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Fulltext Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease: The Gut and Obesity Asia initiative

Pitisuttithum P, Chan WK, Goh GB, Fan JG, Song MJ, Charatcharoenwitthaya P, et al.

World J Gastroenterol, 2020 May 21;26(19):2416-2426.
PMID: 32476802 DOI: 10.3748/wjg.v26.i19.2416

BACKGROUND: Gamma-glutamyl transferase (GGT) is associated with the risk of cardiovascular disease (CVD) in the general population.
AIM: To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).
METHODS: This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as "GO ASIA") workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis.
RESULTS: A total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] vs 49 [41-55] years; P < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk (P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02).
CONCLUSION: The CVD risk of NAFLD patients is higher than that of healthy individuals. Baseline GGT level cannot predict CVD risk in NAFLD patients. However, advanced fibrosis is a predictor of a high CVD risk.

Matched MeSH terms: Liver Cirrhosis/complications
Management of primary liver cell carcinoma

Balasegaram M

Am J Surg, 1975 Jul;130(1):33-7.
PMID: 50750

A review of 352 patients with primary liver cell carcinoma treated by the author is presented. The poor rate of resectability (7 per cent) has necessitated various forms of treatment over the years. These are described in detail. Based on this experience, the current form of treatment for nonresectable carcinoma is summarized. Although it is too early to assess this form of treatment, initial results appear to be promising. A second report in the near future is planned.

Matched MeSH terms: Liver Cirrhosis/complications
Management of hepatitis C virus infection in the Asia-Pacific region: an update

Lim SG, Aghemo A, Chen PJ, Dan YY, Gane E, Gani R, et al.

Lancet Gastroenterol Hepatol, 2017 01;2(1):52-62.
PMID: 28404015 DOI: 10.1016/S2468-1253(16)30080-2

The Asia-Pacific region has disparate hepatitis C virus (HCV) epidemiology, with prevalence ranging from 0·1% to 4·7%, and a unique genotype distribution. Genotype 1b dominates in east Asia, whereas in south Asia and southeast Asia genotype 3 dominates, and in Indochina (Vietnam, Cambodia, and Laos), genotype 6 is most common. Often, availability of all-oral direct-acting antivirals (DAAs) is delayed because of differing regulatory requirements. Ideally, for genotype 1 infections, sofosbuvir plus ledipasvir, sofosbuvir plus daclatasvir, or ombitasvir, paritaprevir, and ritonavir plus dasabuvir are suitable. Asunaprevir plus daclatasvir is appropriate for compensated genotype 1b HCV if baseline NS5A mutations are absent. For genotype 3 infections, sofosbuvir plus daclatasvir for 24 weeks or sofosbuvir, daclatasvir, and ribavirin for 12 weeks are the optimal oral therapies, particularly for patients with cirrhosis and those who are treatment experienced, whereas sofosbuvir, pegylated interferon, and ribavirin for 12 weeks is an alternative regimen. For genotype 6, sofosbuvir plus pegylated interferon and ribavirin, sofosbuvir plus ledipasvir, or sofosbuvir plus ribavirin for 12 weeks are all suitable. Pegylated interferon plus ribavirin has been replaced by sofosbuvir plus pegylated interferon and ribavirin, and all-oral therapies where available, but cost and affordability remain a major issue because of the absence of universal health coverage. Few patients have been treated because of multiple barriers to accessing care. HCV in the Asia-Pacific region is challenging because of the disparate epidemiology, poor access to all-oral therapy because of availability, cost, or regulatory licensing. Until these problems are addressed, the burden of disease is likely to remain high.

Matched MeSH terms: Liver Cirrhosis/complications
Sengstaken-Blakemore tube malposition with esophageal rupture

Chuah YY, Lee YY, Chen WC, Kao SS

Acta Gastroenterol Belg, 2018 10 24;81(3):447-448.
PMID: 30350541
Matched MeSH terms: Liver Cirrhosis/complications
Patients with clinically metabolically healthy obesity are not necessarily healthy subclinically: further support for bariatric surgery in patients without metabolic disease?

Haskins IN, Chang J, Nor Hanipah Z, Singh T, Mehta N, McCullough AJ, et al.

