RESUMO
The limited literature on the clinical course of COVID-19 among patients with underlying liver disease (LD) is available from India. The present study aimed to evaluate the clinical and mutational profile of SARS-CoV-2 among LD cases. This was a retrospective study including admitted LD cases in whom SARS-CoV-2 RT-PCR testing was performed. Complete demographic and clinical details were retrieved from Hospital Information System. Detailed mutational analysis was performed by comparing LD COVID-19 positive study group, i.e. LD-CoV(+) with COVID-19 positive outpatients without any underlying LD as control, i.e. NLD-CoV(+). Out of 232 enrolled LD cases, 137 (59.1%) were LD-CoV(+). LD cases with existing co-morbidities were affected more (P = 0.002) and had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher odds of succumbing to COVID-19 (P = 0.006). On multivariate regression analysis, ascites (P = 0.05), severe COVID-19 pneumonia (P = 0.046), and an increased levels of bilirubin (P = 0.005) and alkaline phosphatase (P = 0.003) were found to be associated with adverse outcome in LD-CoV(+).On mutational analysis, we found certain differences between LD- and NLD-CoV(+) infected with Delta [LD- and NLD-CoV (+ /D)] and Omicron [LD- and NLD-CoV(+/O)]. More mutations were shared between LD- and NLD-CoV(+/O) compared to LD- and NLD-CoV(+/D). There were differences in prevalence of indel mutations specific to LD-CoV ( +) for both Delta and Omicron. Moreover, we also reported an interesting genic bias between LD- and NLD-CoV( +) in harbouring deleterious/tolerated mutations. To conclude, LD cases with comorbidities were affected more and had higher odds of mortality due to COVID-19. The definite difference between LD- and NLD-CoV(+) groups with respect to frequency of harboured mutations and an inherent genic bias between them is of noteworthy importance.
Assuntos
COVID-19 , Hepatopatias , SARS-CoV-2 , Humanos , COVID-19/virologia , COVID-19/genética , Estudos Retrospectivos , Masculino , Feminino , SARS-CoV-2/genética , Pessoa de Meia-Idade , Hepatopatias/virologia , Hepatopatias/genética , Adulto , Índia/epidemiologia , Idoso , Mutação , ComorbidadeRESUMO
AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.
Assuntos
Técnicas de Ablação/métodos , Neoplasias dos Ductos Biliares/terapia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Colangiocarcinoma/terapia , Neoplasias Hepáticas/terapia , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Ablação por Radiofrequência , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Pancreatic-pleural fistula (PPF) is a rare sequela of pancreatitis. High degree of clinical suspicion is required to diagnose a PPF. Confirmation is done by high amylase content in pleural fluid analysis. Here, we present two cases with varied presentation of PPF. A 43-year-old man presented with acute on chronic pancreatitis with bilateral (predominantly right) pleural effusion. Another 57-year-old man, previously diagnosed with chronic calcific pancreatitis, presented with left pleural effusion. Both cases were effectively managed with endoscopic pancreatic duct stenting.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Ductos Pancreáticos/cirurgia , Fístula Pancreática/cirurgia , Pancreatite Crônica/complicações , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/cirurgia , Stents , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Fístula Pancreática/complicações , Fístula Pancreática/diagnóstico por imagem , Pancreatite Crônica/diagnóstico por imagem , Doenças Pleurais/diagnóstico por imagem , Doenças Pleurais/terapia , Derrame Pleural/etiologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Carvedilol is effective in the primary prophylaxis for large oesophageal varices. We investigated its use in preventing progression of small to large oesophageal varices. METHODS: Consecutive cirrhotics with small oesophageal varices were prospectively randomised to either carvedilol (n=70) or placebo (n=70) and followed up for a minimum of 24â months. Endoscopy was done at baseline and six monthly intervals. Hepatic vein pressure gradient (HVPG) was measured at baseline and at 12â months. The primary endpoint was development of large varices. RESULTS: Baseline characteristics in two groups were comparable. The predominant aetiology of cirrhosis was non-alcoholic fatty liver disease in both the groups. The mean dose of