Yogesh Chawla

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

IntroductionThe Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations.MethodsThe working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements.ResultsParticipants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

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.

Hepatic outflow obstruction (Budd-Chiari syndrome). Experience with 177 patients and a review of the literature.

Budd-Chiari syndrome (BCS) may not be as uncommon as was once believed. Our study has substantiated the existence of 2 major clinical forms. The acute syndrome is invariably associated with extensive blockage of the major hepatic veins, resulting in congestive liver cell necrosis. In a small, but significant, number of patients the inferior vena cava (IVC) is also occluded. The important etiologic factors are related to hypercoagulability of blood. Immediate placement of a shunt improves survival. The chronic syndrome is characterized by portal hypertension and is associated with a variable abnormal vascular anatomy. The causes of the chronic syndrome are not clear, but a substantial number of cases are related to the presence of an IVC membrane. Shunt surgery is effective but procedures aimed at the primary pathology are likely to be even more so. The natural history of BCS should be viewed over a long period of time. The very long survival of several patients urges a more cautious approach to surgical remedies. Budd-Chiari syndrome probably represents a spectrum of disease caused primarily by a hypercoagulable state and having a varied presentation depending on the balance between rate of formation and the extent of the thrombosis and the bodys own rate of thrombolysis and recanalization. The extent and efficacy of the individuals collateral circulation and the rate of development of liver fibrosis are other determinants. It is thus possible to view BCS as a continuum of a single pathogenetic spectrum. Pregnancy-related BCS in India probably has strong social determinants, and is usually acute and fulminant. We have, however, documented a chronic form not described earlier. Children usually do not have acute BCS, but chronic BCS in children and adolescents is similar to that in adults. Membranous obstruction of the inferior vena cava (MOVC) is common and was found even at a young age. The association of MOVC with hepatocellular carcinoma, however, did not appear to be as clear as was previously believed. There has been a wide geographical variability in the causes and manifestations of BCS. Our study has clearly shown that--Kiplings categorical statement to the contrary--East and West do meet in India, in the Budd-Chiari syndrome.

Hepatitis E virus transmission to a volunteer

Hepatitis E virus (HEV) causes an enteric non-A, non-B hepatitis. The disease occurs in epidemic settings and sporadically, and viral transmission is thought to be faecal-oral. We present here a single volunteer study of HEV transmission followed by disease. Clinical and biochemical features of the infection correlated with HEV detection in the stools and sera by reverse transcription/polymerase chain amplification. IgG antibody has persisted for 2 years. The presence of HEV in serum before clinical signs appeared suggests that in endemic areas sporadic transmission of HEV may also occur parenterally.

Herbal Medicines for Liver Diseases

Herbal medicines have been used in the treatment of liver diseases for a long time. A number of herbal preparations are available in the market. This article reviews four commonly used herbal preparations: (1) Phyllanthus, (2) Silybum marianum (milk thistle), (3) glycyrrhizin (licorice root extract), and (4) Liv 52 (mixture of herbs). Phyllanthus has a positive effect on clearance of HBV markers and there are no major adverse effects; there are no data from randomized controlled trials on clinically relevant outcomes, such as progression of chronic hepatitis to cirrhosis and/or liver cancer, and on survival. Silymarin does not reduce mortality and does not improve biochemistry and histology among patients with chronic liver disease; however, it appears to be safe and well tolerated. Stronger neominophagen C (SNMC) is a Japanese preparation that contains 0.2% glycyrrhizin, 0.1% cysteine, and 2% glyceine. SNMC does not have antiviral properties; it primarily acts as an anti-inflammatory or cytoprotective drug. It improves mortality in patients with subacute liver failure and improves liver functions in patients with subacute hepatic failure, chronic hepatitis, and cirrhosis with activity. SNMC does not reduce mortality among patients with cirrhosis with activity. SNMC may prevent the development of hepatocellular carcinoma in patients with chronic hepatitis C, however, prospective data are lacking. Liv 52, an Ayurvedic hepatoprotective agent, is not useful in the management of alcohol-induced liver disease. Standardization of herbal medicines has been a problem and prospective, randomized, placebo-controlled clinical trials are lacking to support their efficacy. The methodological qualities of clinical trials of treatment with herbal preparations are poor. The efficacy of these herbal preparations need to be evaluated in rigorously designed, larger randomized, double-blind, placebo-controlled multicenter trials.

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.

Diagnosis and Prognostic Significance of Minimal Hepatic Encephalopathy in Patients with Cirrhosis of Liver

