COVID-19 and the Liver: Lessons Learnt from the EAST and the WEST, A Year Later.

Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause for significant morbidity and mortality. Since the start of the pandemic, several hepato-biliary manifestations in coronavirus disease 2019 (COVID-19) have been described and unique considerations raised. The review aims to summarize the pathogenesis and hepato-biliary manifestations in COVID-19 and discuss the similarities, contrasting features and disease-specific management across a range of hepato-biliary diseases from the EAST and the WEST. Published studies and regional society guidelines from the EAST and the WEST were comprehensively reviewed and summarized. A wide range of hepato-biliary manifestations, including the infrequent and chronic manifestation of cholangiopathy, has been observed in COVID-19. The pathogenesis of liver injury is multifactorial and with scant evidence for a direct SARS-CoV-2 infection of the liver. Patients with non-alcoholic fatty liver disease, cirrhosis, and liver cancer are potentially at increased risk for severe COVID-19, and there are unique considerations in chronic hepatitis B or C, hepatocellular carcinoma, and in those immunosuppressed such as autoimmune hepatitis or liver transplant recipients. With the surges in SARS-CoV-2 infection, liver transplant activity has variably been impacted. Preliminarily, SARS-CoV-2 vaccines appear to be safe in those with chronic liver disease and in transplant recipients, while emerging data suggest the need for a third dose in immunosuppressed patients. In conclusion, patients with chronic liver disease, particularly cirrhosis, and liver transplant recipients, are vulnerable to severe COVID-19. Over the past year, several unique considerations have been highlighted across a spectrum of hepato-biliary diseases. Vaccination is strongly recommended for those with chronic liver disease and liver transplant recipients.

Thailand guideline 2020 for medical management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most prevalent and bothersome functional gastrointestinal disorders worldwide, including in Thailand. After a decade of the first Thailand GERD guideline, physician and gastroenterologist encountered substantially increase of patients with GERD. Many of them are complicated case and refractory to standard treatment. Concurrently, the evolution of clinical characteristics as well as the progression of investigations and treatment have developed and changed tremendously. As a member of Association of Southeast Asian Nations, which are developing countries, we considered that the counterbalance between advancement and sufficient economy is essential in taking care of patients with GERD. We gather physicians from university hospitals, as well as internist and general practitioners who served in rural area, to make a consensus in this updated version of GERD guideline focusing in medical management of GERD. This clinical practice guideline was constructed adhering with standard procedure. We categorized the guideline in to four parts including definition, investigation, treatment, and long-term follow up. We anticipate that this guideline would improve physicians' proficiency and help direct readers to choose investigations and treatments in patients with GERD wisely. Moreover, we wish that this guideline would be applicable in countries with limited resources as well.

Randomized clinical trial: 7-day vonoprazan-based versus 14-day omeprazole-based triple therapy for Helicobacter pylori.

BACKGROUND AND AIM: Vonoprazan has more potent and sustained acid inhibitory effects than proton pump inhibitors; therefore, Helicobacter pylori eradication rates are expected to improve with the use of vonoprazan-based regimens. To date, no randomized trial has compared the efficacy of 7-day vonoprazan-based triple therapy (7-VAC) with 14-day omeprazole-based triple therapy (14-OAC). This study aimed to compare the H. pylori eradication rates of 7-VAC and 14-OAC. METHODS: This randomized clinical trial was performed at a tertiary hospital in Bangkok. Patients with active H. pylori infection who were naive to treatment were included and randomized (1:1) into either a 7-VAC group (vonoprazan 20 mg bid. pc., amoxicillin 1000 mg bid. pc., and clarithromycin 500 mg bid. pc.) or a 14-OAC group (omeprazole 20 mg bid. ac., amoxicillin 1000 mg bid. pc., and clarithromycin 500 mg bid. pc.). Eradication success was evaluated by urea breath test 4-6 weeks after completion of treatment. RESULTS: A total of 122 subjects were randomized to receive 7-VAC (n = 61) or 14-OAC (n = 61). The H. pylori eradication rates of the 7-VAC and 14-OAC groups were 96.7% and 88.5% (P = 0.083), respectively, by intention-to-treat analysis and 98.3% and 93.1% (P = 0.159), respectively, by per-protocol analysis. All treatment-related adverse events were mild and not significantly different between the two groups. Common side effects included bitter taste, nausea, and dizziness. CONCLUSIONS: The 7-VAC regimen was well tolerated and achieved similar eradication rates and side effects to those of 14-OAC; therefore, 7-VAC may be considered an alternative regimen for H. pylori treatment with the benefit of shorter duration.

