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.

Imaging features of breast cancer subtypes on contrast enhanced ultrasound: a feasibility study.

The objective of this research was to study the contrast enhancement patterns of the different molecular subtypes of breast cancer on contrast-enhanced ultrasound (CEUS) using both qualitative and quantitative parameters. This prospective study included females with a single breast mass which was histopathologically proven carcinoma. B mode ultrasound (USG) and CEUS were performed in all patients during baseline assessment. Qualitative CEUS assessment encompassed enhancement pattern, presence of fill-in and washout. Quantitative assessment included measurement of peak enhancement, time to peak; area under the curve and mean transit time. A p-value < 0.05 was considered statistically significant for differentiating the subtypes. The included thirty masses were categorised into two subtypes-triple negative breast cancer (TNBC) (36.7%) and non-TNBC (63.3%) subtypes. With B-mode USG, a statistically significant difference was observed between the two groups with respect to their shape and margins. TNBC lesions showed an oval shape, circumscribed margins and peripheral nodular enhancement on CEUS with the absence of fill-in even in the delayed phase (p-value - 0.04). The two subtypes did not significantly differ in terms of quantitative perfusion parameters. The various subtypes of breast cancer therefore possess distinct contrast enhancement patterns. CEUS potentially allows differentiation amongst these molecular subtypes that may aid in radiology-pathology (rad-path) correlation and follow up of the patients.

Adapting the Utility of Lipiodol CT in Treating Small Hepatocellular Carcinoma.

Introduction: Multiphase MRI liver is the gold-standard imaging modality for staging hepatocellular carcinoma (HCC) in patients with cirrhosis. Often, small HCCs diagnosed on multiphase MRI are occult on B-mode ultrasound and multiphase CT (MPCT) and thus pose a challenge for loco-regional therapy. We adapted the technique of lipiodol CT in treating two such patients of small HCC. Methods: Lipiodol-CT involved an intra-arterial lipiodol injection through the hepatic artery followed by a noncontrast CT liver. CT delineated small, hyperdense, lipiodol-laden hepatic nodules, which served as a target for executing ablation of the nodule and also revealed the true disease stage by depicting the additional number of tumors in the liver. Results: Case one was a 51-year female, known case of chronic hepatitis C who presented with ascites for two months. She was diagnosed with a small HCC (LI-RADS-4) in a cirrhotic liver on multiphase MRI. Percutaneous radiofrequency ablation was planned, but the mass was not located on ultrasound or multiphase CT. Lipiodol-CT was undertaken, which delineated the lipiodol-laden small HCC, which served as a target for executing ablation. Case 2 was a 55-year male, Child-Pugh A cirrhotic, who had undergone right extended hepatectomy for hepatitis B-related HCC. Follow-up MRI revealed a 5 mm segment III nodule, which had increased in size on repeat MRI at 3 months (LI-RADS-4). This nodule, too, was occult on both ultrasound and MPCT. Lipiodol CT revealed additional multiple, variable-sized lipiodol-laden nodules in the liver remnant. Treatment of trans-arterial chemoembolization was performed at one month. Both patients showed complete response to treatment. Conclusion: Lipiodol CT can be safely used in a new role of facilitating treatment of small HCCs diagnosed on MRI but occult on ultrasonography and MPCT.

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.

Role of Indocyanine Green in Predicting Post-Transarterial Chemoembolization Liver Failure in Hepatocellular Carcinoma.

