Global burden of liver disease: 2023 update.

Liver disease accounts for two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and non-alcoholic fatty liver disease. Hepatotropic viruses are the aetiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.

Primary Intestinal Lymphoma: Clinicopathological Characteristics of 55 Patients.

INTRODUCTION: Gastrointestinal (GI) tract is the most common site of extranodal lymphoma accounting for 30-40% of the cases. In Western countries, stomach is the most common site of GI lymphoma, whereas in the Middle East and Mediterranean countries, small intestine is commonly involved. Studies about primary intestinal lymphoma (PIL) are heterogeneous in anatomical distribution, presentation, and histological subtypes. The present study was aimed at studying the anatomical distribution, histological subtypes, and clinical characteristics at tertiary care centers. MATERIALS AND METHODS: The present study was retrospective, conducted between 2006 and 2020. Patient's data were collected from institutional medical records. PIL was diagnosed by Lewin's criteria. After histological diagnosis, PIL was classified as per the World Health Organization (WHO) criteria and staging was done according to the Ann Arbor classification as modified by Musshoff. RESULTS: A total of 941 lymphoma cases were diagnosed during the study period between 2006 and 2020 consisting of 238 Hodgkin's lymphoma and 703 non-Hodgkin's lymphoma (NHL) cases. PIL constituted 5.8% of all lymphoma cases (55 out of 941) and 50.9% (55 of 108) of all primary GI lymphoma. Median age at diagnosis was 44 years and comprised predominantly males (85.45%). Diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma were the most common histological subtype (78%) seen. Two patients with primary Hodgkin's lymphoma involving the intestine were seen. T-cell lymphoma was seen in three (5.4%) patients. Ileocecal region was the most common site involved (27%). The common presenting complaints were intestinal obstruction (40%) requiring surgical resection and abdominal pain (32%). Majority of the patients presented in the early stages (I and II). CONCLUSION: Our study demonstrates the pattern of distribution and various histological subtypes of PIL including the rare variants like primary intestinal Hodgkin's lymphoma. Relatively more number of patients presented with intestinal obstruction requiring surgery in comparison with other studies. HOW TO CITE THIS ARTICLE: Malipatel R, Patil M, Rout P, et al. Primary Intestinal Lymphoma: Clinicopathological Characteristics of 55 Patients. Euroasian J Hepato-Gastroenterol 2021;11(2):71-75.

Lessons of the month: Massive gastrointestinal bleeding in a young woman with idiopathic thrombocytopenic purpura (ITP).

Cytomegalovirus (CMV) is a ubiquitous pathogen, belongs to the herpes virus family and can infect the gastrointestinal (GI) system. The disease is usually noted in immunocompromised patients such as solid organ transplant recipients on immunosuppressive drugs, patients with malignancy receiving chemotherapy, patients with AIDS, patients on steroids for autoimmune disorders, and is rarely seen in immunocompetent individuals. In the GI system, CMV most commonly involves the colon, followed by oesophagus, stomach and, rarely, the small intestine. The GI manifestation of CMV infection is usually anorexia, diarrhoea, and blood in stools, abdominal pain and fever. Very rarely, CMV infection may present with a massive GI bleed. We report a case of 36-year-old pregnant woman with idiopathic thrombocytopenic purpura (ITP) who presented with massive GI bleeding following delivery, attributed to isolated CMV enteritis.

Plummer-Vinson syndrome: A decade's experience of 132 cases from a single center.

BACKGROUND AND AIM: Plummer-Vinson syndrome (PVS) comprises triad of iron deficiency anemia, dysphagia, and post-cricoid esophageal web. PVS is rare nowadays due to improved nutritional status. However, we encountered patients with PVS regularly at our center. Data regarding PVS are limited; hence, we aimed to study the clinical features, treatment outcomes, and development of complications in patients with PVS. METHODS: The study was conducted over a 10-year period (January 2008 to January 2018) in a medical college setting. All adults with dysphagia, anemia, and post-cricoid web or those with iron deficiency anemia and post-cricoids web were included in the study. Patients were treated with iron supplementation and Savary-Gilliard bougie dilation of the web. Patients were followed-up for the recurrence of dysphagia and development of complications. RESULTS: Overall, 153 patients exhibited esophageal web, of which 132 (86.27%) patients had concomitant PVS and 21 (13.7%) patients did not. The mean age was 43.50 years (range 16-76) and 113 (85.6%) were women. Single session of Savary-Gilliard bougie dilation was successful in 90.7% of patients in relieving dysphagia and 9.3% developed recurrence, requiring repeated dilations. Four patients had concomitant squamous cell carcinoma of esophagus along with PVS and two developed upper gastrointestinal malignancy during follow-up. CONCLUSION: Plummer-Vinson syndrome is predominantly seen in middle aged women and present with symptoms of iron deficiency anemia and early grade dysphagia. Single session of Savary-Gilliard bougie dilation was successful in majority of patients in relieving dysphagia. Overall risk of developing upper gastrointestinal malignancy was 4.5%.

