Simultaneous Liver and Kidney Transplantation in a Patient With Telomere Biology Disorder: A Case Study.

Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.

Intravenous BCAA Infusion Does Not Lead to a Sustained Recovery From Overt HE in ACLF - An Open Label Randomized Clinical Trial.

Background: Hepatic encephalopathy (HE) in acute-on-chronic liver failure (ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study the efficacy of intravenous branched chain amino acids (IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24 h, day 3, and day 7. The primary outcome was an improvement in encephalopathy by ≥ 1 grade at 72 h. Patients and methods: European association for study of liver (EASL) defined ACLF patients with overt HE were assessed and randomized into the experimental arm (IV-BCAA - 500 mL/day for 3 days + Lactulose; n = 39) and the comparator arm (Lactulose alone; n = 37). Six patients developed COVID-19 after randomization and were excluded (4-experimental arm and 2-comparator arm). Results: Of 222 screened patients, 70 (35 in each arm) were included in the analysis. Baseline characteristics, including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7; P = 0.86) and (chronic liver failure) CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7; P = 0.65), were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%; P = 0.14). Improvement in hepatic encephalopathy scoring algorithm (HESA) by ≥ 1 grade at 24 h occurred in 14 patients (40%) in the BCAA arm and 6 patients (17.1%) in the control group (P = 0.03) which translated to a shorter intensive care unit (ICU) stay. The median change in HESA at 24 h was greater in the BCAA arm than the control arm (P = 0.006), which was not sustained at days 3 or 7. Ammonia levels did not correlate with the grade of HE (Spearman's correlation coefficient (ρ) = - 0.0843; P = 0.29). Conclusion: Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. Trial registration no: NCT04238416 (clinicaltrials.gov).

Clinical and patient-reported outcome profile of patients with hepatitis B viral infection from the Global Liver Registry™.

Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p < 0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p < 0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p < 0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real-life Global Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.

Idiopathic Hypercalcemia in Decompensated Cirrhosis: Reexploring an Entity in Oblivion.

Hypercalcemia is a rare metabolic abnormality seen in patients with cirrhosis and is usually considered a paraneoplastic manifestation of hepatocellular carcinoma. Idiopathic hypercalcemia in cirrhosis is a diagnosis of exclusion, which is considered when all the causes of hypercalcemia have been ruled out. Here, we report a rare case of idiopathic hypercalcemia presenting as acute kidney injury in a case of decompensated cirrhosis, managed with adequate hydration and injection of ibandronate and intranasal calcitonin, leading to the normalization of serum calcium and resolution of acute kidney injury.

Intrahepatic Arterioportal Fistula: A Rare Cause of Portal Hypertension After Deceased Donor Liver Transplant.

A 43-year-old male patient, who received a deceased donor liver transplant for background ethanol-related decompensated cirrhosis, presented 7 months after transplant with mild abdominal distension and pain. On evaluation, the patient had thrombocytopenia, high serum-ascites albumin gradient ascites, and deranged liver functions. The Doppler study of the splenoportal axis showed hepatofugal flow in the recipient's portal vein, normal hepatic veins, a normal liver, splenomegaly, mild ascites, and multiple periportal collaterals. A transjugular liver biopsy and a hepatic venous pressure gradient measurement were done, which suggested mild portal tract inflammation with portal tract fibrosis with prominent portal venous thickening and normal hepatic venous pressure gradient (4 mm). However, the patient had a progressive increase in ascites and a dramatic increase in serum bilirubin level. A triple-phase computed tomography was done that showed rapid contrast flow in both the portal and hepatic arterial phase, suggesting arterialization of the portal flow with possible suspicion of a communicating arterioportal fistula. The patient underwent digital subtraction angiography, which was followed by an embolization of the arterioportal fistula. After embolization, serum bilirubin gradually decreased and ascites resolved. A repeat Doppler of the portal venous system showed established hepatopetal flow with progressively rising portal flow velocities.

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.

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.

Role of radiofrequency ablation in unresectable hepatocellular carcinoma: An Indian experience.

AIMS: To evaluate the role of radiofrequency ablation (RFA) as an ablative technique in patients with unresectable hepatocellular carcinoma (HCC). SETTINGS AND DESIGN: A tertiary care center, prospective study. MATERIALS AND METHODS: The subjects comprised 31 patients (30 males, one female; age range 32-75 years) with HCC (41 lesions) who were treated with image-guided RFA. The follow-up period ranged from 3 months to 6 years, and included a multiphasic computed tomography (CT) at 1, 3 and 6 months post-RFA, and every 6 months thereafter. Patient outcome was evaluated and the tumor recurrence, survival and complications were assessed. STATISTICAL ANALYSIS USED: Discrete categorical data were presented as n (%) and continuous data as mean ± SD. Pearson correlation coefficient was used to determine the relationship between the different variables. Kaplan-Meier survival curve and Log-rank test were used to test the significance of difference between the survival time of the different groups. RESULTS: The ablation success rate was 80.5% (33/41 HCC lesions). 12.2% (5/41) of the lesions were managed with repeat RFA due to tumor residue. 4.9% (2/41) of the lesions were managed with repeated RFA and transarterial chemoembolization. Eight patients had tumor recurrence (five patients (16.1%) had local recurrence and three patients (9.6%) had distant recurrence). Eleven patients died within 3.5-20 months post-RFA. The survival rate at 1 year in patients who completed at least 1 year of follow-up was 63.3%. There was one major complication (1/31, 3.2%) in a patient with a subcapsular lesion and ascites. This patient developed hemoperitoneum in the immediate postprocedure period and was managed with endovascular treatment. She, however, had hepatic decompensation and died 48 h post-RFA. CONCLUSION: RFA is an effective and safe treatment for small unresectable HCC.

Non-alcoholic Fatty Liver Disease: East Versus West.

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West.