UNASSIGNED: Increasing incidence of hepatocellular carcinoma (HCC) in India is a matter of concern and need for adequate profiling and streamlining management strategies cannot be over-emphasized.
UNASSIGNED: This is a prospective multi-centric observational cohort study comprising of an oncology center, one university tertiary hospital with specialized hepatology service, one public hospital with gastroenterology service, and a private liver transplant center located within a 3-km radius. The demographic and clinical parameters were recorded on a prospectively maintained database. The clinical profile, demographics, characteristics of HCC and the allocated treatment were noted and compared among the four centers.
UNASSIGNED: In total, 672 patients were enrolled from June 2016 till January 2020. Abdominal pain (64.3%) and weight loss (47.3%) were the most common symptoms. Most common identified etiology was hepatitis B (39%). The cancer center received lesser patients with hepatitis C and those with advanced stage of HCC. The private transplant center reported the highest proportion of NASH, which was also significantly higher in those belonging to higher socioeconomic strata, and lowest proportion of alcoholic cirrhosis. Metastasis was seen in almost one-fifth (19%) cases at diagnosis. Portal vein thrombosis was evident in 40%. Adherence to treatment guidelines was seen in three-fourth cases (76%).
UNASSIGNED: Hepatitis B is the most common underlying cause for HCC, whereas other causes like NASH are on the rise. Etiologic profile may vary with selective specialization of centers catering to patients with HCC. Adherence to guideline while allocating treatment was high among all centers with highest non-adherence in BCLC A.

UNASSIGNED: Subclinical hypothyroidism (SCH) often leads to alterations in lipid profile, which may negatively impact humans health. Whether lipids in turn affect the natural history of SCH is unknown. We aimed to assess the association between longitudinal changes in serum lipid levels and the natural history of SCH.
UNASSIGNED: This retrospective cohort study using data from the REACTION study included 581 patients with SCH who were enrolled between July 1, 2011, and December 19, 2014, with a median follow-up of three [IQR, 2·86-3·21] years. Patients with missing data or conditions that can affect thyroid function were excluded. Changes in serum lipid levels were calculated from serum lipid measurements 3 years apart and classified in two ways: 1) the first, second, and third tertiles of the difference between baseline and follow-up and 2) the percent change from baseline, namely, serum lipid decrease ≥ 25%, minor change, and serum lipid increase ≥ 25%. The natural history of SCH includes regression to euthyroidism, SCH persistence, or progression to overt hypothyroidism (OH). Odds ratios (ORs) were estimated by multivariable logistic regression. Validation was performed on data from a health management cohort study conducted from January 1, 2012, to December 31, 2016, with a median follow-up of two [IQR, 1·92-2·08] years. After using the same inclusion and exclusion criteria as the REACTION cohort study, 412 patients with SCH were eligible for the validation analysis.
UNASSIGNED: There were 132 (22·7%) men and 449 (77·3%) women in the study, with a median age of 56 [IQR,49-62] years. During follow-up, 270 (46·5%), 266 (45·8%), and 27 (4·6%) patients had regression to euthyroidism, persistent SCH, and progression to OH, respectively. Both grouping manners showed a significant association between changes in lipid levels and the natural history of SCH. A total cholesterol (TC)-level increase was independently associated with a greater risk of progression to OH (OR for ≥ 25% TC increase vs. minor change: 5·40; 95% CI 1·46-21·65), whereas TC-level declines increased the likelihood of regressing to euthyroidism (OR for ≥ 25% TC decrease vs. minor change: 3·45; 95% CI 1·09-12·43). Similarly, the likelihood of regression according to changes in triglyceride (TG) levels exhibited a consistent trend with that according to TC-level changes. A similar pattern of association was observed in the validation cohort.
UNASSIGNED: Changes in serum lipid levels in SCH are associated with future progression or regression risk, suggesting that the changes in serum lipid levels may affect the natural history of SCH. Clinicians should pay attention to the long-term control of serum lipids levels in populations with SCH, which may benefit thyroid function.
UNASSIGNED: This work was supported by grants from the National Key Research and Development Program of China (2017YFC1309800), the National Natural Science Foundation (81430020, 82070818), and the \"Outstanding University Driven by Talents\" Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).

