Vol. 14 Issue 1
On the cover: The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for Study of the Liver and the Canadian Association for the Study of the Liver
Traditional Chinese Medicine (TCM) with its focus on herbal use became popular worldwide. Treatment was perceived as safe, with neglect of rare adverse reactions including liver injury. To compile worldwide cases of liver injury by herbal TCM, we undertook a selective literature search in the PubMed database and searched for the items Traditional Chinese Medicine, TCM, Traditional Asian Medicine, and Traditional Oriental Medicine, also combined with the terms herbal hepatotoxicity or herb induced liver injury. The search focused primarily on English-language case reports, case series, and clinical reviews. We identified reported hepatotoxicity cases in 77 relevant publications with 57 different herbs and herbal mixtures of TCM, which were further analyzed for causality by the Council for International Organizations of Medical Sciences (CIOMS) scale, positive reexposure test results, or both. Causality was established for 28/57 different herbs or herbal mixtures, Bai Xian Pi, Bo He, Ci Wu Jia, Chuan Lian Zi, Da Huang, Gan Cao, Ge Gen, Ho Shou Wu, Huang Qin, Hwang Geun Cho, Ji Gu Cao, Ji Xue Cao, Jin Bu Huan, Jue Ming Zi, Jiguja, Kudzu, Ling Yang Qing Fei Keli, Lu Cha, Rhen Shen, Ma Huang, Shou Wu Pian, Shan Chi, Shen Min, Syo Saiko To, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, and Zhen Chu Cao. In conclusion, this compilation of liver injury cases establishes causality for 28/57 different TCM herbs and herbal mixtures, aiding diagnosis for physicians who care for patients with liver disease possibly related to herbal TCM.
Portal vein thrombosis (PVT) is one of the most common vascular disorders of the liver with significant morbidity and mortality. Large cohort studies have reported a global prevalence of 1%, but in some risk groups it can be up to 26%. Causes of PVT are cirrhosis, hepatobiliary malignancy, abdominal infectious or inflammatory diseases, and myeloproliferative disorders. Most patients with PVT have a general risk factor. The natural history of PVT results in portal hypertension leading to splenomegaly and the formation of portosystemic collateral blood vessels and esophageal, gastric, duodenal, and jejunal varices. Diagnosis of PVT is made by imaging, mainly Doppler ultrasonography. According to its time of development, localization, pathophysiology, and evolution, PVT should be classified in every patient. Some clinical features such as cirrhosis, hepatocellular carcinoma, and hepatic transplantation are areas of special interest and are discussed in this review. The goal of treatment of acute PVT is to reconstruct the blocked veins. Endoscopic variceal ligation is safe and highly effective in patients with variceal bleeding caused by chronic PVT. In conclusion, PVT is the most common cause of vascular disease of the liver and its prevalence has being increasing, especially among patients with an underlying liver disease. All patients should be investigated for thrombophilic conditions, and in those with cirrhosis, anticoagulation prophylaxis should be considered.
Aim. Anemia is the most common adverse event in patients with chronic hepatitis C virus (HCV) treated with telaprevir (TVR) combined triple therapy. We examined the effects of drug dose adjustment on anemia and a sustained viral response (SVR) during combination therapy. Material and methods. This study enrolled 62 patients treated with TVR (2,250 mg) for 12 weeks plus pegylated interferon-alpha-2b and ribavirin for 24 weeks. The patients were assigned randomly to the TVR-standard or -reduced groups before treatment. At the occurrence of anemia (hemoglobin < 12 g/dL), the TVR-reduced group received 1500 mg TVR plus the standard dose of ribavirin, whereas the TVR-standard group received the standard TVR dose (2,250 mg) and a reduced dose of ribavirin (200 mg lower than prescribed originally). The safety and SVR at 24 weeks were compared between the TVR-standard (n = 28) and TVR-reduced (n = 25) groups. Results. No differences in the proportion of patients who became HCV RNA-negative were detected between the TVRstandard and -reduced groups (72 and 72% at week 4, 79 and 84% at the end of treatment, and 76 and 80% at SVR24, respectively). Two groups had comparable numbers of adverse events, which led to the discontinuation of TVR in 14 patients of TVR-standard group and in 14 of TVR-reduced group. A lower incidence of renal impairment was observed in the TVR-reduced group (6%) than the TVR-standard group (11%, not statistically significant). Conclusions. TVR dose adjustment could prevent anemia progression without weakening the anti-viral effect during triple therapy in HCV-patients.
