Ministry of Health clinical practice guidelines: Chronic Hepatitis B Infection.

The Ministry of Health (MOH) publishes clinical practice guidelines on Chronic Hepatitis B Infection to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Chronic Hepatitis B Infection, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=26108). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

GaN/ZnO nanorod light emitting diodes with different emission spectra.

Light emitting diodes (LEDs) consisting of p-GaN epitaxial films and n-ZnO nanorods have been fabricated and characterized. The rectifying behavior and emission spectra were strongly dependent on the electronic properties of both GaN film and ZnO nanorods. Light emission under both forward and reverse bias was obtained in all cases, and emission spectra could be changed by annealing the ZnO nanorods. The emission spectra could be further tuned by using a GaN LED epiwafer as a substrate. Both forward and backward diode behavior has been observed and the emission spectra were significantly affected by both the properties of the GaN substrate and the annealing conditions for the ZnO nanorods.

Minimal hepatic encephalopathy runs a fluctuating course: results from a three-year prospective cohort follow-up study.

INTRODUCTION: Minimal hepatic encephalopathy (mHE) has been reported in up to 84 percent of cirrhotics. The natural history of mHE has not been well-described. We designed a three-year prospective cohort study to determine the prevalence and natural history of mHE among cirrhotic patients. METHODS: The patient cohort comprising 62 consecutive outpatients with cirrhosis were assessed at baseline and followed-up with a repeat assessment three years later. The assessments include: (1) Neuropsychometric analysis (digit-symbol substitution test, block-design test, number-connection test A); (2) Clinical, biochemical assessment; and (3) Quality of life (QOL) assessment (abbreviated sickness impact profile). RESULTS: Baseline characteristics were: age 52.9 +/- 11.0 years; Child's A:B:C was 46:14:2. mHE was detected in 33.9 percent of the cohort. Older age, a higher Child-Pugh score and female gender were independently associated with mHE. mHE was associated with a poorer QOL. Follow-up assessment three years later showed that seven patients had died, while six were lost to follow-up; these patients had significantly higher baseline Child's scores. Of the remaining patients, 36/49 (73 percent) agreed to a repeat evaluation. In this group, none had mHE. QOL remained impaired despite the resolution of mHE. CONCLUSION: It has been shown for the first time that mHE can revert to a normal state in a significant proportion of patients with well-compensated cirrhosis.

Prospective evaluation of transient elastography for the diagnosis of hepatic fibrosis in Asians: comparison with liver biopsy and aspartate transaminase platelet ratio index.

BACKGROUND: Transient elastography (TE) is a reliable non-invasive predictor of hepatic fibrosis, but data on TE in Asians are limited. AIM: To evaluate prospectively the accuracy of TE for diagnosis of hepatic fibrosis in Asians compared with APRI (aspartate transaminase to platelet ratio index). METHODS: One hundred and twenty consecutive patients who underwent liver biopsy were enrolled. TE (Fibroscan) was performed by two independent operators. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) were used to evaluate the accuracy of TE and APRI in diagnosing significant fibrosis (F >or= 2) and cirrhosis (F4). RESULTS: Predominant aetiologies were hepatitis B (48%), non-alcoholic steatohepatitis (14%) and hepatitis C (8%). TE was unsuccessful in five patients (4.2%) because of small inter-costal space (three patients), obesity and ascites. There was good correlation between TE and fibrosis (r = 0.606). AUROC for diagnosis of significant fibrosis was 0.856 (95% CI 0.779-0.932) for TE and 0.673 (95% CI 0.568-0.777) for APRI. AUROC for diagnosis of cirrhosis was 0.924 (95% CI 0.857-0.990) for TE and 0.626 (95% CI 0.437-0.815) for APRI. Optimal TE value was 9.0 kPa for diagnosis of significant fibrosis and 16.0 kPa for cirrhosis with specificity/sensitivity/PPV/NPV/accuracy of 82.6%/85.2%/80.9%/86.7%/84.1% and 88.9%/82.7%/32.0%/98.8%/83.2%, respectively. CONCLUSIONS: Transient elastography is a reliable predictor of hepatic fibrosis in Asians. Failure of TE in Asians is commonly because of small inter-costal space. TE is superior to APRI for non-invasive diagnosis of hepatic fibrosis and cirrhosis.