Real-world effectiveness and safety of sofosbuvir and nonstructural protein 5A inhibitors for chronic hepatitis C genotype 1, 2, 3, 4, or 6: a multicentre cohort study.

BACKGROUND: We investigated real-world effectiveness and safety of sofosbuvir and the nonstructural protein 5A inhibitors in the treatment of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, 4, or 6. METHODS: We analyzed data from 1021 patients with HCV infection (506 with genotype 1; 16 with genotype 2; 314 with genotype 3; 13 with genotype 4; 166 with genotype 6) who received 12 to 24 weeks of daclatasvir plus sofosbuvir (n = 767), ledipasvir/sofosbuvir (n = 197), or sofosbuvir/velpatasvir (n = 57), with or without ribavirin in 12 centers across Thailand to estimate sustained virologic response at post-treatment week 12 (SVR12). RESULTS: Overall, SVR12 rate was 98.0% (95% confidence interval [CI], 96.7-98.8%) with daclatasvir plus sofosbuvir, 97.9% (95% CI, 94.8-99.2%) with ledipasvir/sofosbuvir, and 96.5% (95% CI, 88.1-99.0%) with sofosbuvir/velpatasvir. SVR12 was achieved by 99.2% (95% CI, 97.9-99.7%) of subjects with genotype 1 infection, 100% (95% CI, 78.5-100%) of those with genotype 2 infection, 96.7% (95% CI, 94.0-98.2%) of those with genotype 3 infection, 90.9% (95% CI, 62.3-98.4%) of those with genotype 4 infection, and 96.7% (95% CI 92.5-98.6%) of those with genotype 6 infection. Patients with advanced liver disease were at risk of treatment failure. Only four patients discontinued treatment before week 4 due to non-hepatic adverse events. CONCLUSIONS: In this large cohort of patients with various HCV genotypes managed in the real-world practice setting, daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir achieved high SVR rates with good safety profile, comparable to those observed in clinical trials.

Clinical Characteristics, Treatment Outcomes and Risk Assessment of Patients with Acute Upper Gastrointestinal Bleeding in Rajavithi Hospital, Thailand.

Background: Acute upper gastrointestinal bleeding (UGIB) is common and carries significant morbidity worldwide. Effective risk assessment for UGIB is required in order to deliver the optimal therapeutic plans. Objectives: To describe clinical characteristics and treatment outcomes of acute UGIB in Thailand and to evaluate predictors for rebleeding and complications. Material and Method: Consecutive patients with acute UGIB who underwent esophagogastroduodenoscopy at Rajavithi Hospital, Bangkok, between 2012 and 2015 were retrospectively analyzed. Important clinical data, endoscopic findings and hospital course were reviewed. Multivariate analysis was performed to identify the predictors of rebleeding and complications within 4 weeks. Results: 286 patients were included of whom 180 were non-variceal UGIB (NVUGIB) and 106 were variceal UGIB (VUGIB). Males accounted for 71.7% of participants and had amean age of 53.6 years. Of patients with NVUGIB, 43.4% were taking NSAIDs/ASA, and the most common causes of bleeding were peptic ulcers (62.8%) and gastritis (32.2%). All patients with VUGIB had cirrhosis, and 54.7% were Child-Pugh B/C. When compared to NVUGB, patients with VUGIB were more likely to have active bleeding on presentation, longer prothrombin time, and lower serum albumin and platelet counts. Endoscopic treatments were more commonly performed in VUGIB patients than in NVUGI Bones (62.3% vs. 20.6%, p<0.001). The overall rebleed in grate was 7.3% and mortality was 1%; with no significant difference between NVUGIB and VUGIB. Hospital complications (39.6% vs. 11.7%, p<0.001) and units of blood transfusion (1.85 vs. 1.46 units, p<0.001) were significantly higher in patients with VUGIB than in those with NVUGIB. In the NVUGIB cohort, lower serum sodium and bleeding from duodenal ulcers were independent predictors of rebleeding, where as female gender, hemodynamic instability, and rebleeding were independent predictors of complications. In the VUGIB cohort, lower platelet count was an independent predictor of rebleeding, and lower serum sodium was an independent predictor of complications. Based on the AIMS65 system, the overall rebleeding rates were 5.3% (8/151), 7.0% (6/86), 18.2% (6/33), 7.1% (1/14), 0% (0/1) and 0% (0/1), and complication rates were 9.3% (14/151), 23.2% (20/86), 48.5% (16/33), 78.6% (11/14), 100% (1/1) and 100% (1/ 1), corresponding to the AIMS65 score of 0, 1, 2, 3, 4 and 5 respectively. Conclusion: The overall outcomes of UGIB were good, with better outcomes in NVUGIB than in VUGIB. AIMS65 score and serum sodium may be useful in predicting rebleeding and complications in UGIB.

