The long-term quality of life following liver transplantation in a developing country with a free health care system.

Introduction: Developing countries with limited resources are yet to establish universal liver transplant (LT) services to cater to their population free of charge. In this unique setting, no data are published on the long-term Quality of life (QOL) of LT survivors. Objectives: Compare the long-term quality of life of post-liver transplant patients with a matching cohort of pretransplant cirrhotic patients and a matching non cirrhotic control group. Methods: Of the 45 liver transplants that were performed there were 24 patients who completed over 6 months of follow-up. Of these, 4 patients died (including one lost to follow-up) after six months. The remaining 20 post-transplant patients were the subjects for QOL assessment. One post-transplant recipient was matched with two pre-transplant cirrhotic patients and non-cirrhotic healthy control group. QOL was evaluated by the SF-36 questionnaire. Results and conclusions: The median age was 54 years (27-67) and 85% (n=17) were male. The median follow up was 24 months (6- 94 months). The median MELD score was 17 (11-22) and 75% (n=15) were due to cryptogenic cirrhosis. Post-operatively three (15%) developed graft rejection, five (25%) had infections and ten (50%) suffered drug related complications. 95% (n= 19) of the population had satisfactory drug compliance. The study population had significantly better QOL compared to control in all eight domains (p<0.05) including physical functioning (76% vs 52.7%), physical health (80% vs 7.9%), emotional problems (93% vs 17.1%), energy (77% vs 47%), emotional wellbeing (80% vs 61.1%), social functioning (86.9% vs 56.9%), pain (82% vs 47.5%) and general health (67.5% vs 37.5%). The study population had similar quality of life compared to the healthy control group with better-perceived emotional well-being. Conclusion: Long-term survivors after LT have significantly improved QOL in a setting with limited resources.

Validation of the World Health Organization/ International Society of Hypertension (WHO/ISH) cardiovascular risk predictions in Sri Lankans based on findings from a prospective cohort study.

INTRODUCTION AND OBJECTIVES: There are no cardiovascular (CV) risk prediction models for Sri Lankans. Different risk prediction models not validated for Sri Lankans are being used to predict CV risk of Sri Lankans. We validated the WHO/ISH (SEAR-B) risk prediction charts prospectively in a population-based cohort of Sri Lankans. METHOD: We selected 40-64 year-old participants from the Ragama Medical Officer of Health (MOH) area in 2007 by stratified random sampling and followed them up for 10 years. Ten-year risk predictions of a fatal/non-fatal cardiovascular event (CVE) in 2007 were calculated using WHO/ISH (SEAR-B) charts with and without cholesterol. The CVEs that occurred from 2007-2017 were ascertained. Risk predictions in 2007 were validated against observed CVEs in 2017. RESULTS: Of 2517 participants, the mean age was 53.7 year (SD: 6.7) and 1132 (45%) were males. Using WHO/ISH chart with cholesterol, the percentages of subjects with a 10-year CV risk <10%, 10-19%, 20%-29%, 30-39%, ≥40% were 80.7%, 9.9%, 3.8%, 2.5% and 3.1%, respectively. 142 non-fatal and 73 fatal CVEs were observed during follow-up. Among the cohort, 9.4% were predicted of having a CV risk ≥20% and 8.6% CVEs were observed in the risk category. CVEs were within the predictions of WHO/ISH charts with and without cholesterol in both high (≥20%) and low(<20%) risk males, but only in low(<20%) risk females. The predictions of WHO/ISH charts, with-and without-cholesterol were in agreement in 81% of subjects (ĸ = 0.429; p<0.001). CONCLUSIONS: WHO/ISH (SEAR B) risk prediction charts with-and without-cholesterol may be used in Sri Lanka. Risk charts are more predictive in males than in females and for lower-risk categories. The predictions when stratifying into 2 categories, low risk (<20%) and high risk (≥20%), are more appropriate in clinical practice.

Challenges for Liver Transplantation During Recovery From the COVID-19 Pandemic: Insights and Recommendations.

The coronavirus disease 2019 (COVID-19) pandemic is placing an increasing burden on liver transplant (LT) services worldwide. At the peak of the pandemic, many LT services worldwide reduced or halted their activities. With the gradual easing of lockdowns, LT teams face new challenges when restarting activities. The numbers of LTs are likely to drop in the immediate post-COVID era. Prolonged and intermittent lockdowns are likely to lead to a shortage of supplies, especially in poor resource settings. Special attention is needed to avoid nosocomial COVID-19 infection among cirrhotic patients awaiting transplant, post-transplant patients, and members of transplant teams. LT programs may have to revise existing strategies in selecting donors and recipients for transplants. Redesigning service provision, restructuring outpatient care, carefully screening and selecting donors and recipients, and performing LT with limited resources will have to be initiated in the post-COVID era if long-term recovery of LT services is to be expected. Costs involved with LT are likely to increase, considering the change in protocols of testing, quarantining, and interstate traveling. This paper discusses the different elements affecting and the widespread impact of the COVID-19 pandemic on LT and strategies to minimize the impact of these factors and to adapt so LT services can meet the health care needs during this pandemic and beyond.

