensitivity, specificity, and AUROC of BDG (80 pg/mL) and Galactomannan index (GMI [0.5]) for diagnosing IFI were 97.4%, 60%, 0.770% and 43.6%, 100%, 0.745 respectively. CONCLUSIONS: Invasive fungal infections constitutes an important cause of mortality in ACLF patients. BDG and GMI can be useful markers to guide antifungal therapy in patients at high risk for IFI.

Systemic inflammatory response syndrome in acute-on-chronic liver failure: Relevance of 'golden window': A prospective study.

BACKGROUND AND AIM: Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis. METHODS: Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death. RESULTS: Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin > 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P < 0.001). CONCLUSION: Liver failure predicts the development of SIRS. New onset SIRS in the first week is an important determinant of early sepsis, organ failure, and survival. Prompt interventions in this 'golden window' before development of sepsis may improve the outcome of ACLF.

Comparison of radiofrequency ablation alone & in combination with percutaneous ethanol injection for management of hepatocellular carcinoma.

Background & objective: It has been shown that the combined use of alcohol before radiofrequency ablation (RFA) helps to augment the therapeutic advantage of RFA. The present study was conducted to compare the outcome of treatment with RFA alone and RFA with alcohol as ablative technique in patients with small hepatocellular carcinomas (HCCs), who were not candidates for surgery. Methods: Fifty patients with chronic liver disease and concurrent HCC were enrolled in this prospective study. The patients were treated with either RFA alone (n=25) or RFA combined with alcohol (n=25). Patient outcome was evaluated, and the tumour recurrence and survival of the patients were assessed in the two groups. Results: The survival rates at six months in patients who completed at least six months of follow up were 84 and 80 per cent in patients treated with RFA alone and combination therapy, respectively. During the follow up period, 11 and four patients treated with RFA alone showed local and distant intrahepatic tumour recurrence, respectively. All local recurrences were at one to 18 months of the follow up period. The distant recurrences occurred at 6-36 months of the follow up period. During the follow up period, eight and six patients treated with combination therapy showed local and distant intrahepatic tumour recurrence, respectively. All local recurrences were at 1.5-15 months during the follow up period. The distant intrahepatic recurrences occurred at 6-72 months during the follow up period. Interpretation & conclusions: No significant difference was seen between the survival time of the patients treated with RFA alone and RFA with alcohol as well as in the local recurrences and distant intrahepatic recurrences in RFA compared to RFA and alcohol group patients. Combined use of RFA and alcohol did not improve the local tumour control and survival in patients with HCC compared to RFA alone.

Viral hepatitis: Indian scenario.

Viral hepatitis is a cause for major health care burden in India and is now equated as a threat comparable to the "big three" communicable diseases - HIV/AIDS, malaria and tuberculosis. Hepatitis A virus and Hepatitis E virus are predominantly enterically transmitted pathogens and are responsible to cause both sporadic infections and epidemics of acute viral hepatitis. Hepatitis B virus and Hepatitis C virus are predominantly spread via parenteral route and are notorious to cause chronic hepatitis which can lead to grave complications including cirrhosis of liver and hepatocellular carcinoma. Around 400 million people all over the world suffer from chronic hepatitis and the Asia-Pacific region constitutes the epicentre of this epidemic. The present article would aim to cover the basic virologic aspects of these viruses and highlight the present scenario of viral hepatitis in India.

Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial.

BACKGROUND & AIMS: Little is known about whether probiotics can affect outcomes of patients with cirrhosis and hepatic encephalopathy (HE). We assessed the efficacy of a probiotic preparation in preventing the recurrence of HE (primary outcome) and reducing the number of hospitalizations and severity of liver disease in patients with cirrhosis. METHODS: We performed a double-blind trial at a tertiary care hospital in India. Patients with cirrhosis who had recovered from an episode of HE during the previous month were assigned randomly (using computer-generated allocation) to groups given a probiotic preparation (VSL#3, 9 × 10(11) bacteria; CD Pharma India Private Limited, New Delhi, India) (n = 66) or placebo (n = 64) daily for 6 months. RESULTS: There was a trend toward a reduction in the development of breakthrough HE among patients receiving the probiotic (34.8% in the probiotic group vs 51.6% in the placebo group; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.38-1.11; P = .12). Fewer patients in the probiotic group were hospitalized for HE (19.7% vs 42.2%, respectively; HR, 0.45; 95% CI, 0.23-0.87; P = .02) or for complications of cirrhosis (24.2%) than in the placebo group (45.3%) (HR, 0.52; 95% CI, 0.28-0.95; P = .034). Child-Turcotte-Pugh and model for end-stage liver disease scores improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group. There were no adverse events related to VSL#3. CONCLUSIONS: Over a 6-month period, daily intake of VSL#3 significantly reduced the risk of hospitalization for HE, as well as Child-Turcotte-Pugh and model for end-stage liver disease scores, in patients with cirrhosis. ClinicalTrials.gov number: NCT01110447.