Background and AimsMinimal hepatic encephalopathy is the mildest form of the spectrum of hepatic encephalopathy (HE) that impairs health-related quality of life. We assessed (1) the usefulness of psychometric hepatic encephalopathy score and critical flicker frequency for the diagnosis of minimal hepatic encephalopathy, and (2) prognostic significance of minimal hepatic encephalopathy.MethodsOne hundred patients with liver cirrhosis without overt HE were subjected to psychometric hepatic encephalopathy score and critical flicker frequency evaluation. Eighty-three age- and sex-matched healthy volunteers served as controls. Minimal hepatic encephalopathy was diagnosed when the psychometric hepatic encephalopathy score was ≤−5. An age-adjusted Z score <−2 on the critical flicker frequency was considered abnormal.ResultsForty-eight (48%) patients had minimal hepatic encephalopathy as indicated by altered psychometric hepatic encephalopathy score. Critical flicker frequency was altered in 21 patients; 17 also showed impaired psychometric hepatic encephalopathy score thus providing additional information in only 4 patients. Forty-six of 48 patients with minimal hepatic encephalopathy and 48 of 52 patients without minimal hepatic encephalopathy completed the follow-up. Eighteen (39.1%) patients died among those who had minimal hepatic encephalopathy compared to 11 (22.9%) patients who did not have minimal hepatic encephalopathy. Among the several variables analyzed in this study, univariate analyses showed that age, serum bilirubin level, Child-Turcotte-Pugh score and psychometric hepatic encephalopathy score were associated with a poor prognosis. The multivariate analysis identified two variables as significant independent prognostic factors; psychometric hepatic encephalopathy score ≤−6 [hazard ratio 2.419 (95% CI, 1.014–5.769)] and Child-Turcotte-Pugh score ≥8 [hazard ratio 2.466 (95% CI, 1.010–6.023)] predicted poor survival.ConclusionsPsychometric hepatic encephalopathy score is a useful tool for the diagnosis of minimal hepatic encephalopathy in an outpatient setting. Both psychometric hepatic encephalopathy score and Child-Turcotte-Pugh score have prognostic value on survival.

Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy

BACKGROUND & AIMS Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encephalopathy. This cross-sectional study was carried out to elucidate the role of bacterial overgrowth of the small intestine and delayed intestinal transit among patients with MHE. METHODS Two-hundred-thirty patients with cirrhosis were screened; 102 patients (44.4%) who met the eligibility criteria were included in the study. MHE was diagnosed when the psychometric hepatic encephalopathy score was ≤-5. All patients underwent a glucose breath test for small intestinal bacterial overgrowth (SIBO) and lactulose breath test for oro-cecal transit time (OCTT). RESULTS Fifty-seven (55.9%) patients with cirrhosis had MHE. Among these patients with MHE, 22 (38.6%) had SIBO, while 4 (8.9%) without MHE had SIBO (p = 0.001). The prevalence of SIBO was higher in patients with CTP classes B and C (69.2%) compared to those in CTP class A (30.8%); p = 0.054. OCTT was significantly prolonged in patients who had SIBO than in those who did not have SIBO (p<0.0001). Univariate analysis demonstrated that increased age, female gender, low educational status, low albumin, presence of SIBO, and prolonged OCTT were associated with the presence of MHE. Multivariate analysis demonstrated SIBO as the only factor associated with MHE. CONCLUSIONS Our study conclusively demonstrates high prevalence of SIBO in patients with cirrhosis with MHE. This study gives the rationale of treatment directed against SIBO and gut dysmotility, which may include non-absorbable antibiotics such as rifaximin, probiotics, and prokinetics.

Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: A randomized study

BACKGROUND & AIMS Various vasoconstrictors are useful in the management of hepatorenal syndrome (HRS). Terlipressin is the drug of choice; however, it is expensive. In this study, we evaluated safety and efficacy of terlipressin and noradrenaline in the treatment of HRS. METHODS Forty-six patients with HRS type 1 were managed with terlipressin (group A, N=23) or noradrenaline (Group B, N=23) with albumin in a randomized controlled trial at a tertiary center. RESULTS HRS reversal could be achieved in 9 (39.1%) patients in group A and 10 (43.4%) patients in group B (p=0.764). Univariate analysis showed baseline Child Turcotte Pugh score (CTP), model of end stage liver disease (MELD), urine output on day 1(D1), albumin, and mean arterial pressure (MAP) were associated with response. However, on multivariate analysis only CTP score was associated with response. Fourteen patients in group A and 12 in group B died at day 15 (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 noradrenaline is as safe and effective as terlipressin, but less expensive in the treatment of HRS and baseline CTP score is predictive of response.

Portal hypertensive biliopathy

Extrahepatic portal venous obstruction (EHPVO) is a common cause of portal hypertension in the developing countries, and constitutes up to 40% of all patients with portal hypertension.1,2 EHPVO is a common cause of major upper-gastrointestinal bleeding among children.2–4 The most common presentation in children is well-tolerated variceal bleeding and splenomegaly. In adults, EHPVO is often recognised when evaluating for other disorders or with uncommon presentations such as jaundice, pruritus, acute cholecystitis-like syndrome, ascites and so on, resulting from prolonged portal hypertension.5–7 The portal vein in EHPVO is transformed into a cavernoma, which is a bunch of multiple collateral veins around the obstructed portion of portal vein (fig 1). Marked improvements in the management of variceal bleeding in patients with EHPVO have resulted in an improved survival, thus presenting with unusual symptoms in adulthood. Figure 1  Splenoportovenogram showing multiple collaterals (portal cavernoma) replacing the portal vein (arrows) in a patient with extrahepatic portal venous obstruction. The splenic vein is normal (arrowheads). The reasons for EHPVO are obscure in approximately half of the patients. Omphalitis and intra-abdominal sepsis are the common causes in neonates and children. Adults develop EHPVO due to increased blood coagulability, local inflammation, intra-abdominal sepsis, myeloproliferative disorders, underlying cirrhosis, or tumours in the liver, bile ducts or pancreas.7,8,9,10 Gibson et al 11 first reported the relationship between EHPVO and jaundice in 1965. Since then, several cases of obstructive jaundice due to common bile duct (CBD) obstruction caused by cavernomatous transformation of portal vein (portal cavernoma) have been described. Williams et al 12 were the first to report cholangiographic changes caused by choledochal varices. We, for the first time, describe abnormalities on endoscopic retrograde cholangiography (ERC) in a prospective study.13 These abnormalities were similar to those of primary sclerosing cholangitis and …