Colangiocarcinoma y hepatocolangiocarcinoma combinado en pacientes con cirrosis / Cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma in cirrhotic patients

Background: Cholangiocarcinoma (CCA) is a primary hepatic tumor, frequently found in patients with liver cirrhosis and biliary tract diseases. Its varieties include isolated CCA or "combined hepatocellular-cholangiocarcinoma" (cHCC-CCA). The latter is uncommon, with poorly defined diagnostic criteria and natural history. Aim: To characterize patients with cirrhosis with a pathological diagnosis of CCA and cHCC-CCA. Material and Methods: Forty-nine liver biopsies with a pathological diagnosis of CCA were reviewed. The clinical records of patients were reviewed to fetch demographic variables, etiology of cirrhosis and clinical presentation. Results: Eight of the 49 patients had cirrhosis (16% of CCA biopsies reviewed). Their median age was 64 (27-71) years and five were females. Four patients had CCA, three patients cHCC-CCA and one had a bifocal tumor. Patients in the CCA group were more commonly symptomatic. Alpha-fetoprotein and CA 19-9 levels were elevated in one of eight and four of six patients, respectively. Within 12 months from diagnosis, five of eight patients died. Conclusions: In most of these cases, the diagnosis of cHCC-CCA and CCA was made in the liver explant study without previous imaging diagnosis. This reinforces the usefulness of the histological study, in specific cases, prior to liver transplantation and emphasizes the importance of systematic explant exploration in these cases.

Colangitis biliar primaria: experiencia de cinco años en el Hospital Clínico de la Universidad de Chile / Primary biliary cholangitis. Experience in 179 patients

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease, which can progress to cirrhosis. It mainly affects middle-aged women. Its most frequent form of presentation is asymptomatic with biochemical cholestasis and the presence of antimitochondrial antibodies (AMA). AIM: To describe the epidemiological characteristics, clinical presentation and treatment for patients with PBC at a clinical hospital. MATERIAL AND METHODS: Descriptive, observational, retrospective study, carried out between January 2015 and December 2020. Results: 179 patients (158 women) were cared in the study period. At the time of diagnosis, the median age was 54 years (range 24-76), 55% of them were asymptomatic, 45% had fatigue and 28% had pruritus. Positive AMA were present in 65% of patients, antinuclear antibodies (ANA) in 51%, and anti-smooth muscle antibodies (ASMA) in 9%. Immunoglobulin M (IgM) was elevated in 30% of the patients and 50% of patients were biopsied. Splenomegaly and esophageal varices were present in 24 and 22% of patients, respectively. PBC was associated with Sjogren's syndrome in 15%, hypothyroidism in 14%, osteoporosis in 13%, and scleroderma in 8%. CONCLUSIONS: The epidemiological characteristics of our patients agree with those published abroad. Laboratory cholestasis associated with the presence of AMA, currently allows diagnosis without the need for histological study. Ursodeoxycholic acid (UDCA) is the first-line treatment for patients with PBC. The use of biochemical response criteria is essential to identify patients who require other UDCA alternatives for isolated or combined treatment.

Embolización de colaterales portosistémicas espontáneas como tratamiento de la encefalopatía hepática refractaria / Embolization of spontaneous portosystemic shunts as treatment for refractory hepatic encephalopathy

BACKGROUND: Hepatic encephalopathy (HE) is a common complication of cirrhosis associated with a reduced survival. The presence of high-flux spontaneous porto-systemic shunts can induce HE even in patients with preserved liver function. AIM: To evaluate the effect of spontaneous porto-systemic shunt embolization (SPSE) over HE and its long-term evolution. MATERIAL AND METHODS: Retrospective analysis of 11 patients (91% males) with severe HE non-responsive to medical treatment in whom a SPSE was performed. The grade of HE (employing West Haven score), survival, MELD and Child-Pugh score, ammonia levels, degree of disability (employing the modified Rankin scale (mRs)) were evaluated before and at thirty days after procedure. RESULTS: The most common etiology found was non-alcoholic steatohepatitis (63.6%). A reduction of at least two score points of HE was observed in all patients after thirty days. There was a significant reduction on median (IQR) West Haven score from 3 (2-3) at baseline to 1 (0-1) after the procedure (p < 0.01). Twelve months survival was 63.6%. There was a decrease in median ammonia level from 106.5 (79-165) (ug/dL) to 56 (43-61) after SPSE (p = 0.006). The median mRS score before and after the procedure was 3 (3-5) and 1 (1-2.5), respectively (p < 0.01). Conclusions: According to our experience, SPSE is a feasible and effective alternative to improve HE and functionality of patients with refractory EH.