Surg Obes Relat Dis, 2018 03;14(3):342-346.
PMID: 29519663 DOI: 10.1016/j.soard.2017.11.032

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized.
OBJECTIVES: To determine the prevalence and characteristics of NAFLD in individuals with metabolically healthy obesity.
SETTING: A tertiary, academic, referral hospital.
METHODS: All patients who underwent bariatric surgery with intraoperative liver biopsy from 2008 to 2015 were identified. Patients with preoperative hypertension, dyslipidemia, or prediabetes/diabetes were excluded to identify a cohort of metabolically healthy obesity patients. Liver biopsy reports were reviewed to determine the prevalence of NAFLD.
RESULTS: A total of 270 patients (7.0% of the total bariatric surgery patients) met the strict inclusion criteria for metabolically healthy obesity. The average age was 38 ± 10 years and the average body mass index was 47 ± 7 kg/m2. Abnormal alanine aminotransferase (>45 U/L) and asparate aminotransferase levels (>40 U/L) were observed in 28 (10.4%) and 18 (6.7%) patients, respectively. A total of 96 (35.5%) patients had NAFLD with NALFD Activity Scores 0 to 2 (n = 61), 3 to 4 (n = 25), and 5 to 8 (n = 10). A total of 62 (23%) patients had lobular inflammation, 23 (8.5%) had hepatocyte ballooning, 22 (8.2%) had steatohepatitis, and 12 (4.4%) had liver fibrosis.
CONCLUSION: Even with the use of strict criteria to eliminate all patients with any metabolic problems, a significant proportion of metabolically healthy patients had unsuspected NAFLD. The need and clinical utility of routine screening of obese patients for fatty liver disease and the role of bariatric surgery in the management of NAFLD warrants further investigation.

Matched MeSH terms: Liver Cirrhosis/complications
Fulltext Survival in hepatitis-B cirrhosis compared to alcoholic cirrhosis in patients with Child's C liver disease: a prospective study of endoscopic sclerotherapy for bleeding oesophageal varices

Lee SM, Wong NW

Singapore Med J, 1994 Feb;35(1):53-6.
PMID: 8009280

A prospective comparative study was carried out on thirty-seven consecutive patients presenting with bleeding oesophageal varices at University Hospital, Kuala Lumpur. All patients received injection sclerotherapy if active bleeding was seen at the time of initial endoscopy, followed by repetitive courses of sclerotherapy to obliterate the varices. Predominant aetiological factors were hepatitis-B cirrhosis (43%) and alcoholic cirrhosis (30%). Chinese ethnic group accounted for 62.5% of hepatitis-B cirrhotics and Indian 73% of alcoholic cirrhotics. After excluding patients lost to follow-up, analysis of the remaining thirty-four patients showed reduced long-term survival in patients with Child's C disease. Log-rank analysis of survival curves between hepatitis-B cirrhosis and alcoholic cirrhosis in patients with Child's C liver disease showed no significant difference in long-term survival (p = 0.07). However, six deaths were seen in hepatitis-B cirrhosis compared to one death in alcoholic cirrhosis in the first eight months of follow-up. Most patients died from progressive liver failure. Median survival for Child's C hepatitis-B cirrhosis was 7.5 months whereas this had not been reached for Child's C alcoholic cirrhosis (median follow-up 11.6 months). We conclude that variceal haemorrhage in Child's C hepatitis-B cirrhosis is a bad prognostic sign and is associated with reduced survival with a median survival of 7.5 months despite control of the variceal bleed.

Matched MeSH terms: Liver Cirrhosis/complications*
Fulltext Immuno-pathomechanism of liver fibrosis: targeting chemokine CCL2-mediated HIV:HCV nexus

Ansari AW, Schmidt RE, Shankar EM, Kamarulzaman A

J Transl Med, 2014;12:341.
PMID: 25528160 DOI: 10.1186/s12967-014-0341-8

Even in the era of successful combination antiretroviral therapy (cART), co-infection of Hepatitis C virus (HCV) remains one of the leading causes of non-AIDS-related mortality and morbidity among HIV-positive individuals as a consequence of accelerated liver fibrosis and end-stage liver disease (ESLD). The perturbed liver microenvironment and induction of host pro-inflammatory mediators in response to HIV and HCV infections, play a pivotal role in orchestrating the disease pathogenesis and clinical outcomes. How these viruses communicate each other via chemokine CCL2 and exploit the liver specific cellular environment to exacerbate liver fibrosis in HIV/HCV co-infection setting is a topic of intense discussion. Herein, we provide recent views and insights on potential mechanisms of CCL2 mediated immuno-pathogenesis, and HIV-HCV cross-talk in driving liver inflammation. We believe CCL2 may potentially serve an attractive target of anti-fibrotic intervention against HIV/HCV co-infection associated co-morbidities.

