Pankaj Puri

Non‐cirrhotic portal fibrosis (idiopathic portal hypertension): Experience with 151 patients and a review of the literature

Background: Non‐cirrhotic portal fibrosis (NCPF), the equivalent of idiopathic portal hypertension in Japan and hepatoportal sclerosis in the United States of America, is a common cause of portal hypertension in India. The clinical features, portographic and histological findings, and management of 151 patients with non‐cirrhotic portal fibrosis are presented.

Biliary changes in extrahepatic portal venous obstruction: Compression by collaterals or ischemic?

BACKGROUND The postulated mechanisms of biliary abnormalities in extrahepatic portal venous obstruction (EHPVO) are either extrinsic compression by collaterals or ischemic injury due to venous thrombosis. If the former hypothesis is correct, then biliary changes should revert to normal after portasystemic shunt surgery. METHODS Five patients with EHPVO who underwent portasystemic shunt surgery were studied. One of these patients had obstructive jaundice due to portal cavernoma. Endoscopic retrograde cholangiography (ERC) was performed before as well as after the shunt surgery. Doppler ultrasound and splenoportovenography were obtained to confirm the diagnosis of EHPVO as well as shunt patency. RESULTS All patients had biliary abnormalities on pre-shunt ERC. The post-shunt ERC showed partial reversal of biliary abnormalities in 3 patients, complete reversal in 1 patient, and no reversal in 1 patient. Smooth strictures opened after shunt surgery and proximal dilatation disappeared in most patients. The indentations and caliber irregularities disappeared after shunt surgery, whereas angulations and ectasias of biliary ducts persisted. CONCLUSION Shunt surgery results in regression of some of the biliary abnormalities and relieves biliary obstruction, suggesting that mechanical compression by collaterals is the mechanism behind biliary abnormalities in EHPVO. However, some biliary changes persist after shunt surgery signifying fixed obstruction due to ischemia or fibrous scarring. Thus, the two theories are not mutually exclusive.

Jaundice in malaria

Jaundice is not an unusual accompaniment of malaria. It can occur due to intravascular hemolysis, disseminated intravascular coagulation, and, rarely, ‘malarial hepatitis’. Although the primary schizogony of the malarial parasite always leads to the rupture of the infected hepatocyte, alteration of the hepatic functions is uncommonly recorded due to this event. Histologically, the hepatitis or the actual inflammation in the liver has never been demonstrated. Nonetheless, the term ‘malarial hepatitis’ (MH) has been used in the literature to describe the occurrence of hepatocellular jaundice in patients with Plasmodium falciparum infection. The authors’ own data and review of the literature indicate that it is not an uncommon entity. In endemic areas, jaundice is seen in approximately 2.5% of patients with falciparum malaria. It also appears to be a heterogeneous syndrome and one can recognize two clinical subsets. In one group there was an acute, virulent presentation with coma, renal failure and in some cases even hemorrhagic manifestations. It is only in this setting that jaundice signified a ‘severe’ disease as noted by the World Health Organization action program. This presentation is often confused with acute viral hepatitis and acute hepatic failure in non‐endemic areas, but can be clinically differentiated.

Tackling the Hepatitis B Disease Burden in India

Globally, approximately 240 people have been infected worldwide with hepatitis B Virus (HBV). India has approximately HBV carrier rate of 3.0% with a high prevalence rate in the tribal population. With a population of more than 1.25 billion, India has more than 37 million HBV carriers and contributes a large proportion of this HBV burden. While horizontal transmission in childhood appears to be a major route of transmission, the role of vertical transmission is probably underestimated. Blood transfusion and unsafe therapeutic injections continue to be important modes of transmission of HBV. There is a need for large field studies to better understand HBV epidemiology and identify high prevalence areas, and public health measures to prevent disease transmission and decrease the burden of the disease.

Consensus Statement of HCV Task Force of the Indian National Association for Study of the Liver (INASL). Part I: Status Report of HCV Infection in India

Globally, around 150 million people are infected with hepatitis C virus (HCV). India contributes a large proportion of this HCV burden. The prevalence of HCV infection in India is estimated at between 0.5% and 1.5%. It is higher in the northeastern part, tribal populations and Punjab, areas which may represent HCV hotspots, and is lower in western and eastern parts of the country. The predominant modes of HCV transmission in India are blood transfusion and unsafe therapeutic injections. There is a need for large field studies to better understand HCV epidemiology and identify high-prevalence areas, and to identify and spread awareness about the modes of transmission of this infection in an attempt to prevent disease transmission.