BACKGROUND/AIM: Post-Transarterial Chemoembolization (TACE) Liver Failure (LF) is common in patients with Hepatocellular Carcinoma (HCC). No definitive objective parameters predict its occurrence. We assessed the role of Indocyanine Green (ICG) in prediction of post-TACE LF. METHODS: Consecutive HCC patients with Child A/B class, categorized as Barcelona Clinic Liver Cancer (BCLC) staging A/B, were included between August 2012 and July 2014. All underwent ICG dynamics: Plasma Disappearance Rate (PDR) was recorded on the day of TACE. Area Under Receiver Operator Characteristic Curve (AUROC) of ICG-PDR was compared with existing prognostic scores: Model for End Stage Liver Disease (MELD), MELD-Na and Child-Turcotte-Pugh (CTP) using Hanley and McNeil method. RESULTS: A total of 43 patients, mean age (±sd) 55.1 ± 12.8 years were included; 35 (81.4%) patients were males. Post-TACE LF developed after 17 (28.8%) of 59 procedures. Patients with post-TACE LF had significantly elevated baseline bilirubin (P = 0.006), alkaline phosphatase (P = 0.040) and prolonged international normalized ratio (P = 0.004). The median prognostic scores were higher in patients with post-TACE LF (CTP 7 vs 6; P < 0.001 and MELD 10.5 vs 6.3; P = 0.005). There was no difference in the MELD-Na score. ICG-PDR values were lower in those patients who developed post-TACE LF (7.4%/min vs 10.6%/min; P = 0.008). AUROC for ICG-PDR was 0.72 and a cut-off value <9.25%/min predicted the development of post-TACE LF with a sensitivity, specificity, positive predictive value and negative predictive value of 64.7%, 61.9%, 40.7% and 81.2%, respectively. There were no differences in the AUROC between ICG-PDR and other prognostic markers (Hanley and McNeil, P: 0.244-0.900). CONCLUSION: ICG-PDR performs similar to MELD, MELD-Na and CTP score for predicting development of post-TACE LF.

Long-term outcomes of transjugular intrahepatic portosystemic shunt in Indian patients with Budd-Chiari syndrome.

BACKGROUND/AIM: Transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice in Budd-Chiari syndrome (BCS) based on current data. Our objective was to evaluate outcomes and assess prognostic factors in BCS patients undergoing TIPS. PATIENTS AND METHODS: In this retrospective analysis of a propectively maintained database, all consecutive BCS patients undergoing TIPS from September 2010 to February 2017 were included. Complete response after TIPS was defined as resolution of symptoms (ascites/pedal edema) with no requirement of diuretics at the end of 4 weeks. The Cox proportional hazard regression model was used to assess predictors of outcome and complications. RESULTS: Eighty patients with BCS who underwent TIPS were included; 40 (50%) were male. The mean age at onset of symptoms was 24.2±8.7 years. The median (range) follow-up was 660 (2-2400) days. The 1-, 3-, and 5-year rates for TIPS stent patency were 89, 81, and 81%, respectively. Cumulative encephalopathy-free rates were 91, 86, and 86%, respectively, and survival rates were 93, 89, and 84%, respectively. Eight (10.0%) patients died during follow-up, five within the first year (three of these five had incomplete response). On univariate analysis, serum bilirubin, response to intervention, serum creatinine, Child class, model for end-stage liver disease, and All India Institute of Medical Sciences-hepatic venous outflow tract obstruction score were significantly different between survivors and nonsurvivors. On multivariate analysis, response to therapy after TIPS (hazard ratio: 8.37; 95% confidence interval: 1.60-43.82) was independently associated with mortality. The 1-year survival was 97% in patients with complete response, compared with 59% in those with incomplete response (P<0.004). CONCLUSION: Incomplete symptom response after TIPS is associated with poor outcome and can be used for selection of patients for liver transplantation.

Hepatocellular Carcinoma: An Unusual Complication of Longstanding Wilson Disease.

Wilson disease is caused by the accumulation of copper in the liver, brain or other organs, due to the mutation in ATP7B gene, which encodes protein that helps in excretion of copper in the bile canaliculus. Clinical presentation varies from asymptomatic elevation of transaminases to cirrhosis with decompensation. Hepatocellular carcinoma is a known complication of cirrhosis, but a rare occurrence in Wilson disease. We present a case of neurological Wilson disease, who later developed decompensated cirrhosis and hepatocellular carcinoma.

Assessment of liver fibrosis in chronic hepatitis: comparison of shear wave elastography and transient elastography.

