Systematic review: combination therapies for treatment-naïve chronic hepatitis B

Background: There is a renewed interest in use of combination therapies in treatment-naïve chronic hepatitis B (CHB) because of limitations of monotherapies. Aim: To discuss the current status of combination therapies in treatment-naive CHB. Methods PubMed search was done using 'combination', 'sequential' and 'chronic hepatitis B' as the search terms. Results: The two most popular combination therapies include 'combination of nucleos(t)ide analogues' and 'combination of interferons and nucleos(t)ide analogues'. Combination therapies using two nucleos(t)ide analogues do not lead to higher long-term efficacy. However, addition of a nucleos(t)ide analogue with a good resistance profile to a nucleos(t)ide analogue with a lower genetic barrier to resistance decreases the risk of emergent resistance to the latter. Greater sustained virological, biochemical and seroconversion rates are observed with addition of lamivudine to conventional interferon, but pegylated-interferon monotherapy is equally effective as combination with lamivudine. Again, resistance to lamivudine is lower with its combination with interferons. Conclusions: The answer to the question whether hepatitis B can be treated better with combination or monotherapy remains largely unknown. Additional trials are warranted of combination therapies of peginterferon and potent nucleos(t)ide analogues or therapies with the combined use of nucleos(t)ide analogues or immunomodulators

Health problems in geriatric population of age group ≥70 years in rural Kerala, India: a cross sectional study

Background: The proportion of elderly population is increasing considerably world over. The health and socio-economic issues of this section is to be considered separately and in depth insights about them is needed for formulating elderly friendly health policy. This study intends toidentify the important health concerns of elderly population above the age group of 70 years in a rural area in North Kerala, India.Methods: It is a community based cross-sectional descriptive study involving all individuals above the age group of 70 years in a randomly selected panchayath ward from rural North Kerala. The data regarding demography, socioeconomic aspects, medical history, access to health care and treatment of chronic illnesses were collected through interview of study participants by a trained health care volunteer using a pre-validated questionnaire.Results: A total of 93 individuals above the age group of 70 years were included in the study out of which 63% were females and 37% males. In the study population 55.9% of the elderly were widowed and 87.1 % were staying along with their children. Almost 75% of the elderly received social welfare pension from government agencies and 14.3% received service pensions. 67.74% of the study population were hypertensive and 35.56% were diabetic. Other health issues included arthritis, coronary artery disease, chronic kidney disease, genito urinary symptoms and cerebrovascular accident.Conclusion:  The study provide valuable insights into the health and social issues of elderly in Kerala and points to the importance of formulating an elderly friendly health policy in the state

Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease

Background: Small-intestinal bacterial overgrowth (SIBO) is known to be present in patients with cirrhosis, predisposing to various complications. Aim To determine the frequency of SIBO in cirrhotics and correlate with severity of cirrhosis. Methods: Small-intestinal bacterial overgrowth was determined by glucose-hydrogen breath test (GHBT). A basal breath-hydrogen >20 ppm or a rise by ≥12 ppm above baseline following glucose administration was taken as positive test. Prevalence of SIBO in cirrhotics was compared with healthy controls and correlated with severity of cirrhosis. Results: Of the 53 cirrhotics, 26 (49%) had SIBO, compared to one (8%) control (P = 0.010). The prevalence of SIBO increased with severity of cirrhosis (Child-Pugh A 20%, B 52% and C 73%; P = 0.013). On multivariate analysis, SIBO was independently associated with serum bilirubin and ascites. The best cut-off of serum bilirubin was ≥2 mg/dL [AUROC 0.77 (95% CI 0.64-0.90)] predicting SIBO with sensitivity 65%, specificity 81%, positive predictive value 77%, negative predictive value 71% and accuracy 74%. Patients having combination of ascites and serum bilirubin ≥2 mg/dL had 82% chance, while patients having neither had only 10% chance of having SIBO. Conclusions: Small-intestinal bacterial overgrowth was prevalent in about half of cirrhotics. Its frequency increased with increase in severity of cirrhosis. Ascites and raised serum bilirubin reliably predicted presence of SIBO

COVID-19 Vaccine Effectiveness in Preventing Severe Infections and Mortality among Patients in Kerala, India.