UNASSIGNED: Gut-barrier dysfunction is well recognized in pathogenesis of both non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). However, comparison of components of this dysfunction between the two etiologies remains unexplored especially in early stages of NAFLD.
UNASSIGNED: Components of gut-barrier dysfunction like alterations in intestinal permeability (IP) by lactulose mannitol ratio (LMR) in urine, systemic endotoxemia (IgG and IgM anti-endotoxin antibodies), systemic inflammation (serum tumor necrosis factor alpha [TNF-α] and interleukin-1 [IL-1] levels), tight junction (TJ) proteins expression in duodenal biopsy and stool microbiota composition using Oxford Nanopore MinION device were prospectively evaluated in patients with NAFLD (n = 34) with no cirrhosis, ALD (n = 28) and were compared with disease free controls (n = 20).
UNASSIGNED: Patients with ALD had more advanced disease than those with NAFLD (median liver stiffness -NAFLD:7.1 kPa [5.9-8.9] vs. ALD:14.3 kPa [9.6-24], P < 0.001]. Median LMR was significantly higher in NAFLD and ALD group when compared to controls (NAFLD 0.054 [0.037-0.17] vs. controls 0.027 [0.021-0.045] (P = 0.001)) and ALD 0.043 [0.03-0.068] vs. controls 0.027 [0.021-0.045] (P = 0.019)]. Anti-endotoxin antibody titer (IgM) (MMU/mL) was lowest in NAFLD 72.9 [3.2-1089.5] compared to ALD 120.6 [20.1-728]) (P = 0.042) and controls 155.3 [23.8-442.9]) (P = 0.021). Median TNF-α (pg/mL) levels were elevated in patients with NAFLD (53.3 [24.5-115]) compared to controls (16.1 [10.8-33.3]) (P < 0.001) and ALD (12.3 [10.1-42.7]) (P < 0.001). Expression of zonulin-1 and claudin-3 in duodenal mucosa was lowest in NAFLD. On principal co-ordinate analysis (PCoA), the global bacterial composition was significantly different across the three groups (PERMANOVA test, P < 0.001).
UNASSIGNED: While remaining activated in both etiologies, gut-barrier dysfunction abnormalities were more pronounced in NAFLD at early stages compared to ALD despite more advanced disease in the latter.

UNASSIGNED: This study analyzes the changing levels of circulating inflammatory cytokines Interferon gamma (IFN-γ) and interleukin (IL)-10 (as the main cytokines of T-helper-1 and T-helper-2 immune responses) in patients with chronic hepatitis C virus (HCV) infection undergoing therapy with direct-acting antivirals (DAAs) and to correlate them with laboratory markers.
UNASSIGNED: This Pilot study included 50 HCV monoinfected patients who received DAAs for 12 or 24 weeks. They were followed up monthly during therapy and 3 months after the end of the treatment. Liver disease was determined by transient elastography, in addition to FIB-4 indices. Analysis of IFN-gamma and IL-10 was carried out using an enzyme-linked immunosorbent assay.
UNASSIGNED: All patients carried HCV genotype 4. The Sustained virological response was 100% and 92% in cirrhotics and noncirrhotics, respectively. There was no significant difference between groups in baseline IL-10 or IFN-gamma. In noncirrhotics, IL-10 showed a significant reduction at Week 4 after treatment start. In cirrhotics, IL-10 showed a significant reduction at Week 4 after treatment starts and a significant reduction at Week 12 after the end of the treatment. At Week 12 after the end of the treatment, serum IL-10 levels were significantly lower in cirrhotics. IFN-γ showed nonsignificant changes in noncirrhotics. A significant increase of IFN-γ occurred in cirrhotics from Week 4 after treatment starts to 12 weeks after the end of the treatment. IFN-γ was significantly higher in cirrhotics at Week 12 after the end of the treatment. IFN-γ and IL-10 showed different correlations with laboratory markers.
UNASSIGNED: Viral eradication induced by DAAs caused a significant change in IL-10 and IFN-gamma.

BACKGROUND: Saroglitazar-a unique dual peroxisome proliferator-activated receptor agonist was approved marketing authorization in India in 2013 for diabetic dyslipidemia. Postmarketing studies have additionally shown improvement in liver parameters in diabetic dyslipidemia patients with nonalcoholic fatty liver disease (NAFLD) who received saroglitazar.
OBJECTIVE: The aim of this study was to evaluate the effect of saroglitazar on liver function test, liver fibrosis score by FibroScan, lipid profiles, HbA1c in NAFLD patients with diabetic dyslipidemia in southern India.
METHODS: A prospective, interventional, pilot study was performed to study the safety and efficacy of saroglitazar in NAFLD patients having type 2 diabetes mellitus. About 97 patients were screened, of which 85 patients were involved in the study based on the inclusion criteria. The clinical parameters and liver stiffness were measured at the baseline and also after 12 weeks of treatment with administration of saroglitazar 4 mg once daily. The change in the parameters at the baseline and after the end of the treatment was measured and was subjected to statistical analysis using SPSS software.
RESULTS: The recruited patients received saroglitazar and were followed up for a period of 12 weeks. The clinical parameters such as fasting blood sugar, postprandial blood sugar, HbA1c, total cholesterol, triglycerides, SGPT, and liver stiffness showed significant difference after 12 weeks of treatment when compared with the baseline values. No adverse drug reaction was reported in patients receiving saroglitazar during the study.
CONCLUSIONS: Saroglitazar was found to show significant improvement in liver parameters in NAFLD patients with a significant reduction in liver fibrosis and triglycerides level.

