The potential liver donor with tuberculosis: A fresh look at international recommendations based on a survey of practice in Indian liver transplant centres.

Background The western recommendations for the use of organs from liver donors with tuberculosis (TB) come from an environment where the burden of disease is low and cadaveric organ donation rates are high-in complete contrast to the Indian scenario, where these recommendations may be too restrictive. Methods A questionnaire relating to current practice on the use of organs from liver donors with TB was sent to all liver transplant centres in India. Results Responses were obtained from 94% of centres. Two-thirds accepted organs from deceased donors with TB in the elective setting, especially for recipients with a high MELD (Model for end-stage liver disease) score. The proportion rose by 1.5 times in the setting of acute liver failure. Two-thirds advised anti-TB treatment (ATT) for corresponding recipients, and the remaining advised isonicotinic acid hydrazide (INH) prophylaxis. Untreated living donors with TB were not accepted. Half the respondents accepted living donors after completion of ATT, and did not treat recipients postoperatively. The remainder accepted them after 8 weeks of treatment and advised INH prophylaxis or ATT for recipients. Conclusions That this practice has not impacted recipient outcomes suggests that the guidelines for management of liver donors and recipients may need to be altered for populations endemic for TB.

Current and New Drugs for COVID-19 Treatment and Its Effects on the Liver.

Corona virus disease (COVID)-19 is caused by the novel severe acute respiratory syndrome coronavirus-2 (commonly referred to as SARS-CoV-2). In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. Though the target organ for the virus is primarily the lungs, with the recent understanding of the pathobiology of this disease and the immune dysregulation associated with it, it is now clear that COVID-19 affects multiple organ systems. Several drugs and therapies have been tried or repurposed to combat the wrath posed by this disease. On October 22, 2020, the USA Food and Drug Administration approved remdesivir for use in adults and pediatric patients (12 years of age and older). Several of the drugs being tried against COVID-19 have hepatotoxicity as their potential side effect. This review aims to provide the latest insights on various drugs being used in the treatment of COVID-19 and their effects on the liver.

Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting.

BACKGROUND & AIMS: The prevalence of anti-hepatitis C virus antibody in Punjab, India is 3.6%, with 728,000 people estimated to have viremic chronic hepatitis C (CHC). The Mukh-Mantri Punjab Hepatitis C Relief Fund, launched on 18th June 2016, provides no-cost generic direct-acting antivirals (DAAs) with sofosbuvir + ledipasvir ±â€¯ribavirin or sofosbuvir + daclatasvir ±â€¯ribavirin with the goal of eliminating CHC from Punjab. We assessed the safety and efficacy of decentralized treatment of CHC in a public health care setting. METHODS: Primary care providers from 3 university and 22 district hospitals were trained to provide algorithm-based DAA treatment and supervised by telehealth clinics conducted fortnightly. The diagnosis of cirrhosis was based on clinical and radiological evidence, including aspartate aminotransferase-to-platelet ratio index (APRI ≥2.0) and FIB-4 score (>3.25), or on liver stiffness measurement ≥12.5 kPa on Fibroscan®. RESULTS: We enrolled 48,088 individuals with CHC (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhosis; 69.9% genotype [GT] 3) between 18th June 2016 to 31st July 2018. While 36,250 (75.4%) patients completed treatment, 5,497 (11.4%) had treatment interruptions and 6,341 (13.2%) patients are currently ongoing treatment. Sustained virological response at 12 weeks after treatment completion (SVR12) was achieved in 91.6% of patients per protocol, 67.6% in intention-to-treat (ITT) analysis, where all interruptions were treated as failures, and 91.2% in a modified ITT analysis where all patients with successful SVR12 in the interruptions arm were included as cured. SVR12 rates in patients with and without cirrhosis and GT3 versus non-GT3 were comparable. The SVR12 rate was 84.4% in patients who had treatment interruptions. CONCLUSION: Decentralized care of patients with CHC using generic all-oral DAA regimens is safe and effective regardless of genotype or presence of cirrhosis. ClinicalTrials.gov number: NCT01110447. LAY SUMMARY: We assessed the safety and efficacy of public health care using no-cost all-oral generic direct-acting antiviral drugs against hepatitis C in the state of Punjab, India. The goal is elimination of chronic hepatitis C (CHC) by 2030 and involves primary care providers at 25 sites in the state. We enrolled 48,088 individuals (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhotic; 69.9% genotype 3) between 18th June 2016 to 31st July 2018. Cure was achieved in 91.6% of patients, demonstrating that decentralized care of CHC with generic all-oral regimens is safe and effective.