Matched MeSH terms: Liver Cirrhosis/complications
Treatment of chronic hepatitis B virus infection in special groups of patients: decompensated cirrhosis, immunosuppressed and paediatric patients

Merican I

J Gastroenterol Hepatol, 2000 May;15 Suppl:E71-8.
PMID: 10921386
Matched MeSH terms: Liver Cirrhosis/complications*
Race-related morphologic variations in hepatocellular carcinoma

Sumithran E, Looi LM

Cancer, 1985 Sep 1;56(5):1124-7.
PMID: 2990666

In West Malaysia, hepatocellular carcinoma (HCC) is common in the Chinese and in the members of the Senoi aboriginal tribe, two racial groups with diametrically opposite life-styles. Certain fundamental differences exist between the liver tumors in the two races. In the Senoi, the tumor occurs in a younger age group and there is a greater male preponderance than in the Chinese. There is also a very close relationship between hepatitis B virus infection, chronic active hepatitis, cirrhosis, liver cell dysplasia, and HCC in the Senoi and the tumors generally present as multiple nodules studding both lobes of the liver. In the Chinese, although a relationship between hepatitis B virus infection, HCC, and cirrhosis exists, this association is not as strong as in the Senoi and the tumors are generally large and solitary. The data suggest that, although the hepatitis B virus is probably an important oncogenic agent in both racial groups, there may be a difference in the pathogenesis of HCC in the two races.

Matched MeSH terms: Liver Cirrhosis/complications
Fulltext Anthropometric, biochemical and clinical assessment of malnutrition in Malaysian patients with advanced cirrhosis

Tai ML, Goh KL, Mohd-Taib SH, Rampal S, Mahadeva S

Nutr J, 2010;9:27.
PMID: 20576106 DOI: 10.1186/1475-2891-9-27

There is limited data on the nutritional status of Asian patients with various aetiologies of cirrhosis. This study aimed to determine the prevalence of malnutrition and to compare nutritional differences between various aetiologies.

Matched MeSH terms: Liver Cirrhosis/complications*
Fulltext Congenital hepatic fibrosis in a child with autosomal dominant polycystic kidney disease

Kanaheswari Y, Hamzaini AH, Wong SW

Med J Malaysia, 2008 Aug;63(3):251-3.
PMID: 19248702 MyJurnal

The association of congenital hepatic fibrosis (CHF) with autosomal recessive polycystic kidney disease (ARPKD) is well known and occurs in approximately 50% of cases. However the association of CHF with autosomal dominant polycystic kidney disease (ADPKD) is less well known and less well documented. We report a child with neonatal onset of hypertension due to ADPKD who later develops portal hypertension due to CHF in childhood. A review of this rare association follows.

Matched MeSH terms: Liver Cirrhosis/complications*
Infections in patient with decompensated cirrhosis

Suresh RL

Med J Malaysia, 2005 Jul;60 Suppl B:16.
PMID: 16108167
Matched MeSH terms: Liver Cirrhosis/complications*
Spontaneous bacterial peritonitis [SBP]

Chutaputti A

Med J Malaysia, 2005 Jul;60 Suppl B:12-4.
PMID: 16108166
Matched MeSH terms: Liver Cirrhosis/complications*
Fulltext The correlation between cytopenia and esophageal varices in patients with liver cirrhosis

Gue CS, Yap CK, Ng HS

Med J Malaysia, 2004 Dec;59(5):604-8.
PMID: 15889562

This retrospective study analysed the case records of 200 patients in the Department of Gastroenterology, Singapore General Hospital from February 2000 to January 2001 who had liver cirrhosis and underwent gastroscopy for the detection of varices. The aim of this study was to determine any relationship between leucopenia, thrombocytopenia and the occurrence of esophageal varices in a cirrhotic population. Our results showed that the diagnostic yield of varices grade 2 and 3 was 6.3% if platelet count was > 150,000/mm3, 25% if platelet count was 100,000 to 150,000/mm3, 38.9% if platelet count was 50,000-99,000/mm3 and 100% if platelet count was <50,000/mm3. Similarly, the diagnostic yield of varices grade 2 and 3 was 19.4% if total white count was > 4,000/mm3, 66.7% if total white count was 3,000- 4,000/mm3 and 94.8% if total white count was < 3,000/mm5. We conclude that thrombocytopenia and leucopenia can be used to stratify risk for occurrence of esophageal varices in cirrhotic patients and gastroscopy will have a high yield for varices when platelet count is < 150,000/mm3 or total white is < 4,000/mm.

Matched MeSH terms: Liver Cirrhosis/complications
Fulltext Prevalence of peptic ulcer in 82 Kelantanese Malaysians with non-alcoholic cirrhosis

Raj SM

Med J Malaysia, 1992 Sep;47(3):208-11.
PMID: 1491646

A review of 82 (68 male) Kelantanese patients with non-alcoholic cirrhosis who underwent gastroduodenal endoscopy revealed duodenal and gastric ulcers in 4.9% and 7.3% of patients respectively. Comparing with prevalence rates of peptic ulcer disease reported in the literature, there was no evidence to suggest that duodenal ulcers occur more frequently in patients with non-alcoholic cirrhosis. There is a suggestion, albeit a tenuous one, that non-alcoholic cirrhosis may be associated with gastric ulceration.