Resumen ejecutivo: Enfermedad por hígado graso no alcohólico en sujetos con diabetes mellitus tipo 2: Postura conjunta de la Asociación Chilena de Hepatología (ACHHEP) y la Sociedad Chilena de Diabetología (SOCHIDIAB) / Non-alcoholic fatty liver disease in type 2 diabetes: a joint statement of the Chilean Hepatology and Diabetology Societies

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence and risk of progression to cirrhosis and other complications in patients with type 2 diabetes mellitus (T2DM). Likewise, the presence of NAFLD implies a high risk of developing T2DM, determining a bidirectional relationship between them. The diabetology and hepatology societies, developed a joint initiative aiming to unify criteria, reviewing the definitions, diagnostic criteria, risk stratification, treatment, and follow-up of patients with NAFLD and T2DM. The key questions to be discussed were defined by a panel of specialists in diabetology and hepatology. The Delphi methodology was used to reach consensus on the respective recommendations. Based on the discussion generated among the experts, diagnostic and treatment algorithms were proposed, as well as an indication for referral and the role of the different specialists involved in the management of these patients. Strengthening multidisciplinary work with patients with NAFLD and T2DM will allow the early recognition of the disease, the prevention of the progression to cirrhosis, and reducing the associated complications.

Hepatitis aguda por virus C: reporte de siete casos en centro de referencia en Chile

Hepatitis C virus infection is a major global public health problem. Treatment with direct-acting antivirals is intended to eradicate the chronic form of this infection by 2030. Although uncommon, the acute form of presentation is increasingly recognized, especially in some high-risk populations, such as men who have sex with men without protection. Its virological and serological diagnosis is not standardized, so clinical suspicion is essential. Its early detection allows a timely treatment. We report seven cases of acute HCV hepatitis in a national reference center, its presentation, diagnosis and treatment. We discuss populations at risk and the change in therapeutics with the use of direct-acting antiviral drugs.

Cirugía en el paciente cirrótico: características clínicas y complicaciones en una cohorte de pacientes chilenos / Surgical complications in cirrhotic patients: analysis of 102 cases

Background: Cirrhotic patients have an increased surgical risk due to potential intra and postoperative complications. Aim: To describe the clinical characteristics and surgical complications of cirrhotic patients undergoing surgery in a Chilean university hospital. Patients and Methods: Review of medical records of 102 cirrhotic patients aged 60 ± 11 years (52% males) who underwent elective or urgency surgery at an university hospital between 2010 and 2016. General, pre-surgical, and post-surgical complications were recorded. Results: The main etiologies of cirrhosis were non-alcoholic steatohepatitis (31%), and alcoholic cirrhosis (28%). Child-Pugh scores were A, B and C in 50, 28 and 22% of cases respectively. Median MELD (Model for End-stage Liver Disease) score was 11 (interquartile range: 10-15). The surgical procedure was elective in 71% of cases, with predominance of abdominal surgery (86%). The American Society of Anesthesiologists (ASA) score was three or more in 52% of patients. The frequency of any adverse outcome was 62%. The frequency increased along with the severity of cirrhosis and when surgery was urgent. The most common complications were acute renal failure (24%), increased ascites (23%) and encephalopathy (22%). Admission to intensive care unit occurred on 26% of patients, with six hospital deaths. Conclusions: In these patients, surgical complications were common, although with low mortality.

Tumores hepáticos primarios malignos no hepatocarcinoma ni colangiocarcinoma / Primary malignant hepatic tumors other than hepatocarcinoma or cholangiocarcinoma: a series of cases

Background: There are several types of primary malignant hepatic tumors (PMHT) other than hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC): they are infrequent and poorly known. Imaging studies could help characterize the lesions and may guide the diagnosis. However, the definitive diagnosis of PMHT is made by pathology. Aim: To review a registry of liver biopsies performed to diagnose hepatic tumors. Patients and Methods: Review of a pathology registry of liver biopsies performed for the diagnosis of liver tumors. Among these, 25 patients aged 57 ± 17 years, 60% males, in whom a liver tumor other than a HCC or CC was diagnosed, were selected for review. The medical records of these patients were reviewed to register their clinical characteristics, imaging and the pathological diagnosis performed during surgery and/ or with the percutaneous liver biopsy. Results: Ten patients (40%) had neuroendocrine tumors, six (24%) had a lymphoma and four (16%) had hepatic hemangioendothelioma. Angiosarcoma and sarcomatoid carcinoma were diagnosed in one patient each. In 22 patients (88%), neither clinical features nor imaging studies gave the correct diagnosis. Four patients (16%) had chronic liver disease. The most frequent symptoms were weight loss in 28% and abdominal pain in 24%. Conclusions: The most common PMHT other than HCC and CC were neuroendocrine tumors and lymphomas. Imaging or clinical features were not helpful to reach the correct diagnosis.

