2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

Preventive hepatology: An ounce of prevention or pounds of cure to curb liver diseases.

Liver diseases are now the leading cause of both morbidity and mortality profile globally with rising trends due to unhealthy lifestyle. Most of the liver diseases are preventable. Scientific evidences have well supported and documented that almost 90 percent of all major liver diseases are either the manifestations of asymptomatic hepatitis virus infections or poor lifestyle choices leading to accumulation of fat in liver that could be detected even before they present themselves as chronic liver diseases. Understanding liver diseases as a preventable disease and practising necessary preventive measures will help in lowering the risks of various types of liver diseases as well as liver cancer.

Spectrum of Autoimmune Liver Disease and Real-World Treatment Experience from a Tertiary Care Hospital.

Background and aims: Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. Methods: A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Results: Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P = 0.034), high albumin (OR 1.91 [1.05-3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P = 0.020) predicted complete response. Conclusion: AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.

Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

Should We Treat Immune Tolerant Chronic Hepatitis B? Lessons from Asia.

BACKGROUND: Chronic hepatitis B (CHB) remains a public health burden, with more than 257 million persons living with hepatitis B virus globally. Despite the availability of a safe and efficacious vaccine, access to immunization remains poor. As per current estimates, if Asian countries rely only on immunization to reduce the burden of disease, the timelines for HBV elimination will be extended to 2060-2090, a far cry from the World Health Organization's clarion call for viral hepatitis elimination by 2030. METHODS: Currently, all practice guidelines lay stress on immunization, prevention of mother-to-child transmission and treatment of immune active disease or cirrhosis. In this review, we critically examine the data from the Asian cohorts, clinical and public health rationale of early treatment, risk of HCC, and assess the need for revision of guidelines. DISCUSSION: Patients in the immune tolerant phase (IT) remain untreated till they meet variable age, transaminase, or fibrosis criteria, are often lost to follow up and continue transmitting the infection. With global migration patterns, immunization programmes alone cannot prevent the complications of HBV like cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC). In addition, data from Asian cohorts from Taiwan and Korea suggest that HBV DNA levels are directly associated with increased risk of HCC. Histological evidence of advanced fibrosis or immune reactive T cell subsets in the IT phase also raises doubts about the viability of current guidelines that focus on age, alanine transaminase levels, and liver stiffness as markers of risk of inflammation and fibrosis. Current practice does not take into account the histological subsets with minimal inflammation, HBV genome integration or risk of HCC with high viral loads. CONCLUSION: New data from Asian cohorts argue the case of expanding access to care to IT-CHB from public health and clinical perspective.

Comparison of virtual computed tomography enteroscopy using carbon dioxide with small-bowel enteroclysis and capsule endoscopy in patients with small-bowel tuberculosis.

OBJECTIVE: Comparison of virtual CT enteroscopy (VCTE) using carbon dioxide with small-bowel enteroclysis (SBE) and capsule endoscopy (CE) in small-bowel tuberculosis (SBTB). METHODS: This prospective study comprised consecutive patients suspected to have SBTB. VCTE and SBE were performed on the same day and evaluated by independent radiologists. CE was performed within 2 weeks. VCTE was performed following insufflation of carbon dioxide via catheters in the jejunum and anorectum. A contrast-enhanced CT was followed by a delayed non-contrast CT. Image processing was done using virtual colonoscopy software. Findings on VCTE, SBE, and CE were compared. The final diagnosis of SBTB was based on either histopathological or cytological findings, response to antitubercular treatment, or a combination of these. RESULTS: Of the 55 patients in whom VCTE was performed, complete data was available in 52 patients. A final diagnosis of SBTB was established in 37 patients. All patients had VCTE and SBE. CE was performed in 34 patients. Adequate luminal distension was achieved in all patients with SBE and 35 patients with VCTE. SBE showed more strictures in jejunum (10.8%) and ileum (75.7%) compared with VCTE (jejunum, 8.1%, and ileum, 64.9%) and CE (jejunum, 5.9%, and ileum, 61.8%). However, difference was not statistically significant. VCTE revealed a greater length of strictures in both the jejunum and ileum compared with SBE and CE. CONCLUSION: VCTE allows adequate evaluation of the bowel in most patients with SBTB. It allows detection of greater length of abnormality in jejunum and ileum compared with SBE and CE. KEY POINTS: • The use of VCTE using CO2 bowel insufflation in patients with SBTB should be considered. • VCTE allows detection of a greater length of abnormality in the jejunum and ileum.

Indian National Association for the Study of Liver Consensus Statement on Acute Liver Failure (Part-2): Management of Acute Liver Failure.

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.

Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis.

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.

2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.

High potency multistrain probiotic improves liver histology in non-alcoholic fatty liver disease (NAFLD): a randomised, double-blind, proof of concept study.