Persistence of cognitive impairment after resolution of overt hepatic encephalopathy.

OBJECTIVES: Hepatic encephalopathy (HE) represents a spectrum of neurocognitive impairment seen in cirrhotic patients and is considered to be fully reversible with treatment; however, recent evidence suggests otherwise. This longitudinal study was carried out to evaluate the persistence of cognitive impairment in cirrhotics with prior overt HE (OHE) episode despite treatment. METHODS: Of the 213 patients screened, 107 patients who met the eligibility criteria were enrolled and 102 patients completed the study (52 patients without prior OHE episode and 50 patients with prior OHE). All patients underwent psychometric hepatic encephalopathy score (PHES) evaluation at three separate visits (day 1, day 3, and between 30 and 60 days). A one-point improvement in PHES between the first and second evaluation was considered as a measure of learning. RESULTS: Patients with a previous OHE episode showed learning impairment in PHES on repetition on day 3 (P=0.084), whereas patients without a previous OHE episode demonstrated learning effect (P<0.0001) irrespective of whether they had minimal HE (MHE) or not. Univariate analysis demonstrated that Child-Turcotte-Pugh score, lactulose and/or rifaximin therapy, the presence of MHE, and a previous OHE episode were associated with learning impairment. Multivariate analysis demonstrated that only the presence of a previous episode of OHE (adjusted odds ratio 38.398; 95% confidence interval 9.192-160.4; P<0.0001) significantly affected learning. CONCLUSIONS: This study conclusively demonstrated learning impairment in cirrhotic patients with a previous episode of OHE despite normal mental status. Improvement in PHES on repetition may be a measure of learning.

Levels of hepatitis B virus replicative intermediate in serum samples of chronic hepatitis B patients.

Hepatitis B virus (HBV) cccDNA levels is an absolute marker of HBV replication in the liver of HBV infected patients. This study aimed to quantify the HBV cccDNA levels in sera and liver tissue samples of treatment naïve patients with chronic hepatitis B. Eighty one chronic hepatitis B (CHB) treatment naïve patients were enrolled from January 2009 to June 2011. Total HBV DNA and HBV cccDNA levels were quantified using sensitive real time PCR assay. The mean age of recruited patients was 34 ± 11.5 years. Fifty four (66.7%) patients were HBeAg negative. Liver tissue samples were available from 2 HBeAg positive and 21 HBeAg negative CHB patients. The amount of total intrahepatic HBV DNA ranged from 0.09 to 1508.92 copies/cell. The median intrahepatic HBV cccDNA was 0.31 and 0.20 copies/cell in HBeAg positive and HBeAg negative cases, respectively. Serum HBV cccDNA was detectable in 85.2 % HBeAg positive and 48.1% HBeAg negative CHB patients. Median serum HBV cccDNA was 46,000 and 26,350 copies/mL in HBeAg positive and HBeAg negative subjects, respectively. There was a significant positive correlation between the levels of intrahepatic total HBV DNA and intrahepatic HBV cccDNA (r = 0.533, p = 0.009). A positive correlation was also seen between serum HBV cccDNA levels and serum HBV DNA levels (r = 0.871, p < 0.001). It was concluded that serum HBV cccDNA could be detectable in higher proportion of HBeAg positive patients compared to HBeAg negative patients. Moreover, the median level of serum HBV cccDNA was significantly higher in HBeAg positive patients in contrast to HBeAg negative subjects.

