Applicability of Risk Scores to an Indian Cohort of Hepatitis B-Related Hepatocellular Carcinoma Patients.

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Long-term entecavir therapy of chronic hepatitis B in real-life setting-Importance of quantitative HBsAg level.

BACKGROUND: The global burden of chronic hepatitis B remains high and the best possible treatment remains long-term viral suppression expecting cure. METHODS: Total 154 patients of chronic hepatitis B (48 HBeAg positive, e + ve) treated with oral entecavir (0.5 mg/1 mg per day) were recruited from June 2007 and followed prospectively until December 2022 for persistent HBV DNA negativity, HBeAg and HBsAg loss/seroconversion and other liver and drug-related events in real-life settings. RESULTS: The mean duration of therapy was 6.78 (2-14) years with 1364 person-years of follow-up. All patients were HBV DNA negative by 15 months and remained so until the last follow-up. As many as 16.7% lost HBeAg after eight to 13 years of therapy, but not HBsAg. The mean fall in serum HBsAg level per year was 0.158 log IU/mL, being significantly higher in e + ve patients at baseline and until two years of therapy. The decline was significant until six years in e + ve patients compared to two years in e - ve ones. None had biochemical or virological breakthrough (except eight defaulters), flares or any untoward effects. The incidence of liver-related events, hepatocellular carcinoma and death was 10.4%, 1.9% and 14.3%, respectively, and 5.2% deaths were liver-related whose predictors were presence of cirrhosis (log rank 46.5, p > 0.001) and higher HBsAg level > 4 log IU/mL (log rank 18.15, p < 0.001) at baseline. CONCLUSION: Long-term entecavir therapy provides additional benefits of continuous reduction of serum HBsAg levels beyond suppression of HBV DNA.

Epidemiology of Disorders of the Gut-Brain Interaction: An Appraisal of the Rome IV Criteria and Beyond.

Disorders of the gut-brain interaction (DGBIs) are presently classified into mutually exclusive anatomical area-related symptom-based categories according to the Rome IV criteria. The pathophysiology of visceral nociception, which contributes to the wide range of symptoms of DGBIs, involves complex psychobiological processes arising from the bidirectional interactions of multiple systems at the gut and brain levels, which affect symptom expression and illness behaviors. The attitude toward an illness and expression of pain and bowel habit vary across cultures with variable interpretation based on sociocultural beliefs, which may not tally with the medical definitions. Thus, psychological factors impact DGBI definitions, their severity and health care utilization. Due to the poor localization and multisegment referral of visceral pain, the anatomical site of pain may not correspond to the affected segment, and there may be a variable degree of overlap among symptoms. The somewhat restrictively defined Rome IV criteria assume one-to-one correlation of symptoms with underlying pathophysiology and ignore overlapping DGBIs, nonstandardized symptom categories, and change or shift in category over time. The microorganic nature of DGBIs resulting from systemic, metabolic or motility disorders, gut dysbiosis and inflammation are not addressed in the Rome IV criteria. Although there is a multidimensional clinical profile that does address these factors, it is not followed rigorously in practice. Threshold changes for diagnostic criteria or addition/deletion of symptoms leads to wide variation among different DGBI criteria resulting in uncertain comparability of results. Although the Rome IV criteria are excellent for research studies and therapeutic trials in homogenous populations, further improvement is needed for their wider applicability in clinical practice.

The Efficacy and Safety of Sofosbuvir and Daclatasvir Treatment in Children and Adolescents With Thalassemia and Hepatitis C Virus Infection.

Background/Aim: Thalassemia patients are susceptible to hepatitis C virus (HCV) infection due to blood transfusions. Currently, data on treating HCV in thalassemic children with direct-acting antivirals is lacking. This study was performed to determine the efficacy and safety of sofosbuvir-daclatasvir combination therapy in thalassemic children and adolescents. Methods: A nonrandomized, open-label, interventional study was carried out in a tertiary care hospital. Consecutive noncirrhotic treatment-naïve thalassemic patients with HCV infection with viremia, within the age group of 6-18 years, were treated with the combination of sofosbuvir-daclatasvir: 200 mg + 30 mg for age 6-11 years (Group A) and 400 mg + 60 mg for age 12-18 years (Group B). The primary endpoint was sustained virological response at 12 weeks (SVR12). Results: A total of 70 patients (Group A 45, 64% male; Group B 25, 40% male) were recruited. The mean age was 8.5 years and 13.9 years in the two groups. Mean HCV Ribonucleic acid (RNA) levels in Groups A and B were 446906.1 IU/ml and 256187.8 IU/ml, respectively. SVR12 was achieved in 43 of 45 (95.5%) patients on an intention-to-treat basis and 43 of 44 (97.7%) patients on a perprotocol basis in Group A, and all patients in Group B (100%). In both groups, there was a significant improvement in biochemical parameters. Among the two patients who did not achieve SVR12 in Group A, one required termination of therapy due to urticaria. Conclusion: Sofosbuvir-daclatasvir based treatment in noncirrhotic, treatment-naive thalassemic children and adolescents infected with HCV is effective and safe.

