Kaushal Madan

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL)

The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on acute-on-chronic liver failure (ACLF) in 2004, with a mandate to develop consensus guidelines on various aspects of ACLF relevant to disease patterns and clinical practice in the Asia-Pacific region. Experts predominantly from the Asia–Pacific region constituted this working party and were requested to identify different issues of ACLF and develop the consensus guidelines. A 2-day meeting of the working party was held on January 22–23, 2008, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and subsequently presented at the Annual Conference of the APASL at Seoul, Korea, in March 2008. The consensus statements along with relevant background information are presented in this review.

Association of extent and infection of pancreatic necrosis with organ failure and death in acute necrotizing pancreatitis

BACKGROUND & AIMS Organ failure is the usual cause of death in acute necrotizing pancreatitis. Our objective was to study whether the extent and infection of pancreatic necrosis correlate with organ failure and mortality. METHODS All consecutive patients with acute pancreatitis were prospectively studied. They underwent a detailed clinical and investigative evaluation. Pancreatic necrosis, diagnosed on a computed tomography scan, was graded as <30%, 30%-50%, and >50% necrosis and characterized as either sterile or infected. Logistic regression analysis was done to find out the association of the extent and infection of pancreatic necrosis with organ failure and mortality. RESULTS Of 276 patients (mean age, 41.25 years; 172 men), 104 had pancreatic necrosis: 30 had <30% necrosis, 37 had 30%-50% necrosis, and 37 had >50% necrosis; 74 had sterile necrosis, and 30 had infected necrosis. Of them, 37 (35%) patients developed organ failure. Two significant factors were associated with the development of organ failure, the extent of necrosis (<30% necrosis vs 30%-50% necrosis: P = .03; odds ratio [OR], 5.82; 95% confidence interval [CI], 1.15-29.45; <30% necrosis vs >50% necrosis: P = .0004; OR, 18.86; 95% CI, 3.75-94.92) and infected pancreatic necrosis (P = .02; OR, 3.29; 95% CI, 1.17-9.24). The overall mortality was 22%. Infected pancreatic necrosis (P = .006; OR, 4.99; 95% CI, 1.56-16.02) and Acute Physiology, Age, and Chronic Healthy Evaluation II score (P = .004; OR, 1.28; 95% CI, 1.08-1.52) were 2 independent predictors of mortality. CONCLUSIONS Extent of necrosis and infected pancreatic necrosis were associated with the development of organ failure in patients with acute necrotizing pancreatitis. Infected pancreatic necrosis was the most significant predictor of mortality.

Viral hepatitis in India

Viral hepatitis is a major public health problem in India, which is hyperendemic for HAV and HEV. Seroprevalence studies reveal that 90%-100% of the population acquires anti-HAV antibody and becomes immune by adolescence. Many epidemics of HEV have been reported from India. HAV related liver disease is uncommon in India and occurs mainly in children. HEV is also the major cause of sporadic adult acute viral hepatitis and ALF. Pregnant women and patients with CLD constitute the high risk groups to contract HEV infection, and HEV-induced mortality among them is substantial, which underlines the need for preventive measures for such groups. Children with HAV and HEV coinfection are prone to develop ALF. India has intermediate HBV endemicity, with a carrier frequency of 2%-4%. HBV is the major cause of CLD and HCC. Chronic HBV infection in India is acquired in childhood, presumably before 5 years of age, through horizontal transmission. Vertical transmission of HBV in India is considered to be infrequent. Inclusion of HBV vaccination in the expanded programme of immunization is essential to reduce the HBV carrier frequency and disease burden. HBV genotypes A and D are prevalent in India, which are similar to the HBV genotypes in the West. HCV infection in India has a population prevalence of around 1%, and occurs predominantly through transfusion and the use of unsterile glass syringes. HCV genotypes 3 and 2 are prevalent in 60%-80% of the population and they respond well to a combination of interferon and ribavirin. About 10%-15% of CLD and HCC are associated with HCV infection in India. HCV infection is also a major cause of post-transfusion hepatitis. HDV infection is infrequent in India and is present about 5%-10% of patients with HBV-related liver disease. HCC appears to be less common in India than would be expected from the prevalence rates of HBV and HCV. The high disease burden of viral hepatitis and related CLD in India, calls for the setting up of a hepatitis registry and formulation of government-supported prevention and control strategies.

Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD).

