Hepatocellular Carcinoma Evaluation and Management for Physicians: Joint Gastroenterology Research Society and Association of Physicians of India Guidelines

Hepatocellular carcinoma (HCC) is the most common cause of, and accounts for almost 90% of all liver cancers. Data from India is limited especially due to cancer not being a reportable disease and in view of wide variation in diagnostic modalities. This document is a result of a consensus meeting comprising Hepatologists, Interventional Radiologists, Hepatobiliary surgeons, medical and surgical Oncologists nominated by the Association of Physicians of India and Gastroenterology Research Society of Mumbai. The following Clinical Practice Guidelines for practicing physicians is intended to act as an up to date protocol for clinical management of patients with hepatocellular carcinoma. The document comprises seven sections with statements and sub-statements with strength of evidence and recommendation.

Low frequency of factor V Leiden and prothrombin G20210A mutations in patients with hepatic venous outflow tract obstruction in northern India: a case-control study.

BACKGROUND: Factor V Leiden (FVL) and prothrombin gene (G20210A) mutations are known to be associated with venous thromboembolism. Several studies have shown an association of these mutations with hepatic venous outflow tract obstruction (HVOTO). We studied the prevalence of these mutations among patients with HVOTO in northern India in comparison with healthy population. METHODS: Genomic DNA from patients with HVOTO and healthy controls was analyzed for the presence of FVL and prothrombin gene G20210A mutations, using PCR and restriction-fragment length polymorphism. RESULTS: Fifty-nine patients with HVOTO (age 5-69 years, median 27; 39 male) and 49 unrelated healthy controls from the same geographic region were studied. Of the 59 patients, 19 had a block in the hepatic vein, 7 in inferior vena cava, and 33 had mixed block. Presentation was with acute thrombosis in 9 patients and with long-standing obstruction in 50 patients. Among 49 controls, heterozygous and homozygous FVL mutations were observed in 2 and 0 subjects, respectively, with an allele frequency of 2% (2 of 98). In comparison, among 59 patients with HVOTO, four had heterozygous and none had homozygous FVL mutation, with an allele frequency of 3.4% (p=ns versus controls). The G20210A prothrombin gene mutation was not found in any of the patients or controls. CONCLUSION: FVL and prothrombin G20210A mutations appear to have no role in the pathogenesis of HVOTO in our patients with Budd-Chiari syndrome, consisting largely of those with long-standing obstruction of the inferior vena cava.

Profile of liver involvement in dengue virus infection.

BACKGROUND: Data are scarce on liver involvement in adult patients with dengue virus infection. METHODS: During a recent outbreak of dengue fever in Uttar Pradesh, India, we looked for evidence of liver dysfunction among patients with dengue fever. RESULTS: A total of 45 patients with dengue fever (age 7-65 [median 33] years; 29 men; 39 adults) were studied, including 23 with uncomplicated dengue fever, 15 with dengue haemorrhagic fever and 7 with dengue shock syndrome. The median platelet count was 34 x 10(9)/L (9-99 x 10(9)). Seven patients (15%) had jaundice, 11 (24%) hepatomegaly and 9 clinically detectable ascites; none had splenomegaly. Twelve patients (30%) had hyperbilirubinaemia. Serum alanine and aspartate aminotransferase activities were elevated in 43 patients (96%) each; 5-fold elevated levels were more frequent in severe disease. Hypoalbuminaemia was found in 31/41 patients (76%). Seven patients died, including 2 with acute liver failure. CONCLUSION: Our data show that liver injury is common in adult patients with dengue infection. Further studies are needed to determine the mechanism of liver injury in this disease.

Hepatitis E virus is responsible for decompensation of chronic liver disease in an endemic region.