Matched MeSH terms: Liver Cirrhosis/complications*
Abdominal cocoon: a report of two cases

Seng LK, Mahadaven M, Musa A

Br J Surg, 1993 Sep;80(9):1149.
PMID: 8402117
Matched MeSH terms: Liver Cirrhosis/complications
Diastolic dysfunction in patients with liver cirrhosis: A short-term, observational study at a Malaysian hospital

Abdul Aziz KA, Draman N, Wan Isa WYH, Mustaffa N

Med J Malaysia, 2020 07;75(4):396-399.
PMID: 32724001

Cirrhotic cardiomyopathy is a recognised complication of liver cirrhosis and predicts poor outcomes. Detection of diastolic dysfunction, an early indicator of left ventricular dysfunction can help identify those patients at risk of disease progression. In our study we showed that there was a high prevalence of diastolic dysfunction amongst patients with liver cirrhosis at our outpatient clinic, with the majority being Child-Pugh A/low MELD score. Multiple regression analysis indicated that age and sodium levels were significantly associated with the presence of diastolic dysfunction. This further reinforces the importance of dietary sodium restriction amongst patients with liver cirrhosis.

Matched MeSH terms: Liver Cirrhosis/complications*
HBAg-positive chronic liver disease associated with cirrhosis and hepatocellular carcinoma in the Senoi

Sumithran E, Prathap K

Cancer, 1977 Oct;40(4):1618-20.
PMID: 198100

Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer.

Matched MeSH terms: Liver Cirrhosis/complications*
Fatty liver is associated with advanced fibrosis but does not predict adverse outcomes in patients with chronic hepatitis B

Wong SW, Chan WK, Mohamed R

J Viral Hepat, 2020 12;27(12):1297-1305.
PMID: 32668489 DOI: 10.1111/jvh.13361

Hepatic steatosis is increasingly common and has been implicated in progression of liver fibrosis in chronic hepatitis B (CHB) patients. We aimed to investigate the impact of hepatic steatosis on liver fibrosis and clinical outcomes in CHB patients. Consecutive CHB patients who underwent transient elastography between 2013 and 2017 at a tertiary hospital were included in this longitudinal cohort study. Presence of hepatic steatosis was defined as controlled attenuation parameter, CAP ≥ 248 dB/m, while advanced liver fibrosis was defined as liver stiffness measurement, LSM ≥ 9.4 kPa. Cardiovascular events, liver-related complications, malignancy and mortality and a composite of these outcomes were evaluated with Kaplan-Meier analysis and Cox proportional hazards regression. Our study cohort included 614 patients with median follow-up of 45 (32-63) months. Hepatic steatosis was present in 294 patients (47.9%), and advanced liver fibrosis was present in 127 patients (21.0%). Presence of hepatic steatosis (OR: 1.956, 95% CI: 1.250-3.060) and diabetes mellitus (OR: 3.507, 95% CI: 2.069-5.944) was independently associated with advanced fibrosis. Advanced fibrosis was independently associated with composite outcome (HR: 2.496, 95% CI: 1.352-4.606), liver-related complications (HR: 3.765, 95% CI: 1.380-10.271) and mortality (HR: 3.632, 95% CI: 1.342-9.826), but not cardiovascular events and malignancy. Hepatic steatosis was not associated with any adverse outcomes. We conclude that hepatic steatosis is common and associated with advanced fibrosis in CHB patients. Unlike advanced fibrosis, hepatic steatosis does not predict adverse outcomes in CHB patients.

Matched MeSH terms: Liver Cirrhosis/complications
Hepatocellular carcinoma in the Malaysian Orang Asli

Sumithran E, Prathap K

Cancer, 1976 May;37(5):2263-6.
PMID: 177187

Necropsies were performed on 285 consecutively unclaimed Orang Asli bodies from Gombak Orang Asli Hospital during an eight-year period from May 1967 to April 1975. Of the 25 malignant neoplasms, hepatocellular carcinoma was by far the commonest (36%). The nine patients with this neoplasm had coexistant macronodular cirrhosis. There were 20 cases of cirrhosis; 45% of these had coexistant hepatocellular carcinoma. The 53,000 Orang Aslis living in West Malaysia comprise three tribes, the Negrito, Senoi, and Melayu Asli (Proto Malays). The Sinoi appear to have a high predilection for liver cancer, all our nine cases occurring in this group. These aboriginal people live in the jungles where they practice shifting cultivation and maintain their own dietary and social customs. Detailed studies of their dietary habits may provide a clue to the etiology of liver cancer in these people.

Matched MeSH terms: Liver Cirrhosis/complications

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