Background. We compared mortality and complications of chronic hepatitis C between treated and untreated Mexican patients after long-term follow-up. We used a time-to-event analysis and identified the prognostic factors. Material and methods. Seventy-four patients with chronic hepatitis C were studied. They were ≥ 18 years of age and had a molecular diagnosis of chronic hepatitis C and ≥ 6 months of follow-up. Patients with neoplasia or those infected with human immunodeficiency virus or hepatitis B Virus were excluded. Kaplan-Meier analysis, log-rank test, annualized incidence per 100 person-years, and stepwise discriminant analysis were used to analyse mortality and complications. Results. The end-point of annualized incidence was lowest in sustained virological responders, intermediate in non-responders, and highest in untreated patients. The absence of treatment impacted adversely on cirrhosis development and the occurrence of portal hypertension and hepatic decompensation/hepatocellular carcinoma (logrank,p < 0.05). Diabetes impacted adversely on liver-related death/liver transplantation among untreated patients. Stepwise discriminant analysis showed that diabetes, high blood pressure, and no retreatment predicted cirrhosis development (eigenvalue ≥ 0.8; p < 0.05). A MELD score ≥ 18 and age ≥ 50 years predicted hepatic decompensation/hepatocellular carcinoma (eigenvalue < 0.8; p < 0.05). APRI ≥ 1.5 predicted mortality/liver transplantation and liver-related death/liver transplantation (eigenvalue < 0.8; p < 0.05). Conclusions. This is the first long-term study of chronic hepatitis C among Mexican patients. Treated patients showed less progression of liver disease. Treated patients showed less progression of liver disease; and older patients, those with metabolic comorbidities, with MELD score ≥ 18 and APRI ≥ 1.5 exhibited adverse effects.
Background. Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic in some countries because of the lack of availability. Aim. Assess benefits and harms of boceprevir (BOC)and telaprevir (TLV) in treatment of genotype 1 HCV infection, and identifying subgroups with most benefit. Material and methods. Search from 2009-2013 in PubMed, EMBASE, and gray literature of published and unpublished randomized trials reporting sustained viral response (SVR) or adverse events (AE) with BOC or TLV + pegylated interferon and ribavirin (PR) in HCV-infected patients; cohorts or case reports for comparison protease inhibitors (PI), evaluation of predictors of SVR, and resistant variants. Cochrane guidelines were applied. Comparisons between PI + PR vs. PR were performed. Main outcomes were expressed as risk-ratios with 95% CIs. Meta-regression and trial sequential analysis were performed. Results. 33 studies (10,525 patients) were analyzed. SVR was higher for PI + PR (RR, 2.05; 95% CI 1.70-2.48). In meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47; 95% CI, 2.78-4.33). AE were higher with PI + PR (RR, 1.01; 95% CI, 1-1.03; NNH 77.59), also the discontinuation rate (RR, 1.69; 95% CI, 1.36-2.10, NNH, 18). Predictors of SVR were IL-28 TT, nonblack race, low viral load, age, no cirrhosis,statin use, undetectable viral load at the first anemia episode and at week 2 of treatment, and low IL-6 levels.In conclusion SVR was higher in patients treated with PIs, patients previously exposed to PR showed superior response rates. Specific predictors will determine the best candidates for treatments that will offer real-life therapeutic alternatives.