Direct-acting antiviral Therapy Is Safe and Effective in Pediatric Chronic Hepatitis C: The Public Health Perspective.

OBJECTIVES: We assessed the efficacy of decentralized public health services and safety of direct-acting antiviral agents (DAAs) in the treatment of pediatric chronic hepatitis C (CHC) in the Mukh-Mantri Punjab Hepatitis C Relief Fund, a public-health initiative for prevention and control of CHC in Punjab, India. METHODS: Consecutive children with CHC [age ≥12 to <18 years; both treatment-naïve (TN) and treatment-experienced (TE)] were enrolled. Genotyping was not recommended for non-cirrhotic patients and were treated with sofosbuvir (SOF)+ daclatasvir (DCV) for 12 weeks, while genotyping was recommended for patients with cirrhosis. Patients with cirrhosis and genotype (G2) were treated with SOF+DCV+ribavirin (RBV) for 12 weeks, G3 with SOF+DCV+RBV for 24 weeks and G1, 4, 5, and 6 patients were treated with SOF+ledipasvir (LDV)+RBV for 12 weeks. Treatment duration was increased to 24 weeks if RBV was not tolerated. RESULTS: In the first 16 months (June 18, 2016-October 31, 2017), 88 children (mean age 15.8 years; 69.3.3% boys, 72.3% rural) were enrolled. The mean baseline hepatitis C virus RNA log10 IU/mL was 6.0 (range 4.2-7.5 log10 IU/mL), 65.5% with G3, and 2 (2.5%) with cirrhosis. Of 57 with completed treatment, sustained virological response (SVR) 12 was achieved in 56 (98.2%). Unsafe medical practices (55.5%), IV drug abuse (11.1%), and prior surgery (2.7%) were risk-factors for transmission (n = 36). Comparable results were noted in G3 (SVR at 12 weeks [SVR12], 94.3%) versus non-G3 (SVR12, 100%; P = 0.073). No serious adverse effects like anemia and decompensation were reported. CONCLUSIONS: The study demonstrates that the decentralized algorithm-based public-health program can ensure high efficacy (SVR12, 98.2%) and low-cost DAA-based treatment of pediatric patients with CHC.

Monocyte human leukocyte antigen - Antigen D related, neutrophil oxidative burst and cytokine analysis in patients of decompensated cirrhosis with and without acute-on chronic liver failure.

BACKGROUND AND AIM: Due to a dysregulated immune response, patients with acute-on-chronic liver failure (ACLF) have increased risk of infection and multi organ failure in comparison to compensated cirrhosis. The comparative data on the presence of 'immune paresis' in patients with ACLF and decompensated cirrhosis without ACLF is not available. Aim of the present study was to compare the immunological parameters in patients with decompensated cirrhosis with and without ACLF. METHODOLOGY: In a prospective study, 76 patients with decompensated cirrhosis with (n = 38) and without (n = 38) ACLF and 10 healthy controls (HC) were evaluated for monocytic human leukocyte antigen-antigen D Related (HLA-DR) expression, mean density of HLA-DR expressed on the surface of these cells, neutrophil oxidative burst (NOB) capacity and serum levels of cytokines (IL-1, IL-6, IL-8, IL10, IL-12, and TNF-α). RESULTS: Patients of decompensated cirrhosis with and without ACLF demonstrated significantly lower mean percentage of monocytes expressing HLA-DR and quantitative increase in the NOB after stimulation with PMA when compared to HC. However there was no difference in mean percentage of monocytes with HLA-DR expression (43.61±26.56% vs. 43.10±20.98%) (p = 0.91), mean density of HLA-DR expression on the surface (30.34±29.32 vs. 41.71±52.13) (p = 0.42) and quantitative increase in NOB after stimulation with PMA (16.55±11.91 vs. 17.24±16.18) (p = 0.47) amongst patients with decompensated cirrhosis with and without ACLF. Patients with ACLF had significantly higher pro-inflammatory and anti-inflammatory cytokines in comparison to patients with decompensated cirrhosis without ACLF. CONCLUSION: Patients with decompensated cirrhosis demonstrate a component of immune-paresis, however there is similar impairment in HLA-DR expression and NOB capacity in patients with and without ACLF. Both inflammatory and anti-inflammatory cytokines are increased in patients with ACLF in comparison to patients with decompensated cirrhosis without ACLF.

