Chronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible ''trial endpoints") that could be used across different clinical trials.

The HDIN registry confirms the severity of hepatitis delta but also highlights the heterogeneity of patient characteristics and clinical outcomes in different regions. There is an urgent need for novel treatment options for HDV infection.

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In patients with urinary magnesium wasting, oral and intravenous supplementation often fail to adequately improve serum magnesium levels. Glucose intolerance and diabetes mellitus frequently accompany hypomagnesemia. Clinical trials examining inhibitors of the type 2 sodium glucose cotransporter (SGLT2) show small but significant increases in serum magnesium levels in diabetic patients. This report describes dramatic improvement in serum magnesium levels and associated symptoms after initiating SGLT2 inhibitor therapy in 3 patients with refractory hypomagnesemia and diabetes. Each patient received a different SGLT2 inhibitor: canagliflozin, empagliflozin, or dapagliflozin. One patient discontinued daily intravenous magnesium supplements and exhibited higher serum magnesium levels than had been achieved by magnesium infusion. 2 of the 3 patients exhibited reduced urinary fractional excretion of magnesium, suggesting enhanced tubular reabsorption of magnesium. These observations demonstrate that SGLT2 inhibitors can improve the management of patients with otherwise intractable hypomagnesemia, representing a new tool in this challenging clinical disorder.

In Italy, HDV infection endemicity has greatly decreased overtime. Migratory flow may change this scenario as migrants often come from high HDV endemicity areas. Here, we studied characteristics of HDV infection in Italy, particularly addressed to the birth area of subjects. Chronic HBsAg carriers consecutively referring to 9 units in Italy prospectively enrolled for a six‐month period in 2019 were tested for anti‐HDV by ELISA. Multiple logistic regression analysis was performed to identify anti‐HDV positivity independent predictors. A total of 894 HBsAg‐positive subjects were enrolled. Of them, 786 (87.9%) were tested for anti‐HDV. Anti‐HDV overall prevalence was 9.9% (6.4% in Italian natives and 26.4% in non‐natives; P < .001). HDV‐RNA was checked in 63 (80.8%) of the 78 anti–HDV+ subjects, and 49 (77.8%) tested positive. Compared to non‐natives, Italians were more likely males (male/female 1.6 vs 0.6; P < .05) and older (median age 57 years vs 46 years; P < .05). Multivariate analysis showed that non‐natives (OR = 6.02; CI 95% = 3.06‐11.84) and cirrhosis (OR 9.6; CI 95% = 5.39‐17.30) were independently associated with anti‐HDV positivity. A remarkable changing pattern in some characteristics of anti–HDV‐positive subjects was observed over 1987‐2019: a decreasing male/female ratio, an increasing mean age and proportion of cirrhotic subjects. Anti‐HDV prevalence decreased from 7.4% to 6.4% among Italians, increasing from 12.2% to 26.4% among non‐natives during 2001‐2019. Hence, HDV infection in Italians is further decreasing and mostly affects old people and subjects with advanced disease reflecting a survival effect. Conversely, non‐natives are sixfold more likely anti–HDV‐positive with an increasing trend. Migratory flow may be a new challenge for HDV infection at the beginning of the third millennium.

The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents.

Hepatitis D virus (HDV) is a small, defective RNA virus that depends on hepatitis B virus (HBV) for virion assembly and transmission. It replicates within the nucleus of hepatocytes and interacts with several cellular proteins. Chronic hepatitis D is a severe and progressive disease, leading to cirrhosis in up to 80% of cases. A high proportion of patients die of liver decompensation or hepatocellular carcinoma (HCC), but the lack of large prospective studies has made it difficult to precisely define the rate of these long-term complications. In particular, the question of whether HDV is an oncogenic virus has been a matter of debate. Studies conducted over the past decade provided evidence that HDV is associated with a significantly higher risk of developing HCC compared to HBV monoinfection. However, the mechanisms whereby HDV promotes liver cancer remain elusive. Recent data have demonstrated that the molecular profile of HCC-HDV is unique and distinct from that of HBV-HCC, with an enrichment of upregulated genes involved in cell-cycle/DNA replication, and DNA damage and repair, which point to genome instability as an important mechanism of HDV hepatocarcinogenesis. These data suggest that HBV and HDV promote carcinogenesis by distinct molecular mechanisms despite the obligatory dependence of HDV on HBV.