Introduction. Hepatocellular carcinoma is the most common primary tumor of the liver and is diagnosed in more than a half million people worldwide each year. This study aims to assess factors associated with the recurrence and survival of patients with hepatocellular carcinoma and liver transplantation in a cohort of patients from Medellín, Colombia. Material and methods. This was a descriptive retrospective study of a consecutive series of liver transplant patients from the Pablo Tobon Uribe Hospital of Medellín from January 2004 to May 2013. Demographic, clinical, imaging, and pathology variables were analyzed. Results. Three hundred thirty liver transplants were performed during the study period, 54 cases (16.4%) had one or more hepatocellular carcinomas in the explant, and 79.6% of these patients were men. Cirrhotic patients had different etiologies, but most of them were due to alcohol abuse (22.2%), followed by hepatitis B virus infection (20.4 %), and hepatitis C virus infection (18.5%). In the pathology specimen, 51.9% had only one focus of hepatocellular carcinoma, 22.2% had two foci and 12.9% had three tumors. Recurrence of hepatocellular carcinoma occurred in 7.4% patients with an average time of 81 months. During follow-up,25.9% of the patients died in an average time of 67.9 months (CI95 59.1-80.1 months). Conclusion. Recurrence and survival of patients with liver transplantation for hepatocellular carcinoma in this study had a similar behavior as that reported in the world literature. The factors associated with these outcomes were vascular invasion, poor tumor differentiation and satellitosis.
Background and aim. Hepatocellular carcinoma (HCC) is the most common primary liver cancer diagnosed worldwide. Deregulation of Wnt/?-catenin pathway has been associated with the development of HCC in a substantial number of cases in Europe and far less in Asia. Nothing is known about this pathway in HCC cases from South America. This study aimed to investigate the frequency of mutations in ?-catenin gene (CTNNB1) and the subcellular localization of ?-catenin in HCC cases from Colombia. Material and methods. We determine by direct sequencing the frequency of mutations in exon 3 of CTNNB1 gene and by immunohistochemistry the subcellular localization of ?-catenin in 54 samples of HCC obtained from three pathology units in Bogota and Medellin cities. Results. Only three HCC cases (5.6%) were found mutated at residues (G34E, S45P, P44S, T41I) important for phosphorylation and ubiquitination of ?-catenin protein. Strikingly, nuclear or cytoplasmic accumulation of ?-catenin, hallmark of Wnt pathway activation, was found in 42.6% HCC cases (23/54). Interestingly, ?-catenin accumulation was significantly more frequent in young patients and hepatitis B virus-related HCC. Conclusions. Although, CTNNB1 exon 3 mutations are not frequent in HCC from Colombian patients, our findings indicate that Wnt/?-catenin signaling is activated in 42.6% of HCC samples. Furthermore, Wnt signaling was demonstrated in HCC cases associated of HBV infection, one of the most important HCC risk factors in Colombia.
Hepatocellular carcinoma (HCC) is a development of severe liver disease frequently due to HBV and/or HCV infection. The aim of this retrospective study was to evaluate the development of HCC in patients with HBV-HCV chronic infection compared with patients with single HBV or HCV infection and the viral and host factors correlated to HCC in co-infected patients. We studied 268 patients with histology proven chronic hepatitis: 56 had HBV-HCV co-infection (HBV-HCV group), 46 had HBV infection (HBV group) and 166 had HCV infection (HCV group). Patients were followed up for at least 3 years. Viral and host factors were studied. HCC was more frequent in HBV-HCV group (14%) compared with HBV (2%, p = 0.006) and HCV monoinfected (4%, p = 0.006). The Mantel-Haenszel test used to investigate the relationship between HBV-HCV co-infection and development of HCC indicated an association between development of HCC and HBV-HCV co-infection (p < 0.001). In the HBV-HCV group, patients with HCC were significantly older (p = 0.000), had longer disease duration (p = 0.001), higher blood glucose levels (p = 0.001), lower levels of steatosis (p = 0.02), higher levels of fibrosis (p = 0.000), higher HCV RNA (p = 0.01) than those without HCC. ALT, lipid profile, PNPLA3 variant distribution and HBV viral load did not differ among co-infected patients with or without HCC. In conclusion HCC was more frequent in our patients with HBV-HCV co-infection, than in those with HBV or HCV mono-infection; possible associated risk factors for HCC development seem a long duration of disease, high levels of fibrosis and carbohydrate intolerance.