Can Alcoholic Liver Disease and Nonalcoholic Fatty Liver Disease Co-Exist?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) by definition would require exclusion of significant alcohol intake. Present study was aimed to assess the prevalence of various components of metabolic syndrome (MS) in patients with alcoholic cirrhosis (AC) and to study the affect of its presence on the severity of liver disease, testing the hypothesis if alcoholic liver disease (ALD) and NAFLD could co-exist. METHODS: In a retrospective analysis of 16 months data, 81 patients with AC were analysed for the prevalence of MS. The diagnosis of AC was based on the history of alcohol intake, clinical examination, serum biochemistry, hematological parameters, exclusion of other causes of chronic liver disease, imaging and upper gastrointestinal endoscopy. Severity of liver disease was assessed by Child-Turcott-Pugh (CTP) score. MS was assessed as per the ATP III criteria and the affect of MS on CTP score was evaluated. RESULTS: All 81 patients with AC were male [mean age 50.9 ± 9.5, mean CTP score 8.38 ± 1.66]. But for three patients (3.7%) all other 78 patients (96.3%) with AC had at least one component of MS. Forty-three (53.0%) patients had full blown MS with three or more components of MS. Sixty-one (75.30%) patients were either overweight [22 (27.1%)] or obese [39 (48.1%)], with a mean BMI of 25.35 ± 3.86 kg/m2. Type II DM was present in 40 (25%) and 28 (34.5%) patients were hypertensive. Twenty-two (27.2%) patients had hypertriglyceridemia and 52 (64.2%) had low HDL. Eleven (13.6%) patients had Child's A cirrhosis, 46 (56.8%) had Child's B and 24 (29.6%) patients had Child's C cirrhosis. Even though not significant statistically, patients with Child's C cirrhosis (17, 70.83%) had higher presence of MS in comparison to Child's A (7, 63.6%) and B (19, 41.3%) cirrhosis. CONCLUSION: MS is common in patients with AC. Presence of MS may be contributing towards severity of liver disease in these patients indirectly suggesting the co-existence of ALD and NAFLD.

Vitamin D supplementation in patients with nonalcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND AND AIM: Deficiency of vitamin D may be related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the effect of vitamin D supplementation in patients with NAFLD. METHODS: A total of 81 patients with NAFLD with normal or raised (n = 47) serum alanine aminotransferase (ALT) having vitamin D deficiency were randomized prospectively. Group 1 (n = 51) received lifestyle modifications and a single injection of vitamin D (600 000 U) (standard medical treatment [SMT] + vitamin D) and group 2 (n = 30) received lifestyle modifications (SMT) for 6 months. The primary objective of this study was to assess the improvement in insulin resistance (IR) and serum ALT (in patients with raised ALT) and the secondary objective was to assess the change in cytokine profile in the SMT + vitamin D group. RESULTS: After 6 months, significant improvement in serum levels of ALT was observed in the SMT + vitamin D group when compared to the SMT group (ALT [87 ± 48 and 59 ± 32 IU/mL, P < 0.001] vs [64 ± 35 and 62 ± 24 IU/mL, P = 0.70]). Mean insulin levels and homeostasis model assessment-IR remained unchanged at 6 months in the SMT + vitamin D group while there was a significant increase in mean insulin and homeostasis model assessment-IR in the SMT group. SMT + vitamin D group had significant increase in mean serum levels of adiponectin (836 ± 309 and 908 ± 312 (pg/mL), P = 0.018) compared with the baseline; tumor necrosis factor-α levels decreased from baseline but the change was not significant. CONCLUSION: Patients with NAFLD given vitamin D in addition to lifestyle modifications have significant improvement in serum ALT and serum adiponectin levels.