El polimorfismo rs12979860 C> T en el gen Interferón lambda 4 no está asociado a riesgo de fibrosis hepática en pacientes chilenos con hepatitis crónica por virus C / Interferon Lambda 4 RS12979860 C> T polymorphism is not associated with liver fibrosis in patients with hepatitis C

Background. Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. Aim: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. Material and Methods: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR. Fibrosis present in liver biopsies was assessed using the METAVIR score, comparing patients with either no fibrosis, mild fibrosis, or intermediate fibrosis (F0+F1+F2, n = 96), with patients with severe fibrosis or cirrhosis (F3+F4, n = 54). Results: In F0-F2 patients the distribution of rs12979860 genotypes was 22 CC, 57 CT and 17 TT, whereas in patients F3-F4 the distribution was 10, 29 and 15, respectively. No association between IFNL4 rs12979860 genotype and risk of fibrosis was observed in uni or multivariate analyses. Conclusions: IFNL4 rs12979860 C>T polymorphism is not associated with risk of liver fibrosis in this group of patients with CHC.

Escleroterapia endoscópica asistida mediante balón oclusivo como tratamiento de varices gástricas cardiofúndicas de alto riesgo: reporte de dos casos y revisión de la literatura / Fundal variceal bleeding treated with balloon occluded endoscopic inyection sclerotherapy: report of two cases

Management of gastrointestinal bleeding caused by fundal varices is particularly difficult to manage. The options are: transjugular intrahepatic portosystemic shunt (TIPS), endoscopic injection of cyanoacrylate or balloon-occluded retrograde transvenous obliteration (BRTO). We report a 63 year-old male with a cirrhosis caused by hepatitis C and a 66 year-old female with a cirrhosis caused by a non-alcoholic steatohepatitis. Both patients had a gastrointestinal bleeding caused by fundal varices and were treated with sclerotherapy with cyanoacrylate assisted with BRTO. Flow was interrupted in the gastro-renal shunt by a femoral access in both patients. The male patient had a new bleeding two months later and died. In the female patient an endosonography performed nine months after the procedure showed absence of remaining varices.

Evaluación de parámetros clínicos y de laboratorio relacionados con el diagnóstico de insulino resistencia / Evaluation of clinical and laboratory parameters related to the diagnosis of insulin resistance

The evaluation of insulin resistance (IR) in clinical practice is based on the determination of fasting insulin (I0) and insulin level after 2 hours in an oral glucose tolerance test (OGT). However, there are not adequate cutoff points to discriminate IR patients. Objectives: to evaluate the reliability of insulin levels in the diagnosis of IR using the intravenous insulin tolerance test (IVITT) as the gold standard. Patients and Method: The OGT and IVITT of patients who participated as cases or controls in research protocols were analyzed. We excluded those cases with fasting glycemia over126 mg/dl. Results: 128 cases, 111 F, 17 M; Age: 40.3 +/- 14.8 years; BMI: 33 +/- 8 kg/m2; Waist circumference, M: 100.3 +/- 9.4 cm, F: 96 +/- 15 cm. According to IVITT (KITT), 103 (80.5 percent) were IR (KITT < 4.5 percent) and 25 (19.5 percent) were non IR (KITT > 4.5 percent). Fasting (G0) and 120 minutes after glucose challenge glycemia (G120), I0 and I120, HOMA and area under the glycemia and insulin curve, were significantly higher in the IR, as the same as, hypertension and acanthosis nigricans features (p < 0.05). According to G120, 45 cases (35.2 percent) had glucose intolerance, 9 (7 percent) diabetes and 74 (57.8 percent) were normals. In addition to G0, only IVITT was significantly different among the 3 groups (p = 0.025), identifying most insulin resistant subjects. The sensitivity and specificity for a cutoff point of I120 at 60 µIU/mL, were 30 percent and 88 percent, respectively. Conclusion: Baseline and 120 minutes post glucose charge insulin levels and HOMA, do not discriminate insulin resistant subjects, especially when there is fasting or post-stimulus hyperglycemia. Therefore, they are not recommended for individual diagnosis or therapeutic decisions