ABSTRACT Background: India has a top status among world countries, related to the COVID-19 mortality that had crossed the 3-lakh level. The second wave of COVID19 had ravaged the world countries, created havoc of the highest order, leaving many hapless, thanks to the low availability of oxygen, ICU facilities, vaccines and counselling prospects. There is a lack of information about how COVID-19 vaccines have affected mortality in specific geographic areas. Method: A Retrospective record-based design. Patients were matched for age, sex, ethnicity, co-morbidities and grouped into fully immunized, partially immunized and non-immunized. The primary outcome was in-hospital deaths and secondary outcome was severe covid infections. (Severe covid infections are defined as Category C in WHO and ICMR classification) Results: Vaccines administered in standard dosage confer considerable benefit by reducing severe illness, hospitalization and death. This is clearly visible by the lower proportions of those with hypoxia, high levels of markers, those requiring ICU support and death in vaccinated individuals. The type of vaccine administered did not have any influence on the severity and outcome of illness. Conclusion: The second wave that peaked in May 2021 would have been less disastrous had more people been vaccinated. Without a reimagined vaccination strategy, reaching the desired full vaccination status was a difficult endeavor. The signs are unmistakable that a combined approach involving swift vaccination and scientific measures to curb transmission holds great promise. A zero covid world looks less imminent. But humans can make the microbe less lethal

Early identification of haemodynamic response to pharmacotherapy is essential for primary prophylaxis of variceal bleeding in patients with 'high-risk' varices

Background: A beta-blocker is recommended for primary prophylaxis of variceal bleeding; however, only one-third have hepatic venous pressure gradient (HVPG) response. The role of addition of isosorbide-5-mononitrate (ISMN) to beta-blocker and benefits of HVPG-guided 'a la carte' approach remain unclear. Aim: To determine the benefits of HVPG-guided pharmacotherapy in primary prophylaxis of variceal bleeding using beta-blocker and ISMN. Patients and methods: Consecutive patients of cirrhosis, with high-risk varices, with no previous variceal bleeding were included. After baseline HVPG, patients received incremental propranolol to achieve HR of 55/min. After one-month, HVPG was repeated to determine response (<12 mmHg or ≥20% reduction). ISMN was added in nonresponders and HVPG repeated. Patients were followed up for 24 months. Results: Of 56 patients (age 47 ± 13, males 79%) from 89 eligible patients, 21 (38%) responded to beta-blocker alone. Six additional patients responded to combination. Thus, overall 48% (27/56) patients responded. Variceal bleeding occurred in seven of 56 (13%) patients [one of 27 (4%) responder, five of 23 (22%) nonresponders and one of six (17%) with unknown response; P = N.S.]. The actuarial probability of variceal bleeding at median 24 months was 4% in responders and 22% in nonresponders (P < 0.05). Ten (18%) patients developed adverse effects to propranolol and six of 35 (17%) to nitrates requiring dose reduction. Risk factors of variceal bleed were grade IV varices and haemodynamic nonresponse. Conclusions: For primary prophylaxis, a beta-blocker is effective in 38% and addition of ISMN raises the response rate to about half of patients. The HVPG-guided 'a la carte' approach may be considered for these patients

A randomized controlled trial of lamivudine to treat acute hepatitis B

The role of antivirals in patients with acute viral hepatitis B (AVH-B) has not been evaluated in controlled trials. The aim of this study was to evaluate the efficacy of lamivudine in patients with AVH-B. AVH-B patients with serum bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of lamivudine daily for 3 months (group 1, n = 31) or placebo (group 2, n = 40). Patients were considered to have severe AVH-B if they fulfilled 2 of 3 criteria: (1) hepatic encephalopathy; (2) serum bilirubin ≥ 10.0 mg/dL; and (3) international normalized ratio (INR) ≥ 1.6. At week 4, HBV DNA levels were significantly lower (P = 0.037) in group 1 (median: 3.6721 log copies/mL) than group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR values was similar in the 2 groups. Twenty-two patients (71%) in group 1 and 25 patients (62.5%) in group 2 had severe AVH-B. Results were similar when patients with severe AVH-B were analyzed separately. After 12 and 18 months, 93.5% and 92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%, respectively, of patients in the placebo group lost HBsAg. There were no deaths in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients (85%) in group 2 developed protective anti-HBs titers (P = 0.096). All HBeAg-positive patients in both groups lost e antigen and anti-HBe developed in 71% and 87.5% of patients in groups 1 and 2, respectively (P = 0.132). Conclusion: Though lamivudine causes a greater decrease in levels of HBV DNA, it does not cause significantly greater biochemical and clinical improvement as compared to placebo in patients with acute hepatitis B

Analysis of cerebrospinal fluid adenosine deaminase level in tuberculous meningitis and validation of sensitivity and specificity