PURPOSE: To evaluate the diagnostic accuracy of shear wave elastography (SWE) and transient elastography (TE) in the evaluation of liver fibrosis in chronic hepatitis B (CHB) and C (CHC) patients taking liver biopsy as gold standard. METHODS: Ethics committee approved this prospective cross-sectional study. Between October 2012 and December 2014, consecutive CHB/CHC patients fulfilling the inclusion criteria were included-age more than 18 years, informed written consent, willing and suitable for liver biopsy. SWE, TE, and biopsy were performed the same day. Liver stiffness measurement (LSM) cut-offs for various stages of fibrosis were generated for SWE and TE. AUC, sensitivity, specificity, and positive/negative predictive values were estimated individually or in combination. RESULTS: CH patients (n = 240, CHB 172, CHC 68), 176 males, 64 females, mean age 32.6 ± 11.6 years were enrolled. Mean LSM of patients with no histological fibrosis (F0) was 5.0 ± 0.7 and 5.1+1.4 kPa on SWE and TE, respectively. For differentiating F2 and F3-4 fibrosis on SWE, at 7.0 kPa cut-off, the sensitivity was 81.3% and specificity 77.6%. For TE, at 8.3 kPa cut-off, sensitivity was 81.8% and specificity 83.1%. For F3 vs. F4, SWE sensitivity was 83.3% and specificity 90.7%. At 14.8 kPa cut-off, TE showed similar sensitivity (83.3%) but specificity increased to 96.5%. Significant correlation between SWE and TE was observed (r = 0.33, p < 0.001). On combining SWE and TE, a drop in sensitivity with increased specificity for all stages of liver fibrosis occured. CONCLUSION: SWE is an accurate technique for evaluating liver fibrosis. SWE compares favorably with TE especially for predicting advanced fibrosis/cirrhosis. Combining SWE and TE further improves specificity.

Role of Transcatheter Intra-arterial Therapies for Hepatocellular Carcinoma.

Transcatheter intra-arterial therapies play a vital role in treatment of HCC due to the unique tumor vasculature. Evolution of techniques and newer efficacious modalities of tumor destruction have made these techniques popular. Various types of intra-arterial therapeutic options are currently available. These constitute: bland embolization, trans-arterial chemotherapy, trans-arterial chemo embolization with or without drug-eluting beads and trans-arterial radio embolization, which are elaborated in this review.

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

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.

Role of contrast enhanced ultrasound in hepatic imaging.

Grey scale ultrasound (US) is the first line imaging modality used for the evaluation of liver by the radiologists and clinicians worldwide. It is a simple, inexpensive, safe and an easily available technique. US has the ability to delineate the hepatic parenchyma and differentiate the cystic from solid hepatic lesions. However, it has limited accuracy in the detection and characterization of focal liver lesions (FLL). CEUS is a major breakthrough in ultrasound imaging which evolved with the aim of overcoming these limitations of US. With the use of ultrasound contrast agents (UCAs), CEUS has the ability to detect the intranodular hemodynamics and thereby provide information of the enhancement pattern of the lesion resulting in reliable characterization of the FLL. This capability brings it at par with the cross sectional contrast enhanced imaging techniques of computed tomography and magnetic resonance imaging. UCAs are safe, non-nephrotoxic and thus can be used to evaluate patients with renal failure as well. The technique of CEUS is simple, requires few minutes to perform, portable, lacks ionising radiation and above all is a cost-effective modality. These advantages have made CEUS an established modality for hepatic imaging. Besides detection and characterization of FLL, it also plays a vital role in the management and repeated follow up of treated patients of FLL. Newer clinical applications of CEUS with promising results are also being unravelled . This review highlights the multifaceted role of CEUS in hepatic imaging and its upcoming clinical applications.

Ribavirin therapy for hepatitis E virus-induced acute on chronic liver failure: a preliminary report.

Hepatitis E virus (HEV) is a common cause of acute on chronic liver failure (ACLF) in HEV hyperendemic regions with high mortality. Treatment for HEV-induced ACLF is currently not available. Recently, efficacy of ribavirin in genotype 3 chronic hepatitis E patients has been reported; however, whether ribavirin is effective in genotype 1 HEV infection is not yet known. The present study includes four patients with HEV-induced ACLF treated with ribavirin in a genotype 1 HEV hyperendemic region. Diagnosis of ACLF was made by conventional criteria and HEV as the cause of ACLF was confirmed by detection of HEV RNA by reverse transcriptase PCR. Ribavirin dose ranged from 200 to 600 mg/day and was used for a median duration of 12 (range 3-24) weeks. All patients had undetectable HEV in 3-8 weeks, survived and none had serious adverse effects. This preliminary observation from a single centre indicates that ribavirin may be an effective therapeutic agent for HEV-induced ACLF and a randomized control trial is needed to establish its efficacy.