Imatinib mesylate-related fatal acute hepatic failure in a patient with chronic myeloid leukaemia and chronic hepatitis B infection.

Imatinib mesylate (Gleevec) is widely-used in the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour. Up to four percent of patients treated with imatinib may develop hepatotoxicity, which usually resolves with discontinuation of the drug. We report a 45-year-old Chinese man with CML and chronic hepatitis B virus infection, on imatinib treatment, presenting with herpetic rash and acute liver failure. This case illustrates the diagnostic challenges in the management of such a patient, as well as the need for greater vigilance in the monitoring of liver function tests for patients treated with imatinib. A short review on imatinib-related hepatotoxicity is also presented.

Management of pyogenic liver abscesses - percutaneous or open drainage?

This pictorial essay aims to review the literature on the management of pyogenic liver abscess, focusing on the choice of drainage. Articles on the treatment of pyogenic liver abscess, accessed through a MEDLINE search using PubMed, were reviewed. A case series of the authors' experience with clinicopathological correlation is presented to highlight the indication and outcome of each modality of drainage. Intravenous antibiotic is the first line, and mainstay, of treatment. Drainage is necessary for large abscesses, equal to or larger than 5 cm in size, to facilitate resolution. While percutaneous drainage is appropriate as first-line surgical treatment in most cases, open surgical drainage is prudent in cases of rupture, multiloculation, associated biliary or intra-abdominal pathology. Percutaneous drainage may help to optimise clinical condition prior to surgery. Laparoscopic drainage is a feasible surgical option with promising results in the future. Liver resection is reserved for concomitant localised intrahepatic disease and tumour, after control of sepsis. The final verdict on the outcome of percutaneous versus open surgical drainage of pyogenic liver abscesses requires further studies in a controlled trial setting. Nevertheless, in current good clinical practices, the choice of therapy needs to be individualised according to patient's clinical status and abscess factors. They are complementary in the management of liver abscesses.

A study into the characteristics and outcome of variceal bleeding in a tertiary hospital in Southeast Asia.

This retrospective study evaluated patients admitted to the Department of Gastroenterology, Singapore General Hospital for variceal bleeding in the year 2004. Improvement in outcome of variceal bleeding has been reported in the West. There is no regional data on this condition. This study aims to determine the characteristics and outcome of variceal bleeding in a tertiary hospital in Southeast Asia. Twenty-two patients were eligible. The main aetiologies of liver cirrhosis were chronic hepatitis B (38%) and alcohol (33%). Child's A, B and C were 29%, 48% and 24% respectively. Nineteen patients (86%) had bleeding oesophageal varices (band ligation performed). The remaining three patients (14%) had bleeding gastric varices (N-butyl-2-cyanoacrylate injection performed). Detailed description of certain endoscopic findings was absent in up to 18 patients (82%). All patients received antibiotics and vasoactive drug. In-hospital mortality and rebleeding were 9% and 18% respectively. We conclude that the relatively low in-hospital mortality and rebleeding rates in our series are most probably due to the smaller proportion of patients with severe liver dysfunction and management which adhered to recommendations. Documentation of endoscopic findings needs to be improved to facilitate the continuation of care.

Clinical mimicry of hepatocellular carcinoma: imaging-pathological correlation.

This pictorial essay aims to show the clinical mimicry of hepatocellular carcinoma (HCC) and its diagnostic difficulty, and to create awareness among clinicians and radiologists of potential diagnostic pitfalls. A selected consecutive series of hepatectomies with proven HCC over a three-year period, identifying clinical presentation, blood results and imaging of patients with difficult preoperative diagnosis, was reviewed. The imaging of the focal liver lesions is presented pictorially with pathological correlation. Six patients out of 34 cases of resected HCC were diagnosed to have benign (three liver abscesses) and neoplastic (one Klatskin tumour, one colorectal liver metastasis, one gallbladder cancer) conditions. Compared to the rest in the series, all six patients had normal serum alpha fetoprotein levels. On computed tomography, the mosaic appearance of HCC mimicked locules of liver abscess while HCC with pseudocapsule (rim enhancement) was misdiagnosed as unilocular abscess or metastatic lesion. Arterial enhancement on contrast-enhanced triphasic computed tomography was useful in diagnosis of HCC. In summary, HCC can mimic benign and neoplastic clinical syndromes. The diagnosis of liver abscess can delay subsequent diagnosis of HCC and potentially complicate the treatment plan. Contrast-enhanced triphasic computed tomography or magnetic resonance imaging is useful to resolve difficult diagnosis, especially when the serum alpha fetoprotein level is not raised.