Background One of the major pathogenic mechanisms for progression of nonalcoholic fatty liver disease (NAFLD) is oxidative stress. Recently, many studies have demonstrated the role of oxidative stress in NAFLD however, studies describing the antioxidant status in these patients are lacking. Aim To study the levels of oxidative stress and antioxidant status among patients with NAFLD. Patients and Methods It was a prospective study in which 29 patients with NAFLD, 25 diseased controls with chronic viral hepatitis, and 23 healthy controls were enrolled. Apart from standard biochemical parameters, lipid peroxidation products were measured as thiobarbituric acid reactive substances. As measures of antioxidant capacity, superoxide dismutase, vitamin C levels and ferric reducing ability of plasma were measured. Results Level of thiobarbituric acid reactive substances was significantly higher among NAFLD patients as compared with diseased [4.7 nmol/mL (1.0 to 10.2) vs. 2.4 nmol/mL (0.8 to 10.7); P=0.02] or healthy controls [4.7 nmol/mL (1.0 to 10.2) vs. 1.8 nmol/mL (0.5 to 4.1); P=0.0001]. FRAP was found to be significantly higher in patients with NAFLD as compared with healthy controls [450.3 (197.6 to 733.3) vs. 340.8 (141.6 to 697.5) μmol Fe2+ liberated; P=0.04], even though it was similar between NAFLD and diseased controls. Among NAFLD patients, there was no significant correlation between histological grading or staging and levels of pro and antioxidants. Conclusions Products of lipid peroxidation are significantly increased among patients with NAFLD as compared with chronic viral hepatitis or healthy controls. Larger studies and newer markers of oxidative stress are required to clarify the association between oxidative stress and histological severity in NAFLD.

Minimal hepatic encephalopathy: Consensus statement of a working party of the Indian National Association for Study of the Liver

Hepatic encephalopathy (HE) is a major complication that develops in some form and at some stage in a majority of patients with liver cirrhosis. Overt HE occurs in approximately 30–45% of cirrhotic patients. Minimal HE (MHE), the mildest form of HE, is characterized by subtle motor and cognitive deficits and impairs health‐related quality of life. The Indian National Association for Study of the Liver (INASL) set up a Working Party on MHE in 2008 with a mandate to develop consensus guidelines on various aspects of MHE relevant to clinical practice. Questions related to the definition of MHE, its prevalence, diagnosis, clinical characteristics, pathogenesis, natural history and treatment were addressed by the members of the Working Party.

Primary Conservative Treatment Results in Mortality Comparable to Surgery in Patients With Infected Pancreatic Necrosis

BACKGROUND & AIMS The standard treatment for patients with infected pancreatic necrosis (IPN) is surgical necrosectomy. We compared the outcomes of surgical treatment versus primary conservative treatment (patients kept in intensive care unit and treated with antibiotics, organ support, intensive nutritional support, and, if required, percutaneous drainage) among patients with IPN. METHODS We performed retrospective comparative (with prospectively acquired database) and prospective observational studies; data were collected from all consecutive patients with acute pancreatitis (n = 804), and those with IPN formed the study group. Patients with IPN were divided into 2 groups on the basis of diagnosis of IPN during 1997-2002 (group 1, n = 30) or 2003-2006 (group 2, n = 50). Eighteen patients in group 1 were treated by surgical necrosectomy, and 40 patients in group 2 were given primary conservative treatment; surgery was performed on patients if conservative treatment failed (n = 10). The primary outcome measure was mortality. RESULTS The mortality was comparable in group 1 versus group 2 (43% vs 28%; P = .22). During a period of 10 years, the patients who received primary conservative treatment had significantly higher survival rates than those who received surgery (76.9% vs 46.4%; P = .005). In the prospective study during 2007-2008, the mortality from infected necrosis was 29.6% after primary conservative treatment, confirming the results of the comparative study. CONCLUSIONS In treating patients with IPN, a primary conservative strategy resulted in mortality that was comparable with that after surgery, and 76% of the patients were able to avoid surgery; 54.5% of IPN patients were successfully managed with the primary conservative strategy.

Evaluating Patients with Cirrhosis for Hepatocellular Carcinoma : Value of Clinical Symptomatology, Imaging and Alpha-Fetoprotein

Objective: This study was undertaken to assess the value of clinical symptomatology, abdominal ultrasound (US), triple-phase CT (TPCT) and serum alpha-fetoprotein (AFP) estimation in predicting presence of hepatocellular carcinoma (HCC) among patients with cirrhosis. Materials and Methods: In this cross-sectional study, Child’s A/B cirrhosis patients were subjected to clinical evaluation, US, TPCT and serum AFP estimation. Sensitivity and specificity of clinical symptoms and of AFP at different cut-off levels were determined. Detection rate of HCC and agreement between US and TPCT was estimated. Results: A high proportion of enrolled subjects had HCC at first presentation (40.7%). Significantly higher prevalence of abdominal pain, weight loss, and anorexia was seen in patients with cirrhosis with HCC compared to those without HCC. Sensitivity and specificity of any of these symptoms was 73 and 79%, respectively (positive and negative predictive values of 65 and 85%, respectively). A 100% agreement between TPCT and US was observed for diagnosing HCC cases. However, TPCT detected a greater number of smaller HCCs. Sensitivity of AFP at 400 ng/ml cut-off was only 25.7%, too low to be useful. Best mix of sensitivity (77.2%) and specificity (78.1%) of AFP was found to be at 10.7 ng/ml cut-off which falls within the conventional limits of normalcy. Conclusion: The study highlights the importance of symptomatology of weight loss, abdominal pain or anorexia as markers for HCC in patients with cirrhosis. AFP was not found to be a useful screening test. TPCT should be undertaken in all cirrhotics presenting to the hospital for the first time.