Treatment outcomes and validation of the stopping rule for response to peginterferon in chronic hepatitis B: A Thai nationwide cohort study.

BACKGROUND AND AIMS: Peginterferon has demonstrated effectiveness in clinical trials in patients with chronic hepatitis B (CHB). However, its efficacy in real-life settings remains unclear. We investigated the efficacy of peginterferon for CHB and validated the performance of previously identified response predictors in clinical practice. METHODS: We analyzed prospectively collected data from a Thai nationwide cohort of CHB patients treated with peginterferon alfa-2a (180 µg/week, 48 weeks). RESULTS: Among a total of 233 patients, mostly with genotype B or C, sustained response was observed in 23% of 135 hepatitis B e antigen (HBeAg)-positive patients (HBeAg seroconversion with hepatitis B virus [HBV] DNA < 2000 IU/mL) and 42% of 98 HBeAg-negative patients (HBV DNA < 2000 IU/mL with aminotransferase normalization) at 24 weeks after treatment. Age, sex, presence of cirrhosis, genotype, and pretreatment levels of aminotransferase, HBV DNA, and hepatitis B surface antigen (HBsAg) were not identified as significant predictors of sustained response. In HBeAg-positive patients, HBsAg > 20 000 IU/mL at week 12 provided a good stopping rule, with a negative predictive value of 96%. In HBeAg-negative patients, the performance of 12-week stopping rules of no decline in HBsAg with a < 2log10 decline in HBV DNA and a < 10% log10 decline in HBsAg showed modest negative predictive values of 80% and 66%, respectively, for achieving sustained response. CONCLUSION: Outcomes in CHB patients treated with peginterferon in a clinical setting are similar to those demonstrated in clinical trials. Application of the early stopping rule based on HBsAg quantification may allow individualization of therapy, particularly in HBeAg-positive patients.

Bone Mineral Density and Renal Function in Chronic Hepatitis B Patients Receiving Nucleotide versus Nucleoside Analogs: A Pilot Prospective Study.

BACKGROUND: The use of nucleotide analogs (NTAs) can be associated with negative effects on renal function and bone mineral density (BMD) due to proximal tubular dysfunction and hypophosphatemia; however, prospective data assessing the bone and renal safety of these agents are limited. OBJECTIVE: This study aimed to evaluate the prevalence of bone diseases among chronic hepatitis B (CHB) patients without cirrhosis and the changes in BMD and glomerular filtration rate (GFR) between patients receiving NTAs versus nucleoside analogs (NSAs). MATERIAL AND METHOD: We prospectively collected data from non-cirrhotic CHB patients who had been treated for < 1 year in Rajavithi Hospital (Bangkok, Thailand) between 2012 and 2014. Patients with significant comorbidities or those being treated for bone diseases were excluded. BMD assessment was performed at the lumbar spine (LS) and femoral neck (FN). BMD T-scores were used to define osteopenia (-2.5 to -1) and osteoporosis (< -2.5), and the GFR was estimated using the Cockcroft-Gault method. RESULTS: Twenty patients were included: 65% were men; 40% were HBeAg positive; and the median age was 42.7 (25.6-64.2) years. Ten patients had been treated with NTAs (7 with tenofovir 3 with adefovir) and 10 patients had been treated with NSAs (8 with lamivudine, 2 with entecavir), with a median follow-up period of 1.5 years (1.2-1.6). At baseline, the overall prevalence of osteopenia was 45% and the median GFR was 94 (51-144) mL/min. BMD in CHB patients was slightly lower than in an age-matched population based on Z-scores. Changes in LS-BMD and FN-BMD were not significantly different between groups. The annual reduction in GFR was more pronounced in the NTA group (-7.4% vs. -1.39%, p = 0.018). CONCLUSION: Osteopenia is common in CHB patients without cirrhosis. Changes in BMD were not significantly different between groups. The annual reduction in GFR was more pronounced in the NTA group.