Portal Cavernoma Cholangiopathy: Consensus Statement of a Working Party of the Indian National Association for Study of the Liver

Portal cavernoma cholangiopathy (PCC) is defined as abnormalities in the extrahepatic biliary system including the cystic duct and gallbladder with or without abnormalities in the 1st and 2nd generation biliary ducts in a patient with portal cavernoma. Presence of a portal cavernoma, typical cholangiographic changes on endoscopic or magnetic resonance cholangiography and the absence of other causes of these biliary changes like bile duct injury, primary sclerosing cholangitis, cholangiocarcinoma etc are mandatory to arrive a diagnosis. Compression by porto-portal collateral veins involving the paracholedochal and epicholedochal venous plexuses and cholecystic veins and ischemic insult due to deficient portal blood supply or prolonged compression by collaterals bring about biliary changes. While the former are reversible after porto-systemic shunt surgery, the latter are not. Majority of the patients with PCC are asymptomatic and approximately 21% are symptomatic. Symptoms in PCC could be in the form of long standing jaundice due to chronic cholestasis, or biliary pain with or without cholangitis due to biliary stones. Endoscopic retrograde cholangiography has no diagnostic role because it is invasive and is associated with risk of complications, hence it is reserved for therapeutic procedures. Magnetic resonance cholangiography and portovenography is a noninvasive and comprehensive imaging technique, and is the modality of choice for mapping of the biliary and vascular abnormalities in these patients. PCC is a progressive condition and symptoms develop late in the course of portal hypertension only in patients with severe or advanced changes of cholangiopathy. Asymptomatic patients with PCC do not require any treatment. Treatment of symptomatic PCC can be approached in a phased manner, coping first with biliary clearance by nasobiliary or biliary stent placement for acute cholangitis and endoscopic biliary sphincterotomy for biliary stone removal; second, with portal decompression by creating portosystemic shunt; and third, with persistent biliary obstruction by performing second-stage biliary drainage surgery such as hepaticojejunostomy or choledochoduodenostomy. Patients with symptomatic PCC have good prognosis after successful endoscopic biliary drainage and after successful shunt surgery.

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment

BACKGROUND Antituberculosis treatment (ATT) induced hepato-toxicity is common, but risk factors predicting its development are poorly understood. The present study evaluates the clinical risk factors predicting the development of hepatotoxicity in Indian patients with tuberculosis on antituberculosis treatment. METHODS Three groups of patients were studied at three service hospitals over a 3 year period from 2000-2002. Patients given ATT were followed up with monthly LFTs. Consecutive patients who developed Liver dysfunction (rise in SGPT > 5 times upper limit of normal) were studied, along with matched controls who did not. Markers for hepatitis B were also noted in these patients once in 6 months. A third group of patients who did not receive ATT but were HBsAg positive, were also similarly followed up. The possible association of age and sex of the patient, alcoholism, unrecognized chronic liver disease, hepatitis B virus carrier status and nutritional status with ATT-induced hepatitis was assessed. Statistical analysis was carried out by Chi square test/Fishers exact test using WHO provided software Epi Info 6. Sixty-nine patients with ATT-induced hepatotoxicity were prospectively studied. In addition 128 patients on anti-tuberculosis drugs without hepatotoxicity and 39 HBsAg carriers not on ATT were followed up for 1 year. RESULTS Age, Sex, history of alcohol intake and BMI were not found to be related to development of hepatotoxicity. Presence of HBV infection or an underlying silent chronic liver disease were found to significantly increase the risk of development of ATT-induced hepatotoxicity. Continuation of ATT after development of jaundice was associated with a high fatality rate. It was possible to re-introduce isoniazid in 96% and rifampicin in 88% of patients with ATT induced hepatotoxicity. CONCLUSION ATT-induced hepatitis is common and is potentially fatal. It is likely to occur in those with underlying silent chronic liver disease, HBV infection and have been given ATT without a definite evidence of tuberculosis. Discontinuation of ATT leads to rapid recovery in most cases and drugs can safely be introduced after recovery in a majority of cases.