Lessons of the month 1: Cardiac tamponade: don't forget the pancreas.

Cardiac tamponade is a medical emergency, caused by rapid accumulation of fluid in the pericardium resulting in reduced ventricular filling which may result in pulmonary oedema, shock and death. The common causes of cardiac tamponade include malignancy, uraemia, infectious/idiopathic pericarditis, connective tissue diseases, post-cardiac surgery etc. Early recognition and treatment of the underlying cause of the tamponade along with pericardiocentesis improves the prognosis, otherwise untreated cardiac tamponade universally results in death. We report a rare case of 32-year-old man, who presented with cardiac tamponade due to a pancreatico-pericardial fistula secondary to pancreatitis and was successfully treated by endoscopic therapy.

Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure.

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors.

Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.

Wilson Disease Presenting With Acute on Chronic Liver Failure: A Single-Center Experience of Outcome and Predictors of Mortality in 68 Patients.

BACKGROUND AND AIMS: Acute on chronic liver failure (ACLF) is an emerging entity whose unique pathogenesis, presentation, and outcome are different from those with decompensated cirrhosis. Patients with Wilson disease (WD) often present with ACLF. The outcome in this setting and predictors of mortality have not been well delineated. We describe the clinical features, laboratory characteristics, and prognostic factors in patients with WD with ACLF. We compared the outcome in those without criteria for ACLF. PATIENTS AND METHODS: We analyzed the admission characteristics of 68 patients with WD presenting with features of ACLF among a cohort of WD patients from 1997 to 2017. WD was diagnosed as per European association for the study of the liver (EASL)/Leipzig criteria and ACLF by the Asia-Pacific Association of Study of Liver and World Gastroenterology Organization consensus criteria. Factors associated with mortality were analyzed by univariate followed by multivariate analysis and receiver operating characteristic curve. RESULTS: Of the 272 patients with WD, 68 fulfilled criteria for ACLF. The mean age was 14.4 years (Range 5-42 years). Males constituted 38/68 (56%). Acute viral or drug induced hepatitis as precipitating factors was seen in 11.7%. Forty-nine patients (49/67; 73%) died including 30/32 (93.8%) with encephalopathy and 45/62 (72.6%) with ascites. Prognostic factors on univariate analysis significant for mortality included encephalopathy, international normalized ratio, white blood cell count and model for end-stage liver disease (MELD) score. On multivariate analysis, only encephalopathy was significant with 82% accuracy in differentiating survivors versus non-survivors. Post mortem liver biopsy in 21 patients and explant biopsy in 2 patients showed features of cirrhosis in all. CONCLUSIONS: WD with ACLF is associated with a high mortality Precipitating factors such as viral and drug-induced hepatitis was seen in 11.7% patients. Liver histology in patients subjected to biopsy showed cirrhosis in all. Only encephalopathy is a prognostic marker of non-survival with an accuracy of 82%.

Drug-induced liver injury.

Drug-induced liver injury (DILI) is an adverse reaction to drugs or other xenobiotics that occurs either as a predictable event when an individual is exposed to toxic doses of some compounds or as an unpredictable event with many drugs in common use. Drugs can be harmful to the liver in susceptible individuals owing to genetic and environmental risk factors. These risk factors modify hepatic metabolism and excretion of the DILI-causative agent leading to cellular stress, cell death, activation of an adaptive immune response and a failure to adapt, with progression to overt liver injury. Idiosyncratic DILI is a relative rare hepatic disorder but can be severe and, in some cases, fatal, presenting with a variety of phenotypes, which mimic other hepatic diseases. The diagnosis of DILI relies on the exclusion of other aetiologies of liver disease as specific biomarkers are still lacking. Clinical scales such as CIOMS/RUCAM can support the diagnostic process but need refinement. A number of clinical variables, validated in prospective cohorts, can be used to predict a more severe DILI outcome. Although no pharmacological therapy has been adequately tested in randomized clinical trials, corticosteroids can be useful, particularly in the emergent form of DILI related to immune-checkpoint inhibitors in patients with cancer.

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.

Wilson's Disease: Clinical Practice Guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India.