Nutritional Status and its Impact on Clinical Outcomes for Patients Admitted to Hospital with Cirrhosis.

BACKGROUND: In patients with cirrhosis, nutritional status is an important predictor of clinical outcomes that can be assessed in clinical practice using conventional methods. Previous studies have shown that malnutrition is associated with increased morbidity and mortality in patients with cirrhosis. However, there have been very few reports from Southeast Asia. OBJECTIVE: To determine the prevalence of malnutrition in patients with cirrhosis who are admitted to hospital and to assess its correlation with mortality, complications, length of stay, and total cost of hospitalization. MATERIAL AND METHOD: This prospective non-interventional study included 60 consecutive patients with cirrhosis admitted to Rajavithi Hospital, Bangkok, Thailand, from August 2013 to February 2014. Baseline demographic and clinical data during their hospitalizations were collected prospectively. Nutritional status was assessed by subjective global assessment (SGA) and anthropometry (body mass index (BMI) and mid-arm circumference (MAC)). Malnutrition was defined as SGA class B/ C and MAC of < 5th percentile of the age- and gender-matched reference population. RESULTS: Of the 60 patients, 70% were male. The most common causes of cirrhosis were alcohol (50%) and hepatitis C infection (35%). Most patients were classified as Child-Pugh class B (41.7%) or C (36.7%). The mortality rate was 26.7%, and the most common complications were infections (60%) and renal failure (43.3%). The median length of stay in hospital was 8.5 (1-51) days, with a median cost of 1,163 (183-9,969) US dollars. The prevalence of malnutrition varied between 18% and 92% depending on the assessment method employed: 18% were considered malnourished when assessed by BMI, 63% by MAC, 78% by serum albumin, 65% by absolute lymphocyte count, and 92% by SGA. Patients with malnutrition showed a trend toward increased mortality, complications, length of hospital stay and cost; however, the differences were not statistically significant. Significant predictors of mortality included Child-Pugh class B (16% mortality) and C (50% mortality), severe malnutrition as assessed by SGA (35% mortality), presence of ascites (relative risk, RR: 2.3), hepatic encephalopathy (RR: 2.5), hepatorenal syndrome (RR: 4.1) and renal failure (RR: 3.3). CONCLUSION: Malnutrition is common in hospitalized patients with cirrhosis, and patients with malnutrition showed a trend toward increased complications and mortality. Severe malnutrition, as identified by SGA, and advanced cirrhosis were predictors of in-hospital mortality.

Distinct features in natural history and outcomes of acute hepatitis C.

BACKGROUND: Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. GOALS: This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. STUDY: Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. RESULTS: A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care-associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon α-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. CONCLUSIONS: AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance.

Transjugular intrahepatic portosystemic shunts in liver transplant recipients.