Manifestaciones cutáneas en adultos con trasplante hepático del Hospital Clínico de la Universidad de Chile / Skin manifestations in adults with a liver allograft

Background: Skin manifestations after liver transplantation are increasing due to long term immunosuppressive therapy along with an increase in patient survival. Several studies have reported dermatologic complications following renal transplant, but few have studied dermatologic problems after liver transplantation. Aims: To describe the different types of cutaneous lesions encountered in adults receiving a liver allograft. To evaluate the frequency of cutaneous manifestations of patients in the liver transplant waiting list. Material and Methods: Eighty patients submitted to a liver transplant and 70 patients in the liver transplant waiting list were evaluated with a complete dermatological physical examination. Results: Sixty one percent of patients with a liver allograft had at least one skin manifestation. Of these, 34% had superficial fungal infections, 31% had viral infections, 20% had cutaneous side effects due to immunosuppressive treatment, 10% had malignant lesions, 2% had bacterial infections and one patient had a graft versus host disease. Only 28% of patients in the liver transplant waiting list had dermatologic problems, and the vast majority were lesions linked to liver cirrhosis. Conclusions: Cutaneous infections were the most common skin problems in liver transplant patients. Although neoplastic lesions are the most commonly mentioned lesions in the literature, only a 10% of our liver transplant patients presented these type of lesions.

Eliminación espontánea de virus hepatitis C en trasplantado hepático: a propósito de dos casos / Spontaneous clearance of hepatitis C virus after liver transplantation: Report of two cases

The spontaneous clearance of hepatitis C virus infection is rare, especially after liver transplantation, condition in which recurrence is almost universal. We report two cases in which clearance of the virus was achieved after liver transplantation. We reviewed the literature and described possible mechanisms explaining this phenomenon, with emphasis on therapeutic implications.

II Consenso de la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.

Lesiones focales hepáticas benignas: un hallazgo frecuente a la tomografía computada / Benign focal liver lesions detected by computed tomography: Review of 1,184 examinations

Background: Multidetector computed tomography (MDCT) of the abdomen, with use of contrast medium, is able to detect and differentiate most focal liver lesions. Aim: To determine the prevalence and features of benign focal liver lesions (BFLL) detected by abdominal MDCT. Patients and Methods: We reviewed the reports of contrast abdominal MDCT performed to outpatients between August 2011 and July 2012. Clinical data of examined patients and imaging findings in terms of description of the hepatic parenchyma and the presence of BFLL, were recorded. Results: Data from 1,184 studies were analyzed. Of these, 461 studies (38.4%) reported BFLL. The most prevalent lesions were simple cysts in 290 studies (24%) and hemangiomas in 61 studies (5.1%), granuloma-calcification in 39 (3.2%), focal nodular hyperplasia in 19 (1.6%) and one adenoma. If patients with known causes of liver disease were excluded, the prevalence of BFLL did not change substantially (lesions were found in 396 (37.5%) patients). Compared with livers with signs of damage, normal livers had more cystic lesions (27 and 16.2% respectively, p = 0.014) and hemangiomas (5.3 and 1.1% respectively, p = 0.043). Conclusions: BFLL are very common findings in MDCT studies. Most of these lesions are simple cysts and hemangiomas.

Trasplante hepático en cirrosis por virus B: profilaxis con gammaglobulina antiHBs en dosis a "demanda" / Hepatitis B virus immunoglobulin on demand to prevent infection recurrence among liver allograft recipients: Report of three cases

Infection recurrence rates among hepatitis B virus infected liver allograft recipients, may be as high as 80%. Immunoprophylaxis with anti HBVgammaglobulin may reduce these rates and improve survival. The dose of anti HBV gammaglobulin that must be used is not clearly defined. The most commonly accepted protocol uses 10,000 units during the anhepatic phase and 10,000 units daily during one week, followed by weekly doses of 10,000 units during one month and maintenance with 10,000 units monthly, without measuring anti hepatitis B surface antigen antibodies (antiHBs). Some reports recommend the use of immunoglobulin on demand, to maintain antiHBs titers between 100 and 250 U/l. The infection recurrence rates among patients treated with immunoglobulin and Lamivudine fluctuates between 0 and 10%, during follow up periods of 13 to 30 months. We report three liver allograft recipients that received immunoglobulin on demand, using a mean of41,000 units, maintaining adequate antiHBs titers.