Comparative evaluation of nasoenteral feeding and jejunostomy feeding in acute corrosive injury: a retrospective analysis

BACKGROUND Nutritional support in corrosive injury patients is traditionally achieved through total parenteral nutrition (TPN) or jejunostomy feeding (JF). There are no reports of nasoenteral tube feeding in patients with corrosive ingestion. OBJECTIVE We report our experience with nasoenteral tube feeding (NETF) and compare the outcome of these patients with those undergoing JF. SETTING Tertiary medical center in North India. DESIGN AND INTERVENTION The records of 53 and 43 patients with severe acute corrosive injury who underwent NETF and JF, respectively, were reviewed. All had received a 50-kcal/kg, 2-g/kg protein homogenized liquid diet for 8 weeks. A contrast study was performed at 8 weeks, and body weight and serum albumin levels were recorded at hospitalization and at 8 weeks. MAIN OUTCOME MEASUREMENTS Change in weight and serum albumin at 8 weeks and stricture development rate. RESULTS Strictures developed in 41 (80.39%) and 36 (83.72%) patients in the NETF and JF groups, respectively. Development of esophageal stricture (P = .71) and gastric stenosis (P = .89) was comparable in the 2 groups. No significant changes in serum albumin and weight were noted at 8 weeks in either group. The complication rate was lower in the NETF group compared with the JF group. Although all of the patients in the NETF group had a patent lumen, 5 in the JF group had total obstruction precluding endoscopic intervention. LIMITATIONS Retrospective study design. CONCLUSION NETF is as effective as JF in maintaining nutrition in patients with severe corrosive injury. The stricture development rate is similar, but nasoenteral tube placement provides a lumen for dilatation should a tight stricture develop.

Autophagy Modulation As a Potential Therapeutic Target for Liver Diseases

Autophagy is a critical intracellular pathway which maintains cellular function by lysosomal degradation of damaged proteins and organelles besides elimination of invading pathogens. Its primary function is to prevent cell death. Autophagy has diverse physiological functions namely; starvation adaptation, prevention of tumorigenesis, energy homeostasis, intracellular quality control and degradation of abnormal intracellular protein aggregates. Understanding the molecular mechanisms of autophagy has given key insights into the pathogenesis of various diseases like Non Alcoholic Steato-Hepatitis, Hepatitis B and C infections, Alpha-1 antitrypsin deficiency and hepatocellular carcinoma. Pharmacological modulation of autophagy may have a therapeutic potential in management of these liver diseases.

First prospective study on brain stem death and attitudes toward organ donation in India.

Organ donation following brain stem death is infrequent in India. There is no prospective study on prevalence of brain stem death and causes of non‐donation. Consecutive patients admitted to intensive care unit from Sep 2006 to Sep 2008 were studied prospectively. Families of those with brain stem death were approached for organ donation by transplant coordinator. Extensive awareness drive was launched. Reasons for non‐donation, if any, were documented. Of 2820 patients admitted, 994 (35%) were on mechanical ventilator and 657 (23%) died. Brain stem death could be diagnosed in 55, 37 males, median age 46 years (range 7 to 87 years) i.e., 1.9% of all admissions and 8.3% of all deaths. Among neurology and neurosurgery patients brain stem death was seen in 45 of 1037 (4.3%) admissions and 45 of 161 (27.9%) deaths. Complications of brain stem death were hypotension in 49, diabetes insipidus in 17 and hypertension in 5 patients. Of 33 families counselled, 16(48%) consented to organ donation. In 14(42%), organs and tissues retrieved and transplanted included 13 livers, 23 kidneys, 25 corneas and 5 cardiac valves. Consent was more likely in females (10 of 14 as compared to 6 of 19 males, p = 0.037). Consent did not correlate with age of donor or medico‐legal issues (p = 0.227 & 0.579 respectively). Trained staff with requisite systems in place produced significant organ donation rates. Religious issues and medico legal concerns were not a major hurdle towards organ donation. Female patients with brain stem were more likely to become organ donors. Liver Transpl 15:1443–1447, 2009.