The insertion of a transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive procedure used to relieve the signs and symptoms of portal hypertension in patients with liver disease. The most common indications for placement are refractory ascites and variceal hemorrhage. In properly selected candidates, TIPS placement can serve as a bridge to liver transplantation. Expertise in TIPS placement after transplantation has significantly increased, which has allowed the procedure to become a viable option for retransplant candidates suffering the consequences of recurrent portal hypertension due to portal vein thrombosis, recurrent liver disease, or hepatic venous outflow obstruction (HVOO). However, TIPSs in liver transplant recipients are associated with a lower clinical response rate and a higher rate of complications in comparison with patients with native liver disease, and they are, therefore, generally reserved for patients with a Model for End-Stage Liver Disease (MELD) score ≤ 15 and ≤ 12 in patients with HCV. The role of TIPS placement in nonliver transplant recipients has been well studied in large trials, and it translates well into clinical applicability to candidates for orthotopic liver transplantation (OLT). However, the experience with OLT recipients is heterogeneous and restricted to small series. Thus, we focus here on reviewing the current literature and discussing the proper use of TIPSs in liver transplant recipients.

Prevalence of asymptomatic gastroduodenal lesions and Helicobacter pylori infection in kidney transplant candidates.

BACKGROUND: Upper gastrointestinal (UGI) diseases are more common in patients with end-stage renal disease (ESRD) compared to general populations. Previous studies demonstrated that ESRD patients with UGI disease are at increased risk for developing complications following kidney transplantation (KT). Prevalence of UGI lesions and Helicobacter pylori in asymptomatic KT candidates remain unclear OBJECTIVE: To evaluate the prevalence of UGI lesions and Helicobacter pylori in nondyspeptic KT candidates. MATERIAL AND METHOD: The authors retrospectively and prospectively enrolled consecutive patients with ESRD who underwent esophagogastroduodenoscopy (EGD) as part of pre-KT evaluation at a single tertiary center (Rajavithi Hospital, Bangkok) between 2008 and 2013. Patients with significant dyspeptic symptoms, known UGI disease and received PPI/NSAIDs/antibiotics within two weeks before EGD were excluded. EGD was performed with random biopsies for rapid urease test and histology. RESULTS: In all, 107 ESRD patients were included; 53.0% were men and a median age was 38.7 (15.9-65.0) years. A total of 95% of patients had been on hemodialysis with the median duration of 2.1 (0.2-15.3) years. Significant EGD findings (defined as lesions other than normal and nonerosive gastritis) were encountered in 46% of patients; most lesions were erosive gastroduodenitis and peptic ulcers. Among several baseline demographic and laboratory parameters analyzed, only older age was significantly associated with significant EGD findings (p = 0.026). Helicobacter pylori infection was documented in 27.1% of patients. This prevalence tended to be lower than the prevalence of H. pylori of 39% in 105 sex- and age-matched, nonESRD patients without significant EGD findings who underwent EGD during the same time, but not statistically significant (p = 0.08). CONCLUSION: The authors demonstrated a considerable prevalence of acid-related UGI diseases and H. pylori infection in nondyspeptic KT candidates. Therefore, EGD is a reasonable part of routine preKT evaluations, at least in our part of the world, to promptly detect and precisely manage the problem.

Effects of vitamin E on chronic hepatitis C genotype 3: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with chronic inflammation and oxidative damage, with hepatic steatosis being common in genotype 3 cases. Vitamin E, a potent antioxidant protective against oxidative stress-induced liver damage in vitro and in vivo, has beneficial effects on alanine aminotransferase (ALT) and histological outcomes in patients with non-alcoholic steatohepatitis. OBJECTIVE: To assess the effect of vitamin E on ALT status in patients with HCV genotype 3. MATERIAL AND METHOD: This randomized, placebo-controlled, double-blind trial was conducted in a single tertiary-care hospital (Rajavithi Hospital, Bangkok) between 2010 and 2011. We included patients with HCV genotype 3 infection, unable to receive or tolerate, or did not respond to standard therapy. Responders were defined as patients exhibiting a decrease in serum ALT of at least 5% below the baseline value after 12 weeks of treatment. RESULTS: Thirty-seven eligible patients were randomly assigned either to receive vitamin E 400 IU twice daily (n = 19) or placebo (n = 18; 1 dropped outearly) for 12 weeks. In all, 11 of 19 patients in the vitamin E group (57.8%) and 5 of 17 patients in the placebo group (29.4%) were ALT responders. Among responders, serum ALT levels were greatly decreased in the vitamin E group (reducing from 122.6±80.1 IU/L to 68.4±25.3 IU/L, p = 0.016), when compared with the placebo group (reducing from 89.2±40.6 IU/L to 73.6±30.6 IU/L, p > 0.05). Vitamin E treatment was well-tolerated with no serious adverse events in the present study. CONCLUSION: Vitamin E treatment decreased serum ALT levels in patients with HCV genotype 3. Because of its good safety profile, vitamin E may be a worthwhile supportive therapy for patients with HCV particularly for those who were unable to achieve viral eradication by standard therapy.