Clinical characteristics and outcomes of hepatocellular carcinoma: results from prospective study, from a tertiary referral center in 
Sri Lanka

Introduction: Hepatocellular carcinoma is increasing globally. Compared to global patterns, hepatitis B and C are rare in Sri Lanka whilst non-alcoholic fatty liver disease (NAFLD) and alcohol are the commonest causes of hepatocellular carcinoma. Objectives: To determine the characteristics of a cohort of Sri Lankan patients with hepatocellular carcinoma of non-viral aetiology. Methods: Details of 550 consecutive patients with hepatocellular carcinoma referred from 2012 to 2017 were collected prospectively. Demographic data, clinical and biochemical details, aetiology, comorbidities, tumor characteristics and type of treatment offered were retrospectively analyzed. Results: Median age was 62.9 years (range 12 - 88) with male preponderance (n = 473; 86%). Overall median BMI was 35.8 kgm-2. Majority (n=309; 56 %) had NAFLD induced cirrhosis, second commonest cause was alcohol (n=203;36.9 %). Tumour was single nodular 233(42.4%) and diffusely infiltrating 92(16.7%). Diagnostic rise in serum alpha-fetoprotein (over 200 micrograms) was seen in 30.2%. Venous invasion was present in 28.5% [portal vein 136 (24.7%), hepatic vein 9 (1.6%) and cava 12(2.2%)]. Extra hepatic tumor spread was seen in 6.9% [lungs 20(3.6%), bones 4(0.7%), peritoneal 6 (1.1%) and metastases at other sites 8 (1.45%)]. Curative surgery was offered in 78(14.2%). Tumour embolization was done in 192(34.9%), radio frequency ablation 34(6.2%), alcohol injection 42(7.6%) and 204(37.1%) patients were offered palliative care. Overall median survival was 20.6 months. Conclusions: In a large Sri Lankan cohort, most hepatocellular carcinomas were due to cryptogenic cirrhosis and it was aggressive at presentation. Screening of high-risk NAFLD patients needs to be considered and further palliative care needs to be improved.

The prevalence of upper respiratory symptoms in a cohort of adults presenting with symptoms of gastro-oesophageal reflux disease.

INTRODUCTION: Gastro-oesophageal reflux disease (GORD) is the pathological reflux of gastric contents into the oesophagus. The oesophagus and the upper respiratory tract have a common origin from the foregut. There is increasing evidence for multiple associations of GORD with the upper respiratory tract. OBJECTIVES: To study the presence of and association of upper respiratory symptoms (URS) with GORD. METHODS: Seventy adults scoring ≥12.5 on a previously validated GORD symptom score (GORD patients) and 70 healthy controls who had infrequent GORD symptoms or no upper gastro-intestinal complaints completed a pre-tested URS questionnaire on the frequency of 14 URS in 5 categories (laryngeal, nasal, pharyngeal, sinusal and aural). All GORD patients underwent upper gastro-intestinal endoscopy. The calculated URS score was correlated against the GORD symptom score and endoscopy findings. RESULTS: URS scores and individual symptom scores were higher in GORD patients compared to controls (mean ± SE, 4.7 ± 4.0; 1.9 ± 2.3). Individuals with higher GORD symptom scores reported more frequent URS. Pharyngeal symptoms had the highest correlation with the GORD symptom score (r=0.507, p<0.001). The presence of oeso-phagitis did not seem to influence the frequency of reporting URS. CONCLUSION: Upper respiratory symptoms are common in individuals with GORD symptoms though there appears to be no association with oesophageal mucosal damage.

Association between road accidents and low-grade hepatic encephalopathy among Sri Lankan drivers with cirrhosis: a prospective case control study.