Clinical practice guidelines for Wilson's disease (WD) have been published by the American Association for the Study of Liver Diseases and European Association for the Study of the Liver in 2008 and 2012, respectively. Their focus was on the hepatic aspects of the disease. Recently, a position paper on pediatric WD was published by the European Society of Pediatric Gastroenterology Hepatology and Nutrition. A need was felt to harmonize guidelines for the hepatic, pediatric, and neurological aspects of the disease and contextualize them to the resource-constrained settings. Therefore, experts from national societies from India representing 3 disciplines, hepatology (Indian National Association for Study of the Liver), pediatric hepatology (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition), and neurology (Movement Disorders Society of India) got together to evolve fresh guidelines. A literature search on retrospective and prospective studies of WD using MEDLINE (PubMed) was performed. Members voted on each recommendation, using the nominal voting technique. The Grades of Recommendation, Assessment, Development and Evaluation system was used to determine the quality of evidence. Questions related to diagnostic tests, scoring system, and its modification to a version suitable for resource-constrained settings were posed. While ceruloplasmin and 24-h urine copper continue to be important, there is little role of serum copper and penicillamine challenge test in the diagnostic algorithm. A new scoring system - Modified Leipzig score has been suggested with extra points being added for family history and serum ceruloplasmin lower than 5 mg/dl. Liver dry copper estimation and penicillamine challenge test have been removed from the scoring system. Differences in pharmacological approach to neurological and hepatic disease and global monitoring scales have been included. Rising bilirubin and worsening encephalopathy are suggested as indicators predicting need for liver transplant but need to be validated. The clinical practice guidelines provide recommendations for a comprehensive management of WD which will be of value to all specialties.

Burden of liver diseases in the world.

Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.

Drug-induced liver injury with skin reactions: Drugs and host risk factors, clinical phenotypes and prognosis.

While dermatologic manifestations of adverse drug reactions are frequent, drug-induced liver injury is rare. Numerous drugs are implicated in either Drug-Induced Liver Injury or Drug-Induced Skin Injury. However, concomitant Drug-Induced Liver Injury and Drug-Induced Skin Injury are uncommon, not well characterized and appear to be caused by a limited number of drugs. These are often associated with immuno-allergic or hypersensitivity features such as fever, skin rash, blisters or peeling of skin, eosinophilia, lymphadenopathy and mucositis. Liver injury can range from asymptomatic elevation of liver biochemical tests to severe hepatitis and acute liver failure needing liver transplantation. Severe cutaneous adverse reaction, particularly drug reaction with eosinophilia and systemic symptoms is commonly associated with internal organ involvement, the liver being the most frequently involved in approximately 90% of the cases. In Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, abnormalities in liver biochemistry tests are common but severe liver disease is rare. There is a strong association of Human Leukocyte Antigen genotype with both drug reaction with eosinophilia and systemic symptoms and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis. It is likely that the delayed immune-mediated reaction triggering skin reaction is also responsible for hepatitis. Drug-specific lymphocytes are found in the organs involved and also in circulating blood, which along with the cytokines and chemokines play a role in pathogenesis. Anti-epileptic drugs, allopurinol, sulfonamides, antibiotics and nevirapine are the top five causes of concomitant liver and skin injury. This review will focus on drug and host factors causing concomitant Drug-Induced Skin Injury and Drug-Induced Liver Injury and discuss the characteristics of liver involvement in patients with severe cutaneous adverse reaction.

Primary Gastric Lymphoma: Clinicopathological Profile.

INTRODUCTION: Gastrointestinal tract (GIT) is the most common site of involvement of extranodal non-Hodgkin's lymphoma (NHL). There is regional variation in anatomical distribution of extranodal NHL, stomach being the most common site followed by small intestine. Primary gastric lymphoma (PGL) predominantly involves the antrum and corpus of the stomach. It arises from mucosa-associated lymphoid tissue (MALT) and is of B-cell lineage and often associated with Helicobacter pylori infection. Primary gastric lymphoma often presents with nonspecific symptoms. The present study was undertaken to ascertain the clinicopathological characteristics of PGL at a tertiary care center in South India. MATERIALS AND METHODS: It is a retrospective study from 2006 to 2016. Patient's data were obtained from institutional medical records. The histopathology slides were reviewed. The relevant immunohistochemistry (IHC) markers done were leukocyte common antigen (LCA), CD3, CD20, CD79a, CD10, Bcl-2, Bcl-6, CD5, Cyclin D1, CD138, and Ki-67. Correlating with the immunoprofile, further subtyping was done. RESULTS: A total of 405 patients of NHL were seen during the study period, out of which 43 patients were PGL. There were 32 males and 11 females, with M:F of 2.9:1. The mean age at diagnosis was 58 years. Abdominal pain and new-onset dyspepsia were the commonly observed presenting symptoms. The common site of involvement was antrum (20). Diffuse large B-cell lymphoma (DLBCL) was the most common histological subtype. Helicobacter pylori infection was seen in 18 (41%) patients. Majority of the patients were in stages II and III. CONCLUSION: In our study, the initial presentation of PGL was with nonspecific symptoms like abdominal pain and new-onset dyspepsia. High degree of suspicion of such symptoms and biopsy of all suspicious lesions is essential for early detection. Diffuse large B-cell lymphoma was the most common histological subtype seen in our study.How to cite this article: Malipatel R, Patil M, Rout P, Correa M, Devarbhavi H. Primary Gastric Lymphoma: Clinicopathological Profile. Euroasian J Hepato-Gastroenterol 2018;8(1):6-10.