OBJECTIVE: Hepatitis B virus (HBV) infection is a major health problem in the world. Barbers deal with frequent abrasions/lacerations due to sharp equipment, making them a high-risk group. Determination of HBsAg positive status excludes most reservoirs of transmission in the population. However, Occult Hepatitis B continues to be a source of transmission. The aim of this study was to study the prevalence of occult HBV infection in barbers serving the armed forces clientele and evaluate their knowledge and preventive practices against HBV transmission.
METHODS: Seventy-nine HBsAg negative barbers were included in this study and interviewed for the status of immunisation and preventive practices. Anti-HBc total and HBV DNA levels were measured along with a complete haemogram, LFT, PT INR, ultrasound abdomen and Fibroscan of the liver.
RESULTS: The prevalence of occult Hepatitis B status was 3.79%. Among barbers who were anti-HBc total positive, 100% were found to have replicative HBV DNA status. All barbers (100%) were unaware of the existence and modes of HBV transmission and were never screened for HBV; 98.73% of barbers followed improper disinfection practices and were never immunised.
CONCLUSIONS: The prevalence of occult HBV infection in barbers, absence of immunisation, unawareness and improper disinfection practices are significantly at risk for transmission to the unaware clients. It is important to educate barbers, establish a universal disinfection procedure and implement a system of compulsory Hepatitis B vaccination before the commencement of their trade work.

UNASSIGNED: There are conflicting data regarding the epidemiology of hepatocellular carcinoma (HCC) arising in the context of non-alcoholic and metabolic-associated fatty liver disease (NAFLD and MAFLD). We aimed to examine the changing contribution of NAFLD and MAFLD, stratified by sex, in a well-defined geographical area and highly characterised HCC population between 1990 and 2014.
UNASSIGNED: We identified all patients with HCC resident in the canton of Geneva, Switzerland, diagnosed between 1990 and 2014 from the prospective Geneva Cancer Registry and assessed aetiology-specific age-standardised incidence. NAFLD-HCC was diagnosed when other causes of liver disease were excluded in cases with type 2 diabetes, metabolic syndrome, or obesity. Criteria for MAFLD included one or more of the following criteria: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation.
UNASSIGNED: A total of 76/920 (8.3%) of patients were diagnosed with NAFLD-HCC in the canton of Geneva between 1990 and 2014. Between the time periods 1990-1994 and 2010-2014, there was a significant increase in HCC incidence in women (standardised incidence ratio [SIR] 1.83, 95% CI 1.08-3.13, p = 0.026) but not in men (SIR 1.10, 95% CI 0.85-1.43, p = 0.468). In the same timeframe, the proportion of NAFLD-HCC increased more in women (0-29%, p = 0.037) than in men (2-12%, p = 0.010) while the proportion of MAFLD increased from 21% to 68% in both sexes and from 7% to 67% in women (p <0.001). From 2000-2004 to 2010-2014, the SIR of NAFLD-HCC increased to 1.92 (95% CI 0.77-5.08) for men and 12.7 (95% CI 1.63-545) in women, whereas it decreased or remained stable for other major aetiologies of HCC.
UNASSIGNED: In a populational cohort spanning 25 years, the burden of NAFLD and MAFLD associated HCCs increased significantly, driving an increase in HCC incidence, particularly in women.
UNASSIGNED: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, increasingly arising in patients with liver disease caused by metabolic syndrome, termed non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). We assessed all patients with HCC between 1990 and 2014 in the canton of Geneva (western Switzerland) and found an increase in all HCC cases in this timeframe, particularly in women. In addition, we found that HCC caused by NAFLD or MAFLD significantly increased over the years, particularly in women, possibly driving the increase in overall HCC cases.

UNASSIGNED: Liver cirrhosis is a chronic disease in which normal liver tissue is replaced by fibrous tissue, leads to liver malfunction. Although transplantation is the most certain cure, stem cell therapies are shedding light on efforts to regenerate cirrhotic liver. The purpose of this study was to evaluate the regenerative potential of mesenteric fat stem cells in CCL4-induced liver cirrhosis in an animal model.
UNASSIGNED: Thirty rats were treated with the mixture of CCL4 and olive oil intraperitoneally by a dose of 0.2 ml (0.1 ml CCL4 and 0.1 ml olive oil) every other day for 16 weeks till cirrhosis signs appeared. Fifteen rats were randomly selected as control group. Others treated by mesenteric fat derived mesenchymal stem cells transferred into the liver parenchyma.
UNASSIGNED: After 5 weeks, rats received stem cells had improved clinically by increased movements, appetite, improvement in overall behavior and decreased abdomen size. Histopathologically, liver cells showed state of regeneration and forming new colonies.
UNASSIGNED: Liver cirrhosis was induced. The mesenchymal stem cells derived from mesenteric adipose tissue could improve hepatic status of the rats, as cirrhotic livers were regenerated back into normal appearing parenchyma. Rats\' clinical behavior also reached healthy status.

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug-induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.