Clinical profile, etiology and therapeutic outcome in 324 hepatocellular carcinoma patients at a tertiary care center in India.

OBJECTIVE: To study the profile and outcome of therapy for hepatocellular carcinoma (HCC) in India. METHODS: Data analysis of HCC patients enrolled in liver clinic between 1990 and 2005. RESULTS: We registered 324 HCC patients [males 284 (88%), mean age 52.4 +/- 13.1 years]. The etiology of HCC was: hepatitis B virus 165 (51%), hepatitis C virus 38 (12%), alcohol 20 (6%), combined 31 (10%) and unknown 70 (21%). Serum alpha-fetoprotein was >400 ng in 36%, portal vein invasion was seen in 40% and distant metastases in 13%. Therapy was offered to 141 (43.5%) patients, but survival data was available in only 130 (93%) of them. Treatment given and median survival time was as follows: surgical resection, 19 months (n = 14); transarterial chemoembolization, 11 months (n = 23); transarterial rhenium therapy, 26 months (n = 7); radiofrequency ablation, 24 months (n = 4); acetic acid ablation, 13 months (n = 17); oral chemotherapy, 26 months (n = 33), and combination therapy, 26 months (n = 32). Vascular invasion, Okuda staging and therapy were independent factors associated with survival. Treated patients had longer median survival compared to untreated ones (16 months vs. 7 months, p < 0.05). CONCLUSIONS: Hepatitis B infection is the predominant cause of HCC in India. Serum alpha-fetoprotein was diagnostic in only one third of our patients. Most patients present late, when curative therapies are not possible. Treated patients had better survival than untreated ones.

Palliative treatment in advanced hepatocellular carcinoma: has it made any difference?

Hepatocellular carcinoma (HCC) is a global health problem, the fifth most common cancer in the world. HCC occurs in a histologically abnormal liver due to underlying chronic liver disease resulting as a sequele of the chronic viral infections, hepatitis B and C. Since these two viral infections are endemic in Asia and Africa, more than 80% of cases are encountered in these regions. In India, a large proportion of the population is "at risk" for developing chronic liver disease and, therefore, HCC. Due to the lack of screening programmes in the country, the majority of HCC patients are diagnosed at an advanced stage of the disease, thus treatment remains a challenge. Palliative therapy forms the mainstay of treatment for this group of patients. The current era provides a plethora of options for the palliative management of HCC. This review concisely summarises the historical perspective and the current status of palliative treatment in advanced HCC.

Percutaneous glue embolization of a visceral artery pseudoaneurysm in a case of sickle cell anemia.

Although aneurysmal complications of sickle cell anemia have been described in the intracranial circulation, visceral artery pseudoaneurysms in this disease entity have not previously been reported in the literature. Conventional treatment of visceral pseudoaneurysms has been surgical ligation or resection of the aneurysm. Transcatheter embolization has emerged as an attractive, minimally invasive alternative to surgery in the treatment of these lesions. In certain situations, however, due to the unfavorable angiographic anatomy precluding safe transcatheter embolization, direct percutaneous glue injection of the pseudoaneurysm sac may be considered to achieve successful occlusion of the sac. The procedure may be rendered safer by simultaneous balloon protection of the parent artery. We describe this novel treatment modality in a case of inferior pancreaticoduodenal artery pseudoaneurysm in a patient with sickle cell anemia. Although a complication in the form of glue reflux into the parent vessel occurred that necessitated surgery, this treatment modality may be used in very selected cases (where conventional endovascular embolization techniques are not applicable) after careful selection of the balloon diameter and appropriate concentration of the glue-lipiodol mixture.