Falla hepática fulminante por virus hepatitis B en paciente coinfectado por VIH: un desafío terapéutico. Caso clínico / Fulminant hepatic failure by hepatitis B virus in a patient with human immunodeficiency virus infection: Report of one case

The human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection is a common problem in the world, with an estimated prevalence of up to 8 percent. We report a 27-year-old man admitted to the intensive care unit with an acute liver failure by HBV. During hospital stay, a co-infection with HIV virus was detected. Treatment with early antiviral therapy was started with emtricitabine, tenofovir and raltegravir, to cover both HBV and HIV. Despite therapy, the patient died two weeks after admission.

Trasplante hepático en Chile: Aspectos generales, indicaciones y contraindicaciones (Documento de consenso) / General considerations, indications and contraindications for liver transplantation in Chile: A multicenter consensus development document

Liver transplantation is an excellent therapeutic option for terminal liver disease. During the last decades the results of liver transplantation have improved significantly with a patient survival rate of nearly 90 percent at one year and 80 percent at 5 years of follow-up. The main indications for liver transplantation include: end-stage liver disease associated to cirrhosis, acute liver failure, and hepatic tumors (mainly hepatocarcinoma). The absolute contraindications for a transplant are less frequent than in the past, and include: severe co-morbidity (cardiac or pulmonary), sepsis, advanced HIV disease and extra-hepatic malignancy. This document presents a Consensus of the main groups performing liver transplantation in Chile, about its indications and contraindications. It also reviews general aspects of liver transplantation, including the selection and referral of liver transplant candidates, allocation of organs and the evaluation of severity of liver disease.

Effects of weight loss on liver and erythrocyte polyunsaturated fatty acid pattern and oxidative stress status in obese patients with non-alcoholic fatty liver disease

Our aim was to study the influence of weight loss on the fatty acid (FA) composition of liver and erythrocyte phospholipids and oxidative stress status in obese, non-alcoholic, fatty liver disease (NAFLD) patients. Seven obese NAFLD patients who underwent subtotal gastrectomy with a gastro-jejunal anastomosis in roux and Y were studied immediately and 3 months after surgery. Seven non-obese patients who underwent anti-reflux surgery constituted the control group. Serum F2-isoprostane levels were measured by GS/NICI-MS/MS and FA composition was determined by GC. At the time of surgery, controls and obese patients exhibited a hepatic polyunsaturated fatty acid (PUFA) pattern that correlated with that of erythrocytes. Three months after surgery, NAFLD patients lost 21 percent of initial body weight; serum F2-isoprostane levels decreased by 76 percent; total PUFA, long-chain PUFA (LCPUFA), n-3 PUFA, and n-3 LCPUFA increased by 22, 29, 81, and 93 percent, respectively; n-6/n-3 LCPUFA ratio decreased by 51 percent; docosahexaenoic acid/docosapentaenoic acid ratio increased by 19-fold; and the n-3 product/precursor ratio (20: 5 + 22: 5 + 22: 6)/18: 3 increased by 164 percent (p<0.05). It is concluded that weight loss improves the n-3 LCPUFA status of obese patients in association with significant amelioration in the biomarkers of oxidative stress, membrane FA insaturation, and n-3 LCPUFA biosynthesis capacity, thus representing a central therapeutic issue in the improvement of obesity-related metabolic alterations involved in the mechanism of hepatic steatosis.

Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women

CYP2E1 enzyme is related to nonalcoholic steatohepatitis (NASH) due to its ability for reactive oxygen species production, which can be influenced by polymorphisms in the gene. The aim of this study was to investigate hepatic levels, activity, and polymorphisms of the CYP2E1 gene to correlate it with clinical and histological features in 48 female obese NASH patients. Subjects were divided into three groups: (i) normal; (ii) steatosis; and (iii) steatohepatitis. CYP2E1 protein level was assayed in microsomes from liver biopsies, and in vivo chlorzoxazone hydroxylation was determined by HPLC. Genomic DNA was isolated for genotype analysis through PCR. The results showed that liver CYP2E1 content was significantly higher in the steatohepatitis (45 percent; p=0.024) and steatosis (22 percent; p=0.032) group compared with normal group. Chlorzoxazone hydroxylase activity showed significant enhancement in the steatohepatitis group (15 percent, p=0.027) compared with the normal group. c2 rare allele of RsallPstl polymorphisms but no C allele of Dral polymorphism was positively associated with CHZ hydroxylation, which in turn is correlated with liver CYP2E1 content (r=0.59; p=0.026). In conclusion, c2 allele is positively associated with liver injury in NASH. This allele may determine a higher transcriptional activity of the gene, with consequent enhancement in pro-oxidant activity of CYP2E1 thus affording liver toxicity.