A Study of Impact of Fixed-Dose Albumin Infusion on Outcome in Patients With Cirrhosis and Infection: A Randomized Open-label Clinical Trial.

Background and aim: Antibiotics and albumin infusion constitute the standard of treatment in patients with decompensated cirrhosis who have spontaneous bacterial peritonitis (SBP). Recent studies have also shown that the use of albumin in patients with advanced liver disease who have infections other than SBP leads to the resolution of acute and chronic liver failure and prevents the development of nosocomial infections. The recommended dose of albumin for these patients is out of reach for many in resource-limited settings like India. The evidence for this recommendation is also scarce. This study aimed to assess the efficacy of a lower dose of albumin infusion in addition to antibiotics on short-term mortality and morbidity in patients with cirrhosis and infections. Patients and methods: A prospective, open-label, randomized control study was performed. Consecutive patients with cirrhosis and infections were randomized in a 2:1 ratio into two groups: group A (116) and group B (58) patients. In addition to antibiotics and standard medical therapy, group A was given albumin in a dose of 20 g/day for five days, and group B was given the recommended dose (1.5 g/kg/body weight and 1 g/kg body weight on days one and three, respectively). The primary outcome was in-hospital mortality. Secondary outcomes were improvements in clinical and laboratory parameters. Results: Except for etiology, all the baseline clinical and laboratory variables in both groups were comparable. The in-hospital mortality in groups A and B was (11 [10.67%] vs. 6 [10.09%], (P = 0.965). The duration of hospitalization, 30-day mortality, improvement in shock and sensorium, and absolute improvements in serum creatinine, international normalized ratio (INR), and serum bilirubin were also comparable in both groups. Conclusion: Low-dose albumin infusion in patients with cirrhosis and infections can have the same results as standard-dose albumin and can be used in resource-limited situations. Clinical trial registration number: CTRI/2020/03/023794.

Expert consensus on the diagnosis and treatment of end-stage liver disease complicated by infections.

End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.

2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

Overexpression of microRNA-122 enhances in vitro hepatic differentiation of fetal liver-derived stem/progenitor cells.

MicroRNAs (miRNAs) are a versatile class of tiny non-coding RNAs involved in regulation of various biological processes. miRNA-122 (miR-122) is specifically and abundantly expressed in human liver. However, the role of miR-122 in differentiation of fetal liver stem/progenitor cells into hepatocytes remains unclear. In this study, dual positive CD34+/CD117+ expressing human fetal liver stem/progenitor cells was enriched by magnetic cell sorting and cultured in vitro. The level of miR-122 was found to be increased at specific time intervals. Interestingly, during the differentiation process of hepatocyte-like cells, the increase in expression of miR-122 was positively correlated with expression of hepatocyte-specific genes. The status of differentiation process was improved by transfection of miR-122 into enriched stem/progenitor cells. The expression level of hepatic-specific genes as well as liver-enriched transcription factors (LETFs) was significantly increased by overexpression of miR-122 in fetal liver stem/progenitor cells. Thus, the study delineated the role of hepato-specific miR-122 in differentiation of fetal liver stem/progenitor cells into hepatocyte-like cells which could be used as a therapeutic target molecule to generate abundant hepatocytes.

Hepatitis B virus reverse transcriptase mutations in treatment Naïve chronic hepatitis B patients.

Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome lead to decreased susceptibility to nucleos(t)ide analogs approved for treatment of HBV infection. The aim of this study was to detect and analyze pre-existing HBV RT mutations in treatment naïve patients with chronic hepatitis B. Seventy one chronic HBV treatment naïve patients were enrolled from January 2009 to June 2011. HBV RT sequence analysis was done by using direct bidirectional sequencing of semi-nested PCR products. HBV genotypes were determined by multiplex PCR. Genotype D was found in 64 patients (90.1%) followed by genotype C and A which were present in 5 (7.0%) and 2 (2.8%) patients respectively. The results of the RT sequence analysis showed mutations in 34 (47.9%) patients. The rtH248N mutation was the most common mutation, accounting for 47.1% patients. Other common mutations included rtD263E/S, rtM129L, rtF122L/V/I, rtS135Y/H, rtQ149K, rtL91I, rtH126R, rtC256S/G, rtY257W, rtS259T and rtE271D, which were present in 26.5% (9/34), 29.4% (10/34), 20.6% (7/34), 20.6% (7/34), 20.6% (7/34), 17.6% (6/34), 14.7% (5/34), 14.7% (5/34), 11.8% (4/34), 11.8% (4/34) and 11.8% (4/34) patients respectively. The known primary drug resistance mutations were found in 3 (8.8%) patients. The present study shows the presence of RT amino acid substitutions in treatment-naïve patients with chronic hepatitis B, which may decrease susceptibility to available oral antiviral drugs. On the basis of the finding of this study, genotypic testing is recommended before the start of therapy in naïve patients, so that suitable antiviral drugs can be prescribed.