Randomised controlled trial of long term portographic follow up versus variceal band ligation following transjugular intrahepatic portosystemic stent shunt for preventing oesophageal variceal rebleeding.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the prevention of variceal rebleeding but requires invasive portographic follow up. This randomised controlled trial aims to test the hypothesis that combining variceal band ligation (VBL) with TIPSS can obviate the need for long term TIPSS surveillance without compromising clinical efficacy, and can reduce the incidence of hepatic encephalopathy. PATIENTS/METHODS: Patients who required TIPSS for the prevention of oesophageal variceal rebleeding were randomised to either TIPSS alone (n = 39, group 1) or TIPSS plus VBL (n = 40, group 2). In group 1, patients underwent long term TIPSS angiographic surveillance. In group 2, patients entered a banding programme with TIPSS surveillance only continued for up to one year. RESULTS: There was a tendency to higher variceal rebleeding in group 2 although this did not reach statistical significance (8% v 15%; relative hazard 0.58; 95% confidence interval (CI) 0.15-2.33; p = 0.440). Mortality (47% v 40%; relative hazard 1.31; 95% CI 0.66-2.61; p = 0.434) was similar in the two groups. Hepatic encephalopathy was significantly less in group 2 (20% v 39%; relative hazard 2.63; 95% CI 1.11-6.25; p = 0.023). Hepatic encephalopathy was not statistically different after correcting for sex and portal pressure gradient (p = 0.136). CONCLUSIONS: TIPSS plus VBL without long term surveillance is effective in preventing oesophageal variceal rebleeding, and has the potential for low rates of encephalopathy. Therefore, VBL with short term TIPSS surveillance is a suitable alternative to long term TIPSS surveillance in the prevention of oesophageal variceal rebleeding.

MARS therapy in critically ill patients with advanced malignancy: a clinical and technical report.

BACKGROUND/METHODS: Molecular Adsorbent Recirculating System (MARS) was used in three consecutive critically ill patients at the Singapore General Hospital with advanced malignancy and acute liver failure (ALF). Case 1 was a male patient with hepatocellular carcinoma (HCC) for which initial right hepatectomy was followed by left hepatectomy 5 months later for recurrent HCC. The postoperative course following second surgery was complicated by severe methicillin-resistant Staphylococcus aureus (MRSA) sepsis, mild azotaemia and subacute cholestatic liver failure. MARS was used thrice in this patient. Case 2 was a female patient with advanced acute lymphoblastic leukaemia (ALL) with post bone marrow transplantation (BMT) acute haemolytic-uraemic syndrome (HUS) secondary to cyclosporin A (Cy A), cytomegalovirus (CMV) infection, severe nosocomial pneumonia, acute renal failure (ARF) treated with continuous haemofiltration and acute veno-occlusive disease resulting in Budd-Chiari syndrome. The latter precipitated ALF. MARS was instituted twice. Case 3 was a male patient with advanced, refractory Hodgkin's disease previously treated with multiple courses of chemotherapy. ALF developed secondary to acute viral hepatitis B flare. He was given a trial of MARS once in the ICU. All the three patients eventually died. RESULTS: Mean MARS intradialytic systemic pressures were as follows: systolic pressure range was 95 +/- 17 to 128 +/- 17 mmHg and diastolic pressure range was 51 +/- 5 to 67 +/- 7 mmHg. Pressure at albumin dialysate exit point from dialyser 1 (Ae) ranged from 253 +/- 11 to 339 +/- 15 mmHg and that at albumin dialysate entry point into dialyser 1 (Aa) ranged from 142 +/- 11 to 210 +/- 6 mmHg. Ultrafiltration (UF) was 633 +/- 622 mL over mean treatment duration of 6.3 +/- 0.9 h with a total heparin dose of 1583 +/- 817 IU. Coagulation status pre- and 6-h post-MARS was similar: aPTT (P=0.116) and platelet count (P=0.753). There were no bleeding complications or circuit thromboses. MARS had a significant de-uraemization effect (pre- and post-MARS serum creatinine and urea: P=0.046 and 0.028, respectively) but did not significantly attenuate blood lactate, ammonia or total bilirubin levels. Albumin dialysate (Ae - Aa) urea and creatinine concentrations appeared to be sharply attenuated after 6 h of MARS. In contrast, the removal of total bilirubin by albumin dialysate from the blood compartment appeared to plateau after 4 h of continuous MARS operation. CONCLUSIONS: MARS was well-tolerated in critically ill patients with advanced and complicated cancer. Low-dose heparin was safe and did not compromise MARS circuit integrity. Although MARS had a significant de-uraemization effect, this appeared to be limited by the duration of MARS operation. Our data suggested that such a limit was reached earlier for total bilirubin. More data are needed to confirm the present findings and further delineate the saturation limit of MARS for different toxins that accumulate in ALF. This would affect the optimal duration of MARS therapy.

Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating beta-blocker, in patients with cirrhosis and portal hypertension.

BACKGROUND: Carvedilol is a non-selective vasodilating beta-blocker with weak alpha1 receptor antagonism. Recent studies have demonstrated its potential as a portal hypotensive agent. AIM: To assess the haemodynamic effects and patient tolerability of the acute and chronic administration of low-dose carvedilol. METHODS: Haemodynamic measurements were performed in ten cirrhotic patients before and 1 h after the administration of 12.5 mg oral carvedilol. The study was repeated 4 weeks after daily administration of 12.5 mg carvedilol. RESULTS: After acute administration of carvedilol, there was a 23% reduction in the hepatic venous pressure gradient from 16.37 +/- 2.14 to 12.56 +/- 3.91 mmHg (P < 0.05), with significant falls in the heart rate, mean arterial pressure and cardiac output. Chronic administration resulted in a further fall in the hepatic venous pressure gradient from a baseline of 16.37 +/- 0.71 to 9.27 +/- 1.40 mmHg (P < 0.001) with the mean arterial pressure being unaffected. The drug was well tolerated with only one patient experiencing asymptomatic hypotension. CONCLUSIONS: The results show that low-dose carvedilol is an extremely potent portal hypotensive pharmacological agent, and is worthy of further investigation in large randomized trials to assess its effect in preventing variceal haemorrhage.

Transjugular intrahepatic portosystemic stent-shunt insufficiency and the role of diabetes mellitus.

BACKGROUND/AIMS: Maintenance of long-term patency of transjugular intrahepatic portosystemic stent-shunts (TIPSS) has proved problematic. Various prognostic variables have been assessed as predictors, but the role of diabetes mellitus, which induces vascular endothelial cell dysfunction, has not been assessed. METHODS: We analysed the records of 248 patients who underwent TIPSS between July 1991 and July 1997, followed-up through to August 1998. Patients with at least one shunt assessment by portography and available blood glucose levels were eligible (177 patients; median follow-up, 15.0 months). Fourteen patients had a pre-procedural diagnosis of diabetes (one insulin dependent, seven oral hypoglycaemic treated and six diet controlled). In another 14 patients, diabetes was diagnosed at TIPSS insertion, giving a 28/177 (15.8%) prevalence of diabetes in our patients. Fifty-nine patients were excluded from the final analysis (including five diabetics), as they either died or had early shunt insufficiency (within 1 month of stent placement), leaving 118 patients (including 23 diabetics) to be included in the final analysis. RESULTS: Mean age, sex distribution, median follow-up (months) and pre-shunt portal pressure gradient were comparable in the two groups (diabetics versus non-diabetics). Child-Pugh classes A and B were more common in the diabetic group (P < 0.01), and the mean inserted stent diameter was larger in the diabetic group (P < 0.05). The presence of diabetes was associated with a higher incidence of delayed shunt insufficiency (P = 0.02), but there was no evidence of an association between presence of diabetes and variceal haemorrhage post TIPSS. Kaplan-Meier analyses revealed earlier insufficiency in diabetic patients compared with those without diabetes (P = 0.04). Age, gender and presence of diabetes are included in the final logistic regression model. Individuals who have diabetes are more likely to experience shunt insufficiency independent of age and gender. CONCLUSIONS: Diabetes mellitus is common in patients undergoing TIPSS and is associated independently with increased incidence of primary delayed shunt insufficiency.