BACKGROUND: Hepatitis A virus infection in patients with previously stable chronic liver disease is associated with liver decompensation. Whether infection with hepatitis E virus (HEV) also does so is not known. METHODS: We studied 32 patients with decompensated liver disease and definite evidence of underlying cirrhosis for evidence of recent HEV infection. RESULTS: Of 32 patients, 14 (44%) had detectable IgM anti-HEV in their serum. In comparison, only 3 of 48 (6%) patients with stable cirrhosis and no recent decompensation had such antibodies (p<0.0001). Of the 14 patients with evidence of recent HEV infection, 11 had history of prodrome. The etiology of cirrhosis in these patients was: hepatitis B 6, hepatitis C 2, both hepatitis B and C 2, Wilson's disease 1, autoimmune 1 and cryptogenic 2. Two of these 14 patients died. Twelve patients survived, as compared to 9 of 18 patients without evidence of recent HEV infection (p<0.01). CONCLUSION: HEV infection is a frequent cause of decompensation in patients with liver cirrhosis in HEV-endemic regions.

Minimal hepatic encephalopathy: diagnosis by neuropsychological and neurophysiologic methods.

Minimal hepatic encephalopathy (mHE) consists of cognitive deficits found on neuropsychological and/or neurophysiologic methods in patients with liver disease, present most commonly in cirrhosis. Patients suffering from mHE may have psychomotor slowing and cognitive deficits affecting their ability to perform many activities of daily life, especially driving and other activities requiring subtle cognitive abilities. It has been now been shown that patients with mHE improve after treatment with agents like lactulose and other therapeutic interventions. Neuropsychological and neurophysiologic tests have been widely used and have shown the greatest promise for the detection of mHE. Commonly used psychometric tests include trailmaking tests (number and figure connection tests) and Wechsler Adult Intelligence Scale (WAIS) for verbal and performance skills. Among the various neuropsychological or psychometric tests, trailmaking tests and block design and digit symbol tests from WAIS-performance battery appear to be adequate for diagnosis of mHE. Standardized tests including NCT A and B, line tracing, serial dotting test and digits-symbol test (PSE syndrome test) validated in German patients need validation in other populations. Both exogenous evoked potentials and endogenous event-related potentials have been used extensively in diagnosing mHE. However, the event-related P300 wave is the most consistent wave and can be considered the electrophysiological counterpart of the psychometric tests as both involve active use of the cognitive faculties. Other new tests like the critical flicker frequency have shown some promise but further studies are required to substantiate initial results. In conclusion, a combination of at least two psychometric (trailmaking tests [NCT or FCT], block design and digit symbol test) and neurophysiological tests (P300 auditory evoked potential or electroencephalography with mean dominant frequency) appears to be optimal in detecting mHE.

Occult hepatitis B virus infection as a cause of cirrhosis of liver in a region with intermediate endemicity.

BACKGROUND: Serological tests may fail to identify hepatitis B virus (HBV) infection as a cause of liver cirrhosis in a proportion of patients. The frequency of such occult infection in regions with intermediate HBV endemicity is not known. Such cases may be diagnosed by incremental testing for IgG anti-HBc, serum HBV DNA, and HBV DNA in liver tissue. METHODS: We tested sera of 111 patients with cirrhosis, including 39 with history of significant alcohol ingestion, for HBsAg, anti-HBc and serum HBV DNA. In addition, in a subset of 14 patients, HBV DNA was looked for in liver tissue. RESULTS: On HBsAg and anti-HBc testing, 66 patients had HBV infection. Serum HBV DNA testing identified HBV infection in 13 additional cases. Of 18 patients labeled as 'cryptogenic' on serological testing, HBV DNA was detected in the serum in 7 patients. Of 14 patients in whom paired liver tissue and serum specimens were tested, 4 additional patients with HBV infection were detected after liver biopsy analysis. CONCLUSIONS: Serological tests for HBsAg and anti-HBc antibody are insensitive in identifying HBV infection in patients with liver cirrhosis. HBV DNA testing in serum and liver can help in establishing HBV infection as etiology, either alone or in addition to another cause.