Infections in cirrhosis.

Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population.

Review and expert opinion on MAFLD, oxidative stress and multifunctional management.

Metabolic-associated fatty-liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most widespread and emerging chronic liver disease worldwide, with increasing prevalence rates also in the Asia-Pacific region. The disease has a high socio-economic burden as it negatively impacts the finances and quality of life of individuals affected and has a major burden on healthcare systems. The most important pathological event in MAFLD aetiopathogenesis is oxidative stress, which leads to functional and structural abnormalities in the liver as well as being involved in the development of other concomitant cardiometabolic diseases. MAFLD is a rather complex multisystemic clinical condition involving liver damage and a wide spectrum of extrahepatic manifestations such as obesity, type 2 diabetes, metabolic syndrome and cardiovascular diseases. This complexity requires the cooperation of multiple experts to identify MAFLD at an early stage, treat associated comorbidities, and promptly refer the patient to the hepatologist when needed. This review summarizes the current knowledge about MAFLD and reports the opinion of a group of experts on the increasing prevalence and burden of the disease in the southeast Asia region, the current journey of patients with MAFLD in developing countries, the role of oxidative stress and antioxidant treatment, and the importance of a multidisciplinary approach for early diagnosis and disease management. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

Sarcopenia and Frailty in Cirrhosis: Assessment and Management.

Sarcopenia and frailty are frequent in cirrhosis, and both contribute to increased morbidity and mortality. The complex pathogenesis of sarcopenia in cirrhosis is mainly determined by hyperammonemia and malnutrition. Sarcopenia/frailty screening and reevaluation should be undertaken in all cirrhotic patients. Frailty tests are useful in the ambulatory setting, whereas the computed tomography scan is the diagnostic gold standard for sarcopenia. To manage sarcopenia/frailty, a multidisciplinary team should develop a personalized comprehensive care plan that includes patient education, protein/calorie intake goals, late evening meals, exercise programs, and micronutrient replenishment. In selected patients, branched-chain amino acid and testosterone supplements may also be beneficial.

Characteristics of Drug-induced Liver Injury in Chronic Liver Disease: Results from the Thai Association for the Study of the Liver (THASL) DILI Registry.

Background and Aims: The impact of drug-induced liver injury (DILI) on patients with chronic liver disease (CLD) is unclear. There are few reports comparing DILI in CLD and non-CLD patients. In this study, we aimed to determine the incidence and outcomes of DILI in patients with and without CLD. Methods: We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies, causes, and the severity of DILI. We compared the causative agents, clinical features, and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry. Subjects with definite, or highly likely DILI were included in the analysis. Results: A total of 200 subjects diagnosed with DILI were found in the registry. Of those, 41 had CLD and 159 had no evidence of CLD in their background. Complementary and alternative medicine (CAM) products were identified as the most common class of DILI agents. Approximately 59% of DILI in the CLD and 40% in non-CLD group were associated with CAM use. Individuals with pre-existing CLD had similar severity including mortality. Twelve patients (6%) developed adverse outcomes related to DILI including seven (3.5%) deaths and five (2.5%) with liver failure. Mortality was 4.88% in CLD and 3.14% in non-CLD subjects over median periods of 58 (8-106) days and 22 (1-65) days, respectively. Conclusions: In this liver disease registry, the causes, clinical presentation, and outcomes of DILI in subjects with CLD and without CLD patients were not different. Further study is required to confirm our findings.

A randomized trial of 48 versus 24 weeks of combination pegylated interferon and ribavirin therapy in genotype 6 chronic hepatitis C.