Background: Tuberculous meningitis is an important cause of morbidity and mortality in developing countries especially in India. The mortality associated with tuberculous meningitis is very high if not detected early and meticulous treatment is not given. CSF analysis and imaging are the most commonly used tools for diagnosis of meningitis. But these are often inadequate in making a definitive diagnosis. CSF Adenosine Deaminase estimation (ADA) is useful in differentiation of tuberculous meningitis from non-tuberculous meningitis. Though few studies have proved efficacy of Adenosine Deaminase level for the diagnosis, studies to assess the sensitivity and specificity of ADA levels were limited. This study was conducted to assess its usefulness and to validate the sensitivity and specificity of ADA level in tuberculous meningitis (TBM).Methods: This was a prospective study conducted at Academy of Medical Sciences, Pariyaram for a period of 18 months from December 2013 to June 2015, Adenosine deaminase level was studied in the cerebrospinal fluid of 50 patients who got admitted with symptoms and signs of meningitis in the medical wards and intensive care units who fulfilled the inclusion criteria.Results: In this study 50 patients were diagnosed clinically and with CSF analysis as meningitis. The mean cerebrospinal fluid adenosine deaminase activity was 23.08+17.5in Tuberculous meningitis 3.8 +1.92U/l in Bacterial meningitis and 4.8+2.3U/l in Viral meningitis. The adenosine deaminase activity in Tuberculous meningitis cases were significantly higher than non-tuberculous meningitis. The sensitivity and specificity of this test for diagnosis of tuberculous meningitis was 90% and 100% respectively with ADA value of more than 10U/L.Conclusions: This study found out that estimation of CSF Adenosine level is a very useful test for the diagnosis of tuberculous meningitis. The sensitivity and specificity attained in this study were comparable to other studies. This study also found out that ADA estimation is very useful in distinguishing tuberculous and viral meningitis

Study to assess the changing pattern of clinical profile and determine the prognosis in hepatic encephalopathy

Background: Hepatic encephalopathy (HE) is a common complication of liver disease that requires intensive care management. The prevalence of HE is increasing during recent period. The most important factors of HE are alcohol consumption, chronic hepatitis, hepatotoxic drugs and unhealthy changes in life style. There were only relatively few studies from our region on the changing profile of hepatic encephalopathy under the background of life style changes. This study was conducted with the aim to detect the changing pattern of clinical profile, precipitants and to assess the prognosis of patients with hepatic encephalopathy.Methods: This was a prospective study for a period of 18 months since January 2012 at Academy of Medical Sciences, Pariyaram, Kannur, a tertiary care centre situated in the northern part of Kerala. Patients admitted in the medical and gastroenterology wards and intensive care units that fulfilled the inclusion criteria were enrolled in this study.Results: Among the 76 patients with HE, 60 were suffering from CLD and 16 due to acute liver failure. The common etiologies for HE in CLD patients were Alcoholic cirrhosis (63%), Cryptogenic cirrhosis (17%) and cirrhosis due to chronic HBV (10%) and HCV hepatitis (7%) respectively. Among the CLD patients at the start of observation majority were in Child Pugh class B and C. Based on West Haven grading most of them had Grade 2 and 3 HE. Majority with Grade 1, 2 and 3 improved where as those with Grade 4 and Grade 3 in Child Pugh class C worsened. The common precipitants of HE were GI bleed, dyselectrolemia, constipation and infections. Among these precipitants a statistically significant association for a worse outcome was present only with infection. Leptospirosis and deliberate self-harm due to ingestion of hepatotoxic rodenticide and paracetamol were the leading cause of hepatic encephalopathy in acute liver failureConclusions: In present study HE was most commonly seen in patients with alcoholic liver disease. Cryptogenic cirrhosis associated with other life style diseases was the second common condition. Among all precipitating factors infection appeared as a statistically significant factor predicting a worse outcome. Health education among alcoholic patients and life style modifications to prevent cryptogenic cirrhosis are of paramount importance in curtailing the increase in incidence of HE in this region

Histological subclassification of cirrhosis based on histological-haemodynamic correlation

Background: Determining a relationship between specific histological parameters in cirrhosis and hepatic venous pressure gradient can be used to subclassify cirrhosis. Aim: To determine the relationship between hepatic venous pressure gradient and specific histological parameters in cirrhosis. Methods: Forty-seven patients (mean age: 46.2 ± 13.6 years; 36 male) with biopsy-proven cirrhosis and hepatic venous pressure gradient measurements within 1 month of biopsy were studied. The following histological parameters were scored semiquantitatively: nodule size, loss of portal tracts and central veins, portal inflammation, periportal inflammation, bile duct proliferation, lobular inflammation, ballooning, fatty change, cholestasis and septal thickness. Results: On multiple ordinal regression analysis, small nodule size (odds ratio: 21.0; 95% confidence interval: 2.1-208.2, P = 0.009) and thick septa (OR: 42.6; CI: 2.3-783.7, P = 0.011) were significantly associated with the presence of clinically significant portal hypertension. A score was assigned to each of the two parameters (nodule size: large = 1, medium = 2, small = 3 and septal thickness: thin = 1, medium = 2, thick = 3). Two subcategories were devised based on the composite score: category A (n = 12): score 1-3 and category B (n = 35): score 4-6. On ordinal regression, subcategory B (OR: 15.5; CI: 3.3-74.2, P = 0.001) was significantly associated with clinically significant portal hypertension. Conclusion: Small nodularity and thick septa are independent predictors of the presence of clinically significant portal hypertension