Estudo de parâmetros metabólicos em pacientes não diabéticos com doença hepática gordurosa não alcoólica - importância da dislipidemia / A study of metabolic parameters in non diabetic patients with non alcoholic fatty liver disease - importance of dyslipidemia

ABSTRACT BACKGROUND: Metabolic risk factors of non alcoholic fatty liver disease (NAFLD) in non diabetic teetotallers who constitute a definite group are not well defined. OBJECTIVE: To identify the metabolic risk factors of NAFLD if any in non diabetic subjects who do not consume alcohol. METHODS: In a cross sectional study the effect of metabolic parameters (BMI, individual lipid levels, hemoglobinA1c (HbA1c), HOMA IR and the metabolic syndrome components) of 150 consecutive non diabetic teetotallers (90 with normal glucose tolerance and 60 prediabetics) on their NFS (quantifiable severity parameter of NAFLD) was studied by linear regression analysis. Similar study was done in the normal glucose tolerance and prediabetes groups separately. These parameters were then compared with those of 75 matched diabetic teetotallers with NAFLD. To analyse further the difference between normal glucose tolerance, prediabetic and overt diabetic groups, binary logistic regression of the factors was carried out taking prediabetes and diabetes as outcome variable. RESULTS: All the metabolic parameters were significantly higher in diabetics compared to non diabetics and in prediabetics compared to those with normal glucose tolerance except high-density lipoprotein cholesterol. Triglyceride, high-density lipoprotein cholesterol and BMI significantly predicted NFS in the overall (adjusted R2 68.7%, P=0.000) and normal glucose tolerance groups (adjusted R2 73.2%, P=0.000) whereas BMI, triglyceride, low-density lipoprotein cholesterol and HbA1c did in prediabetics (adjusted R2 89%, P=0.000). The metabolic syndrome was significantly associated with NFS in the overall and prediabetic groups. High triglyceride (odds ratio1.08), low-density lipoprotein cholesterol (odds ratio1.03) and HbA1c (odds ratio 11.54) were positively associated with prediabetes compared to normal glucose tolerance group. CONCLUSION: In nondiabetic teetotallers dyslipidemias are the prime contributors to the development of NAFLD.

RESUMO CONTEXTO: Os fatores de risco metabólicos da doença hepática gordurosa não alcoólica (DHGNA) em abstêmios não diabéticos, que constituem um grupo distinto, não são bem definidos. OBJETIVO: Identificar os fatores de risco metabólicos da DHGNA em indivíduos não diabéticos e que não consumam álcool. MÉTODOS: Em um estudo transversal, o efeito dos parâmetros metabólicos (IMC, níveis de lipídios individuais, HbA1c, Homa IR e os componentes da síndrome metabólica) de 150 abstêmios não diabéticos consecutivos (90 com tolerância à glicose normal e 60 pré-diabéticos) em sua NFS (parâmetro de gravidade quantificável da DHGNA) foram estudados por análise de regressão linear. Um estudo similar em separado foi feito nos grupos normais da tolerância da glicose e do pré-diabetes. Esses parâmetros foram comparados com os de 75 abstêmios diabéticos pareados com DHGNA. Para analisar ainda mais a diferença entre a tolerância à glicose normal foi realizada a regressão logística binária dos fatores tomando pré-diabetes e diabetes como variável de desfecho, nos grupos diabéticos e pré-diabéticos. RESULTADOS: Todos os parâmetros metabólicos foram significativamente maiores nos diabéticos comparados aos não diabéticos e em pré-diabéticos comparados àqueles com tolerância normal à glicose, exceto HDL. Os índices TG, HDL e IMC previram significativamente o NFS no geral nos grupos de tolerância normal (R2 ajustado 68,7%, P=0,000) e de glicose normal (R2 ajustado 73,2%, P=0,000), enquanto o IMC, TG, LDL e HbA1c predisseram em pré-diabéticos (R2 ajustado 89%, P=0,000). A síndrome metabólica foi associada significativamente com o NFS nos grupos totais e pré-diabéticos. O TG elevado (odds ratio 1,08), o LDL (odds ratio 1,03) e a HbA1c (odds ratio 11,54) foram positivamente associados ao pré-diabetes em comparação com o grupo normal de tolerância à glicose. CONCLUSÃO: Em abstêmios não diabéticos as dislipidemias são os principais contribuintes para o desenvolvimento da DHGNA.