BACKGROUND: Low-grade hepatic encephalopathy (LGHE) comprises minimal hepatic encephalopathy (MHE) and grade 1 hepatic encephalopathy. LGHE has no or minimal recognizable symptoms but has mild cognitive and psychomotor deficits. Studies in Western countries have demonstrated increased road accidents (RA) among patients with MHE. Our objective was to investigate the association between Sri Lankan LGHE phenotype and RA. STUDY DESIGN AND METHODS: A prospective, case-control study was conducted in the University Medical Unit, North Colombo Teaching Hospital, Ragama Sri Lanka. Patients with cirrhosis of any aetiology, without OHE, who had been driving during previous 1 month were included. A similar number of age matched, healthy control drivers were also enrolled. Both groups were subjected to five pencil-paper based psychometric tests used to detect LGHE in cirrhotics. Self-reported RA during the previous 1 month were recorded: categorized as 'major' when resulted in hospitalization of the involved, 'minor' when there were injuries, but not serious enough for hospitalization of the involved and 'other' when limited to damages to vehicle or environment without injuries. RESULTS: Among 55 drivers with cirrhosis and LGHE [males, median age 53 years (range 30-60)], 7 (12.7 %) reported RA compared to 6 (10.9 %) among 55 controls [males; median age 51 years (range 30-60)]. There were no 'major' accidents in either group. 2/55 (3.6 %) cases and 2/55 (3.6 %) controls reported 'minor' accidents. CONCLUSION: There was no increased frequency of RA among Sri Lankan drivers with LGHE compared to healthy controls. This is with the limitation of the study based only on self reported RA.

Cryptogenic cirrhosis is the leading cause for listing for liver transplantation in Sri Lanka.

Hepatitis B and C are rare in Sri Lanka. Nonalcoholic fatty liver disease is increasing in the country. Eighty-one patients referred for liver transplantation (LT) over a period of 18 months were prospectively evaluated. Ninety-two percent (n = 74) were males. Cryptogenic cirrhosis was the leading indication for LT (58%, n = 47) followed by alcohol in 27% (n = 33). Hepatitis B and C were not seen in our cases. The liver biochemistry and clinical status of cirrhosis were similar in cryptogenic and alcoholic cirrhotics. Fourteen patients died while waiting for transplant, and nine transplants were performed. Cryptogenic cirrhosis is the leading cause for LT in Sri Lanka.

Validation of the Sinhala version of the Chronic Liver Disease Questionnaire (CLDQ) for assessment of health related quality of life among Sri Lankan cirrhotics.

OBJECTIVES: The Chronic Liver Disease Questionnaire (CLDQ) is a validated tool measuring Health Related Quality of Life among patients with cirrhosis. The aim of this study was to validate a Sinhala version of the CLDQ (sCLDQ) and to test its correlation with the degree of liver dysfunction in a cohort of Sri Lankan patients with cirrhosis. METHODS: A standard translation method was used. Pilot testing was done with relevant cultural and language adaptations. The final version and the WHO Quality of Life-BREF (WHOQOL-BREF) validated Sinhala version were administered to patients with chronic lever disease (CLD). sCLDQ was re-administered 4 weeks later to test internal consistency and reliability. The validaty and reliability were assessed by Cronabach's alpha, intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. ANOVA and Pearson's correlation were used to assess correlation with the degree of liver dysfunction. RESULTS: Validation was done with 214 participants [mean age 55.6 years (SD 10.4) male 77.6%]. Cronabach's alpha was 0.926. Intra-class correlations varied from 0.431 to 0.912 and all were significant (p< 0.001). Retesting was done on a sub-sample of 18 participants. Test-retest correlation was 0.695 (p = 0.008). WHO-BREF was administered to a sub-sample of 48 subjects. There was a significant correlation (Pearson's r=0.391; p=0.004) between sCLDQ and WHOQOL BREF. sCLDQ was significantly associated with MELD (r=-0.13; p=0.038), MELD sodium (r=-0.223; p=0.002), serum bilirubin (r=-0.124; p=0.036), serum sodium (r=0.172; p=0.009), serum albumin (r=0.201; p=0.003) and Child grade (f=3.687; p=0.027). CONCLUSIONS: CLDQ is a reliable and valid tool to assess quality of life of Sri Lankan patients with cirrhosis and correlates well with known indices of disease severity.

Advanced hepatic fibrosis and cirrhosis due to nonalcoholic fatty liver disease in Sri Lankan children: a preliminary report.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and may progress to advanced hepatic fibrosis and cirrhosis in some patients. Cirrhosis due to NAFLD is considered extremely rare in children in the Asia-Pacific region. We report the characteristics of 5 children with advanced hepatic fibrosis and cirrhosis due to NAFLD. Four of them were obese, and all of them had high alanine transaminase levels and ultrasonographic evidence of fatty liver. None had diabetes mellitus or hyperlipidemia. The calculated HOMA-IR was more than two in all five cases. Liver biopsy showed stage III fibrosis in 2 patients and stage IV fibrosis (cirrhosis) in 3.