OBJECTIVE: Pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still evolving. Probiotics could be a promising treatment option, but their effectiveness needs to be established. The present study aimed to evaluate the efficacy of a high potency multistrain probiotic in adult patients with NAFLD. METHODS: Thirty-nine liver biopsy-proven patients with NAFLD were randomised in a double-blind fashion to either lifestyle modifications plus an oral multistrain probiotic (675 billion bacteria daily, n=19) or identical placebo (n=20) for 1 year. Lifestyle modifications included regular exercise for all and control of overweight/obesity (with additional dietary restrictions), hypertension and hyperlipidaemia in those with these risk factors. Primary objective of the study was the histological improvement in NAFLD activity score (NAS) and its components and secondary objectives were improvement in alanine transaminase (ALT) and cytokine profile. RESULTS: Thirty (76.9%) out of 39 patients with NAFLD completed the study with 1 year of follow-up. A repeat liver biopsy at 1 year could be done in 10 patients (52.6%) in probiotic group and five patients (25%) in placebo group. In comparison to baseline, hepatocyte ballooning (p=0.036), lobular inflammation (p=0.003) and NAS score (p=0.007) improved significantly at 1 year in the probiotic group. When compared with placebo, the NAS score improved significantly in the probiotic group (p=0.004), along with improvements in hepatocyte ballooning (p=0.05) and hepatic fibrosis (p=0.018). A significant improvement in levels of ALT (p=0.046), leptin (p=0.006), tumour necrosis factor-α (p=0.016) and endotoxins (p=0.017) was observed in probiotic group in comparison to placebo at 1 year. No significant adverse events were reported in the study. CONCLUSION: Patients with NAFLD managed with lifestyle modifications and multistrain probiotic showed significant improvement in liver histology, ALT and cytokines. TRIAL REGISTRATION NUMBER: The clinical trial is registered with CLINICAL TRIAL REGISTRYINDIA (CTRI); http://ctri.nic.in, No. CTRI/2008/091/000074.

Rupture of Hepatocellular Carcinoma: A Review of Literature.

Approximately 700,000 people die of Hepatocellular Carcinoma (HCC) each year worldwide, making it the third leading cause of cancer related deaths. Rupture is a potentially life-threatening complication of HCC. The incidence of HCC rupture is higher in Asia and Africa than in Europe. In Asia approximately 10% of patients with a diagnosis of HCC die due to rupture each year. Spontaneous rupture is the third most common cause of death due to HCC after tumor progression and liver failure. The diagnosis of rupture in patients without history of cirrhosis or HCC may be difficult. The most common symptom of ruptured HCC is abdominal pain (66-100%). Shock at presentation can be seen in 33-90% of cases; abdominal distension is reported in 33%. Abdominal paracentesis documenting hemoperitoneum is a reliable test to provisionally diagnose rupture of HCC, it can be seen in up to 86% of clinically suspected cases. The diagnoses can be confirmed by computed tomography scan or ultrasonography, or both in 75% of cases. Careful pre-treatment evaluation is essential to decide the best treatment option. Management of ruptured HCC involves multi-disciplinary care where hemostasis remains a primary concern. Earlier studies have reported a mortality rate of 25-75% in the acute phase of ruptured HCC. However, recent studies have reported a significant decrease in the incidence of mortality. There is also a decrease in the incidence of ruptured HCC due to improved surveillance and early detection of HCC. Transarterial Embolization is the least invasive method to effectively induce hemostasis in the acute stage with a success rate of 53-100%. Hepatic resection in the other hand has the advantage of achieving hemostasis and in the same go offers a potentially curative resection in selected patients.

Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients.

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Irreversible Electroporation for Unresectable Hepatocellular Carcinoma: Initial Experience.

PURPOSE: To evaluate the efficacy and safety of irreversible electroporation (IRE) in the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A retrospective study was conducted from September 2014 to June 2017. A total of 21 HCCs in 21 patients with cirrhosis were treated with IRE. There were eight subcapsular or exophytic, ten perivascular and three peribiliary tumors. The median tumor size was 26 mm (range 14-40 mm). The technical success of the procedure was recorded. Median follow-up, median time to local recurrence, median local tumor progression-free survival (PFS) and complications were recorded. RESULTS: Technical success was achieved in all the patients. The median follow-up was 10 months (range 2-30 months). The median time to local recurrence and local tumor PFS were 4 months (range 3-4 months) and 7 months (range 3-30 months), respectively. The tumor-related factor that was significantly associated with local PFS was the size. Maximum tumor diameter < 25 mm was significantly associated with local tumor PFS (p = 0.045). Other parameters including tumor location, segmental portal vein thrombosis, baseline alpha-fetoprotein level and underlying etiology did not affect local tumor PFS. Complications were noted in nine patients and were classified as grades 1 and 2. No procedure-related mortality was encountered. CONCLUSION: IRE is an effective treatment for ablation of small HCCs. Larger prospective studies with strict selection criteria will establish the safety and efficacy of IRE in the treatment of unresectable HCC in patients who cannot undergo thermal ablation.

Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Association of liver cirrhosis severity with type 2 diabetes mellitus in hepatocellular carcinoma.

Type 2 diabetes mellitus (T2DM) is a major risk factor associated with hepatocellular carcinoma (HCC). However, the association of T2DM with liver cirrhosis and therapy response in HCC patients is not clear. Hence, in this study, we have evaluated the influence of T2DM on liver cirrhosis severity of HCC and sorafenib response. HCC patients were divided in two groups: T2DM (n = 20) and non-T2DM (nT2DM; n = 50). We found significantly higher number of patients in T2DM group had decompensated liver disease with Child-Turcotte-Pugh score ≥ 7. Additionally, 71.4% patients were observed to be sorafenib sensitive in T2DM group which was significantly higher as compared to 30% in nT2DM group. This study has highlighted the predisposition of HCC patients with T2DM toward more severe liver disease who were found to be better respondents of sorafenib. Impact statement We have explored the association of type 2 diabetes mellitus (T2DM) on liver cirrhosis severity along with response toward sorafenib in hepatocellular carcinoma (HCC). Most HCC patients exhibit prior history of liver cirrhosis that results following long span of chronic liver disease. T2DM constitutes as an important risk factor for HCC development which is known to elevate its incidence. Further, sorafenib is the FDA approved therapy for HCC whose therapeutic outcome is not investigated in HCC patients with T2DM till date. This observation-based study has unveiled a positive association between T2DM and severity of liver cirrhosis as well as sorafenib response in HCC as examined in a clinical setting.

Etiology and mode of presentation of chronic liver diseases in India: A multi centric study.

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.

Comparison of radiofrequency ablation alone & in combination with percutaneous ethanol injection for management of hepatocellular carcinoma.

Background & objective: It has been shown that the combined use of alcohol before radiofrequency ablation (RFA) helps to augment the therapeutic advantage of RFA. The present study was conducted to compare the outcome of treatment with RFA alone and RFA with alcohol as ablative technique in patients with small hepatocellular carcinomas (HCCs), who were not candidates for surgery. Methods: Fifty patients with chronic liver disease and concurrent HCC were enrolled in this prospective study. The patients were treated with either RFA alone (n=25) or RFA combined with alcohol (n=25). Patient outcome was evaluated, and the tumour recurrence and survival of the patients were assessed in the two groups. Results: The survival rates at six months in patients who completed at least six months of follow up were 84 and 80 per cent in patients treated with RFA alone and combination therapy, respectively. During the follow up period, 11 and four patients treated with RFA alone showed local and distant intrahepatic tumour recurrence, respectively. All local recurrences were at one to 18 months of the follow up period. The distant recurrences occurred at 6-36 months of the follow up period. During the follow up period, eight and six patients treated with combination therapy showed local and distant intrahepatic tumour recurrence, respectively. All local recurrences were at 1.5-15 months during the follow up period. The distant intrahepatic recurrences occurred at 6-72 months during the follow up period. Interpretation & conclusions: No significant difference was seen between the survival time of the patients treated with RFA alone and RFA with alcohol as well as in the local recurrences and distant intrahepatic recurrences in RFA compared to RFA and alcohol group patients. Combined use of RFA and alcohol did not improve the local tumour control and survival in patients with HCC compared to RFA alone.

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.

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.

Focal hepatic lesions characterisation by different sonographic techniques: a prospective analysis.

INTRODUCTION: Ultrasound is usually the first diagnostic investigation for the assessment of liver lesions. Apart from conventional sonography (CS), new grey-scale sonographic techniques have been developed which have increased the application of ultrasound in liver imaging. The present study was undertaken to compare image quality of CS, real-time compound sonography (RTCS), tissue harmonic sonography (THS) and tissue harmonic compound sonography (THCS) in focal liver lesions. MATERIALS AND METHODS: 100 patients with focal hepatic lesions were enroled. Lesions were divided into solid and cystic group. Solid lesions were evaluated for lesion conspicuity and elimination of artefacts. For cystic lesions, lesion conspicuity, posterior acoustic enhancement and internal echoes within the lesion were evaluated. Grading was done using 3-5-point scales. Overall image quality was assessed depending on the total points. RESULTS: 78 solid and 22 cystic liver lesions were included. THCS showed superior results for lesion conspicuity, elimination of artefacts and overall image quality in solid lesions. RTCS showed similar results as THCS for lesion conspicuity and overall image quality in solid lesions. THS gave better results in cystic lesions for all imaging parameters. Results of THCS though slightly inferior, showed no significant difference from THS, in cystic lesions. CS was found to have least diagnostic value in characterisation. CONCLUSIONS: For evaluation of focal hepatic lesions, a combination of compound and harmonic sonography, i.e. THCS, is the preferred sonographic technique.