Background. Although several prognostic models have been proposed for cirrhotic patients listed for transplantation, the performance of these scores as predictors of mortality in patients admitted for acute decompensation of cirrhosis has not been satisfactorily investigated. Aims. To study MELD, MELD-Na,MESO, iMELD, Refit-MELD and Refit MELD-Na models as prognostic predictors in cirrhotic patients admitted for acute decompensation, and to compare their performance between admission and 48 hours of hospitalization to predict in-hospital mortality. Material and methods. This cohort study included cirrhotic patients admitted to hospital due to complications of the disease. Individuals were evaluated on admission and after 48 h of hospitalization, and mortality was evaluated during the present admission. Results. One hundred and twenty-three subjects with a mean age of 54.26 ± 10.79 years were included; 76.4% were male. Mean MELD score was 16.43 ± 7.08 and 52.0% of patients were Child-Pugh C. Twenty-seven patients (22.0%) died during hospitalization. Similar areas under the curve (AUROCs) for prognosis of mortality were observed when different models were compared on admission (P > 0.05) and after 48 h of hospitalization (P > 0.05). When models executed after 48 h of hospitalization were compared to their corresponding model calculated on admission, significantly higher AUROCs were obtained for all models (P < 0.05), except for MELD-Na (P = 0.075) and iMELD (P = 0.119). Conclusion. The studied models showed similar accuracy as predictors of in-hospital mortality in cirrhotic patients admitted for acute decompensation. However, the performance of these models was significantly better when applied 48 h after admission when compared to their calculation on admission.
Background. Cirrhotic patients present a complex interaction between deficient synthetic liver function, hemodynamic abnormalities and superimposed conditions that alter coagulation system. This alters both coagulation and fibrinolytic processes,increasing bleeding and thrombosis risks. Particularly, critically ill cirrhotic patients represent a diagnostic challenge since they have multiple comorbidities making the thrombotic and bleeding risks unpredictable. The prevalence of bleeding and thrombosis in this subset of patients remains poorly described. The main aim of this article is to describe the prevalence of thrombotic and hemorrhagic complications in cirrhotic patients admitted between 2007 and 2012 at Médica Sur Clinic and Foundation ICU. Material and methods. We performed a five years retrospective study including every cirrhotic patient admitted to ICU between January 2007 and December 2012. Results. The incidence of hemorrhage was 48.5%, the overall incidence of thrombotic complications was 13.66%. Variceal bleeding was the most prevalent hemorrhagic event and portal vein thrombosis the most common thrombotic event. Factors associated with presenting a bleeding episode included kidney injury, infection an thrombosis. Factors associated with increased thrombotic risk included ascitis,infection and bleeding. Conclusion. Critically ill cirrhotic patients have an high risk for both thrombotic and bleeding episodes. The association between the presence of bleeding and thrombotic events was statistically significant.
Introduction. Lower 25-hydroxyvitamin D [25(OH)D] levels have been observed in cirrhotic patients and have been related to disease severity. However, most previous studies included patients with very advanced disease, lacking an adequate control for other variables that could interfere with vitamin D levels. We sought to investigate the prevalence of hypovitaminosis D and the factors related to its occurrence. Material and methods. This cross-sectional study included 133 cirrhotic patients and 30 healthy controls. Bivariate and multivariate analyses were performed to determine factors associated with 25(OH)D levels below the lower tertile. Thirty patients who had been recently hospitalized were compared in two time points. Results. Mean 25(OH)D levels were 32.34 ± 11.38 in controls and 27.03 ± 6.22 ng/mL in patients (P = 0.018). 25(OH)D levels were < 30 ng/mL in 69.9% and < 20 ng/mL in 14.3% of the sample. Levels of 25(OH)D below the lower tertile (< 24 ng/mL) were independently associated with higher triceps skinfold and non-Caucasian race. Parathyroid hormone above the reference value (65 pg/mL) was found in 24.6% of patients without association with 25(OH)D or severity of liver disease. Significantly lower levels of 25(OH)D were found at the time of acute decompensation of cirrhosis. Conclusions. In conclusion, hipovitaminosis D was prevalent in cirrhotics and it was associated with adiposity and non-Caucasian race in stable patients with relatively well preserved liver function. However, significantly lower levels were observed during admission for acute decompensation suggesting an impact of systemic inflammation or liver dysfunction on 25(OH)D levels.