carvedilol administered was 12±1.67â mg/day and the target heart rate achieved was 58±3â bpm. A higher proportion of patients in carvedilol group had non-progression to large varices than placebo (79.4% vs 61.4%; p=0.04); the mean time of non-progression to large varices was 20.8â months (95% CI 19.4 to 22.4) in carvedilol group and 18.7â months (95% CI 17.1 to 20.4) in placebo group (p=0.04). There was a modest reduction of HVPG at 1â year in carvedilol group (-8.64%) compared with placebo (+0.33%) (p=0.22). None of the patients in either group died of variceal bleeding or liver-related causes. No major adverse events were observed in either group. CONCLUSIONS: Carvedilol is safe and effective in delaying the progression of small to large oesophageal varices in patients with cirrhosis. TRIAL REGISTRATION NUMBER: NCT01196507; post-results.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Carbazóis/uso terapêutico , Progressão da Doença , Varizes Esofágicas e Gástricas/prevenção & controle , Propanolaminas/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Adulto , Carbazóis/efeitos adversos , Carvedilol , Intervalo Livre de Doença , Endoscopia Gastrointestinal , Varizes Esofágicas e Gástricas/etiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Veias Hepáticas/fisiopatologia , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Propanolaminas/efeitos adversos , Estudos Prospectivos , Taxa de Sobrevida , Pressão Venosa/efeitos dos fármacosRESUMO
Alcoholic hepatitis is a clinical syndrome with or without pre-existing chronic liver disease (CLD), and the majority of patients present with acute-on-chronic liver failure (ACLF) having a high 28-day mortality. The treatment of alcoholic hepatitis is suboptimal with corticosteroid having one 1month survival benefit but not translated to a survival benefit beyond six months. Survival benefit has been observed in only about 50-60% of treated patients. Long-term survival depends on underlying liver function and abstinence from alcohol. Relapse is reported in nearly half of the patients who recover from alcoholic hepatitis and even up to 17% after liver transplant. The data on repeated episodes of severe alcoholic hepatitis due to relapse and response to therapy are largely unknown. Here, we report a case of alcoholic hepatitis on three occasions in a period of 2 years follow-up and each time treated with steroids and had complete clinical recovery.
RESUMO
Dilated and dysfunctional gut lymphatic vessels (LVs) have been reported in experimental cirrhosis. Here, we studied LVs in duodenal (D2)-biopsies of liver cirrhosis patients and investigated the prognostic role of a LV marker, podoplanin (PDPN), in predicting the mortality of patients with cirrhosis. A prospective, single-center cohort study was performed in liver cirrhosis patients (n = 31) and matched healthy controls (n = 9). D2-biopsies were obtained during endoscopy procedure, immunostained with PDPN, and scored based on 1) intensity and 2) density of positively-stained LVs per high power field. Gut and systemic inflammation were estimated by quantifying duodenal CD3+ intraepithelial lymphocytes (IELs), CD68+ macrophages, and serum TNF-α and IL-6 levels, respectively. Gut permeability and inflammation as assessed by quantifying gene expression of TJP1, OCLN, TNF-α, and IL-6 in D2-biopsies. Gene expression of LV markers, PDPN (8-fold), and LYVE1 (3-fold) was enhanced in D2-biopsies of cirrhosis patients compared to control (p < 0.0001). The mean PDPN score in decompensated cirrhosis patients (6.91 ± 1.26, p < 0.0001) was significantly increased as compared to those with compensated (3.25 ± 1.60). PDPN score positively and significantly correlated with the number of IELs (r = 0.33), serum TNF-α (r = 0.35), and IL-6 (r = 0.48) levels, while inversely correlated with TJP1 expression (r = -0.46, p < 0.05 each). In Cox regression, the PDPN score was a significant and independent 3-month-mortality predictor in patients (HR: 5.61; 1.08-29.109; p = 0.04). The area under the curve for the PDPN score was 84.2, and cutoff value for predicting mortality was ≥6.5 with 100% sensitivity and 75% specificity. Collectively, dilated LVs with high PDPN expression in D2-biopsies is a characteristic feature of patients with decompensated cirrhosis. PDPN score correlates with enhanced gut and systemic inflammation and also associates with 3-month mortality in cirrhosis.