INASL Position Statements on Prevention, Diagnosis and Management of Hepatitis B Virus Infection in India: The Andaman Statements.

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

Pernicious Anaemia with Gastric Carcinoids.

We report the case of a 42 year male with history of chronic anaemia who was found to have pernicious anaemia with beta thalassemia trait and had on esophago-gastric-duodenoscopy, gastric carcinoids with gastric atrophy. Pernicious anaemia and gastric carcinoids occurring simultaneously in a single individual is rare. Our case emphasises the need for esophago-gastric-duodenoscopy in cases of pernicious anaemia.

HIV/AIDS cholangiopathy: clinical spectrum, cholangiographic features and outcome in 30 patients.

BACKGROUND AND AIMS: AIDS cholangiopathy is presently considered rare and has been reported mainly from the West. With the HIV epidemic in India, we have encountered an increasing number of patients. We aimed to study these patients and determine differences from earlier experiences. METHODS: We describe the clinical presentation, cholangiographic features, and outcome and determine differences reported in Western literature. RESULTS: From Jan 1999 to May 2009, 30 patients (27 men) with AIDS cholangiopathy were seen. The most common mode of transmission was heterosexual (n = 28) followed by blood transfusion (n = 2). Abdominal pain (n = 20) of biliary origin, was the commonest manifestation followed by an asymptomatic group (n = 6) and a third group (n = 3) with pain due to pancreatitis. Ultrasonography of the abdomen was abnormal in all patients. Papillary stenosis (n = 23) was the most common cholangiographic feature followed by sclerosing cholangitis (n = 5). Abdominal pain resolved reliably and promptly after endoscopic sphincterotomy. Cholangiographic abnormalities regressed during follow up on antiretroviral therapy in 10 patients. Seven patients on anti retroviral therapy developed de novo cholangiopathy, with a precipitous drop in CD4 count of whom two had a worse prognosis. None had Kaposi's sarcoma. CONCLUSIONS: In contrast to Western literature, HIV cholangiopathy was seen predominantly in patients who acquired HIV by heterosexual transmission. De novo development of cholangiopathy on antiretroviral therapy may indicate the occurrence of resistance. Papillary stenosis is the most common feature. Abdominal pain resolved with sphincterotomy. Regression of cholangiographic abnormality occurred with anti retroviral medications. Median survival following cholangiopathy diagnosis was 34 months, higher than reported in previous studies.

Significance of nodular regenerative hyperplasia occurring de novo following liver transplantation.

Nodular regenerative hyperplasia (NRH) of the liver usually occurs in patients with rheumatological and myelolymphoproliferative disorders; the occurrence post-liver transplantation (LT) has traditionally been ascribed to the use of azathioprine. We report the clinical, biochemical, and radiological features of 14 patients who developed NRH, unrelated to azathioprine in most cases, 3 months to 11 yr after orthotopic LT. A total of 10 patients developed NRH within 4 yr (early onset), and 4 other patients developed the condition beyond 4 yr of LT (late onset). A total of 7 symptomatic patients, all in the early group, had features of portal hypertension with vascular abnormalities on Doppler ultrasonography that were preceded by the diagnosis of NRH. All asymptomatic patients, including each of the 4 patients in the late group, had normal hepatic ultrasound (US) studies. Two symptomatic patients had normalization of histologic abnormalities after correction of vascular abnormalities. In conclusion, observation is appropriate for patients who develop NRH late following LT. Patients in whom NRH is detected on liver biopsy early after transplantation are likely to develop portal hypertension in the future. Intervention aimed at correcting the vascular abnormalities in these patients may result in clinical as well as hepatic histological improvement.