Noradrenaline vs terlipressin in the treatment of type 2 hepatorenal syndrome: a randomized pilot study.

BACKGROUND: Various vasoconstrictors have shown promising results in the management of type 1 hepatorenal syndrome (HRS). However, there are very few studies on vasopressors in the management of type 2 HRS. Terlipressin has been used commonly; however, it is costly and not available in some countries. In this study, we evaluated the safety and efficacy of terlipressin and noradrenaline in the treatment of type 2 HRS. METHODS: Forty-six patients with type 2 HRS were managed with terlipressin (group A, N = 23) or noradrenaline (Group B, N = 23) with albumin in a randomized controlled trial at a tertiary centre. RESULTS: HRS reversal could be achieved in 17(73.9%) patients in group A as well as in group B (P = 1.0). Univariate analysis showed that the baseline model of end-stage liver disease score, urine output, urinary sodium, serum creatinine and mean arterial pressure were associated with response. However, in multivariate analysis only baseline serum creatinine, urine output and urinary sodium were associated with the response. Eight patients in group A and 9 in group B died within 90 days of follow-up (P > 0.05). Noradrenaline was less expensive than terlipressin (P < 0.05). No major adverse effects were seen. CONCLUSIONS: The results of this randomized study suggest that terlipressin and noradrenaline are safe and effective in the treatment of type 2 HRS and baseline serum creatinine, urine output and urinary sodium are predictive of response. Noradrenaline is less expensive than terlipressin in the treatment of type 2 HRS (ClinicalTrials.gov, Number NCT01637454).

Obstetric cholestasis: outcome with active management.

AIM: To study the nature and clinical outcome of pregnancies with obstetric cholestasis on active management and to correlate perinatal outcome to gestational age at delivery. MATERIAL AND METHODS: This prospective randomized study included 69 women with obstetric cholestasis. Fetal surveillance began at 34 weeks or later at diagnosis and included daily maternal record of fetal movements, and biophysical profile (i.e. non stress test, the four quadrant amniotic fluid index). Fetal monitoring was conducted weekly before 36 weeks and biweekly after that. Randomization into two groups was done where one group was planned for delivery at 37 weeks whereas in the other group, pregnancy was carried to 38 weeks under surveillance. The primary outcome variable was correlation of fetal and neonatal complication rates to gestational age at delivery. RESULTS: There were no stillbirths in the study. No episode of fetal asphyxia or bradycardia was observed. The overall rate of meconium passage was 7.46% (5/67). However, there was no case of meconium aspiration syndrome. Women delivering at or after 38 weeks had a lower incidence of cesarean section (17.85% vs 25.8%), neonatal nursery admission (17.85% vs 22.5%), and neonatal jaundice (17.85% vs 19.35%) compared to those delivering at 37 weeks. The differences between the two groups were, however, not found to be statistically significant. CONCLUSION: The current study demonstrates that with active intervention, pregnancies with obstetric cholestasis can be carried to a later gestation under surveillance.

Preventive hepatology: An ounce of prevention or pounds of cure to curb liver diseases.

Liver diseases are now the leading cause of both morbidity and mortality profile globally with rising trends due to unhealthy lifestyle. Most of the liver diseases are preventable. Scientific evidences have well supported and documented that almost 90 percent of all major liver diseases are either the manifestations of asymptomatic hepatitis virus infections or poor lifestyle choices leading to accumulation of fat in liver that could be detected even before they present themselves as chronic liver diseases. Understanding liver diseases as a preventable disease and practising necessary preventive measures will help in lowering the risks of various types of liver diseases as well as liver cancer.