Background. Non-alcoholic fatty liver disease (NAFLD) is correlated with obesity, but specific therapeutic interventions are lacking. Adiponectin is an adipokine with anti-inflammatory activity and is considered a hepatic protector. We aimed to investigate effects of a low-fat diet on the hepatic expression of adiponectin and its receptors in rats with NAFLD. Materials and methods. Sixteen male SD rats were fed a high-fat diet for 8 weeks (HFD1 group) or 16 weeks (HFD2 group) to induce NAFLD, and these rats were compared with rats on a normal diet for 8 weeks (NC1 group) or 16 weeks (NC2 group). Another group of 8 rats was fed an HFD for 8 weeks and then switched to a low-fat diet (DIET group) until the 16th week. The expression of hepatic adiponectin and its receptors was detected by western blotting, immunohistochemistry and RT-qPCR. Results. The NAFLD activity score (NAS) in the HFD groups increased from 3.2 ± 0.45 (8th week) to 6.2 ± 0.84 (16th week) (P < 0.001), reflecting the progression in the NAFLD histology. In contrast to the HFD2 group, the low-fat diet ameliorated the steatosis, ballooning degeneration and inflammation. Dietary intervention augmented the expression of adiponectin and its receptors, which was down-regulated in the HFD2 group. Conclusions. The NAFLD rat model was successfully developed by feeding the animals a high-fat diet. Adiponectin may play a role in the pathogenesis of NAFLD, especially in the progression from steatosis to NASH. The low-fat diet alleviated the histological lesions associated with NAFLD by up-regulating the expression of adiponectin and its receptors.
Non-alcoholic fatty liver disease (NAFLD) is a relevant issue in public health owing to its epidemiological burden. It represents the most common chronic liver disease in the general population and is expected to increase in future as a result of an ageing population. The only currently recommended treatment for NAFLD is lifestyle modification. However, literature reports pre-clinical and clinical studies on the use of antioxidant supplementation in NAFLD. A new antioxidant complex, called Bilirel (BIL) (Pharmaluce, Republic of San Marino), have recently introduced in the Italian market. However no data are reported on his effects on liver steatosis. Here we report on a cases series of seven overweight patients with NAFLD, in which the association of an Italian Mediterranean diet, increased physical activity, and daily administration of two pills of BIL for 6 weeks, have induced the rapid improvement of fatty liver accumulation, glucose and lipid metabolism, and weight reduction.
No definitive indications are provided in the literature for pre-TIPS patient workup, which is often limited to prevent the incidence of refractory hepatic encephalopathy or unacceptable deterioration of liver function. Concerning cardiologic workup, efforts are generally limited at excluding ventricular failure or porto-pulmonary hypertension. The cases presented herein focus the attention of the readers on the possible occurrence of post-TIPS paradoxical embolization in the presence of a patent foramen ovale, frequently recognized in adult population. In conclusion, although this complication has been already reported in literature, in the present manuscript we concentrate on possible additional risk factors which may allow to identify a subset of patients with a higher likelihood to experience paradoxical embolization following TIPS. Another important line of information presented herein is the feasibility of percutaneous closure of a patent foramen ovale before TIPS deployment in the presence of portal vein thrombosis and possibly with additional risk factors.
The first generation protease inhibitors has been the mainstay of hepatitis C treatment for the last couple of years, showing marked improvement in sustained virological response, but also increased side effects. Infection has emerged as a common complication of telaprevir and boceprevir in combination with peginterferon and ribavirin, usually caused by common pathogens. We present the case of a 65 years old man who developed a Mycobacterium abscessus pulmonary infection during treatment with telaprevir, peginterferon and ribavirin. The patient was successfully treated with amikacin, imipenem and chlarithromycin. The present case is relevant for increasing awareness for recognition of opportunistic infections and particularly nontuberculous mycobacterial infections in patients receiving triple therapy for chronic hepatitis C, especially in cirrhotic subjects who develop significant lymphopenia.
Renal dysfunction frequently occurs in liver transplant recipients and is associated with increased morbidity and mortality. BK virus is a human polyoma virus that reactivates during immunocompromised states and is a known cause of renal allograft dysfunction in renal transplant recipients. However, BK nephropathy of native kidneys is rare in non-renal transplant recipients. There is no published data linking BK virus and renal dysfunction in liver transplant recipients. We describe the first confirmed case of native polyomavirus BK nephropathy in a liver transplant recipient. BK nephropathy should be considered in the differential diagnosis of new renal failure in liver transplant recipients.