Dual treatment with sofosbuvir plus ribavirin is as effective as triple therapy with pegylated interferon plus sofosbuvir plus ribavirin in predominant genotype 3 patients with chronic hepatitis C.

BACKGROUND AND AIM: Sofosbuvir (SOF) was the first directly acting antiviral made available for chronic hepatitis C (CHC) in India. We describe our "real life" experience of using SOF with ribavirin (RBV) with or without pegylated interferon (Peg-IFN) in predominant genotype 3 patients with CHC. METHODS: A total of 158 patients (men 99 [62.6%], mean age 40.3 ± 12.8 years) with CHC treated with dual therapy (SOF + RBV) for 24 weeks or triple therapy (Peg-IFN + SOF + RBV) for 12 weeks were included prospectively. Patients with co-infection, decompensated liver disease, and post-organ transplantation were excluded. Data were analysed for the preference of treatment regimen, end of treatment response (ETR), sustained virological response at 12 weeks, and side effects. RESULTS: Genotype 3 was the predominant genotype (105 [66.4%]) followed by genotype 1 (40 [25.3%]) and genotype 4 (13[8.2%]). Forty-eight (30.37%) patients had cirrhosis (LSM ≥ 13 kPa), and 30 (19%) were treatment experienced with Peg-IFN + RBV. A total of 103 (65.18%) patients received dual therapy, and 55 (34.81%) received triple therapy. Resentment to receive injections, inaccessibility to a facility, fear of injection or its side effects, and financial constraints were the reasons to refuse triple therapy. All patients in triple therapy group and all but two patients (98%) in the dual therapy group attained ETR. All those who achieved ETR achieved sustained virological response at 12 weeks in both groups. But for anemia in three patients (two in triple, one in dual therapy), there were no major side effects. CONCLUSIONS: Most patients with CHC prefer an oral treatment with directly acting antivirals. Both oral and interferon-based regimens achieve high response rate.

Tackling the Hepatitis C Disease Burden in Punjab, India.

Hepatitis C virus (HCV) is a globally prevalent pathogen and is a major cause of healthcare burden in India. HCV poses a significant problem in the state of Punjab, India owing to the higher prevalence of risk factors like unsafe medical practices (including unsafe injections and dental procedures) and intravenous drug use. The reported prevalence of HCV in this part of the country was 5.2% in 2012, while a recent study has shown the prevalence to be 3.2% in 2016. Similar to the other geographic belts in India, genotype 3 predominates in the state of Punjab. Control of HCV infection in Punjab requires focusing on several strategies. There is a need to formulate a health educational curriculum targeting not only the high-risk population but also the general population regarding the transmission of HCV. Training of family physicians who form the first link to patients in the community is imperative in the success of healthcare programmes. Adopting the dual approach of treating the old cases (decreasing the reservoir pool of HCV) and decreasing the incidence of new ones would help curtail the disease and decrease liver related mortality. A commendable initiative has been launched by the Punjab state government to eliminate HCV from Punjab. However, besides the initiative by the government, a concerted effort by all other stakeholders in managing the HCV burden in India, namely the doctors, the drug companies and the non-government organizations is required for control of HCV.

Viral hepatitis: Indian scenario.

Viral hepatitis is a cause for major health care burden in India and is now equated as a threat comparable to the "big three" communicable diseases - HIV/AIDS, malaria and tuberculosis. Hepatitis A virus and Hepatitis E virus are predominantly enterically transmitted pathogens and are responsible to cause both sporadic infections and epidemics of acute viral hepatitis. Hepatitis B virus and Hepatitis C virus are predominantly spread via parenteral route and are notorious to cause chronic hepatitis which can lead to grave complications including cirrhosis of liver and hepatocellular carcinoma. Around 400 million people all over the world suffer from chronic hepatitis and the Asia-Pacific region constitutes the epicentre of this epidemic. The present article would aim to cover the basic virologic aspects of these viruses and highlight the present scenario of viral hepatitis in India.