Impact of 24-h esophageal pH monitoring on the diagnosis of gastroesophageal reflux disease: Defining the gold standard

Background and Aims:  The tests that are currently available for the diagnosis of gastroesophageal reflux disease (GERD) lack the desired diagnostic accuracy. To date, only pH monitoring has been shown to have a good sensitivity and specificity, but recent studies have failed to confirm this. Thus there is a need to find a test with acceptable sensitivity and specificity for diagnosing GERD. The present study aimed to find a single test or a combination of tests that could serve as a gold standard for the diagnosis of GERD and to identify an evidence‐based diagnostic work‐up for GERD in clinical and research settings.

Prevalence, severity, and risk factors of symptomatic gastroesophageal reflux disease among employees of a large hospital in Northern India

Background and aimsGastroesophageal reflux disease (GERD) is considered to be a common and chronic gastrointestinal disorder. The prevalence of GERD is believed to be less in Asia than in Western countries. Population-based data on GERD are lacking from India. The present study aimed at determining the prevalence of GERD symptoms in an adult Indian community and the potential risk factors associated with GERD.MethodsThe study population consisted of all the employees of All India Institute of Medical Sciences, New Delhi. An interview-based observational study was done on the basis of an earlier validated questionnaire. The subjects were asked about the frequency and severity of heartburn and/or regurgitation experienced by them in the previous year. These symptoms were then scored from 0 to 18. Subjects with a score of at least 4 were considered to have symptomatic GERD. Association of GERD with factors like age, sex, BMI, Kuppuswamy social class index, smoking, alcohol, NSAID use, and comorbid illness was analyzed.ResultsA total of 4079 employees were interviewed in person on a 29-item questionnaire from June 2003 to January 2005. Of the 4039 eligible subjects, 653 (16.2%) had GERD; 3.6% had heartburn on daily basis and 5.9% on a weekly basis. The corresponding prevalences for regurgitation were 3.3% and 5.0%, respectively. One hundred and eight of 4039 (2.7%) had severe GERD symptoms. Higher BMI (OR = 1.90, 95% CI: 1.4–2.6 for BMI ≥ 25), current smoking (OR = 1.48, 95% CI: 1.19–1.83), asthma (OR = 3.13, CI: 2.06–4.76) and hypertension (OR = 1.71, 95% CI: 1.16–2.50) were associated with the presence of GERD symptoms.ConclusionsPrevalence of GERD in an urban adult population from northern India is 16.2% which is similar to other industrialized countries. Higher body mass index, current smoking, and presence of asthma or hypertension predisposes to GERD in our population.

Hemorrhage in acute pancreatitis: should gastrointestinal bleeding be considered an organ failure?

Objective: To define the magnitude, causes, risk factors, and consequences of hemorrhage in acute pancreatitis (AP). Methods: Consecutive patients with AP were studied for hemorrhagic complication and its impact on mortality. Patients with gastrointestinal (GI) hemorrhage or hemorrhage within the pancreatic bed were managed with transfusions, endotherapy, angiographic embolization, or surgery as appropriate. Results: Of 449 patients, 28 (6.2%) developed hemorrhage. The mean age of patients with hemorrhage was 39 ± 14 years and 25 (89%) were men. Of the 28 patients, 16 had GI hemorrhage, and 12 had hemorrhage into the pancreatic bed. Median interval between the onset of AP and hemorrhage was 26.5 days. Pancreatic necrosis, sepsis, fluid collection, and organ failure were found to be risk factors for hemorrhage. Five patients had pseudoaneurysms; angiographic embolization was successful in 4 of them. The mortality rate in bleeders was higher than that in nonbleeders (28.6% vs 13%; P = 0.02). None of the patients died as a direct consequence of hemorrhage except 1 patient who died after surgery for failed embolization of bleeding pseudoaneurysm. Deaths were mainly caused by sepsis and multiorgan failure. Conclusions: Hemorrhagic complications are usually late manifestations in the course of severe pancreatitis and per se have little bearing on mortality.