BACKGROUND & AIMS: Genotype 6 chronic hepatitis C (HCV) is encountered predominantly in Southeast Asia and data on optimal treatment strategy is limited. This study was aimed at assessing the rate and predictors of sustained virological response (SVR) in genotype 6 chronic HCV following 48 and 24 weeks of pegylated interferon and ribavirin therapy. METHODS: This investigator-initiated, open-label randomized trial was conducted in Vietnam between 2008 and 2010. One hundred and five treatment-naïve HCV genotype 6 patients were randomized to either 48-week (N=70) or 24-week (N=35) duration of pegylated interferon (PEG-IFN) alfa-2a 180 mcg/week and ribavirin (RBV) 15mg/kg/day; 92 patients completed the study (63 in the 48-week and 29 in the 24-week group, respectively). Primary outcome was sustained virological response (SVR) as intention-to-treat analysis. RESULTS: There was no statistical difference in SVR between 48-week and 24-week treated groups (71% vs. 60%, respectively; p=0.24). In the 48-week and 24-week treatment groups, 81% and 80% of cases achieved rapid virological response (RVR) (p=0.86), and 86% and 80% achieved complete early virological response (p=0.45). Among those patients with RVR, SVR was in 86% (48-weeks), and 75% (24-weeks) of cases, whereas following non-RVR, only 8% of cases had an SVR with 48-week treatment duration. CONCLUSIONS: Overall, RVR was achieved in the majority of genotype 6 patients and, in those patients, similar and high rates of SVR were noted following 24-week and 48-week therapy. This observation, however, needs validation in a larger study to demonstrate non-inferiority of the shorter duration therapy. In non-RVR patients, even 48-week therapy achieved low SVR rates.

Tenofovir disoproxil fumarate for prevention of vertical transmission of hepatitis B virus infection by highly viremic pregnant women: a case series.

BACKGROUND: Despite appropriate immunoprophylaxis, up to 10 % of infants born to highly viremic hepatitis B virus (HBV-DNA ≥ 7 log IU/mL) mothers are infected with HBV. Use of TDF to prevent vertical transmission (VT) by such mothers has not been evaluated. PURPOSE: To evaluate the efficacy and safety of TDF in preventing VT from highly viremic HBV-infected mothers. METHODS: Data were collected retrospectively from HBV mono-infected, hepatitis B e antigen (HBeAg) positive, pregnant women between 6/2008 and 11/2010. Cases enrolled were HBV mono-infected mothers who received TDF (300 mg orally once a day) in the third trimester. Those with pregnancy complications or an abnormal fetus on sonography were excluded from use of TDF. All infants received hepatitis B immunoglobulin and vaccination at birth and subsequently. RESULTS: Eleven Asian mothers received TDF at the median gestational age of 29 (28-32) weeks and the median duration of TDF use before delivery was 10 (7-12) weeks. A significant reduction in serum HBV-DNA was achieved at delivery compared with baseline (mean 5.25 ± 1.79 vs. 8.87 ± 0.45 log(10) copies/mL, respectively; p < 0.01). Three had serum ALT levels more than 1.5 times the upper limit of normal and two of these normalized before delivery. The 11 infants were born with no obstetric complication or birth defects. Five infants were breastfed. All infants were hepatitis B surface antigen negative 28-36 weeks after birth. CONCLUSION: Our preliminary data suggest that TDF use in the third trimester is safe, and effectively prevents VT of HBV from high viremic HBeAg-positive mothers.

Current Evidence Concerning Effects of Ketogenic Diet and Intermittent Fasting in Patients with Nonalcoholic Fatty Liver.

Nonalcoholic fatty liver disease (NAFLD) is emerging globally, while no therapeutic medication has been approved as an effective treatment to date, lifestyle intervention through dietary modification and physical exercise plays a critical role in NAFLD management. In terms of dietary modification, Mediterranean diet is the most studied dietary pattern and is recommended in many guidelines, however, it may not be feasible and affordable for many patients. Recently, a ketogenic diet and intermittent fasting have gained public attention and have been studied in the role of weight management. This article reviews specifically whether these trendy dietary patterns have an effect on NAFLD outcomes regarding intrahepatic fat content, fibrosis, and liver enzymes, the scientific rationales behind these particular dietary patterns, as well as the safety concerns in some certain patient groups.