Treatment of lamivudine-resistant hepatitis B infection in post-renal transplant patients with adefovir dipivoxil: preliminary results.

We report the treatment outcome in six post-renal transplant patients with lamivudine-resistant hepatitis B virus (LR-HBV) infection using adefovir dipivoxil and followed for 6 to 18 months. Posttransplant immunosuppressive therapy was not altered. Adefovir dipivoxil effectively suppressed hepatitis B virus DNA and improved alanine transferase, although DNA suppression seemed dependent on continued therapy. Nephrotoxicity led to withdrawal of the drug in three patients. This may limit therapeutic usefulness in a significant proportion of post-renal transplant patients with LR-HBV infection.

Comparison of one week and two weeks of triple therapy for the eradication of Helicobacter pylori in a Sri Lankan population: a randomised, controlled study.

INTRODUCTION: Resistance of Helicobacter pylori to antibiotics may be particularly high in parts of the tropics. Infection may prove difficult to eradicate in such situations, and there is some evidence of benefit in increasing the duration of treatment (triple therapy) from 1 week to 2 or 3 weeks. AIM: To assess the efficacy and tolerability of 1 week versus 2 weeks of triple therapy for eradication of H. pylori in a Sri Lankan population. METHODS: Eighty two patients aged 18-70 years with gastritis or peptic ulcer and testing positive for H. pylori infection were randomly allocated to two treatment groups. Both groups received omeprazole 20 mg, clarithromycin 250 mg, and tinidazole 500 mg. Group A (n = 42) received the trial medication twice daily for 1 week and the Group B (n = 40) twice daily for 2 weeks. H. pylori eradication was defined as a negative 14C labelled urea breath test at 2 weeks after completion of the therapy. RESULTS: H. pylori infection was eradicated in 36 (85.7%) patients in Group A and 36 (90%) patients in Group B (p = 0.9). Twenty three (55%) patients in Group A and 17 (43%) in Group B reported adverse effects attributable to trial medication (p = 0.387); none were serious. Three (7.5%) patients in Group B discontinued treatment due to adverse events that developed on days 7, 9 and 10. CONCLUSION: Twice daily treatment with clarithromycin, tinidazole, and omeprazole for 1 week is well tolerated and provides as good a rate of H. pylori eradication as 2-week therapy in Sri Lankan patients.

Safety of subcutaneous adrenaline as prophylaxis against acute adverse reactions to anti-venom serum in snakebite.

OBJECTIVES: To study the safety of low dose subcutaneous adrenaline given as prophylaxis against acute adverse reactions to anti-venom serum (AVS) in patients bitten by snakes. METHODS: Patients admitted with snakebite envenoming who satisfied inclusion criteria were given 0.25 ml of 1:1000 adrenaline subcutaneously immediately before administration of AVS. They were observed for adverse effects, and pulse and blood pressure (BP) were monitored. RESULTS: 51 patients [35 males, mean age 34.8 years (SD 14)] were included in the study. Adverse reactions to AVS occurred in 15 (29.4%) patients. There was one death from suspected cerebral haemorrhage, and 3 (5.9%) patients developed small haematomas at the subcutaneous injection site. There were no significant changes in mean pulse or BP following administration of subcutaneous adrenaline. CONCLUSIONS: Low dose subcutaneous adrenaline did not cause significant changes in pulse rate or BP. Although the death was unlikely to be directly related to subcutaneous adrenaline, we suggest further studies on the safety of this prophylactic treatment before its routine use.

Variable expression of cathepsin B and D correlates with highly invasive and metastatic phenotype of oral cancer.

The expression levels of cathepsins B, D, and L in oral cancer surgical specimens were determined using immunocytochemical analysis. Cathepsins B and D are frequently overexpressed in squamous cell carcinomas, whereas their overexpression was less frequent in verrucous carcinoma and basaloid squamous cell carcinomas. Elevated level of cathepsin B in oral carcinomas was significantly associated with advanced tumor stage (P < .05) and poor histologic malignancy grade (P < .001). Increased expression of cathepsin D correlated significantly with the presence of metastasis (P < .05), poor histologic malignancy grade (P < .001), and high proliferation rate (P < .05). Cathepsin L was less frequently overexpressed in oral cancers than cathepsin B and D. These findings indicate that there is a strong cause/effect relationship between the expression levels of cathepsin B and D in oral cancers and their local invasive and metastatic growth patterns. Thus, cathepsins B and D are useful prognostic markers as well as promising gene therapy targets for oral cancer.